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					Localization of Lesion
General:     Scope of problem:       neurological, systemic or psychiatric?                                                                     "HAL"
             Location: Central - cerebrum, BS & cord
                         Peripheral - anterior horn cell, nerve roots, peripheral nerves, NM junction or muscle
Motor:
UMN lesion                          UMN: from CNS to pre-synaptic axon of a-motor neuron
          Hypertonia - spastic paralysis                                                                                                 HAL:
                                                                                                                                                           Motor
          No fasciculations                                                                                                              Head
          Babinski                                                                                                                       Arms
          No significant muscle atrophy (only disuse w/ time >> atrophy)                                                                 Legs
          Hyperreflexia, possibly clonus
          Corticospinal:            weakness greater in flexors of LE & extensors of UE >> extended leg, flexed elbow, wrist and fingers
                                    Clasp-knife resistance to mvmt >> tone initially increases as muscle is stretched, then may decrease
                                    Difficulties with fine motor control
          Basal ganglia:            Lead-pipe rigidity >> resistive tone continuous throughout
          Pronator drift: good test >> supination more affected than pronation >> pt shows pronation on outstretched supinated arms                        Sensory
          May have visual field or CN defects

LMN lesion                              LMN: from neuronal cell body of a-motor neuron to the muscle                                                    Myomes:
             Hypotonia - flaccid paralysis                                                                                                      C345    diaphragm
             Fasciculations (due to fatigue)                                                                                                    C4      shoulder shrug
             No babinski                                                                                                                        C5      deltoids
             Significant muscle atrophy                                                                                                         C7      extend elbow
             Hyporeflexia                                                                                                                       C8      abduct fingers
             Neuropathies:              Muscle weakness affects distal muscles > proximal (more difficult to open bottle than use hair dryer)   T1-12   chest exp
             Myopathies:                Muscle weakness affects proximal muscles . distal (more difficult to brush hair than squeeze ball)      S 1-2   plantarflex foot
             CN signs without long tract signs                                                                                                  L2      hip felxion
                                                                                                                                                L3-4    knee extension
Weakness patterns:       Monoparesis: one extremity                          Paraparesis: both LE (THINK CORD)                                  L5-S1   dorsiflexion foot
                         Hemiparesis: 1 side of body                         Quadriparesis: 4 extremities
Motor Syndromes:                                                                                                                                        Dermatomes
          Pure Motor Syndrome:                    ALS or "loe gehrig's dz"             SMA (spinal muscle atrophy)              Poliomyelitis   C4      upper thorax
                                      ALS & polio are symmetrical; SMA is asymmetricSymmetric:                                                  C5      shoulder
                                      Muscle atrophy, fasiculations, hyporeflexia & hypotonis                                                   C6      digits 1 & 2
                                                                                                                                                C7      digits 2 & 3
             Peripheral Neuropathy:Sensory & motor symptoms - may have autonomic sx                                                             C8      medial hand
                                   Stocking glove distribution - begins in toes, fingers >> proximally to legs,arms             ↓reflexes       T1      inner forearm
                                                                                                                                                T2      inner arm
             Mononeuropathy:          Motor & sensory in one peripheral nerve distribution                         Ex. carpal tunnel            L2      anterior thigh
                                                                                                                                                L3      anterior knee
             Neuromuscular junction defect:        Myasthenia Gravis - symmetric                      refelexes may be decreased or nml         L4      medial calf
                                                                                                                                                L5      great toe
Sensory:     May follow distribution of peripheral nerves                   May be dermatomal                                                   S1      lateral foot/heel
             May be a level below which sensory functions are lost - consistent with a cord lesion                                              S2      posterior calf
             Crossed distribution: Sensory loss on face of one side & contralateral hemibody >> BS lesion on side of facial invlvment           S2-5    perineum
             Stocking glove distribution - indicative of peripheral neuropathy
Cord patterns:         8 cervical, 12 thoracis, 5 lumbar & 5 sacral segments
            Spinothalamic:           pain, temperature & crude touch                     enters cord, immediately crosses and ascends to thalamus, synapsing at VPl nucleus
                                     lesions >> loss of pain, temperature contralaterally below level of lesion
            Dorsal Column:           proprioception, vibration and fine/discriminative touch
            (Medial Lemniscus)       path enters cord, stays on same side >> decussates in medulla >> VPL thalamus                                                  DTRs
                                     fasciclus cuneatus - lateral in cord, UE            fasciculus gracilus - medial in cord, LE                      C5           Biceps
                                     lesion >> loss of proprioception & vibration ipsilaterally below the level of the lesion                          C6           Brachioradialis
Bilateral sensory & motor deficits below a level of trunk (nml above) = cord lesion at or above that level - may have pn at level                      C7           Triceps
                                                                                                                                                       C8           Finger flexors
            Reflexes: Tend to be hyperactive in cord lesions                If dysfunction in anterior horn cells >> hypoactive reflexes               L3-4         Patellar
                       Spinal shock: ransient loss of refelxes after acute cord injury >> often follwed by dev't of hyperreflexia                      S1           Achilles

Syndromes:               Anterior spinal artery (stroke)       Brown-Sequard (hemiicord)              Combined (Ex. MN Dz - UMN + LMN)
                         Cord Transection                      Conus Medullaris (leg wekness)         Central cord syndrome

             Brown Sequard: (UMN)Motor deficits of CST and sensory deficits of dorsal columns are ipsilateral               Sensory deficits of ST are contralateral
             (Cord hemi-section) Crossed findings: Ipsilateral spastic paralysis, loss of position/vibration below lesion; contralateral loss of pn & temp below the lesion

             Transection: (UMN)       All tracts involved                                Early spinal shock >> later spastic paralysis below the level of the lesion (UMN)
             (ex. trauma, TM)         Bladder, bowel, sexual dysfunction                 Skin changes & impaired sweating                   Reflex voiding & spasms

             Central Cord syndrome: (UMN)          Crossed spinothalamic tracts          Dissociated sensory loss              "cape-like, pain and temp loss
             (ex. syrinx, glioma)                  Spastic paresis below the level       Flaccid paresis at level of lesion

Brainstem:
           Cranial nerve involvement suggests abnormality of brainstem or CNs upon exit from brainstem
           BS lesions tend to >> multiple signs                CNs are best way to dtermine level of BS lesion (midbrain, poncs or medulla)
           If BS lesion>> associated long tract signs affecting motor, sensory or cerebellar tracts
                         Example: Pt with diplopia, resolves upon covering one eye = disorder of ocular motility
                                     Findings: weakness of L abduction - due to weakness of L abducens (CN VI palsy)                         R hemiparesis = L corticospinal tract
                                     Lesion:      Left ventral low pontine -              L side: lesion will be ipsilateral to CN VI       Corticospinal tract is ventral
                                                                                          CN VI traverse lower pons before exiting BS
           If lesion involved CNs after exit from BS, there will be no long tract signs (Ex. Bell's Palsy)
Crossed Findings:
           Crossed sensory:          Decreased pn/temp on 1 side of face and opposite side of body implies lesion b/t pons & C2 (ipsilateral to facial numbness)
                                     Pn/temp path for face enter pons via trigeminal >> path descends on same side of BS and cord down to C2 >>
                                                  Path then crosses and ascends on opposite side
                                     Descending path (pons to C2) is close to ascending path conveying pn & temp from contralateral body
                                                  Ascending path crosses at C2 >> facial sensation tract & ipsilateral extremity tract are now on same side
                                                  Decreased pn/temp on 1 side of face & same side of body >> contralateral lesion in upper BS or higher
             Crossed Motor:           Facial weakness ipsilateral to to body weakness >> lesion in high pons or above
                                      Facial weakness contralateral to body weakness >> lesion of midpons (affecting CN VII or CS tract) on same side of facial involvement
             Facial weaness:          UMN lesions spare the forehead                     LMN lesions affect entire hemiface
Thalamus: All sensory modalities affected in contralateral hemibody         face = arm = leg
Neuro-Opthalamic:                  LR6 SO4 AR3
          Aniscoria: (pupillary inequality)
                     Increased in dim light implies the miotic (constriction) eye is abnormal - owing to physiologic dilation of normal eye
                     Miosis with ptosis = Horner's syndrome
                     Mydriasis (dilation) with ptosis >> CN III palsy                  More marked ptosis than seen in Horner's
                                   Mydriasis implies a compressive lesion affecting CN III
                     Loss of abduction, with sparing of pupillary fibers >> abnormality of internal fibers (vasculitis or diabetes)

            Diplopia:   due to lesion in BS or periphery, but NOT THE CORTEX
                        Loss of extraocular muscles - should resolve w/ covering one eye             Persistance >> monocular problem of eye, misinterpreted as diplopia

           Gaze palsy: impaired mvmt of both eyes in one direction >> due to lesion in cortex
                       lesion of cerebral hemisphere >> eyes go toward the lesion                 lesion of BS >> eyes go away from lesion
                       can overcome gaze deviation w/ Doll's eye maneauver (but not if deviation is due to BS lesion)

            Vision:     Pathway - retina >> optic nerve >> chiasm >> optic tract >> radiation >> lateral geniculate of thalami >> optic radiations of parietal & temporal lobes >>
                                     calcarine cortex of occiptal lobe (brodman area 17)
                        Pre-chiasm lesions:       affect monocular vision
                        Chiasmal & post-chiasmal lesions: affect visual fields of both eyes                      Chiasm lesion >> bilateral hemianopia (decr peripheral vision)
                                     Post-chiasm >> homonymous hemianopsia (R lesion >> loss of L visual field in both eyes)


Cerebellum:            Acts to dampen oscillations of our body mvmts
          Ipsilateral motor innervation - due to double ccrossing in BS and thalamus
          Lesions >> ipsilateral ataxia                      Midline lesions >> affect trunk & LE                Hemispheric lesions >> affect UE
          Classic findings:        ataxia (wide-based gait)               dymetria (past-pointing)               intention tremor (F-N testing)
                                   nystagmus                              loss of coordination

Cerbral Hemispheres: Frontal, parietal, temporal & occipital lobes                                          L side of brain wants eyes to look R
          Hemispheres connected by several crossing paths - major one is corpus callosum
          Motor:      planning & execution are primarily in frontal lobe           primary moror cortex (B 4) - precentral sulcus
          Sensory:    posterior                                                    primary sensory cortex (B1, 2, 3) - postcentral sulcus
          Broca's: (B 44) center for speech. Inferior frontal gyrus               Wernicke's: language comprehension, temporal lobe
          Primary auditory cortex: (B 41) - superior temporal gyrus                Primary visual cortex: (B 17) - calcarine cortex of occipital lobe

Consciousness:        Maintained by reticular activating system of the BS
          Lesion of one hemisphere will not affect consciousness as long as other hemisphere is functionally intact
What is the Lesion
Neuro sx: Memory change                ∆ LOC        Dizziness    Pain/HA      Tingling      Weakness     Numbness                  Disorders of special senses
Disorders: Of consciousness - syncope, seizures, delirium, coma:                            Of special senses or dizziness                   Of intellect & behavior
           Of motility - myopathy, neuropathy, stroke, mvmt disorders                       Of pain & sensation - HA, neuropathy, radiculopathy
Categories of Disease:                 VITAMIN DEC
           Vascular:      destruction of cerebrovascular sx - usually due to hemorrhage or occlusion
                          infarction may be by thrombosis or embolic occlusion            sx always acute
                          hemorrhagic may be focal (sub-dural hematoma) or diffuse (sub-arachnoid hemorrhage)
            Infectious:   focal (cerebral abscess) or diffuse (meningitis, encephalitis);   Timing is subacute & progressive       More chronic - neurosyphilis, Lyme & HIV
            Traumatic: Generally acute in onset, diffuse or local, static or progressive
            Inflammatory:              Subacute or chronic, with multifocal deficits
                                       AI dz has a relapsing course - MS, SLE, vasculitis, chronic inflammatory demyelinating neuropathy, guillain-barre
            Metabolic/toxic:           Disturbances of cellular metabolism w/o structural lesion                     Generally diffuse
                                       Ex - drug toxicity, hyperglycemia, electrolyte abnormalities, thyroid dz, B12, hepatic dysfunction, hypoxemia
            Iatrogenic:   Unintended complication of medical or surgical therapy
            Neoplastic: Most often chronic, focal & progressive
            Degenerative:              Most often chronic, diffuse & progressive                         Implies dysfunction of 1+ parts of NS after nml functioning for decades
                                       Ex - Alzheimer's & Parkinson's
            Epileptic:    Disordered electrical activity of the brain         Sx may be motor, sensory or psychic - usually acute & transient
            Congenital or familial:    Chronic diffuse dzs                    Ex. MS, Charcon Marie-Tooth dz, Huntington's
Diagnostics:              Hematology, biochemistry, microbiology                                         Imaging - CT, MRI, ultrasound, angiography, myelography
                          Phys - EEG, EMG, NCS, Evoked potentials, sleep studies                         Path - lumbar puncture, biopsy
Cortical Syndromes:
Aphasia:    (or dysphasia)             Loss or impairment of language as a result of damage to language center in dominant hemisphere
            different from dysarthria (problem in speech articulation
            good bedside screening is to have pt read & write a sentence - writing invariably affected in pts with language disturbance
            Broca's:       severe disruption in fluency, w/ impaired expression in both speech & writing              comprehension may be mildly affected
                           usually accompanied by contralateral face & arm weakness due to proximity of Broca's are to motor homunculus                  inferior frontal lesion
             Wernicke's: inability to comprehend spoken or written language                pts speak fluently, content is meaningless         posterior, superior temporal lesion
                           some have contralateral homonymous hemianopsia
            Conduction: inability to repeat a spoken phrase - though pts have nml comprehension                       supramarginal gyrus lesion
            Global:        large frontal lobe lesions >> affects all language areas

Agnosia:    inability to recognize a specific sensory stimulus - despite preserved sensory function                   usually occiptotemporal lesion

Apraxia:    inability to perform learned motor tasks despite sufficient memory & sensorimotor function to understand the command
            lesions usually dominant inferior parietal lobe
            R parietal >> hemispatial neglect (pt ignores L field)                          often accompanied by anosognosia - lack of awareness of deficit
            Extinction: milder form of neglect - pt responds to contralateral stimuli, but when presented with bilateral stimuli >> they respond only to the ipsilateral side
ICP
Anatomy: Meninges: pia, arachnoid & dura mater
         Venous sinuses:          cerebral veins that drain to systemic circulation via jugulars
         Ventricles: Houses CSF
         Choroid Plexus: line ventricles & produces CSF as ultrafiltrate of the blood
         Arachnoid villas:        1-way valves that allow CSF to be absorbed back to blood
                                  CSF enters blood via the venous sinuses
                                  CSF turned over 3x in 24 hr
                                  IF not absorbed correctly >> increased ICP

