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Neurological Medicine



Parkinson’s Disease


                                         Learning Objectives

Dom          LO Title                                               LO Detail
BCS Diagnosis of epilepsy    1. To be able to elicit an appropriate history from and perform an examination on a
                             patient with a recent seizure.
                             2. To be able to outline an appropriate management plan for a patient presenting to
                             hospital with a seizure.
                             3. To be aware of the common investigations used to evaluate patients with epilepsy,
                             such as the electroencephalogram, and imaging procedures such as computerised
                             axial tomography or magnetic resonance imaging of the head – in depth.
                             4. Understanding of these procedures IS NOT REQUIRED.
BCS Mechanisms of            1. To describe the common syndromes of epilepsy.
    epilepsy and seizures    2. To outline the biochemical mechanisms of seizures.
                             3. To outline the mechanism of action of the common anticonvulsant used to treat
ICCP Clinical examination    1. Perform a focussed central nervous system examination for:
                             (a) Cranial nerves (including ophthalmoscopy)
                             (b) Upper or lower limb (power and sensation)
                             (c) Cerebellar function
                             (d) Locomotion.
ICCP Management of           1. Demonstrate the left lateral position for unconscious patients.
     unconscious patient     2. Describe use of Guedel Airway.
PPH Psychosocial             1. Describe the possible psychosocial consequences of a diagnosis of epilepsy.
    consequences (Social
PPH Stigmatization (Social   1. Describe stigmatisation.
    Sciences)                2. Differentiate between ‘felt’ and ‘enacted’ stigma, using a clinical example.
PPH Health policy and        1. What key information should you provide a newly diagnosed patient with epilepsy
    guidelines (Public       regarding the general principles

To be able to assess an unconscious patient
The Examination of the Unconscious Patient
The word COMA provides a pneumonic for 4 major groups of causes of unconsciousness
        C - CO2 narcosis (respiratory failure - uncommon)
        O - Overdose of drugs (tranquillisers, alcohol, salicylates, carbon monoxide, antidepressants)
        M - Metabolic (hypoglycemia, diabetic ketoacidosis, uraemia, hypothyroidism, hepatic coma,
        hypercalcaemia, adrenal failure)
        A - Apoplexy - head injury, CVA, subdural or extradural haematoma, meningitis, encephalitis,

General Inspection
       Is patient breathing? - If no  check airway is clear and providing ventilation
       Deep rapid breathing = sign of Kussmaul breathing secondary to a metabolic acidosis e.g.
        diabetic ketoacidosis

        Look for signs of shock, dehydration and cyanosis
        Take pulse rate and blood pressure

       Look for signs of trauma
       Look for:
      1) Decerebrate or extensor posture which may be held spontaneously or occur in response to
         stimuli and which suggests severe midbrain disease. The arms are held extended and
         internally rotated and the legs are extended.
      2) Decorticate or flexor posture suggests a lesion above the brainstem. It can be unilateral or
         bilateral. There is flexion and internal rotation of the arms and extension of the legs.

Involuntary Movements
        Recurrent or continuous convulsions which may be focal or generalised suggest status
        Myoclonic jerks can occur after hypoxic injury and as a result of metabolic encephalopathy

Level of Consciousness
        Press your knuckles over the sternum firmly to cause pain - determine the level of
        Coma is unconscious with a reduced response to external stimuli
        Coma in which the patient responds semi-purposefully is considered light
        In deep coma there is no response to any stimuli and no reflexes are present
        Stupor is unconsciousness but the patient can be aroused with a considerable amount of effort.
         Purposeful movements occur in response to painful stimuli
        Drowsiness resembles normal sleepiness. The patient can be fairly easily roused to normal
         wakefulness, but when left alone falls asleep again.

The Neck
      Look for evidence of neck trauma, assess for neck stiffness and Kernig's sign (meningitis and

The Head and Face
      Inspect and palpate for head injuries.
             Battle‟s Sign – post-auricular eccymoses
             Raccoon Eyes – periorbital bruising
                                                                       Both are signs of basal
      Look for facial asymmetry                                       skull fracture.
      Note any jaundice or manifestations of mxyoedema