ICP:        Monro-Kellie doctrine: ICP constant as long as nml vol of blood, brain & CSF exists
            Arterial blood pressure to brain is tightly autoregulated b/t/t 50 & 150
                          Increased ICP >> decreased cerebral blood flow & ischemia in brain
                          Blood flow also changes with ∆ in pCO2
                          If pt hyperventilating >> decreased CO2 >> further decrease in cerebral blood flow
            Venous pressure maintained by draining of venous sinuses                      venous sinus thrombosis >> block sagittal sinus >> stroke
            In pts w/o intracranial masses or lesions, pressure in lumbar subarachnoid space will reflect intracranial pressure >> can be obtained via LP
                                       When doing LP - always first get opening pressure, then get fluid sample
            Queckenstedt test:         Normally when doing an LP, should use manometer to look at opening pressure
                                       If you occlude jugular at same time, should be able to see the CSF level in the manometer rise
                                       If you stop occluding jugular >> CSF level should fall - way of testing patent venous circulation
            Cushing's response:        ICP unchecked >> extreme HTN & bradycardia (>>change in LOC)
            At low levels of pressure >> small changes in vol don't lead to large changes in pressure
                          As pressure gets very high, even small changes in volume >> mayhem b/c pt is unable to compensate
Causes of ↑ ICP:
            Stroke >> edema >> herniation            Meningioma (benign - but may be large ) >> mass effect >> shifts brain to one side >> ICP            Herniations
            Hydrocephalus = too much CSF                                                                                                                  1. Cingulate
                          Obstructive Hydrocephalus (ex. tumor in aqueduct of sylvius)       LP contraindicated                                           2. Uncal
                          Non-obstructive or communicating Hydrocephalus - no focal                                                                       3. Cerebellar tonsillar
                          Nml Pressure Hydrocephalus >> Triad: gait disorder, urinary incontinence & dementia (late)                                      4. Upward cerebellar
                                       B/c normal opening pressure on LP >> responds to shunting                                                          5. Transcalvarial
Herniation Syndromes: Sx depend on method of herniation
           Downward herniation phases:
           1st - midbrain phase:  CN III palsy, somnolence due to impingement on RAS & pupillary enlargement
           2nd - pons phase:      EOM problems (use doll's eye test if unconscious - eyes should move opposite)
                                  Cold caloric test >> activates III, IV, VI >>nystagmus to opposite side
                                              (in case of coma, you get slow deviation to same side)
                                              COWS:        Cold opposite, warm same
           3rd - medullary:       abnormal breathing & circulation

Sx:         Acute:        HA, N/V, ∆ LOC, visual disturbances, Cushing's - may progress to herniation syndrome
            Chronic:      HA, lethargy, cognitive changes, papilledema, CN VI palsy, gait disturbances

ICP Rx:     Vasogenic edema (ex. tumor) - rx w/ steroids                     Cytotoxic edema (ex. stroke) - hyperventilate pt & use osmotic agents
            Remove mass if ICP due to mass effect
Diagnostic Approach to ∆ LOC
Causes:     Meningeal irritation        Should test kerning's & brudzinki's reflexes
            Hemispheric mass lesion >> lateral or transtentorial (vertical) herniation
            Brain stem mass lesion
                          Pathways for lateral eye mvmts (pontine gaze center, medial longitudinal fasiculus & oculomotor or CN III nucleus) traverse RAS
                          Impairment of reflex eye movements is critical element of diagnosis
            Non-communicating hydrocephalus - posterior fossa lesions block flow of CSF from ventricles
            Metabolic encephalopathy
            Postictal state of seizures

Separating structural from metabolic coma:                   1. Motor response       2. Pupillary function     3. Reflex eye movements
           Motor response:          Apply painful stimulus
                        Hemispheric masses:
                                    Diencephalic stage (early) >> appropriate mvmt of 1 of upper extremities toward painful stimulus
                                    Late diencephalic (mass expands to thalamus) >> reflex arm flexion & extension & external rotation of legs - decorticate posturing
                                    Midbrain >> both arms & legs respond by extension - decerebrate posturing
                                                pupils also become midposition in size & light reflex is lost
                                    Pons >> no response to painful stimulation
                        Metabolic lesions:      Do not compromise brain in a progressive, level by level manner

            Pupillary reactivity:      In metabolic coma, pupillary reactivity is present
                                       Reactivity is lost only when coma is so deep that pt requires ventilatory & BP support

            Reflex eye movements:      Presence of induced movements reflects integrity of pons & midbrain
                                       Stimulated with doll's eye maneuver and caloric testing
                                       Lack of inducible mvmts in setting of preserved pupillary reactivity >> diagnostic of drug toxicity


Clinical Criteria for Brain Death
            No response to external stimuli
            No reflex activity - except of cord origin
            No pupillary response to light
            No corneal reflex
            No eye mvmt w/ doll's eye or calorics
            No gag reflex
            No cough reflex
            Apnea in presence of adequate O2
CNS Tumors
General:    Benign or malignant               Metastatic > Primary (20 to 40% of systemic tumors metastasize)              Lung, breast, melanoma, renal & colorectal
            Most are glial (brain, cord & Cans), then meningeal and pituitary                     Gliomas (including glioblastoma & meningioma) account for close to 1/2
            Watershed areas:          (junction b/t grey &white ) Most common site of metastasize
                                      Sx:     ICP, seizures, focal deficits, impaired cognition, morning N/V
                                      Rx: depends on disease & tumor type                         May include steroids, radiation, surgery or chemo

Epi:        Incidence low in young adults >> increases with age
            Childhood tumors most common in brain/CN/cord & cerebellum >> most commonly astrocytoma & medulloblastoma
            M> F                    Incidence > in developed countries

Etiology:   Majority idiopathic             Envt'l Carcinogens - vinyl chloride, pesticides, electromagnetic waves, cell phones ??
            Viral or dietary?               Radiation therapy                      Genetic:     Li-Fraumeni (loss of tumor suppressor gene), Tuberous sclerosis

Classification:         Based on histological cell of origin - glial, neuronal, meningeal, germ cell or embryonal
Clinical:   Signs/sx:   Function of location, location, location                  Depends on tumor growth rate, histology, genetics & age
                        May >> obstruction of CSF and increasing ICP
            Non-localizing sx:       HA: initial sx in 20-25% of adults           Classical of ↑ ICP = worse in morning, am lethargy and N/V
                                            Concern if relatively new onset or change in pattern
                                     Vomiting:            in morning, may be projectile
                                     Seizures:            occurs in 35%           more common in low-grade glial/neuronal tumors
                                                          may be focal >> complex partial                  may be generalized
                                     ∆ mental status: emotional lability, ↓lability, blunted affect, memory
                                     Kids: developmental delay or arrest, declining academic performance

            Localizing sx:          Frontal lobe:      seizures, ∆ in intellect/behavior or social skills, focal weakness, expressive aphasia (if dominant)
                                    Partial Lobe:      seizures, sensory (cortical), neglect syndromes
                                                                     R side >> spatial disorientation or L homonymous hemianopsia
                                                                     L side >> receptive aphasia or R homonymous hemianopsia
                                    Temporal:          personality change, auditory hallucinations, complex partial seizures & quandrantanopia
                                    Infratentorial:    (kids)        HA, N/V, am lethargy
                                           Cerebellar: limb ataxia if lateral lobe             truncal or gait ataxia if midline/vermian
                                           Brainstem: crossed hemiparesis, CN issues, diplopia/EOM difficulties, swallowing issue or vomiting
                                           CPA angle: CN VI, VII, VIII
                                           Sellar:     Endocrine - diabetes insipidus, precocious or delayed puberty
                                                       Pineal - lid retraction, decreased upgaze, nystagmus, convergence/retraction (eyes jerk up into brain)

Dx:         MRI most sensitive, CT greater availability              Contrast enhanced more telling

Rx:         Combo of chemo, surgery, radiation & biologics
CNS Malformations - PATH
Neural tube closure defects:         (maternal folate deficiency may contribute to defect)
           Anecephaly:               defective closure of rostral end of neural tube          Absent cranial vault & brain
           Myelomeningocele:         defective closure of caudal end of neural tube           Malformed cord & meninges protrude thru column defect & skin

Arnold - Chiari malformation:        defect in skull formation >> deficient posterior fossa volume
                                     herniation of cerebellum through foramen magnum into cervical spine canal
                                     downward displacement & malformation of BS                            Usually accompanied by hydrocephalus
                                     kinks in neural axis >> medulla overrides cord & roof of mid-brain protrudes as beak-like deformity

Dandy - Walker malformation:         arrested/failed hindbrain development                    cerebellar vermis entirely replaced by dilated/cystic 4th ventricle

CNS Tumors - PATH
Sources:    50% primary, 50% metastatic                                            ↑ in primary brain lymphoma with HIV
            Cells of CNS:             Primitive precursor cells (2%) - medulloblastoma (always in cerebellum)
                                      Gllia (75%) -       (astrocytes, ependymal cells, oligodendrocytes)>> Astrocytoma, ependymoma, oligodendroma
                                      Neurons - ganglion cell tumors                     Meninges (15%) - meningioma             Schwann cells - schwannoma
            Metastatic tumors
            Anterior pituitary -      pituitary adenoma
            Misplaced germ cell precursors - germ cell tumors
            Uncertain histogenesis - craniopharygioma, hemangioblastoma

Pediatric CNS tumor: 50% of all solid CNS tumors in those < 18 y/o            Most are Infratentorial (below tentorium cerebelli)
           Most common:           medulloblastoma in cerebellar vermis or IV ventricle                  ependymoma in IV ventricle
                                  astrocytoma:       Diffuse -    BS or glioblastoma multiforme         Circumscribed - pilocytic astrocytoma or in cerebellar hem.
                                                     Cystic favor cerebellum, solid tumors & glioblastoma multiforme favor cerebrum

Adult CNS tumors:        70% supratentorial, 30% infratentorial
                         Most common:        high grade astrocytomas - glioblastoma multiforme or anaplastic astrocytoma
                                             metastatic carcinoma                 meningioma               pituitary adenoma         schwannoma

General:    morbidity/mortality of CNS tumors poorly correlates w/ conventional benign/malignant criteria             correlates best w/ surgical resectability
            primary CNS tumors rarely metastasize beyond CNS - CNS lacks lymph drainage
            CNS tumors act as space-occupying mass >> infiltrate, expand & displace normal CNS tissue                 Cerebral edema >> increased mass effect
            High grade tumors lack normal CNS BBB                                Fixed cranial vault >> ICP and herniation

Brain herniations:       Subfalcine (cingulate):         cingulate gyrate gets extruded by expanding frontal/parietal mass          may compress ACA
                     Transtentorial (uncal, hippocampal) uncus gets wedged into cleft b/t tentorium & cerebral peduncle of midbrain
                                                         pushes midbrain against contralateral tentorium >>ipsilateral hemiparesis            compresses PCA
                                                         compress CN III >> ipsilateral fixed dilated pupil
                         Tonsillar (cerebellar):         inferior part of cerebellum (tonsils) pushed into foramen magnum >> compresses medullary resp. center
                                                         May result from spinal tap in pt with ICP
                                                         Check for papilledema, get CT or MRI before tapping pt with ICP
Gait Abnormalities
Elements of normal gait:
           posture:      erect body, head straight - muscles include erector spinae & extensors of hips and knees            Evaluation:
           arm swing: hang by side, each moves forward with opposite leg                                                     walk naturally            stand w/ feet together
           stepping:     slightly everted feet, equal steps, heel strikes first                                              eyes open & closed
           base:         medial malleoli almost touch as each foot passes the other (narrow)                                 walk fwd & backwards (eyes open & closed)
           muscle coordination:       flexion of hip & knee, dorsiflexion of foot                                            walk heel to toe, on heels, on toes
           equilibrium:               maintain balance at right angles to direction of mvmt                                  walk, stop & turn briskly
           propulsion: leaning fwd & slightly to one side >> permits body to fall a bit before being checked by the support of the leg

Control:     corticospinal tracts:      controls voluntary, discrete, skilled mvmts
             extrapyramidal basal ganglia subcortical motor systems:           "fine tunes" voluntary mvmt via motor feedback circuits                    proprioception:
                            basal ganglia issuues >> choreiform mvmts, athetosis, tics, etc..                                                             reflexes
             peripheral nerves & muscles:            sensation & strength                                                                                 vestibular system
             cerebellar paths (cerebellar influences are ipsilateral)                                                                                     vision
             prefrontal cortex & associative zones: initiation of mvmt, memory & storage of learned elements of walking (deficit >> APRAXIA)

Apraxia:     Motor strength intact, but pt can't figure out how to walk                 Need to disturb prefrontal regions bilaterally - one side can typically compensate
             Ex. dementia or normal pressure hydrocephalus
                          NPH: dilated ventricles >> enlarged frontal horns >> neurons of legs & bladder stretched bilaterally>> apraxia & bladder dysfunction

Input to anterior horn cell:           Subcortical: reticulospinal tract (from RAS), vestibulospinal (balance proprioceptive info), rubrospinal (cerebellar & vestibular info)
                                                    All three tracts are excitatory
                                       Corticospinal tract:      voluntary mvmt >>inhibitory (damage, as in UMN lesion, >> hyperreflexia
                                                                 Ex. L corticospinal tract injury (MCA) >>R arm stuck in flexion, R leg stiff >> circumducted gait
Gaits:
Cerebellar: wide-based, unsteadiness & irregularity of steps, lateral veering                           can't stand steadily with feet together (eyes opened or closed)
            Ddx:         MS, medulloblastoma tumor, cerebellar degeneration, ETOH
Sensory Ataxia:          wide-based, legs are flung abruptly fwd and feet slap on floor; irregular steps of varying length & height
                         pts carefully watch the ground for guidance                                    Positive Romberg
            Ddx:         Polyneuropathy or posterior column damage - tabes dorsalis, B12 deficiency
Spastic Gait:            hemiplegia or hemiparesis - leg held stiffly, rotates outward (circumducted), foot plantar flexed & scrapes the floor; arm held fixed & flexed
            Ddx:         stroke, trauma, MS
Scissors Gait:           bilateral spastic paresis - gait is stiff, each leg advances slow with thighs crossing fwd on each step; steps are short
                                                                  pt looks like they are "walking through water"
Festinating Gait:        hastening or involuntary acceleration of gait; stooped posture (body trying to catch up to head), rigidity & short, shuffling steps;
                         arms flexed at elbows and at wrist, with decreased arm swing                   pt turns around stiffly "all in one piece"
            Ddx:         Parkinson's
Steppage or equine gait: foot drop, excessive flexion at hip due to weak foot >>slapping noise as foot hits floor
            Ddx:         poliomyelitis, charcot-marie tooth dz
Waddling gait:           weakness of proximal muscles, inability to stabilize weight bearing hip >> cause it to bulge out & opposite side of pelvis to drop
            Ddx:         muscular dystrophy, congenital hip dislocation
Staggering/drunken gait:              pt totters, reels, tips forward & backward, impaired control of trunk & legs, irregular steps
            Ddx:         barbituate or ETOH intoxication
Normal Pressure Hydrocephalus: wide based, short steps, shuffling, slow & decreased arm swing (similar to Parkinson's & frontal lobe gaits)
Frontal Lobe Disorder: flexed posture, wide based, shuffling & hesitant steps, sometimes halting, difficulty initiating steps - feet "glued to floor"
Gait of elderly:         slightly stooped posture, slowness & stiffness of walking, shortening & broadening of stride, decreased ability to correct misstep
Sleep Disorders
Why sleep?    Impaired cognitive function:             inattention, irritability, delayed reaction times, impaired memory, impaired motor function
              Impaired motor function:                 tremor, incoordination, blurred vision, prolonged motor reaction time
              Other incentives:          impaired sexual function, micro sleeps intruding into wakefulness (mini blasts of sleep during the day)
              Medical implications:      ↑ risk of stoke, long-term obesity, impaired immune function, HTN, Dm, CAD, misdiagnosis of ADD, HA, mood disorders, acne
              Social implications:       poor performance, difficulty w/ relationships, accidents, substance/ETOH abuse
                                                       Adults require 7-9 hours of sleep in a regular pattern
Stages:       Must cycle through all 5 stages of sleep, in orderly sequence with adequate time in each stage for it to be restorative
              Stages III & IV are the slow waves sleep that restore you physically
              REM sleep: Occurs every 90-100 minutes                             Dreaming - yet no memories of the dream formed
                             Cognitive cortex off line                           muscle paralysis - atonia
                             Restores psyche                                     Time for learning - learning augmented with 2 nights sleep
                             On EEG - looks like brain is awake and eyes are open >>saw-toothed waves
Normal patterns:                           Young Adults                                                        Elderly                        Sleep in aging:
             REM longer                                                         Dark lines indicate REM                                       longer sleep latency
             in 2nd 1/2 of nt                                                                                                                 ↓total sleep time
                                                                                                                                              ↓ slow wave sleep
                                                                                                                                              ↑ fragmentation
                                                                                                                                              go to bed & get up earlier
              Puberty:          delayed sleep phase (stay up late…)
Sleep onset signals:         day/night & light/dark, process S (# of hours that you have been awake), circadian rhythm of hormones, HABIT
Regulation: Thalamus:        cortical activation & EEG synchronization                      Hypothalamus: sleep/wake switch
               upper Chiasmatic Nucleus: Circadian clock                                    Brainstem: RAS
Insomnia      Symptom not a diagnosis                Sleep onset difficulties, multiple nighttime awakenings, early morning awakenings
                            Onset:      affected by anxiety, delayed sleep phase/internal clock, drugs               Habit becomes perpetuating
                            Multiple night time awakenings:       obstructive sleep apnea, periodic limb mvmts of sleep, reflux, bruxism (teeth grinding)
                            Early am awakening:      depression, disordered chemistry
              Need for sleep study?     loud disruptive snores (esp if obese), limb mvmts, unexplained multiple night time awakenings, unusual nocturnal behaviors
Obstructive Sleep Apnea:                     Intermittent collapse of pharyngeal airway during sleep
              Risk factors:     M>F                                   Short neck or large neck circumference                                Long thin neck
                                Obesity                               Retro- or microagnathia (fore-shortened jaw)                          Age > 50
              Physiology:       Airway collapse >> obstruction >> ↓O2 >> detected by carotid bodies >> arousal response >> pharynx opens >> snort & airflow restored
                                HR slows during apneic phases                     Recurrent nocturnal hypoxemia
              Sx:               loud, disruptive snoring, daytime hypersomnia
              Rx:               CPAP (continuous positive airway pressure)        Wt loss      Dental/jaw advancement devices    UPPP (uvulopalatopharyngoplasty)
Narcolepsy: Chronic neuro disorder characterized by:          excessive sleepiness, sleep paralysis, hypnogenic hallucination, cataplexy & sleep fragmentation
                          Cataplexy: emotionally-induce, brief, reflex muscular atonia (spares respiratory muscles) - laughing is most common inducer
Restless Leg Syndrome & Periodic movements:
              Daytime sx: building tension & limb discomfort, irresistible urge to move, myoclonic jerk-like mvmts, difficulty in confined spaces
              Night:      persists as periodic limb movements