The Eyes
       Inspect the pupils
       Very small pupils occur in pontine lesions and with narcotic overdoses
       One dilated pupil suggests a subdural haematoma, raised intracranial pressure or a SAH from
        a posterior communicating artery aneurysm.
       Conjunctival haemorrhage with no posterior limit suggests skull fracture
       Widely dilated pupils may occur when increased intracranial pressure and coning cause
        secondary brainstem haemorrhage or with atropine like drugs (mydriatics)
       Look in the fundi for papilloedema, diabetic or hypertensive retinopathy, or subhyaloid
       Look at the position of the eyes
       Particular cranial nerve palsies may cause deviation of an eye in various directions
       The 6th nerve is vulnerable to damage because it has the longest intracranial course
       Deviation of both eyes to one side on the unconscious patient may be due to destructive lesion
        in a cerebral hemisphere which causes fixed deviation towards the side of the lesion
       Upward or downward eye deviation suggests a brainstem problem
       Perform 'doll's eyes test' - open patient‟s eyes and roll head from side to side. Normally eyes
        remain fixed on object in distance  if the eyes don't = a brainstem lesion or drugs affecting
        the brainstem and causes the eyes to move with the head so fixation is not maintained.
                      Reflects impairment of the vestibulo-optic reflex

Ears and Nostrils
       Look for any bleeding or drainage of CSF. Presence of glucose confirms it is CSF.
              CSF rhinorrhoea

The Tongue and Mouth
       Trauma may indicate previous seizure
       Corrosion may indicate ingestion of corrosive substance
       Smell the breath for evidence of alcohol ingestion, diabetic ketosis, hepatic coma or uraemia
       Test gag reflex - absence indicates brainstem disease or deep coma.

The Upper and Lower Limbs
      Look for injection marks
      Test tone - test side-side
      Test deep tendon reflexes
      Test for pain sensation - look for withdrawal

The Body
      Look for signs of trauma
      Examine heart, lungs and abdomen

The Urine
      Note incontinence
      Test for glucose, ketones, protein, and blood

Blood Glucose
      If any possibility of Wernicke's encephalopathy must give thiamine with glucose

Stomach Contents
    Evidence of toxic overdose (deliberate)

Glasgow Coma Scale
    1. Eyes - spontaneously, to command, to pain
    2. Best Motor Response - verbal, to pain
    3. Best Verbal Response
Score out of 15
To be able to elicit an appropriate history from and perform an examination on a patient with a
recent seizure. To be able to suggest an appropriate management plan for a patient presenting to
hospital BCS/ with a seizure ICS&CRP

See above - ABC

Check to see if the patient been exposed to anything? Does the breath smell of alcohol? Is there the
pin point pupils associated with heroin overdose?
Fully expose the patient so you can do a head to toe assessment.

Monitor ECG, pulse oximetry, BP, be careful to make sure there is no vomit in the mouth that may be

Get an IV line up, avoiding joints.
10mg Diazepam IV over 2min with most given as a bolus to start with. Be careful of respiratory
depression over the last few mg. Can be given rectally if you cannot get venous access.

        50 ml of 50% glucose unless you are certain that glucose is >5mmol/L (to reverse

        100mg Thiamine if the patient is alcoholic (Wernicke‟s encephalopathy)

        Dexamethasone 10mg IV is seizure due to possible vasculitis or cerebral tumour (Is the
         patient being treated for metastatic cancer?)

If seizures persist then start Phenytoin 15mg/Kg up to a rate of 50mg/min
      Beware of drop in BP and do not use if bradycardic or there is heart block

If seizures continue get expert help, an anaesthetist may be needed to paralyse the patient and ventilate.

Important investigations
    Pulse Ox - hypoxia
    Temperature – febrile  infective
    ECG
    Check the glucose levels to exclude hypo/hyperglycemia
    Blood gases
    Urea and electrolytes
    Ca++
    Full blood count and platelets
    Also be aware or Anticonvulsant levels, Drugs, Possible meningitis  LP
    Blood culture and urine
    EEG and CT scans may be indicated

To be aware of the common syndromes of epilepsy (BCS)

    1. Generalised Seizures
    Bilateral symmetrical seizures without local onset
        Absences (petit mal) - sudden cessation of ongoing conscious activity without convulsive
        muscular activity or loss of postural control. At the end of the absence seizure the patient
        regains awareness of the environment very quickly. Onset usually between 6-14 years.