Parasomnias: Sleep related motor disorders >> brief arousals                    Sleep walking & talking, nocturnal eating, bruxism
Strokes
Epi:         3rd leading cause of death in US, leading cause WW
             more W die from stroke than breast cancer
             leading cause of LT disability WW
General:     stroke = abrupt onset - inadequate blood flow (ischemic) - 80%           area of insult irreversible
                                                  may be focal (thrombotic or embolic or global (↓perfusion)
                                      hemorrhage into brain tissue (parenchyma hemorrhage)
                                      hemorrhage into subarachnoid space (subarachnoid hemorrhage)

Risk factors:             Age - every decade after 55 >> risk doubles
                          HTN         DM           Smoking CAD              Hypercholesterolemia      A fib
Anatomy: brain supplied by 2 major arteries -carotid (anterior) & vertebral (posterior)
Anterior circulation:  common carotid >> internal & external branches
                       ICA >> carotid canal >> cavernous sinus as carotid siphon >> gives off ophthalmic, anterior choroidal & P comm branches >>
                                    then bifurcates into ACA (medial supply) & MCA (lateral, BG & subcortical white
Posterior Circulation: Vertebral arteries go up w/I transverse processes of cervical vertebrae
                       gives off a branch to form anterior spinal artery and posterior inferior cerebellar (PICA) >> 2 Vas unite to form basilar
                       Basilar supplies cerebellum via anterior inferior cerebellar artery (AICA) and superior cerebellar artery (SCA) >>
                                    basilar then bifurcates into posterior cerebral arteries (PCAs)
Circle of Willis:      at base of brain - union of both ACAs via A Comm; union of ICA with PCA via P Comm                     communication b/t posterior and anterior
                       congenital abnormalities of circle are common >> decreased collateral circulation
Ischemic Stroke:
General:     Cerebral ischemia may result from thrombotic or embolic occlusion OR decreased cerebral perfusion
             Classified as either pale (anemic) or "hemorrhagic" (areas of endothelial necrosis)
             core:        immediately infarcted &irreversible
             ischemic penumbra:         moderately ischemic tissue in b/t normal tissue & infarcted central core
                                        viability for a few hours, can be salvaged target of acute stroke therapy
             global ischemia usually due to cardiac arrest or v fib - pure hypoxia rarely causes irreversible injury
             Atherosclerosis accounts for 2/3rds of strokes - by embolization to distant vessels or in situ thrombosis
Cerebral edema:           Intracellular (cytotoxic): develops rapidly in ischemic neurons due to ion pump failures
                          Interstitial (vasogenic): due to damage to endothelial cells >> BBB breaks down
                          Fluid accumulates over 3-5 days after ischemic stroke >> can result in herniation/death
TIA:         reversible focal dysfunction - usually lasts minutes        most resolve w/i an hour
             TIA pts who go to ED - 5% have stroke in next 2 days, 25% have recurrent event in next 3 months
                                                                                                                                 Predisposed to Atherosclerotic Plaque
Lacunar:                                                                                                usually associated w/ chronic HTN (also DM & smoking)
             Small, deep infarction due to athero sclerosis of penetrating branch of large cerebral artery
             pure motor hemiparesis due to lesion in internal capsule                      ataxic hemiparesis - weakness & ataxia due to lesion in internal capsule or pons
             pure sensory syndrome - if lesion in thalamus                                 may >> multi-infarct dementia (slowly progressive mental deterioration)

Brainstem: Midbrain (Weber's syndrome) - Ipsilateral CN III (eye down & out), contralateral hemiparesis
           Pons: quadri- or hemiparesis, horizontal gaze paresis, facial weakness, ataxia, dysarthria
           Medulla: (Wallenberg syndrome) - ipsilateral facial & contralateral body numbness, ipsilateral ataxia, ipsilateral Horner's, vertigo, N/V, dysarthria, dysphagia
           Cerebellum: dysarthria, ipsilateral ataxia, vertigo, tremor, nystagmus
Major Stroke Syndromes:
ICA:        retinal artery or MCA distribution >> variable ipsilateral blindness * MCA syndrome
MCA:        Main trunk:               Contralateral hemiplegia, hemianesthesia (face & arm > leg)                homonymous hemianopsia, gaze deviation toward infarct
                                      global aphasia (dominant side)                                             anosognosia/ unawareness of illness (non-dominant)
            Superior trunk:           faciobrachial weakness                            expressive (Broca's) aphasia - dominant         motor neglect: non-dominant
            Inferior trunk:           sensory impairment (astereognosis)                fluent (Wernicke's )aphasia - dominant
ACA:        contralateral hemiparesis & hemisensory loss (leg > arm/face)               abulia: lack of initiative & akinetic mutism                   urinary incontinence
VA/PICA: Ipsilateral facial sensory loss, hemitaxia, nystagmus, Horner's                Contralateral loss of pn/temp         dysphagia
SCA:        Gait ataxia, nausea, vertigo, dysarthria
BA:         quadriparesis, dysarthria, dysphagia, diplopia, somnolence, amnesia
PCA:        contralateral homonymous hemianopsia, amnesia, sensory loss

DDx:        If sudden onset & persistent focal deficit >>      ischemic stroke          intracerebral hemorrhage              postictal paralysis      subdural hematoma
                                                               abscesses w/ seizure     tumor w/ bleed or seizure             hypoglycemia             MS
ER evaluation:            Vital signs & finger stick glucose                  EKG                   Chest X-ray               Head CT (non-contrast)
                          Labs:        platelets, PT/PTT, glucose, electrolytes, CBC, LFTs, BUN/Cr, cardiac enzymes
Rx:         Prevention focused on antiplatelet therapy
TPA:        Inclusion criteria:     18 y/o in setting of acute ischemic stroke           clearly defined onset time & able to treat within 3 hours
                                    measurable neuro deficit                             baseline CT w/ no evidence of intracranial hemorrhage
            Exclusion criteria:     Improving sx (indicates artery opening)              stroke or head trauma w/I 3 months
                                    major surgery w/I 14 days                            Hx of ICH                             Suspected SAH           BP > 185/110
                                    GI or UT bleed w/I 21 days                           Seizure                               Heparin w/I 48 hours & elevated PTT
                                    PT > 15 secs               platelets > 100,000       glucose < 50 or > 400
            TPA drawbacks:          Increased risk of ICH                   RISK: 10 fold increase in hemorrhage conversion w/ TPA                     low rate of recanalization
                                    Reperfusion injury                      systemic bleeding complications                    anaphylaxis             high rate of reocclusion
            Acute rx options:       < 3 hours IV TPA                        > 3 hours: IA TPA (up to 6 hrs), desmoteplase (TPA-like, up to 9 hours)
            ASA w/I 48 hours >> improves outcome & decreases mortality (give as soon as hemorrhage ruled out)
            Heparin & Coumadin: NO BETTER than ASA for prevention of non-cardiogenic recurrent stroke
                                  Indications: cardiogenic causes (A fib, mechanical MV or AV replacement, cardiac thrombis, MI), venous sinus infarct, arterial dissection

Acute Stoke Unit:         Decreases death, increases ability to live at home, reduce length of stays, fewer pts w/ progression, infx & complications
                          Monitored setting w/ O2, antipyretics, ASA precautions, aspiration precautions, early nutrition, Pt assessment
                          Diagnostics:            MIR brain, carotid Doppler, echocardiogram, lipid profiles

            HTN:       arterial HTN common after stroke (loss of auto-reg, secondary to pn, stress, anxiety, secondary to increased ICP)
                       usually declines spontaneously                    Rx only if > 220/120 or MAP > 130
            Hypotension:            more detrimental than HTN >> treat aggressively (nml saline)                             Glucose:    ↑ or ↓ can mimic focal deficit
            Temperature:            fever worsens outcome (greatest effect in first 24 hours) >> rx aggressively

CEA:        Carotid Endarterectomy                 2 year risk of stroke/death ↓ in symptomatic pts w/ ICA stenosis           Less clear benefit in asymptomatic pts
Hemorrhage
General:    20% of all strokes                   Acute rise in ICP >> loss of consciousness at outset >> some die from herniation

            Causes:     HTN          AV malformation          Bleeding diathesis       Drugs (amphetamines, cocoaine, anticoags, thrombolytics)       Trauma       Tumors

            Classification:    by location - epidural, subdural, subarachnoid, intracerebral
             Epidural Hematoma: beneath skull & dura in a space usually almost non-existent
                                 from ruptured middle meningeal artery - easily torn by bone spicule from c4ranial fracture
                                 arterial blood slowly fills space >> separating bone from dura >> takes several hours before large hematoma formed
                                 once large enough (50-60 mL), may compress brain >> coma - lethal if unrecognized
             Subdural Hematoma: b/t dura & arachnoids                   typically in boxers or elderly falling out of bed
                                 sudden mvmt of brain in 1 direction, and dura in the other >> tearing effect on bridging veins
                                 coagulated blood covers lateral hemisphere like a cap
       Subarachnoid Hemorrhage: space b/t arachnoid & pia mater                       most often due to traumatic contusion              HIGH mortality
                                 blood leaks into subarachnoid space from ruptures cerebral vessels @ base of brain
                                 also due to ruptured congenital aneurysms of circle of willis
                                 saccular/ berry: small & found in 1-2% of population                           may rx surgically w/ clips at origin
                                               aneurysms prone to rupture during exercise, sex or strenuous physical work
                                               HA is "the worst of my life"
       Intracerebral Hemorrhage: common complication of head trauma                                                         Basal Ganglia > cerebellar > pontine
                                 HTN most common cause in pts with no underlying vascular abnormality
                                 results in well-circumscribed hematoma , surrounded by edema
                                 infarct transforms into pseudocyst w/ yellow fluid - the wall of cyst contains hemosiderin laden macrophages


            Dx & Rx: CT test of choice                   Therapy directed at reducing mass effect - medical decompression, controlled hyperventilation
                     In SAH, normal CT does not r/o >> centrifuge CSF >> xanthochromia (yellow coloration that develops 6 hours after SAH)
                     Cerebral angiography is gold standard for dx of aneurysms
                     Management of HTN requires balancing need to maintain perfusion in context of ICP & risk of rebleeding


PATH - more details
Ischemia:   Cardiac failure or vascular collapse may >> widespread infarcts
                         hypoperfusion infarcts typically in parasagittal cortex (marginal zones b/t arterial supply areas)
                         systemic hypoperfusion >> border zone becomes hypoxic = watershed infarct
                         hypoperfusion also >> laminar necrosis of deeper zones of gray matter
            Ischemic brain liquefies >> putty-like mush = encephalomalacia ( may be pale or bland infarct or perfused w/ collateral circulation >> hemorrhagic infarct)
                         white matter infarcts tend to be pale, gray matter tend to be red infarcts
            Brain tissue surrounding infarct is edematous                                  Infarcts cannot heal >>neurological deficits are permanent
                         Brain edema (most imp life-threatening feature) must be treated with corticosteroids & dehydrating hyperosmolar agents

ICH:        clinical features of ICH are more dramatic than cerebral infarct >> 30% lose consciousness
            hemorrhage in BG >> by hemipalegia & hemiparesis                 hemorrhage in cerebellum >> N/V, loss of balance & HA, pt lapses into coma & dies in 48 hours
            pontine hemorrhage >> invariably lethal
Back & Neck Pain
Anatomy:      Vertebral column composed of vertebral bodies, pedicles, lamina, facet joints, intervertebral foramen, ligaments & discs
              Anatomical house:         1st story is disk, 2nd is foramen, 3rd is the pedicle level
              31 pairs of spinal roots
              Cord ends at disc b/t L1 & L2
                           Cervical roots exit above vertebral body for which they are named
                           Lumbar roots exit below vertebral body for which they are named
              Lumbo-sacral nerve roots form cauda equina
                           These roots transverse obliquely a bit before exiting foramen
                           Because of the oblique course of roots in lumbar area >> 1 disc problem can impinge on more than 1 root
              Areas: of involvement: thoracic area rarely involved in radiculopathy
                                        L4, L5, S1 commonly affected (L1, 2 & 3 < common)              C7 (then C6) most common cervical

Pathophys: Degeneration is most common            Ex. Ca overgrowth >> spondylosis; disc pathology; subluxation; stenosis
                         Subluxation can be demonstrated with flexion/extension on x-ray >> more likely candidates for back surgery
           Infection - esp in immunocompromised or diabetics >> spinal abscess (neurological emergency)
           Congenital - ex. spinal stenosis >> claudication                                                                                     Radiculopathy = nerve root pain
           Postural or mechanical - different than neurological pain                   Trauma

Pain:         Sensitive structures:     interspinal ligaments, periosteum, annulous fibrosous (of disc), capsule of articular facet, tendons
                                        Visceral organs also sensitive - may have referred pain (ex. pancreatitis, gallstones, aortic dissection)
              Night pain or 24/7 pain = red flag for abscess or neoplasm
              When sitting, you put the most force on the lumbar region - lumbar radiculopathies are relieved by standing
                                                                                                                                                        Common trigger points
              Trigger points:           push on muscle >>sends tingling down arm/leg (imitating radiculopathy) >> suggests myofascial pn
                          Myofacsial pain:            chronic focal or regional muscle pn that is referred
                                                      present at rest & with movement
              Just neck/back pain that does not go to the limbs is typically not neurological
              Local:      aching, steady or intermittent, worse with mvmt or tenderness >> suggest MSK
              Referred: Upper: flank, groin, anterior thigh                     Lower: butt or posterior thigh                      tendonitis, myofascial or facet joint arthropathy
              Radicular: Paresthesias, burning, electric or shock-like; distal or dermatomal; worse with cough or sneeze
                                        Straight leg raise test (positive when pn reproduced b/t 30-70°) & contralateral SLR
                                        Spurling maneuver: force neck into extension w/ lateral flexion on side of pain (reproduces brachial plexus sx)
              Muscular spasm:           reflexive guarding related to local pain, tautness palpable

Evaluation: Hx & PE
            On PE - important to palpate: interspinous ligaments, articular facet region, paraspinal muscles, sacroiliac region, sciatic notch & nerve (deep in glutts)
            Labs: CBC, ESR, PPD, Ca, phosphate, alk phos, HLA B27, RF, serum protein electrophoresis
            EMG/Nerve conduction - detects deenervation
            Imaging: X-ray - (invasive bone lesions) good for tumor, infx, fracture, congenital abnls
                       CT/MRI - (better for soft tissue) herniated disk, spinal stenosis, paraspinal soft tissues, epidural mass

Rx:           Neck:        NSAIDs, muscle relaxant, cryotherapy, PT, traction, surgery                   Back:        exercise/prevent, rest?, NSAIDs/local analgesia, PT, surgery

              PT generally better for postural or mechanical problems                                    NSAIDs & PT for radiculopathy
              Surgery for intractable pn or neurological deficit that threatens a limb                   Insufficient evidence to support epidural steroids for either back or neck
Mechanical: Usually self-limited, local, worsened by activity & sitting >> relieved by rest             May have local tenderness, but neuro intact

Radiculopathy:          Should be suspected when pts complain of limb pn w/ or w/o neck or back pain
                        May have pn, numbness, tingling or weakness                                    Distinguished from referred by its radiation distally
                        Worse with sitting, prolonged standing, cough or sneeze                        May be ameliorated by position - (lumbar: knees bent or pillow b/t knees)
                        Uncommon to have complete sensorimotor deficit b/c most muscles supplied by more than 1 nerve root
                        Most common objective finding is decreased DTR
                        Cervical: C7 > C6 > C5                                           Lumbosacral: S1 > L5, L4
                                                                                                                                               Reflexes most sensitive test
              Syndromes:                                                                                                                       to confirm radiculopathy
                        C5:         deltoid weakness & sensory loss on shoulder
                        C6:         ↓ biceps jerk, wk biceps, sensory loss on dorsal side of digits 1 & 2
                        C7:         ↓ triceps jerk, wk tricep, sensory loss on dorsal side of 3rd digit
                        C8:         wk interossei, numbness in pinky or digits 4 &5 - may have horner's syndrome
                        L5:         radiates to top of foot & great toe, weakness in tibialis anterior (dorsiflexors), sensory loss on dorsal side of foot
                        S1:         ↓ ankle jerk, weak calf muscle >> plantar flexion weakness, sensory loss on side of foot

             Mimickers: myofascial pain, strain or sprain, facet joint syndrome, sacroiliitis, bursitis, non-articular rheumatism

Cauda Equina Syndrome:
           Damage affecting multiple lumbar and sacral roots with pain & weakness in both legs
           Potential bowel & bladder dysfunction (distended bladder & urinary retention
           Findings: flaccid paresis of legs                 reduced anal sphincter tone            hyporeflexia
                       impaired sensation in legs AND perineal area - saddle anesthesia
           Causes:     tumors, central disk herniation, trauma, CMV infx, aortic occlusion or dissection

Lumbar spinal stenosis:
           Very frx cause of back pain & neurological dysfunction in the elderly
           Pts may c/o leg pain, weakness & numbness with walking >> relieved by rest or bending forward
           Neuro exam is abnormal - helps differentiate this spinal claudication from that caused by PVD
           Imaging: decreased diameter of spinal canal w/ compression or crowding of lumbar roots
           Rx:          PT, pain meds & possibly surgery

Spinal cord compression:
             Causes:    tumors, central or cervical disk herniation or trauma, atlanto-axial dislocation (seen in RA) or infx
             Sx:        pain may radiate to limb with electric-like feelings felt down trunk or with flexing of neck if cervical cord is involved
                        UMN signs:                hyperreflexia, spasticity, babinski & clonus
                        may have bowel &* bladder incontinence
             Acute cord compression may >> spinal shock - areflexia & flaccid paralysis
             Cord compression is a neurological emergency
Dizziness & Vertigo
Dizziness:   Includes:    Vertigo:    definite rotational sensation                    Presyncope: lightheaded, impending fainting, dimming of vision
                          Disequilibrium:           impaired balance or gait           Psychiatric issues:     anxiety, hyperventilation, depression, ETOH/drugs
             Sx may be caused by:     peripheral or central vestibular disorders (vertigo)                                                           Drug toxicity most
                                      systemic or cardiovascular disorders producing impaired cerebral blood flow (presyncope)                       common cause of nystagmus
                                      neurologic disorders producing disordered sensory input to brain (disequilibrium)                              in the ER (direction ∆ing)
Orthostatic hypotension:    Dx by taking BP& pulse lying and standing
            Systemic:       on standing: > 20 mm drop in BP, pulse increases by >10 bpm
            Neurogenic:     on standing: > 20 mm drop in BP, pulse rate fixed or increases by < 10 bpm               Also have abnormal RR
            Rx:             If systemic, correct underlying medical problem
                            If neurogenic, typically can't fix the problem >> try to ↑ NaCl, raise head of bed, pantyhose & pressure suits or drugs to ↑ intravascular volume
Vertigo:     Peripheral:    whirling vertigo with strong movement & positional component                      N/V                             No other sx except possible auditory
                            Unidirectional nystagmus in proportion to vertigo - fast phase usually away from affected ear                     Isolated vertigo is rarely central
             Central:       usually BS lesion - high medulla or low pons                                      less N/V                 Other neurologic sx
                            vertigo not as severe, less positional or movement provocation
                            Nystagmus may be unidirectional (usually up or down beating) or direction changing (look L >> eyes beat L, Look R >> eyes beat R)

Vestibular testing:         Romberg: pts fall toward affected ear
                            Nylen Barany or Dix-hallpike maneuver:             (tests for positional nystagmus)
                                         Pt seated looking forward >> quickly lowered to supine w/ head hanging over edge of table - keeping eyes open
                                         Examiner looks for nystagmus & asks pt about vertigo           Test them repeated w/ pts head turned to the L; then repeated to the R
                                         When test is (+), affected ear is down & fast nystagmus beats toward the floor
                                         Pt will fatigue with repetitive testing - 1st time symptomatic, 2nd time < intense, 3rd time no sx
                            Snellen w/ head shaking:              Test acuity while pt shakes head up & down                    Pts should not lose more than 2 lines
                            Calorics:    Usually done in unconscious pt        COWS: (direction of nystagmus - cold opposite, warm same)
             PE:            Eyes - nystagmus or Horner's (ptosis, miosis & anhydrosis)             Hearing                                 Strength face & trunk
                            Cerebellar testing - findings will be ipsilateral to affected ear      Pin sensation face & trunk (if , lateral medulla affected)
             Labs:          audiometry, electronystagnometry, BS auditory evoked potentials, EEG, other imaging as indicated
Vertigo rx: (Severe)        Immobilize pt, sedate, hydrate        Meds:        meclizine, scopolamine, benadryl                vestibular exercises & BPV maneuvers
When to worry:              Associated neuro sx/signs, pt can't walk, obtundation, direction changing nystagmus, stiff neck/fever, hearing loss/tinnitus

Peripheral: Benign Positional Vertigo: Due to otoconia (Ca breaks off and gets lodged in semicircular canal)                       episodic whirling vertigo (seconds to minutes)
                                                     provoked by specific movements                     no hearing loss or other sx             test w/ nylen barany
                                                     Rx:         fatiguing exercises or positional treatments (head rotations pt can do themselves to clear debris from canal
            Vestibular neuronitis:     Inflammation of nerve                    acute onset, severe vertigo - persistent, then relents over days
                                                     depressed caloric testing on affected side                       may have N/V or nystagmus
            Menier's Disease:          Due to ↑ hydrostatic pressure in affected ear/s                  episodic vertigo, fluctuating hearing loss, fullness in ear/s, tinnitus
                                                     Rx:         restrict salts, diuretics, possibly surgery
            Drug Toxicity:             Insidious or acute, linked to loop diuretics, aminoglycosides, ASA & ETOH                   May adapt, may have hearing loss/tinnitus or N/V
            Acoustic neuroma           Insidious onset due to compression of CN VIII                    Impaired hearing & tinnitus 1 side
            Perilymphatic fistula:     Fistula b/t ear & pharynx                Sudden pop, followed by tinnitus, hearing loss & vertigo                     Worse w/ altitude & press

Central:     Cerebellar infarct or hemorrhage:      Dizziness, N/V, disequilibrium & truncal ataxia (nystagmus uncommon()                     Beware of swelling compressing BS
             Brainstem Stroke (Lateral medullary syndrome):     Due to occlusion of vertebral artery
                            Vertigo with contralateral nystagmus, N/V                Ipsilateral Horner's, ataxia & dysphagia
Neuromuscular Diseases
Categories: Anterior Horn Cells:         (motor neuron dzs) - ALS, polio                             NM Junction Disease:      myasthenia gravis
            Peripheral nerves:           polyneuropathies & mononeuropathies                         Disease of nerve root:    radiculopathies
            Muscle Diseases:             dystrophies & myopathies                                    Disease of plexuses:      plexopathies
Amyotrophic Lateral Sclerosis (ALS):                 Lou-Gehrig's dz                                 Both UMN & LMN involvement in ALS
Clinical:   Anterior horn cell diseases - loss of lateral cerebrospinal paths in cord >est           10% inherited (FALS) in auto-D fashion - gene on chromosome 21
            Pts present w/ focal weakness & atrophy which is progressive                             Initially patchy & symmetrical, painless & without sensory sx
            Ultimately involves all skeletal muscles - doesn't affect smooth muscles                 Usually begins in hand, distal leg or face - esp tongue & pharynx
            UMN signs: spasticity, increased tone, increased reflexes & Babinski                     Fasciculations common                   Intelect unaffected
Dx:           Muscle biopsy & EMG show signs of deenervation                                         Virtually all other labs normal
Rx:           No treatment - dz runs its course anywhere from few months to several years            Pts typically die of progressive respiratory insufficiency
Myopathies: Diseases that affect muscles directly                              5 classes                          Sensation is unaffected in myopathies
            Weakness is most common presenting sx                              usu. proximal weakness             muscle pain (myalgia) uncommon
            Atrophy common with long-standing myopathies                       usu. symmetrical weakness
Atrophic:     proximal weakness (shoulder, neck & hip), reflexes are reduced in proportion to muscle weakness
              chronic & slowly progressive
              may be due to steroids, inactivity, hormonal imbalance (thyroid) or other dz cause disuse
              Dx and rx: nml serum enzymes (CPK & adolase), minor EMG changes, biopsy shows type II muscle atrophy
                           Rx involves correcting underlying abnormality                                                                    Muscle Strength
Necrotic-Inflammatory:   subacute proximal weakness w/ or w/o muscle discomfort & swelling                                    5 - normal
                         may have skin rash (dermatomyositis) or underlying collagen vascular dz                              4 - active mvmt w/ gravity & resistance
                         causes include AI dz, underlying malignancy, infx (HIV), or drugs (AZT)                              3 - active mvmt w/ gravity
              Dx and rx: enzyme levels are very high, EMG very abnormal, biopsy shows inflammation & necrosis                 2 - active mvmt w/ gravity eliminated
                         Rx involves removal of toxin & immunosuppression                                                     1 - trace contraction
                                                                                                                              0 - no contraction
Muscular Dystrophies: Inherited myopathies characterized by progressive muscle weakness & degen with subsequent replacement by fibrous & fatty CT
                        Most of the disorders in this class have a defined genetic mutation with abnormal gene
                        Generally there is no effective treatment for any of these disorders
            Duchenne's dystrophy: Childhood onset, delayed walking >> usually confined to wheelchair by 12                    toe-walking, waddling, lordosis
                                    CHF, arrhythmias, smooth muscle of GI, lower IQ                                           most die of respiratory complications by 20
                        Dx:         Labs - CK and aldolase high, EMG changes                        Rx:          prednisone
            Becker's dystrophy:     Similar to Duchenne's - though later onset, milder weakness, pts ambulate beyond 12 y/o & live until 5th decade
            Myotonic dystrophy: (most prevalent form of dystrophy)
                                    Affects skeletal, cardiac, smooth muscle, eyes, endocrine system & brain
                                    Weakness and stiffness of distal muscles are usually presenting sx in young adults
                                    Systemic findings - cataracts, ptosis, arrhythmias, dysphagia, DM, testicular atrophy, frontal balding              Dx: CK nml
Metabolic:    Inherited disorders of fuel metabolism of muscle cells
                            Affecting glycolytic paths >> cramps, myalgias & myoglobinuria w/ exercise; also may have fixed weakness w/o exercise intolerance
                            Impaired fatty acid metabolism (carnitine deficiency w/ lipid storage) >> progressive myopathy w/ exercise intolerance & myoglobinuria
                            Mitochondrial defects >> multisystemic dz - combo of CNS & PNS problems, associated lactic acidosis
                                                     >> progressive weakness of proximal limbs, extraocular or other CNs & abnormal fatiguability on exertion
                            Muscle fibers appear "ragged red" on biopsy
Myopathies Continued:
Congenital: present from birth, relatively mild & lifelong                                                      disease is non-progressive
            children often born with joint contractures, motor development is poor & delayed                    no effective treatment
            muscles are small & poorly formed, slender body build, long/narrow face with skeletal abnormalities

NM Junction Disorders:
Myasthenia Gravis:       May involve either the EOMs selectively or generally the voluntary muscle system                      If generalized - usually w/i year of onset
                         Sx fluctuate and are exacerbated by exertion, extreme temperatures, infections, menses & excitement
                         Ocular >> bilateral & asymmetrical >> ptosis & diplopia                                               Ocular involvement in nearly all pts after 1 year
                         Other CN involvement >> loss of facial expression, screwy smile, jaw drop, choking, slurred or nasal speech
                         Abnormal fatigability of limb muscles - especially proximal                              2/3rds of pts have thymic hyperplasia
                         Due to auto-Ab directed against post-synaptic ACh receptor
Dx :        Circulating AChR Ab in 80-90% of case                           Repetitive nerve stimulation >>decrease in muscle response >> demonstrating fatiguability
            Edrophonium - given IV, acts w/I minutes & lasts a few seconds >> examiner then evaluates degree of ptosis &range of EOMs
Rx:         Anticholinesterases >> help nerve transmission                  Pts w/ generalized (not responding to anticholinesterases) >> thymectomy
            Alternate day prednisone rx