         Bilateral Myoclonus - sudden, brief, single or repetitive muscle contractions involving one
         body part or the entire body. Can occur in a variety of medical conditions (uremia, hepatic
         Infantile Spasms - seen in infants under 12 months of age and are characterised by abrupt
         movements of the head, trunk or limbs that often occur in clusters of 10-20 movements per
         episode. Often seen in association with other signs of CNS dysfunction (developmental delay,
         mental retardation)

         Clonic seizures

         Tonic/Clonic Seizures (grand mal) - Generally start without warning - some people sense a
         vague sense of impending event

Onset heralded by sudden LOC, a tonic contraction of the muscles, a loss of postural control and a cry
produced by a forced expiration caused by contraction of the respiratory muscles. The individual falls
to the floor and remains rigid for many seconds - there may be cyanosis as respiration is inhibited

Soon a series of rhythmic contractions of all four limbs occurs - this clonic phase can last for a variable
period of time and ends when the muscles relax.

There is a gradual return of consciousness and the patient may have a headache and drowsiness - may
not return to baseline functioning for days.

         Akinetic Seizures (tonic) - sudden occurrence of a rigid posturing of the limbs or torso (not
         followed by clonic phase)

         Atonic - brief losses of consciousness and postural tone not associated with tonic muscular
         contraction. Individual may simply drop to the floor.

    2. Partial Seizures
Seizures beginning locally with
         a) Elementary (simple) symptomatology (without loss of consciousness)
              Motor - recurrent contractions of the muscles of one part of the body without loss of
                    consciousness. Primary motor cortex seizure produces classical Jacksonian attack
                    with twitching in contralateral thumb that then spreads to hand to arm to face.
              Sensory - paraesthesia, simple auditory or visual hallucinations. Produces the classic
                    epileptic aura. Most common are epigastric rising sensations followed in
                    frequency by tingling, numbness; visual phenomenon; vertigo;
              Autonomic/Psychic - déjà vu, unwarranted sense of fear or anger, illusions

         b) Complex symptomatology
                Impaired consciousness (in relation to environment)
                Onset may involve a variety of auras (déjà vu, intense emotions)
                During seizures there may be cessation of activity with only some minor activity
                  being continued e.g. lip smacking, picking at one's clothes (automatisms)
                May also be accompanied by the unconscious performance of highly skilled
                  activities such as driving or playing complicated music.
                When the seizure ends the individual is amnesic for events which took place during
                  the seizure and takes minutes to hours to recover full consciousness.
                Complex hallucinations

         c) Partial seizures becoming generalised seizures - tonic clonic.

    3.   Unclassified Seizures
To be aware of the biochemical mechanisms of seizures BCS

The hallmark of the altered physiologic state of epilepsy is a rhythmic and repetitive hyper-
synchronous discharge of many neurons in a localised area of the brain.
The EEG records the integrated electrical activity generated by synaptic potentials in neurons in the
superficial layers of a localised area of cortex.
A number of metabolic events occur within the brain during the epileptic discharges which may
contribute to the development of the focus, to the transition to seizures, or to post ictal dysfunction.

        During the discharges, extracellular potassium concentration increases and extracellular
         calcium concentration decreases.
        Both these changes have profound effects on neuronal excitability and neurotransmitter
         release and on neuronal metabolism.
        Neurotransmitters and neuropeptides are also released in unusually large amounts during
         seizure discharges. Some of these substances can have prolonged actions on central neurons
         and may be responsible for prolonged postictal phenomena such as Todd's paralysis.
               Todd’s Paralysis: A general term most often used to describe severe or complete loss
                of muscle strength due to motor system disease from the level of the cerebral cortex to
                the muscle fibre. This term may also occasionally refer to a loss of sensory function.

        In addition to the ionic effects, seizures produce increases in cerebral blood flow to the
         primary involved areas, increases in glucose utilization, and alterations in oxidative
         metabolism and local pH. It is possible that these events are not just consequences of the
         seizures but actually contribute to the development of the seizure activity and that
         manipulation of such factors could become an effective means for controlling seizures.

There are many mechanisms by which seizures can develop in either normal or pathologic brains.
Three common mechanisms include
(1) Diminution of inhibitory mechanisms [especially synaptic inhibition due to gamma-aminobutyric
    acid (GABA)],
(2) Enhancement of excitatory synaptic mechanisms [especially those mediated by the N-methyl-D-
    aspartate (NMDA) component of glutamate responses], and enhancement of endogenous neuronal
    burst firing (usually by enhancing voltage-dependent calcium currents).