Neuropathies General:
            Diagnostics: Creatine Kinase (CK) - sensitive indicator of muscle damage & elevated when active destruction
                                     ADH, AST, & ALT are also usually elevated - though less sensitive                           CK > LDH > AST > ALT
                         EMG - normal muscle is electrically silent at rest
                         Nerve Conduction - quantifies compound muscle action potential (CMAP)
                         Repetitive Stimulation tests - CMAP may change in amplitude with successive testing >> indicating fatigue (ex. MG)
Polyneuropathies:
            Generally produce distal sx
            Underlying pathology is usually slowly evolving axonal degeneration - involves end of long fibers preferentially >> "dying back" of nerve fibers
                         axonal degeneration >> ↓amplitude of CAMP out of proportion to velocity
                                               >> distal disturbance of pain & temperature >> extremely painful
                                               >> motor & sensory function served by large myelinated fibers (including reflexes) relatively preserved
                         Can also be from demyelination >> distal weakness & loss of sensation
                                                            >> mostly a reduction in velocity
                         demyelination repair can be rapid compared to axonal regeneration (very slow)
            stocking & glove pattern              early loss of stretch reflexes distally (ankle) & weakness of intrinsic feet muscles
                                                  loss of vibratory sensation in toes
                                                  Hands and arms have similar progression >> ultimately spreading more proximally

Diabetic:     Polyneuropathy parallels length & severity of diabetes as well as other complications of diabetes (nephropathy & retinopathy)
              Pathology due to affect on small arterioles & capillaries                     Symmetric sensorimotor polyneuropathy, mononeuropathy or plexo/radiculaphy
              Sensorimotor polyneuropathy:           distal sensory loss, weakness, areflexia & ANS sx (postural hypotension, impotence, incontinence, ↓ sweating)
                                                     dysesthesias >> unpleasant sensation evoked by normal stimuli (bed sheets on toes at night)
                                                     may have continuous burning or throbbing pn, difficulty walking
              Mononeuropathy:           compressive neuropathy (ex. across elbow or carpal tunnel)                   diabetic nerves prone to compression
              Plexopathy/radiculopathy:              "diabetic femoral neuropathy"          severe thigh pain with weakness in quads
Dx:           EMG/NC                    spinal fluid may show ↑ protein                     diagnosis should only be made in setting of long-standing diabetes
Rx:           Control blood sugar helps prevent sx & slow progression
Polyneuropathies Cont'd:

Charcot-Marie-Tooth Disease:                        Inherited polyneuropathy
           May be modality specific - pure motor, pure sensory or pure autonomic
           Usually manifest b/t 2nd and 4th decades - present for life & slowly progressive                     pts often don't recognize slowly accumulating deficits
           Pts tend not to have the positive sx (tingling, burning, shooting pain)                              stretch reflexes lost first at the ankles
           Usually manifest with insidiously evolving foot drop - distal weakness & wasting of intrinsic foot muscles, peroneal muscles, anterior tibial & calf muscles
           Typically have foot deformity - high arches (pes cavus), hammer toes - due to long-standing muscle imbalance
           Rx:           PT and bracing, especially of ankle

Guillain-Barre Syndrome                  Acquired, auto-immune, inflammatory demyelinating polyneuropathy
             Due to Ab or T cell activity against peripheral nerves
             Follows identifiable infectious disorder in 60% of cases - campylobacter, mono, CMV, herpes & mycoplasm
             Initially pins & needles sensations in feet, may have associated dull, lower back pain >> hours to days, weakness develops >> peaks w/i a month
                            weakness most prominent in legs, though may involve arms or cranial musculature
             Stretch reflexes lost early                          Respiration can be lost w/i few days or hours >> life-threatening
             Rx:            respiratory support                   plasmapheresis                        infusion of IgG

Other:        Toxins, drugs, ETOH, metabolic conditions, neoplastic conditions, HIV

Mononeuropathies:
           Sensory loss or weakness in the territory of a specific nerve
           Ex.          carpal tunnel - median nerve compression at wrist                           precipitated by repetitive mvmts
                                    numbness, burning, tingling in palm & thumb, index & middle fingers (most prominent at night)
                                   Tinel's sign: percussion of median nerve at wrist is provocative
                                 Phalen's sign: flexion of the wrists together may be provocative
                                    Rx:            resting & splinting
                        ulnar palsy - ulnar nerve entrapment at elbow or wrist
                                    muscle weakness & atrophy predominate over sensory sx
Disorders of Vision
Complaints Sensory pathway:        Common complaints: dim vision, visual loss, field loss, blurred vision           Motor pathway:            Diplopia (due to misalignment of eyes)
Hx:         Unilateral or bilateral           Intermittent or permanent                 Blurred or diminished                    Field cut: lateral or vertical
            Onset:       Sudden = vascular Ex. migraine, retinal emboli, temporal arteritis
                                                           Ex. optic neuronitis or ON tumor
                         Progressive = inflammatory or compressive
Pupils:     constriction due to stimulation of PNS division of CN III (oculomotor)                         dilation is SNS
            Anisocoria:unequal pupils            Should examine in both dim & bright light - if it ↑ going from dim to bright >> PNS lesion (lack of constriction in one eye)
            Afferent pupillary defect (Marcus Gun pupil):                  pupil dilates in response to light >> ON abnormality
            Tonic Pupil (Adie's): Unilaterally dilated pupil >> light reaction reduced or slowed >> may be associated with areflexia
            Argyll Robertson pupils:             small irregular pupils >> accommodate, but don't react to light >> CNS syphilis
            Horner's syndrome: miosis (small unreactive pupil), ptosis & anhidrosis >> damage to sympathetic fibers to pupil
            CN III paralysis:       dilated pupil fixed to light & accommodation (PNS supply to III interrupted) - may have ptosis & "down & out" deviation
Transient Monocular Blindness - TMB (Amaurosis Fugax)
General:    Life and or sight threatening                    Usually painless                           Altitudinal presentation - loss of upper visual field
            One eye only & last < 24 hours - quick onset and quick resolution                           Median duration = 4 minutes, 95% last < 1 hour
            Causes:      Ischemia               Orbital tumor/mass (pushing on ON)                      Refractive error or corneal changes (ex. dry eyes)
                                                C
                         Ischemic mechanisms: ardiac - emboli, systemic hypotension (>> decreased supply to orbit)                            Blood -       coagulopathy
                                                Vessels - carotid dz/emboli, arteritis (GCA - swelling of medium & lg vessels >> luminal narrowing)
                                                                          Ipsilateral carotid artery stenosis most associated with retinal claudication
                                                                          Hollenhorst plaque: (cholesterol plaques) - assoc w/ high stroke rate & mortality
                                                             vasospasm, carotid cavernous fistula (>> retrograde flow back to orbit)
            Retinal findings:       Looking for signs of claudication or vessel closure>> Emboli, micro aneurysm, hemorrhages, cotton wool spots (micro infarcts), A-V nicking
            Imaging: Carotid doppler, MRA or aortogram, echocardiogram

DDx:        Ischemia:    Short in duration, also sudden onset/resolution & altitudinal    Migraines: Slower onset/resolution, longer duration , often with "circular defect"
            Ex TIA       Negative scotoma - absence in visual field                                  Positive scotoma - colors or scintillations (mvmts), visible when eyes closed

Risk Factor: Age > 75              Hx of hemispheric TIA/ stroke                          80-94% ICA stenosis
             Male                  Intermittent claudication                              No collateral circulation visible on angiography
Rx:         0- 1 risk factor       Medical rx                2 risk factors: Medical rx = carotid endarterectomy                 >3 risk factors            Carotid endarterectomy
Giant Cell Arteritis (GCA):
            Inflammation of medium & large vessels >> luminal occlusion                 Can lead to blindness             (Most often elderly females)
            Sx:        HA, wt loss, jaw claudication, tender & palpable superficial temporal artery           Swollen optic disc      May become bilateral
            Dx:        Elevated ESR & CRP, anemia         Biopsy at least 1" because of skip lesions          Rx:         High dose steroids
Diplopia
Hx:         Monocular vs. binocular           Intermittent, variable or constant          Other Sx                  Vertical or horizontal pattern or no pattern
                     Monocular: persist when one eye is covered - if it resolves when looking through a pinhole >> signifies refractive error
                                  e
                        Binocular: yes not well aligned - resolves when either eye is covered >> often due to CN palsies, MG, inflammation or muscle entrapment
            Time of day?          MG tends to be worse in p.m.           Thyroid dysfunction worse in am            Constant?               nerve damage, muscle abnormality
            Associated sx:        Ptosis - MG                                             Pupil - dilated (CN II), constricted (Horner's)
                                  Exopthalmos or ciliary injection - thyroid              Disc edema - bilateral (ICP), unilateral (mass)
            Tests:      Saccades (quick mvmts from F-N)                  Pursuits (EOM)                 Cover-Uncover test                  Cover test with prism
                        Cover - Uncover:      Exotropia (eye turned out), Esotropia (eye turned in), Hypertropia (1 eye higher), L estropia (cover R >> L eye moves out)
Visual pathways
Visual acuity:              usually only affected in anterior path, behind chiasm acuity usually normal
Anterior pathway:           (eye to chiasm) >> unilateral defect                               1. Blind right eye
Chiasm:       bilateral /heteronymous, acuity probably nml                                     3. Bitemporal Hemianopsia
              Tumor (80% of time), demyelinating dz or vascular lesions
              Sellar lesion:           Due to pituitary adenoma >> often compresses ventral chiasm
Posterior pathway:          bilateral/homonymous                                               4. Left Homonymous Hemianopsia
              Partial lesion of optic radiation (temporal) >> "pie in the sky"                 5. Homonymous L Superior Quadrantic defect
              Partial lesion of optic radiation (parietal) >> "pie on the floor"               6. Homonymous L Inferior Quadrantic defect
              Complete lesion of optic radiation                                               7. L Homonymous Hemianopsia
                            Each of these posterior pathways with L visual field defect = R sided lesion
                            Farther back the lesion >> more congruous the defect
Cortical blindness:         Complete lesion of visual cortex >> loss of all visual sensation (including light & dark)
                            Pts retain pupillary reflex           Retina & EOMs normal         Hard to dx b/c of normal exams
                            May see loss of lid closure reflex to bright light                 Anton's syndrome: pt unaware of blindness
Optic Nerve Disease
Anterior Ischemic Optic Neuropathy:
             Arteric Type:       GCA                         Elevated ESR, marked loss of vision
             Non-arteric type:   Atherosclerotic             Elderly, painless, altitudinal defects (like TMB), swollen disc
Optic neuritis:           Swelling of ON where it enters the globe       Gradual loss of vision (over a few days)
                          Commonly associated with central vision loss that gradually expands                     Pt may complain of blurred or dim vision
                          May have optic disc swelling, hyperemia, blurred margins or hemorrhages
                          MS is by far the most common etiology
Pseudo tumor cerebri:     Due to elevated ICP >> bilateral disc swelling                                            idiopathic - primarily obese women
                          Enlarged blind spot on visual field >> may have progressive field loss                    CSF chemistry normal
                          Pt may present w/ blurred vision, HA, tinnitus or "whooshing sounds" in ears
Ocular Motility           LR6 SO4 AR3
CN III:     (Oculomotor) Responsible for pupillary constriction, lid elevation (levator palpebrae), adduction (MR), elevation (SR, IO) and depression (IR)
           CN III Palsy: Ptosis: will be severe if damage to CN III, unlike ptosis in Horner's syndrome which is more mild
                         Due to muscle paralysis, pt may present with "down & out" eye                 Midriasis: lack of pupillary constriction
                          painful w/ pupil involvement >> need to r/o PCA aneurysm                     nonpainful, w/ pupil involvement >> more likely mass or inflammation
                         nonpainful, and pupil-sparing >> HTN or DM (If scalp tenderness, temple pain >> think GCA)
CN IV       (Trochlear) Responsible only for superior oblique           Most commonly trauma, also ischemic, aneurysm & idiopathic
           CN IV Palsy: Pt unable to look down & in
                        Head tilt test: pts have a problem when head is tilted toward the lesion >> tend to compensate by keeping their head tilted away from lesion
CN VI       (Abducens) Responsible for lateral rectus
           CN VI palsy: Infranuclear lesion >> abduction weakness                          Most commonly idiopathic, may be vascular or tumor

Internuclear Opthalmoplegia: (INO)               Lesion of medial longitudinal fasciculus (connects nuclei of oculomotor & abducens nerves)              Unilateral or bilateral
                                                 Horizontal gaze >> failure of adduction               Commonly due to MS, vascular dz or MG
Headaches
General:    Primary: (most common) - due to combination of genetics and environmental influences
                       Tension - episodic or chronic                    Migraine                                     Cluster
            Secondary: due to some other problem or systemic disorder
                       Analgesic rebound                    Sinusitis               Meningitis                       PTSD HA                   ICP                         Drugs
                       Refraction Errors                    GCA                     Brain Tumor                      Trigeminal neuralgia      Vasculitis, Lupus

            Red Flags: Worsening HA                             Sever, acute              HA upon awakening                       Persistent HA after head injury
                       Focal neurologic findings                ∆ in LOC                  Ataxia or dizziness                     Double vision            Stiff neck

            Hx:          CLORIDE - PAC            Prodrome, more than 1 HA, Assoc sx (N/V, visual change, dizziness, confusion, numbness)
            PE:          Look for systemic dz; head, neck & sinus, BP, Head circumference, neuro & fundoscopic
Migraine
General:    Disorder of neuronal excitability or membrane channels         neurogenic cause >> exaggerated evoked potentials                                Complications:
            Strongest genetic component of all HA                          W>M                                                                              Status migrainosus
            Usually unilateral (79%), throbbing, pulsating & aggravated by activity                  Also inhibits/prohibits activity                       Migrainous infarction
            +/- N/V                    +/- photophobia/phonophobia
            In kids, often associated with episodic abdominal pain, motion sickness or sleep disturbances

Without aura:            at least 5 attacks, lasting 4-72 hours untreated                   rapid onset >> peaks in 1-2 hours
(common migraine)        2 of following:             unilateral, pulsating, moderate-severe intensity (dysfunctional), aggravated by walking stairs or physical activity
                         1 of following:             nausea and/or vomiting                 photophobia and/or phonophobia
                         PE and history don't suggest other secondary diagnosis

With aura: at least 2 attacks
(classic)  3 of following:           1+ fully reversible aura sx indicating focal cerebral cortical or BS dysfunction                          Visual sx most common
                                     at least 1 aura develops gradually over 4+ minutes OR 2+ sx occur in succession                           May be (+) or (-) phenomenon
                                     No aura lasts more than 60 mines (may precede or occur simultaneously w/ HA)
            PE and history don't suggest other secondary diagnosis

Migraine Variants:       Opthalmopelgic migraine:           Aura involves CN dysfunction which lasts a few days (CN III palsy, dilated pupil, "down & out eye")
                         Retinal migraine:      Only the eye sx w/o the HA
                         Childhood syndromes: Cyclic vomiting            Benign positional vertigo          Benign positional torticollis
                         Abdominal Migraine: N/V, but no other sx