To be aware of the common anticonvulsants used to treat epilepsy (BCS)

Currently available antiepileptic drugs appear to act primarily by blocking the initiation or spread of
seizures. Phenytoin, carbamazepine, valproic acid, and lamotrigine inhibit Na+-dependent action
potentials in a frequency-dependent manner, resulting in a preferential blockade of the sustained high-
frequency activity that is characteristic of burst-firing neurons in a seizure focus. Phenytoin also
appears to suppress seizure spread through inhibition of specific voltage-gated Ca2+ channels.
Benzodiazepines and barbiturates augment inhibition by distinct interactions with GABA receptors.
Valproic acid elevates the concentration of GABA in the brain, perhaps through interaction with
enzymes involved in the synthesis (glutamic acid decarboxylase) and catabolism (GABA transaminase)
of GABA. Gabapentin, which is a structural analogue of GABA, appears to increase GABA levels by
enhancing GABA synthesis and release and may also cause a decrease in glutamate synthesis. The two
most effective drugs for absence seizures, ethosuximide and valproic acid, probably act by inhibiting
T-type Ca2+ channels in thalamic neurons.

In contrast to the relatively large number of antiepileptic drugs that can attenuate seizure activity, there
are currently no drugs known to prevent the formation of a seizure focus following CNS injury in
humans. The eventual development of such "anti-epileptogenic" drugs will provide an important means
of preventing the emergence of epilepsy following injuries such as head trauma, stroke, and CNS

AMPA receptor Antagonists
 Inhibit the initial glutamate-induced neuronal depolarisation and so reduce the likelihood of
  NMDA receptor activation; this will reduce the probability of the generation of PDS‟s. Also help
  inhibit seizure propagation

NMDA receptor Antagonists
 Stops the seizure and therefore powerful anti-seizure agent

Activation of Ca2+ dependent K+ conductances
 K+ conductance  neuron hyperpolarises   excitability   seizure and propagation
 However, may partially be counteracted by the  in concentration of K+ outside the cell, ing the
    excitability of those neurons having a low K+ permeability, thereby ing synchronization of firing
    at the site of seizure generation

GABAB Antagonists
  GABA mediated inhibition and possesses anti-seizure activity

Voltage-gated Ca2+ channel Antagonist
  Generation of dendritic Ca2+ spikes   likelihood of seizure initiation
     May also inhibit seizure propagation by reducing the release of glutamate, although other
        transmitters would be affected

Potentiators of GABA mediated Inhibition
 Reduce all 3 steps in seizures

Voltage-gated Na+ channel Antagonists
 Suppress repetitive firing and limit propagation of seizure activity

Drugs Used
The main three are:
         Phenytoin
         Carbamazepine
         Valproate

 First line drug for partial and tonic-clonic seizures; not useful for absence seizures
 Some side effects e.g. blurred vision, dizziness and unsteadiness, but safer than Phenytoin
 Effective against all seizure types except absence seizures
 Produces a use-dependent block of Na+ channels
 Well absorbed and initial half-life of 36 hours i.e. daily dosing possible
 Induces an hepatic microsomal enzyme system which reduces the half life to 20 hours after a few
   weeks of use

 Useful alternative to carbamazepine in treating partial and tonic-clonic seizures; not useful for
   absence seizures
 Numerous side effects which are more severe than carbamazepine – confusion, intellectual
   deterioration, gum hyperplasia, hirsutism, megaloblastic anaemia, hypersensitivity reactions
 Probably causes increase in foetal malformations, especially cleft palate
 Induces an hepatic microsomal enzyme system but stimulation of its own metabolism is
 The liver enzyme system is almost saturated at therapeutic levels
 Produces a use-dependent block on Na+ channels
 80-90% bound to albumin
 Well absorbed orally with a half life of 24 hours

 Effective against absence seizures (and all the others)
 Side effects include GI irritation, nausea, weight loss, hair loss
 Very rarely exhibit hepatotoxicity, which occasionally is fatal
   Potentiates GABA mediated inhibition and a weak effect on Na+ channels
   Well absorbed orally; plasma half life of 12-15 hours
   Inhibits its own metabolism and that of carbamazepine, phenytoin and phenobarbitone

 First line drug for absence seizures
 Side effects are nausea, anorexia, mood changes, headache
 Unclear as to how it works, but does inhibit Ca2+ channel function
 Long plasma half life of 60 hours

 Tolerance develops
 Marked sedative effect
 Diazepam and lorazepam (status epileticus)
 Clonazepam (absence and myoclonic seizures)
 Clobazam (intermittent add on therapy)
 They work by potentiating GABA-mediated inhibition
 Well absorbed orally; binds to plasma protein
 Half life varies from 8-12 hours (lorazepam), 20-40 hours (diazepam), 50 hours (clonazepam)