Tension-Type Headache
General:    Genetic component        Usually frontal, occipital or generalized - frx pain in neck (unlike migraine)
                                     Pain usually last for days and does not rapidly appear
                                     May relate to sustained craniocervical muscle contraction >> "muscle-contraction HA"
            2 of following:          pressing/tightening (non-pulsating) quality           bilateral location       mild to moderate        not aggravated by physical activity
            Both of following:       NO N/V                     No photophobia or phonophobia
            PE and history don't suggest other secondary diagnosis
                         Episodic: at least 10 episodes, < 15/month, < 180 days/year                     Chronic: 15 days/ moth, for at least 3 months, > 180 days /year
Cluster Headache
General:      Genetic component                       HA coupled with autonomic sx                        M >F         Usually young (20-30 y/o)
              Severe unilateral orbital, supraorbital and/or temporal pain                   Often awakes pt                        Pt CAN"T SIT STILL
              Attacks often precipitated by even small amounts of ETOH
              At least 5 attacks
              1 of following on pain side:            conjunctival injection, lacrimation, nasal congestion, rhinnorrhea, miosis, ptosis or eyelid edema
              Frx:          1 every other day up to 8 per day
              PE and history don't suggest other secondary diagnosis
                            Episodic: lasts 7days to year separated by pan free periods > 14 days         Chronic: attacks for > 1 year or w/ remissions lasting < 14 days

Indomethacin -Responsive Head aches
              Ice pick migraine:      Idiopathic stabbing HA - "jabs & jolts syndrome" w/ no other sx
              Paroxysmal Hemicrania:               F > M, lasts 2-45 minutes with 5-6 attacks per day, need to lat down in dark
              Weight-lifter's or "effort" HA:      Often unilateral, lasts 5-30 minutes
              Hemicrania continua: Continuous unilateral HA w. Ands sx

Secondary Headaches
Analgesic Rebound:        Due to medication withdrawal

Acute sinusitis:          Malaise & low-grade fever              Dull, aching, non-pulsatile & exacerbated by mvmt, coughing or straining
                          Improved with decongestants            Tenderness on palpation of sinuses

Idiopathic Intracranial HTN:           Benign ICP w/o evidence of focal lesions, hydrocephalus or edema
                                       Onset usually b/t 15 & 45 in obese women                     May have visual field disturbances

Post Traumatic HA         Associated w/ irritability, insomnia, memory disturbance & light-0headedness
                          May have anxiety & depression

GCA:          Most over 50 y/o          Malaise, fever, wt loss, jaw claudication         Often w/ polymyalgia rheumatica (pnful stiffness in neck, shoulders & pelvis)
              Visual impairment secondary to optic neuritis                               Ha is aching - exacerbated at night & by cold
              Superficial temporal artery is swollen & tender                             Elevated ESR and anemia

SAH:          Bleeding from ruptured intracranial aneurysm                    Worst headache of my life
              Abrupt and severe onset                                         May have nuchal rigidity, CN II palsy or retinal hemorrhages

Meningitis:               HA, fever & stiff neck                 Confirmed by eliciting Brudzinki's & Kernig's signs              Vomiting in 50% of pts

Headache Treatment
Educational:              Emphasize genetic course & benign nature of most HA                          Discuss lifestyle & triggering factors
Triggers:     Food:        chocolate, processed meals, caffeine, nut & peanut butter, cheddar & aged cheeses, ETOH
              Other:       Sleep, regular meals, weather, stress, hormones, odors, exercise, drugs
Psych:        Stress reduction, rx comorbid anxiety & depression, coping techniques for had, ID stressors & drug/ETOH abuse
Alternative:              Massage therapy, acupuncture, ice mask, botox injection (NO good data on these rxs)
Symptomatic:              Acetaminophen, Ibuprofen, naproxsyn, Midrin, Codeine
Migraines only:           Triptans                               Prophylaxis:             Not curative, though useful when pt can't tolerate sx
Multiple Sclerosis
General:   Immune-mediated dz that affects CNS (brain, cord & optic nerves)                                                                    Epi:      Onset b/t 15-45 y/o
           Name derived from scarring (plaques or sclerosis) caused by inflammatory attacks at multiple sites in CNS                           Uncommon in equatorial regions
           NOT:        fatal, contagious, directly inherited or always severely dehabilitating (may be "benign MS")                            Uncommon in non-whites
           NOT A REASON TO: stop working, doing things one enjoys, not have children                                                           70% women (if M >> more severe)
Sx:        Most common at presentation:         sensory sx (paresthesias) in arms/legs, unilateral vision loss, diplopia       slowly prog. motor deficit > acute motor deficit
           Common sx: Fatigue, depression, focal muscle weakness, visual changes                     Bowel/bladder/sex dysfunction, gait problems/spasticity, paresthesias
           Less common sx:        Dysarthria, scanning speech, dysphagia, neuritic pn                Vertigo/ataxia, cognitive dysfunction, tremor/incoordination
                                  Lhermitte's phenomenon - pt bends neck >>stretches cord >> "shock" experience
           Rare sx:   Decreased hearing, seizures, tinnitus, mental disturbances, paralysis

Natural History:            Average is 1 relapse/year >> fewer over time                    75% of pts loss ability to perform ADLS, 15% severely disabled in short order
                            EDSS: disability score                 Median time to reach 6 (cane to walk) - 15 years; to reach 8 (wheel chair bound) is 46 years
           Relapse:         1. Appearance of new or worsening sx                            Progression:               Worsen by 1 point on EDSS
                            2. Sx last at least 24 hours                                                               Worsen by .5 if EDSS > 5.5
                            3. Sx could be attributed to MS                                                            Confirmed on 2 consecutive visits - 3 months apart
                            4. Sx proceeded by period of stability for 30 days                                         Mortality from MS as primary cause is low

Subtypes: Relapsing Remitting (RR) - plateau >> attack; w/ each attack, pts don't get back to baseline                  Most common at dx:       RR > 1° Progressive
          2° progressive - starts as RR, then changes to gradual, but continuously deteriorating course              Most common 10 years later: 2° Progressive > RR
          1° progressive - from outset, dz continues to deteriorate with time                                           2° progressive hard to rx >> imp to RR early
          progressive relapsing - (RARE) continuous deterioration from outset, couple with acute attacks/exacerbations
Phases:    1. Preclinical               2. RR - increasing in # of lesions & disability, decrease in brain volume                 3. 2° progressive

Path:      Unknown etiology - thought to involve viral infection in genetically susceptible individual            Genetics & environmental factors
           Trigger directs IS to attack myelin & nerve fibers >> slower nerve conduction             Lesions in ON, periventricular white matter, cortex, BS, cerebellum, cord
           Axonal injury & destruction >> permanent neurological dysfunction                         Early lesion: lymphocytes & foamy macrophage
           Major players:             T cells & Cytokines & B cells                                  Late lesion: ractive astrocytes, demyelinated axon - no oligodendroglial cells
                     Inflammation: facilitated by entry of T cells and demyelinating Abs from blood stream into CNS (cross BBB)
                    Demyelization: Mediated by cytokines & T cells, anti-myelin Ab produced by activated B cells                                          Prognosis
                      Axonal- Loss: Inflammation & demyelization >> axonal injury and loss >> brain atrophy                                 GOOD                     POOR
                                                                                                                                            Young at onset           Older
Ddx:       Infx:         Lyme dz, neurosyphilis, HIV                        Metabolic: ↓Vit B12 or E                                        Female                   Male
           Inflamm:      SLE, Sjogren's, Vasculitis, Sarcoid                Other:       CNS lymphoma, ALS, MG                              Normal MRI               ↑ lesions
                                                                                                                                            Complete recovery        Lack of
Dx:        Clinical (no definitive labs)          Evidence of dissemination over space (> 1 part of CNS) & time                                 after 1st relapse       recovery
           CSF:           ↑ IgG index = (IgG CSF/ albumin CSF) / (IgG serum / albumin serum)                                                ↓ relapse rate           ↑ rate
                         Oligoclonal bands - refection of immune response                Overall ↑ IgG                                      No disability            Early disabil
           Increased evoked potentials (visual or somatosensory)                                                                                after 5 years
           MRI:          Instrumental in dx & prognosis >> total lesion load predictor of disability                                                                 Slow motor
                         T1 (hypointense lesions)                           FLAIR (subcortical/cortical lesion ID)                                                       onset
                         T2 (total dz burden)                               Gadolinium (enhances/highlights new or active lesions)
Rx:        Goals:           treat relapses, manage sx, modify or reduce relapses & delay progression to disability, facilitate acceptable quality of life
           Pharm:           Non-specific immunomodulation:        Interferon beta 1-b (Betaseron), beta 1-a (Avonex, Rebif)         Cytokines that ↓ T cell mvmt across BBB
                            Selective immunomodulation:           Glatitramer acetate (Copaxone)                                    Act as myelin decoy for T cells to attack
                            Non-specific immunosuppression:       Corticosteroids (high dose for 3-5 days for relapse )
                                                                  Mitoxantone (Novantron)               Cytotoxic agent that broadly suppresses IS
Movement disorders
General:    Center motor systems have 3 parts: pyramidal, extrapyramidal & cerebellar
            Movement disorders are limited to disturbances of the extrapyramidal & cerebellar systems
                       Extrapyramidal refers to the basal ganglia and their projections
            Basal ganglia:          receive input from the cortex & give feedback to cortex thru thalamic projections
                                    modulate motor cortical activity & activity of association cortex in frontal lobe
                                    Many mvmt disorders therefore have behavioral component
                                    Ex. dementia in Huntington's, ADD & OCD in Tourette's, depression in Parkinson's
            Disorders may be hypokinesia or hyperkinesia
Rigidity:   Implies basal ganglia dysfunction on the contralateral side
            Increased muscle tone throughout ROM - does not vary with passive acceleration by examiner
            Lead-pipe: increased resistance throughout mvmt arc - independent of rate
            Cogwheel: ratchet-like jerkiness due to superimposition of tremor on underlying rigidity
            Paratonic: velocity dependent resistance to passive mvmt (resistance increases with increasing speed)
                        Mitgehen: sudden loss of tone that increases the ease of motion
                        Gegenhalten:              sudden increase in tone that makes movement more difficult
Hyperkinesias:
          Asterixes:    transitory loss of motor tone >> rapid mvmt of a joint                    Ballism:      flailing mvmt - typically unilateral (hemiballism)
          Athetosis:    slow writhing mvmt                                                        Chorea:       irregular flicking, dance-like mvmt
          Dystonia:     sustained contortion due to excess muscle activity across joint           Dyskinesia:   non-specific term for hyperkinesia
          Myoclonus:    rapid, jerking muscular mvmt, rhythmic or irregular                       Tic:          semi-suppressible motor or vocal gestural mvmt
          Tremor:       rhythmic oscillating mvmt - may be resting or intention
Cerebellar signs:       Ataxia                                Ataxic dysarthria (abnl speech)                               Dysmetria, hypometria & hypermetria
                        Intention tremor                      Dysdiadochokinesis: poor RAM precision                        Dysrhythmokinesis:     poor RAM rhythm
                        Dyssynergia                           Titubation (rhythmic rocking tremor of trunk)                 Hypotonia
Hyperkinetic disorders
Essential Tremor:       Typically affects both sides of the body symmetrically, more prominent with action than at rest                Often inherited
                        Frx of tremor is constant, amplitude may vary                            Exacerbated by stress, sleep deprivation & stimulants
                        Rx:          propanolol and primidone
Intention (Cerebellar tremor):       Slow broad tremor that occurs at end of purposeful mvmt
Dystonia: Sustained muscle contractions that result in abnormal postures & contortions                          May be 1° or 2° (ex. Wilson's, Huntington's, cerebral anoxia)
          Antipsychotic drugs may >> blepharospasm, spasmodic torticollis, tardive dyskinesia                   1° are due to basal ganglia dysfunction
          Rx:         Pts with generalized dystonia should receive trial of Levadopa                            IM botox good for focal dystonia
Huntington's Disease:
          Progressive auto-D neurodegenerative dz affecting motor, cognition & behavior                   Premature death & atrophy of neurons - caudate & putamen
          Usually adult onset >> chorea affects limbs & trunk                                             Other mvmt abnmls: dystonia, rigidity, postural instability
          Eye mvmts abnormal early in the dz - slowing of saccadic mvmts & breakdown of smooth eye pursuits                       Chromosome 4 abnormality
          Rx:         No rx slows progression of dz - supportive care only to improve pts quality of life
Tourette's: Hx of both motor and vocal tics for > 1 year & onset before age 18                     Probably auto-D condition
            Tics associated w/ obsessions & compulsive behavior 50% of pts                         Tics accompanied by ADD in 50% of pts
            Disorder is not progressive or fatal - 2/3 of pts outgrow tics                         May have coprolalia - foul language
            Rx:          Strategies to reduce stress are most effective
Parkinson's (Hypokinetic)
General:    Neurodegenerative disorder of unknown cause      #NAME?                                              Age is single most important risk factor
            Projected to surpass cancer as 2nd most common cause of death in the elderly                         Slight male predominance              W>B
Path:       Disease of the basal ganglia - particularly the Substantia Niagra (loss of pigmented neurons)                     Substantia niagra appear pale on gross exam
            Lewy bodies:            esosinophilc cytoplasmic inclusions in pigmented neurons (not exclusively in PD)
            Depletion of dopamine containing cells in SN >> decreased dopamine in the striatum
                        ↓striatum dopamine >> ↑ inhibitory signals to thalamic nuclei
                                                 ↑ inhibitory signals to premotor cortex, other parts of cortex & BS
                        50% loss of dopamine >> asymptomatic                70% loss >> early sx
                        >90% loss >> death
Clinical:   Triad of resting tremor, rigidity & akinesia/bradykinesia
            Rigidity is cogwheeling type            Resting tremor is pill-rolling(↑ by stress, ↓ w/ voluntary mvmt)
            Slow shuffling, festinating gait & postural instability                        Retropulsion & stooped posture
            Meyerson's sign:          failure to inhibit blinking in response to tapping on the bridge of the nose
            Early sign is decreased arm swing while the patient is walking.
            May have dementia & depression                                                                                              Basal Ganglia Wiring
            Therapeutic response to levodopa helps differentiate
                         Secondary features:        Masked facies (facial hypomimia)                     monotonal hypovolemic speech                 diminished olfaction
                                                    micrographia (small, abnl handwriting)               difficulty initiating mvmts                  freezing
                        Atypical features:        early onset               rapid progression        UMN signs                Cerebellar signs        Postural hypotension
Rx:         Goals:    enhance pt functioning, maintain dopaminergic neuronal function, delay need for levodopa, delay onset of levodpa motor complications
            Levodopa: Mainstay of rx           dopamine precursor that requires enzymatic conversion to dopamine within SN neurons
                      Administered with carbidopa - peripherally acting dopa decarboxylase inhibitor that prevents enzymatic conversion of dopa peripherally
                                   Combo of levadopa & carbidopa is known as sinemet
                      Late in therapy, pt may develop motor fluctuations & dyskinesias >>most common problem leading to surgical intervention

            Dopamine agonist:        require no enzymatic conversion, act directly at striatum - bypassing SN
                                     longer half life than levodopa - good adjunctive rx for motor fluctuations, may help delay need to begin levadopa rx

            Anticholinergics:        Help restore balance b/t dopaminergic & cholinergic systems - only good for treating resting tremor

            MAO - B Inhibitors:      (Selegiline) MAO breaks down dopamine - inhibition of it is neuroprotective

            Amantadine: releases pre-synaptic dopamine and has glutamine antagonist properties - used in early symptomatic rx

            COMT Inhibitors:         COMT catalyzes metabolism of levadopa - inhibition makes more dopamine available centrally through the BBB
                                     No role as monotherapy - only in combo with Levodopa
                                     Indicated for pts experiencing end-of-dose "wearing off" with levodopa
            Surgical options:        Ablative therapies, deep brain stimulation