To be aware of the common investigations used to evaluate patients with epilepsy, such as the
electroencephalogram, and imaging procedures such as computerised axial tomography or magnetic
resonance imaging of the head – in depth understanding of these procedures IS NOT REQUIRED

EEG in epilepsy – in some forms there are characteristic EEG patterns during seizures; between attacks
however, abnormalities are difficult to demonstrate. As mentioned previously seizures are now divided
into those that arise from one cerebral hemisphere (partial or local seizures) and those that involve both
hemispheres simultaneously (general onset seizures). Each category is further subdivided. Generalised
seizures on the tonic-clonic type are characterised by loss of consciousness, which usually occurs
without warning. This is followed by a tonic phase with sustained contraction of limb muscles,
followed by a clonic phase with symmetric jerking of the limbs as a result of alternating contraction
and relaxation. There is fast EEG activity during the tonic phase. Slow waves, each preceded by a
spike, occur at the time of each clonic jerk. For a while after the attack, there are slow waves present.
Absence seizures are one of the forms of generalised seizures characterised by a momentary loss of
responsiveness. They are associated with 3/s doublets, each consisting of a typical spike and rounded

CT and MRI
Are indicated for patients with focal neurologic symptoms or signs, focal seizures or EEG findings of a
focal disturbance. Such studies are performed in patients with new onset, clinical evidence of a
progressive disease and in those presenting after the age of 30 years because of the possibility of an
underlying neoplasm.

To be aware of the possible psychological and social consequences of a diagnosis of epilepsy (PPH)

Modes of adjustment – response – is the illness visible/obtrusive or in the case of epilepsy, hidden for
the most part.

3 types of adjusted adaptation –
      Pragmatic – tell people on a need to know basis and minimise the impact
      Secret – go to extreme lengths to conceal the condition
      Quasi-labelled – talking openly to undermine stigma and challenge the discreditable meaning.
         This allows effective control and neutralises the negative impact of stigma on their lives.

Allows persons identity and self worth to be submerged by negative association of stigma – which is
often a stereotype. The diagnostic label dominates the perception that other people have on the person
and the person has on themselves. The status of being an epileptic becomes more prominent than the
person‟s other characteristics, roles, status and determines their whole approach to life.
In addition to providing competent and up to date technical care of epilepsy, the Dr can also give
information, support and if necessary counselling of the psychosocial aspects to facilitate patient
coping strategies and decrease the negative impact on the pt‟s quality of life. Doctor should provide
the patient with a partnership, open agenda, holistic focus and counselling skills.

To be aware of the phenomenon of stigma in relation to epilepsy (PPH)

Stigma – attribute discrediting so that the individual with this attribute is disqualified from full social
acceptance, implying inferiority. Is not the disability itself, but sociocultural meaning which is
attached to it.

When diagnosed with a stigmatised illness – become labelled with a negative image, sometimes
associated with guilt or shame. The label has a powerful negative effect through the attachment of
stigma to the name.
     Epilepsy is an illness that has had variable socio-cultural meaning throughout history
     Today epilepsy is still regarded with suspicion
              o Movies etc.

To develop skills in the management of the unconscious patient such as inserting intravenous lines,
intubation and ventilation (ICS&CRP)
                                           Learning Objectives

Dom             LO Title                                                LO Detail
BCS Pathophysiology and             1. To be able to recognise the symptoms and signs of an extrapyramidal
    diagnosis of Parkinson's        disorder, such as Parkinson’s disease and outline what is known about the
    disease                         changes that occur within the central nervous system to elicit these changes.
                                    2. To be aware of intellectual changes that occur in the later stages of
                                    Parkinson’s disease.
BCS Treatment of Parkinson's        1. To outline the mechanism of action of drugs used to treat Parkinson’s
    disease                         disease.
                                    2. To be able to evaluate the response to drug treatment of a patient with
                                    Parkinson’s disease.
                                    3. To be aware of the effects of long term treatment with levodopa-containing
ICCP Clinical examination           1. Perform a focussed central nervous system examination for:
                                    (a) Cranial nerves (including ophthalmoscopy)
                                    (b) Upper or lower limb (power and sensation)
                                    (c) Cerebellar function
                                    (d) Locomotion.
PPH Retirement (Social Sciences) 1. List key issues that are likely to impact upon an individual’s adjustment to
                                 early retirement.
PPH Parkinson’s disease and         1. Discuss the psychosocial consequences of Parkinson’s disease to patients,
    coordinated care (Social        their families and carers, and the community.
    Sciences)                       2. (a) Describe the role of multidisciplinary teams in the management of patients
                                    with complex medical conditions.
                                    2. (b) Suggest potential barriers to, and possible strategies to enhance,
                                    successful multidisciplinary management.
                                    3. List benefits of the general practitioner’s coordinating role in the management
                                    of a patient with a complex medical condition.
                                    4. Be able to develop a care plan for a patient with a complex medical condition
                                    such as Parkinson’s disease.
Movement Disorders