Parkinson Syndromes: Idiopathic (85% of all cases)              Pseudo parkinsonism due to narcoleptics (8%)                  Vascular Parkinsonism
                     Multisystem atrophy                        Progressive supranuclear palsy                                Toxic Parkinsonism (ex. CO)
Dementia
General:    Progressive loss of intellectual function - memory loss is central feature
            Cognition abnormalities:                language, spatial processing, praxis (learned motor behavior) & executive function ( ability to plan & sequence events)
            neurodegeneration is most common underlying cause - Alzheimer's, frontotemporal lobe dementia, diffuse Lewy body disease
            most are untreatable
            Every pt w/ dementia should have: serum electrolytes, liver, renal & thyroid function, B12, serologic studies for syphilis
                                                    MRI in pts w/ focal signs noted on neuro exam
            Testing:     MMSE                                                              praxis ("show how you would comb your hair, or blow out a match)
                         visuo-spatial processing (clocking drawing)                       sequencing (draw random numbers on page, have pt connect them in order)

Alzheimer's
General: 70% of all cases of dementia                           incidence increases with age >> 30% of people over 85
           average survival after dx is 8 years                 age & family history are strongest known risk factors
           low educational level and mental inactivity also suggested risk factors >>increased synaptic density is protective
           all down syndrome pts ultimately develop AD >> DS is risk factor
           2 types: early onset familial or late-onset sporadic             familial form linked to changes on chromosomes 19 (apolipoprotein E4) & 21(amyloid B protein)

Clinical:   dementia: loss of intellectual ability & personal interaction (decline from previous level) >> interferes w/ daily functioning
                        hallmark - cortical deficits >> memory, apraxia, agnosia
            short-term memory loss:                progressive impairment in learning new info;          recall of remote info may be preserved initially , no new info stored
                                                   later stages >> failure of frank recall for previously well-remembered info
            language: difficulty finding words >> compensatory circumlocutions >> vague language >> anomia on naming tests & impaired cognition of language
            apraxia: disorder of skilled mvmt despite intact strength & coordination                     can't translate ideas into action
            visual:     agnosia, defects in visual attention & breakdown of processing ( contrast, spatial relations, motion detection)
            acalculia: inability to do mathematical calculations
            behavioral: personality changes, passivity & apathy, decreased expression of affection
            anosognosia:             lack of recognition of any cognitive or functional disability by the patient >> major impediment to dx & management
            psych:      psychosis, agitation, delusions, hallucinations & depression
            extrapyramidal signs: late in dz >> rigidity & parkinsonian type sx

Path:       atrophic brain (especially frontal /temporal) with enlarged ventricles & sulci                        senile or neuritic plaques& neurofibrillary tangles
            neuritic plaques:        neural processes with extra amyloid deposition due to enhanced beta secretase activity
            neurofibrillary tangle: intracellular collections of abnormal filaments with distinctive paired helical structure
                                     major component are hyperphosphorylated tau proteins
            widespread cortical neuronal loss
            hirano bodies:           eosinophilic cellular inclusions in hippocampal pyramidal layer                             granovacuolar degeneration
            relative deficiency of cortical acetylcholine

Dx:         Requires:    1 year course of decline in memory or 1 other cognitive domain (language, orientation, judgment, problem-solving)
                         onset b/t 40 & 90 y/o with consciousness preserved                         absence of other illness capable of causing dementia

Rx:         No known treatment - mostly symptomatic
            Increased socialization, improved sleep hygiene, financial planning & legal advice, advanced directives
            Cholinesterase inhibitors - tacrine, donepizil, rivastigmine >> cognitive enhancing                  Other - antioxidants, antidepressants, antipsychotics
Other causes of Dementia
Vascular Dementia:
           Accumulation of ischemic brain lesions >> incremental impairment of memory & behavioral initiation
           If pattern is insidious & has extensive, diffuse ischemic change = Binswanger's disease
           Clinical:      prominent frontal/executive function deficits (less language impairment than in AD)
                          early incontinence, gait disturbances & flattening of affect
                          facial masking, rigidity & babinski are common earlier in VD than AD
           Rx:            rx risk factors - BP, smoking cessation, diet & anticoagulation as necessary
Pick's Disease:
            deficiency of sphyngomyelinase >> accumulation of sphyngomyelin
            front-temporal dementia >> prominent behavioral disturbance (social & interpersonal >> disinhibition, impulsivity & apathy)
            non-fluent language disturbance
            lacks apraxia & visuo-spatial dysfunction - social behavior impaired out of proportion to cognitive deficits
Tay- Sach's Disease:
           deficiency of hexosaminidase enzyme >> accumul;ation of gangliosides in neurons                     early onset >> mental & motor deterioration & blindness
Normal Pressure Hydrocephalus:
          Derangement of CSF hydrodynamics                                        sx evolve over weeks to months
          Triad of dementia, gait instability & urinary incontinence              pts walk with their feet stuck to the floor - w/op lifting knees & wide-based
          Dx & Rx: brain imaging >> ventricular enlargement out of proportion to cortical atrophy
                     LP with removal of large amounts of CSF >> followed by exam of gait & cognitive function
                     Ventriculoperitoneal shunt may be corrective
Wernicke - Korsakoff's Syndrome:
           Triad of disturbances in ocular function, gait & mental function
           Total inability to establish new memory >> pts confabulate response                     ↓ of thiamine in the context of alcoholism - most common causes
           Rx:          thiamine is necessary cofactor for glucose metabolism >> must replenish thiamine & glucose
Delirium:
General:    acute state of confusion that most frx occurs during hospitalization of elderly                       characterized by lack of attentiveness & fluctuating LOC
            disorientation, memory loss & hallucinations
            specific cause usually identifiable: infx, pn, dehydration, electrolyte disorders, medications, surgery, indwelling bladder catheter

Pellagra:   nicotinic acid deficiency >> "3 D's"                                                   Delirium                               Dementia
            dermatitis, diarrhea & delerium                               sensorium                "clouded"                              "clear"
                                                                          onset                    acute                                  insidious
                                                                          course                   fluctuating, lucid at times            generally stable
                                                                          duration                 hours to weeks                         months to years
                                                                          alertness                abnormally low or high                 usually nml
                                                                          perception               illusions & hallucinations             usually nml
                                                                          memory                   immediate & recent impaired            recent & remote impaired
                                                                          though                   disorganized                           impoverished
                                                                          speech                   incoherent, slow or rapid              word-finding difficulty
                                                                          causative                illness or med                         unknown
Seizures
Seizure:    transient disturbance in cerebral function due to paroxysmal neuronal discharge             manifestations may be motor, sensory, ANS or psychic disturbances
Epilepsy:   any disorder characterized by recurrent seizures
            Primary: Idiopathic - no identifiable pathology, nml dev't, relatively self-limited, medication responsive, genetic predisposition
            Secondary: Focal or diffuse cerebral injury, neurologic abnormalities, difficult to control
            Incidence highest among children & the elderly                    M>W
            Cause of death in pts w/ epilepsy:     suicide > status epilepticus > fatal accidents during seizures;   Sudden unexplained death in epilepsy syndrome (SUDEP)

Dx:         History of events (from pt or witness)           PE/neuro exam                         MRI/ CT: help show underlying structural brain pathology
            EEG - primary tool (photic stim, sleep deprivation & hyperventilation increase chance of seeing spikes or sharp waves in the epileptic individual
Generalized Seizures: Tonic Clonic                Absence      Clonic       Tonic        Myoclonic Atonic                         Begin diffusely
Tonic - Clonic:           Grand Mal or Convulsive             Loss of consciousness
                          Ictus:     Tonic: Fall, muscular rigidity, inhibition of respiration >> cyanosis
                                     Clonic: rhythmic jerking, restoration of breathing, tongue biting common, bladder/bowel incontinence
                          Postictal: confusion, lethargy, HA; no aura recall, may have bilateral neuro deficits
Absence:    Petite Mal             Childhood/adolescent onset           Sudden onset, with or w/o aura                      momentary loss of consciousness/staring spell
            Nonconvulsive          10-20 seconds in duration            abrupt post-ictal recovery                          amnesic for ictal event
            May have very minor motor activity: blinking, sporadic myoclonic jerks, automatisms or changes in muscle tone
            Typical:   < 10 seconds, associated w/ diffuse 3 Hz spike& wave discharges on EEG
            Atypical: > 10 secs, more gradual onset w/ loss of muscle tone or autonomic features, associated w/ 1.5-25 Hz discharges
Myoclonic: brief, shock-like muscle contractions (head or UE), bilaterally symmetrical                  No loss of consciousness
           precipitated by awakening or falling asleep                                                  may >> clonic or tonic-clonic
Atonic:     drop attack               Pt has sudden loss of postural tone & if standing will collapse

Partial Seizures:         Simple      Complex Secondarily generalized
Simple Partial:           (focal motor or focal sensory)  No loss of consciousness                      Sx variable (motor, sensory, ANS or psychic)     focal EEG abnormality
Complex Partial:          (temporal lobe or psychomotor)       Clouding, w/o loss of consciousness                   Ictus 1 min                         focal EEG abnormality
                          staring spells                       Automatisms                                           auras are typical                   Amnesic for event

Other Epileptic Syndromes:
Lennox-Gastaut Syndrome:              Onset before 8 y/o, M > F               Triad: mixed seizures, slow spike & wave on EEG, psychomotor retardation/behavioral disorder
                                      risk factors - hx of infantile spasms, devt'l delay before seizure onset

Juvenile Myoclonic Epilepsy:          onset childhood to early adult, family hx in 40 %                                           High incidence of relapse upon AED withdrawal
                                      mild myoclonic seizures plus tonic clonic, tonic-clonic-tonic, or absence                   Frx occur upon awakening
                                      possible precipitants:    lack of sleep, stress, ETOH
Non-epileptic Paroxysmal Events

           Breath-holding Attacks:                6 mos - 6 years            crying, stops breathing >> cyanosis, LOC, limp, tonic posturing or convulsion
                                                  risk factors - crying, head injury, anemia
           Palllid Infantile Syncope:             12-18 months               pallor, cold sweat, LOC, posturing or convulsions                   brief vagal mediated asystole
                                                  risk factors - minor injuries, fright, frustration, anemia
           Cardiac dysrhythmias: prolonged QT
           Migraine: aura, postictal HA
           BPV:        disequilibrium, w/ or w/o nystagmus or torticolllis
           Syncope: risk factors - blood drawing, systemic illness, prolonged standing in heat, orthostatic hypotension, anemia, family hx, hair braiding
           GI reflux: Sandifer's syndrome:        choking, apnea, laryngospasm, opisthotonis (extension of body & head), w/ or w/o vomiting
           Parasomnias:             night terror, sleep walking, sleep talking, nightmares
           Paroxysmal Choreathetosis:             severe dystonia or choreathetosis                      risk factors - stress, excitement, ETOH, caffeine, fatigue, startle
           Other:      mvmt disorders, psuedoseizures, rage attacks, malingering

           Febrile:     most common cause of convulsions in children                   30% have >1 attack, recurrence greatest if first seizure before 1 years old
                        most have no LT consequences, though they increase the risk of developing epilepsy later
                        not associated w/ nor do they cause mental retardation, poor school performance or behavioral problems

Epilepsy Treatment:
General:   recurrence after 1st seizure:          29% at 1 year, 37% at 2 years, 43% at 5 years, 46% at 10 years
           recurrence after 2nd seizure:                72%
           recurrence after 3rd seizure:                81%

Drugs of Choice:     generalized motor seizures:          phenytoin, carbamazepine, valproic acid                    New adjuvants:            Felbamate               Topiramate
                     partial seizures:        phenytoin, carbamazepine                                               Gabapentin                Lamotrigine             Tiagabine
                     absence seizures:        ethosuximide, valproic acid                                            Leveteracetum             Zonisamide              Oxcarbaepine
           up to 30% medically refractory

Diet:      Ketogenic diet            (side effects - refusal to eat, renal stones, hyperuricemia, hypercalciuria, dehydration)
           Epilepsy diet:            high in fat, low in CHO & protein - calories set at growth requirement                       vitamin, mineral, Ca supplements
                                     heavy cream/butter                        no sugar

Surgical Options:       Potentially curative:     lobectomy - best for temporal lobe epilepsy         hemispherectomy - for more severe epilepsy
                        Symptomatic:              vagus nerve stimulation                corpus callosotomy (limits seizure spread to one hemisphere - good for drop attacks)
                        Future therapy:           local delivery of meds, deep brain stimulation, pharmacogenetics
NEUROLOGY AND HIV
neurological manifestations of HIV infx are highly stage specific
during initial infx and mid-course, immune dysregulation → autoimmune conditions; later, neuro complications 2° to opportunistic infx

AIDS Dementia Complex
distinct neurological syndrome characterized by psychomotor retardation                   occurs in advanced AIDS, CD4< 100

Clinical:  begins insidiously and progresses over months to yrs
           mild = diff w/ concentration and mental agility; motor abn = slow movement of limbs or eyes         severe = more diffuse; motor impairment → quadraparesis
           diminished memory, slow thought processes; occasional behavioral abn (social w/drawl & apathy)                   progressive gait ataxia
Vacuolar myelopathy: seen in late stages of HIV, usu in association w/ ADC; clinically = spastic paraparesis w/ hyperreflexia/spastic wkness of LE & incontinence

Diagnosis: best predictor for clinical dementia = absolute numbers of immunocompetent brain macrophages
           MRI :        cortical atrophy, dilated ventricles
           CSF:         typically normal           or, ↑ B2 microglobulin and neopterin

PNS - Peripheral Neuropathies

HIV-associated Primarily Sensory Distal Peripheral Neuropathy
           distal, symmetric peripheral neuropathy = most common presentation
           burning, painful paresthesias of insidious onset in toes; slow progression proximally; feet > hands
           analgesia & ↓ thermalgesia in stocking distribution; mild wkness and muscle atrophy distally; absent ankle tendon reflex
           predominantly axonal degeneration                    may be related to CMV infx

Acute & Chronic Demyelinating Peripheral Neuropathy                                                                           Differentiate from non-HIV via…
           AIDP/Guillain Barre: acute, rapidly progressive CIDP: subacute; can be monophasic or relapsing                     rare progression to severe resp insufficiency
           symmetric wkness in UE & LE; generalized areflexia                                                                 generalized lymphadenopathy
           paresthesias frx, but sensory findings mild relative to motor                                                      coexisting signs of CNS involvement
           clinically similar to pts w/o HIV, except for CSF:                                                                 hx of STD
                         in addition to typically ↑ protein, also see pleocytosis (elevated cell count - mononuclear)

Mononeuritis Multiplex                                                                  (least common of all neuropathies)
           stepwise, abrupt onset of sensory, motor, or mixed syndromes, affecting multiple peripheral nerve distributions in asymmetric fashion
           AIDS Related Complex/CD4 > 200:                   self limited; affects 1-2 nerves; good prognosis
           Severely Immunocompromised:                       pathogenesis due to CMV infx; necrotizing vasculitis; poor prognosis; may improve w/ Gancyclovir

Polyradiculopathy
            Lumbosacral: subacute sensory and motor loss involving lumbar and sacral roots, usu accompanied by low back pn w/ radicular or perianal radiation
            relentless progression over 1-6 wks                loss of urinary and rectal sphincter control & sacral anesthesia = early, distinct features
            weakness of LE, mild sensory loss, arreflexia - spreads rostrally             CSF - pleocytosis, ↑ protein
Myopathy
            subacute onset of proximal UE & LE weakness                      elevated CPK             muscle bx: inflammatory or mitochondrial myopathy
            responds to steroids                  is secondary to AZT & reversible (d/c drug)
CNS FOCAL LESIONS