The Causes:
       1. Physical damage to the bones / muscles moving the limbs
       2. Physical damage to nerves transmitting signals to the limbs
       3. Physical damage to the brain
       4. Chemical temp / permanently affecting one / more of the above
       5. Disease processes temp / permanently affecting one / more of the above
       6. Diseases of muscle
       7. Diseases of neuromuscular junctions
       8. Epilepsy

The Types:
       1.    Flaccid paralysis
       2.    Spastic paralysis
       3.    Lack of movement without paralysis
       4.    Uncoordinated voluntary movement
       5.    Tremor
       6.    Abnormal movement due to defective muscles / bones
       7.    Involuntary movement
       8.    Muscle weakness

The Control of voluntary movement:
                               Movement Areas of the Cortex

                 Cortico-spinal                   Brainstem
                                                           Add‟n Descending Sys‟s

                               Lower Motor Neurone in Spinal Cord
The Corticospinal System
        Signals from the cerebral cortex are carried in the spinal cord to the motor neurons
        Each neuron passes from the cerebral cortex, decussates in the medulla & travels down
            the cord (corticospinal tract)
        The fibres pass into the grey matter of the cord & synapse with the motor neurone
        Damage of the C-S tract results in spasticity & paralysis

The Descending Motor System
        Several brain areas give rise to nerve fibres which form efferent (descending) tracts
           which synapse with motoneurones in the SC
        These tracts are concerned with voluntary movements such as posture, reflexes &
        Most tracts are influenced by the basal ganglia (BG) & cerebellum before reaching the
        This allows the BG & cerebellum to influence voluntary mvts (eg. walking) by
           modulating signals from the cortex
        Damage to the indirect descending motor system produce involuntary movement,
           immobility without paralysis & rigidity

The Basal Ganglia (BG)
        Consists of 3 forebrain structure deep in the cortex:
               1. Caudate nucleus                 (chorea - HD)
               2. Putamen                         (chorea)
               3. Globus pallidus                 (athetosis)
        As well as the midbrain structures:
               4. Substantia nigra      (a/bradykinesia, tremor & rigidity)
               5. Red nucleus
               6. Subthalamic nucleus
        The primary input is from the cerebral cortex with additional input from the thalamus
           & substantia nigra
        The BG have extensive two-way connections with cortical motor areas & cerebellum to
           regulate movement
        Output from the BG is directed through the thalamus back to the prefrontal, pre-motor
           & motor cortices

Example of a Volunatry Movement
                1. First impulses sent by cortex
                2. Movement initiated
                3. Cerebellum compares impulses with outcome  coordination
                4. Cerebellum adjusts mvt
                5. Corrects errors via red nucleus (RN) & midbrain nuclei
                6. BG adjusts tension via RN & midbrain to facilitate movement
The Process of Neurotransmission
       1. Dopamine synthesis
                 Tyrosine                      L-DOPA                    Dopamine
                           tyrosine hydroxlase   dopa decarboxylase
         2.   Dopamine storage
                   Active uptake into pre-synaptic storage vesicles
         3.   Dopamine release
                   Depolarisation  Ca2+ influx  dopamine release
         4.   Action on Dopamine receptors
                   Bind to post-synaptic (D1 & D2) & pre-synaptic (D2)
         5.   Dopamine Inactivation
                   Diffusion or active re-uptake
                   Then stored in vesicles, or
                   Degraded to HVA by COMT, MAO & aldehyde dehydrogenase
                   Degraded to DOPAC by MAO & aldehyde dehydrogenase