Progressive multifocal leukoencephalopathy
            demyelinating dz caused by a papovavirus                           reactivation during immunocompromised period; JC virus infects glia
            presenting sxs may include: dementia, visual impairment, seizures, hemiparesis
            MRI: multiple lesions predominantly involving white matter                       less visible on CT (helps distinguish f/ other mass lesions)
            no specific tx, but often regresses in response to effective antiretroviral therapy

Toxoplasmosis
          causes encephalitis in up to 1/3 of pts in the absence of antiretroviral tx
          fever                      progressive HA and focal neuro abnormalities
          CT or MRI - multiple ring enhancing lesions
          tx w/ drugs that inhibit folic acid production       continue suppressive therapy until sustained rise in CD4 count above 200

Primary CNS Lymphoma
          irradiation provides transient remission
          arises f/ B lymphocytes                predilection for certain cerebral sites

OTHER CNS DISEASES

Aseptic Meningitis
           most common sx = headache            sensorium generally intact & neuro exam nml                           HA, fever, and photophobia can be the presentation
           HA, fever, and inflammation of meninges; no organism by Gram stain or bacterial culture                    of HIV seroconversion; CSF - mononuclear
           typically viral         CSF - incr lymphocytes & protein, nml glc

Cryptococcal Meningitis
           most common cause of chronic mengitis
           HA, fever, difficulty concentrating &/or changes in sensorium              chills, anorexia, vomiting, photophobia, stiff neck
           CSF:         low glc, high protein, mild lymphocytic infiltration          ↑ cells, mostly PMNs
           Dx:          cryptococcal antigen in serum or CSF; positive CSF India Ink prep

Encephalitis
               Meningoencephalitis:    alterations in sensorium f/ mild lethargy to coma                 CMV Encephalitis:          rare and difficult to dx
                                       febrile & neuro exam shows diffuse CNS involvement                                           confusion, CN abn, long tract signs
                                       CT/MRI - nonspecific; EEG - diffuse brain dz
                                       clinical dementia, motor disturbances and seizures
PATHOLOGY - OTHER CNS INFECTIONS (NON-HIV)
Bacterial Infection: hematogenous spread; septic empboli as in endocarditis; open wounds
                     Bacterial Meningitis - Steptococcus pneumoniae - adults; E. coli & Group B strept - neonates; Neisseria meningitidis - adolescents

Localized Encephalitis most common viral cause = Herpes; most common neurotropic virus associated w/ epidemics of encephalitis = Japanese B encephalitis
Path:       localize or diffuse infl of brain parenchyma; viruses invade neural or glial cells Herpes - temporal lobe; foci of necrosis and hemorrhage

Neurotropic = infect exclusively neural tissue
           Rabies - unusual b/c reaches CNS by traveling along peripheral nerves; see intracytoplasmic viral inclusions, Negri bodies in brainstem

Prions - sm infectious particles made of protein; no DNA or RNA; transmitted by direct exposure to infected material; ex. Creutzfeld-Jacob in corneal transplants
Protozoal - Toxoplasmosis, encephalitis in neonates and AIDS pt
Fungi - immunosuppressed, AIDS; Candida, Asergillus, Cryptococcus

Myelitis - dissuse spinal cord infx; usu viral     Polio
Cerebral Abscess: localized suppurative infx; cavity filled w/ pus and capsule made of glial cells and fibroblasts; usu pyogenic bacteria
Meningitis: viral - see lymphocytic exudate in subarachmoid space

Neurosyphilis -        presents as chronic meningitis
                       meninges infiltrated with lymphocytes and plasma cells, typically centered on sm blood vessels
                       healing = meningeal fibrosis → compression of dorsal roots → arophy of afferent, sensory axons → tabes dorsalis
                       perivascula infl of brain → ischemic necrosis of cortical centers → motor and mental changes = syphilitic general paresis of the insane
AIDS-related encephalopathy
           HIV infects macrophages and T lymphocytes, which "import" the virus into the CNS and secrete cytokines that are toxic to the brain
CONGENITAL BRAIN MALFORMATIONS
                                                                                                                              Spina Bifida - any defective closure
Brain Development       Gross abnormalities: 1st 6 wks of gestation                                                                       of the neural tube/vertebrae
                        Neuronal proliferation/migration: late 1st trimester →5th month
                        Myelination: 3rd trimester → postnatal years
                        Organizational changes: throughout life
Neural Tube Development: Neuralation, days 17-27                                    Deficits: anencephaly, encephalocele, meningomyelocele
          Anencephaly           75: still born; F > M
                                large portions of cranium, including bone, are absent; forebrain & deeper structures (i.e. hypothalamus) are absent
          Encephalocele         defective closure of rostral tube associated with bony defect; usually occipital           ↑ ά fetoprotein
                                sacs contain meninges +/- neural tissue (herniation through defect)
                                may be part of Meckel syndrome - microcephaly, micophthalmia, cleft lip & palate, abn genitalia, polycystic kidneys, polydactyly
          Meningomyelocele      incomplete fusion of vertebral bodies and meninges + posterior protrusion of spinal cord                ↑ ά fetoprotein
                                hydrocephalus in 75% of cases                       associated w/ Arnold Chiari II - complex malformation of dura, calvarium,…
Neural Tube Development: Canalization & Differentiation, days 27-50                                 Defects in this phase are covered by skin
          Meningocele           covered by normal skin or a thin-walled membrane
                                only meninges protrude, not nerves?
                                60% clinically silent
          Myelocystocele        localized cystic dilation of central canal of caudal cord
                                associated w/ vertebral abnormalities & cloacal exstrophy
                                cloaca - common passage for feces, urine, reproduction
          Spina Bifida Occulta  vertebral defect w/o herniation of spinal canal contents
          Diastematomyelia      spinal cord divided in half
                                sometimes separated by bony or cartilagenous septum
          Lipoma                common benign tumor composed of fatty tissue




Ventral Induction: 5-6 weeks                                                                          Development of forebrain and facial structures
           Holoprosencephaly         failure of segmentation and cleavage of forebrain into paired cerebral hemispheres
                                     holospheric cerebrum: single ventricle, abn optic structures, agenesis of corpus collosum
                                     single, median eye; rudimentary nose; median cleft lip and palate
Nerve Cell Proliferation: 2-4 months
           Microcephaly Vera       primary microcephaly; autosomal recessive          less common than secondary
                                   most affectedw/ severe MR, seizures spasticity, visual defects
           Macrencephaly           abnormally large brain                may be unilateral
                                   frequently associated w/ heterotopias (mature tissue in a location where it is not normally found
           Down Syndrome           trisomy 21               up to 50% fewer neurons in frontal, temporal lobes, visual cortex, cingulate gyrus
Nerve Cell Migration: 3-5 months                                                                     Process of nerve cells moving f/ place of origin to permanent location
           Agenesis of Corpus Collosum        may occur in isolation or w/ other malformations
                                              lateral ventricles displaced laterally, 3rd ventricle enlarged and dorsally displaced
           Lissencephaly          smooth cortex             lack of normal convolutions/folds
                                  SGA, microcephaly, high forehead, down slanting palpebral fissure, anteverted nares, ocular abn, seizures, hypotonia, dev delay
                                  associated w/ polyhydramnios in pregnancy (↑ levels of amniotic fluid)
           Pachygyria             wide/thick gyri           associated w/ developmental delay, hypotonia, seizures

           Polymicrogyria         multiple small gyri       cobblestone appearance
                                  may be silent, localized or generalized maturational defect
                                  also, associated w/ necrosis after migration is complete, secondary to toxic, infx, vascular events
           Schizencephaly         CSF-filled cleft lined by grey matter extending across entire cerebral hemisphere
                                  MR, seizures, spasticity               may be associated w/ ventricular enlargement, corpus collosum agenesis, heterotopias
Nerve Cell Organization and Maturation          Rubenstein-Taybi Syndrome             facial abn, broad thumbs & great toes, short stature, MR
                                                Congenital Rubella                    deafness, seizures, MR, low birth wt, microcephaly
                                                Down Syndrome
                                                Untreated PKU (phenylketonuria)
           Myelination: 5 months gestation - 18 months
Destructive Prenatal Lesions
            Hydrancephaly         almost complete absence of the cerebral hemispheres
                                  clinically nml until 3-4 mos; poor dev, enlarging FOC, motor dysfxn, seizures, visual dysfxn
           Porencephaly           cyst or cavity in cerebral hemisphere              often extend from surface of hemisphere to ventricle
                                  predilection for parietoccipital region
FETAL ALCOHOL SYNDROME                                                   decreased nerve cell proliferation and nerve cell migration
         prenatal onset growth deficiency
         microcephaly, motor disorders, MR
         short palpebral fissures
APPROACH TO METABOLIC DISEASE CLINICAL PATTERNS

Inborn Errors of Metabolism
Central Feature = loss of developmental milestones; early slowing of acquisition of new skills; later actual loss of skills
R/O:        tumors, epilapsy, meds, hydrocephalus, brain malformations, chromosome disorders
Dx:         evidence of gray matter dysfxn = seizures, MR, dementia
            evidence of white matter dysfxn = spasticity, incr reflexes, cortical blindness
            localized CNS dysfxn = basal ganglia, brainstem, cortex, cerebellum
Fam Hx:     autosomal recessive (M & F)             mitochondrial inheritance (maternal transmission, M = F, but only females pass to offspring)         X linked (Males)
Exam:       Coarsening of facial features           Dysmorphic features         Short stature             Skeletal abnormalities
            Skin & Hair: hair color (lighter); friability, steel wool, hair loss, wiry; photosensitive dermatosis; icthyosis
            Ocular Abn: fundus = direct extension of brain and may mirror CNS abn; cherry red spots, corneal clouding, cataracts, optic atrophy, retinal degeneration
            Abdomen: hx of pyloric stenosis; hepatomegaly; splenomegaly; unexplained vomiting; protein intolerance; polycystic kidneys
            Cardiac: cardiomegaly; arrythymias, respiratory abn
            Neuro: combo of many, but may present as only one sx early on; seizure, cognitive &/or motor delay; spasticity; extrapyramidal sx; hypotonia; microcephaly
            macrocephaly; ataxia; nysstagmus; episodic encephalopathy; abnormal startle; loss of auditory, visual fxn; imp alertness; sleep abn; peripheral neurop
Lab:        Urine - amino acids, metabolic screen, organic acids
            Serum - aa's, lysosomal enzymes, glc/glycogen metabolism, uric acid, acid phosphatase, lactate, pyruvate, ceruplasmin, WBC abn
            CSF - protein, gamma globulin, lacate, glycine, neurotransmitter levels
            Tissue - bone marrow aspirate, liver/muscle bx, skin biopsy

Metabolic Disease: Onset at Birth
           altered consciousness, abn tone, motor automatisms, ocular mvmnts, resp and circ, sucking & swallowing, seizures

Peroxisomal Disorders absent liver peroxisomes (which are for B oxidation of fatty acid chains) → abn accumulation of very long fatty acid chains
                       calcific stippling of epiphyses and sm renal cysts              cortical dysplasia, regressive brain changes
           Group 1: prototype = Zellweger Syndrome (ZWS); also, NALD, Refsum's Syndrome
           ZWS         multiple congenital anomaly dz - high forehead, lg ant fontanelle, epicantal folds, deformed ear lobes; profound neuro abn
                       severe psychomotor retardation, profound hypotonia, neonatal seizures, glaucoma, retinal degeneration, imp hearing, lg liver

Type I glycogen storage disease - von Gierke's                   Clinical     seizures and hepatomegaly              metabolic acidosis w/ hypoglycemia
                                                                 Metabolic    glucose-6-phosphatase deficiency
                                                                 Tx           IV glc and constant feeding

Nonketotic Hyperglycinemia
            inability to break down glycine into ammonia (glycine is major metabolite b/w pyruvate and other molecules)                        presents in first few days of life
            progressing stupor, unresponsive, resp diff, seizures; frx hiccups; abn ocular jerking
            EEG and MRI abn; elevated glycine; CSF:plasma glycine is imp
Metabolic Disease: Onset at 1-3 Weeks

Maple Syrup Urine Dz     well at birth; poor feeding at 3-4 days; urine smells like maple syrup; pos urine ketones
                         untreated → brain swelling (seizures, herniation, death)
                         increased branch chain amino acids - leucine, isoleucine, valine; hypoglycemia, hypoalaninemia
                         tx: decrease the leucine; protein restriction
Sulfate Oxidase deficiency             feeding diff, refractory seizures; axial hypotonia or limb rigidity; pyramidal signs; lens dislocation; dysmorphic facies
                                       MRI: cystic cavities; cortical involvement           Even w/ tx, outcome is poor
Mitochondrial Encephalopathies         multisystem disorder - heart, brain, liver, muscle              dz esp manifests in tissue w/ hi E expenditure
                                       irritable, poor feeding, vomiting, hepatomegaly                 dysmorphic facies, cardiomyopathy, renal cysts
                                       dx: measure lactate, pyruvate in blood and CSF + ratio          ketone bodies, creatinine, organic acids to diff f/ organic acidemias
                                       often cause deficient resp chain fxn; abn oxidative phosphrylation enzymes

Urea Cycle Disorders       defect in breakdown of ammonia
                           full term infants, well for 24-48 hrs → lethargy, vomiting, HV, alkalosis, elevated ammonia
                           Tx: restrict nitrogen intake (i.e. protein)

Organic Acidemias          full term infant, well until 1-3 wks → poor feeding, neuro impairment
                           Lab: abn urine organic acid screen; hyperammonia; hyperglycinemia; ketoacidosis
                           Tx: 10-15% glc and fat; protein load w/ min daily requirements of certain aa's

Progressive Metabolic Encephalopathies
           neurologic regression or arrest of development; severe hypotonia; focal neuro signs; similar disorder in fmaily member

Generalized GM1 Gangliosidosis         coarse facies, hirsutism, nonpitting edema of limbs; hepatosplenomegaly
                                       progress to decerebrate rigidity w/ exaggerated startle, seizures             death by age 2
                                       cherry red spot (macular finding in several lipid storage disorders

Tay-Sachs Disease          exaggerated startle; visual failure - nysagmus; cherry red spot; progressive macrocephaly; seizures
                           Dx: isolated deficiency of hexosaminidase A in leukocytes or fibroblasts

Glycogenesis type II: Alpha glucosidase deficiency (Pompe's dz)               decr motor activity, muscle wkness, inability to hold up head
                                                                              firm muscles w/o evidence of wasting, ↓ DTR, weak suck and swallow
                                                                              cardiomyopathy
                                                                              Dx: acid alpha glucosidase in muscle, liver, lymphocytes
Leukodystrophies
          white matter disorders; peripheral nerves may be involved; de/hypo/dysmyelination

Krabbe Dz                  problems begin by 6 mos              irritability, diminished alertness, vomiting, feeding prob        rigidity, hypertonicity, tonic spasms, seizures, FUO
                           Evaluation - CSF protein elevated; EEG and MRI abn

Biotinidase deficiency     myoclonic seizures in child w/ dev delay, hypotonia            skin rashes               intermittent ataxia, hearing loss, optic atrophy
                           metabolic acidosis w/ lactic acidosis             dx: biotinidase levels in serum, leukocytes; tx: biotin

Menkes Dz                  premature boys           neonatal hypothermia, hyperbilirubinemia            dev arrest before 3rd month of life
                           hallmark: sparse and broken hair that is poor in pigmentation                Lab: low copper and ceruloplasmin

Glutaric Aciduria type I               dystonia, ketoacidosis    MRI - underdeveloped temporal lobes                 def of glutary coA dehydrogenase                   tx: diet

				
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