Interactions between Neurotransmitters


         GABA                                                         ACh


Blue – stimulates
Red – inhibits

         1.   Dopamine neurones fire
         2.   They release dopamine that inhibits cholinergic neurones
         3.   ACh neurones produce nerve impulses which eventually move muscles
         4.   ACh also stimulate GABA neurones
         5.   GABA inhibits the dopamine neurones

In Parkinson‟s disease, the influence of dopamine in the system decreases. This inturn decrease the
inhibition of acetylcholine which produces abnormal muscular symptoms (rigidity, tremor &
This also helps to explain the side effects of many neuroleptic medications, such as haloperidol that
inhibit DA and may produce Parkinsonian symptoms and tardive dyskinesia.
To be able to recognise the symptoms and signs of an extrapyramidal disorder, such as Parkinson’s
disease. (BCS)

        Despite encompassing all things other than the pyramidal system, clinically the
         extrapyramidal system is generally used to refer to the basal ganglia only.

Function & Dysfunction
The overall function is the initiation and modulation of movement. Cortical activity is modulated by a
series of servo loops between the cortex and the basal ganglia structures. It is believed that in many
involuntary movement disorders there are substantial and specific changes in neurotransmitter profile
rather than discrete anatomical lesions.

In disorders of the system either or both of the following features become apparent:

        Reduction in speed of movement (bradykinesia) or no movement (akinesia) with increased
         muscle rigidity
        Involuntary movements:
             o Tremor: rhythmic oscillation of limbs, trunk, head or tongue. 3 types: Resting
                  tremor (worse at rest, feature of parkinsonism); Postural tremor (worst e.g. if arms
                  outstretched); Intention tremor (worst during movement, and occurs in cerebellar

             o    Chorea: a continuous flow of jerky movements, flitting from one limb or part to
                  another (like a dance, hence chorea)

             o    Dystonia: bizarre sustained or spasmodic twisting or turning motions, most but not
                  all of which affect more distal body parts.

             o    Hemiballismus: involuntary movement of one side of the body affecting the
                  proximal limb musculature  jerking, flinging movements of the extremity

             o    Athetosis: Slow, proximally distributed twisting  The movements blend together
                  in a continuous mobile spasm and are usually associated with varying degrees of
                  paresis and spasticity.

All of the features of basal ganglia pathology are caused by the above changes.

Extra pyramidal disorders are classified broadly on clinical grounds into akinetic-rigid syndromes
where poverty of movement predominates, and the dyskinesias in which there are a variety of
excessive involuntary movements.

Parkinson’s Disease
        Parkinson‟s disease is:
                      Idiopathic & progressive
                      Deterioration & death of dopamine producing neurone in the BG (esp.
                         substantia nigra)
                      Produces decreased level of dopamine in this area of the brain
                      Symptomatic when 80% reduction in DA
                      Affects all races and sexes
                      Average age of onset 55
                      1-2% of 70-80 yr olds effected
                      1 in 7 people under 40 effected

Other Causes
       1. Postencephalitic Parkinsonism
           - Due to influenza virus (esp in 1940‟s)
           - Now rare
           - Therapy  anticholinergics
        2.   Neuroleptic Drugs
             - Chloromazine & haloperidol (schizophrenia / Huntington‟s disease (caudate))
             - Block dopaminergic transmission & may lead to hypersensitivity of receptors to
             - Therapy: withdraw causative drugs & symptoms disappear (months)

        3.   MPTP toxicity
             - Contaminent of designer drug (MPTP  MPP+)
             - Acute, severe irreversible Parkinsonism
             - Causes death of neurones in sub. Nigra within days of use
             - Experimental model for use in animals

Symptoms of Parkinsons’ Disease
      1. Muscle rigidity ( muscle tone)
               - Severe cramp  resistance to muscle movement
               - Constant (lead pipe), intermittent (cog wheel)
      2. Resting tremor (rhythmical movement of limb)
               - Affects resting muscles at a frequency of 4-6 per second
               - Affects both upper limbs 1st
               - Absent during sleep;  with anxiety
      3. Akinesia / hypokinesia (lack of movement) & Bradykinesia (slowness of movement)
               - Slow movement, monotonous hypophonic speech, expressionless face and
                   dribbling (Mask-like facies)
               - Clumsy &  co-ordination
               - Problems with daily tasks
      4. Postural abnormalities (flexion at most joints)
               - Neck flexed forward (may rest on chest)
               - Shoulders rounded & trunk flexed
               - Legs slight flexion at hip & knee
      5. Akathesia (motor restlessness – perceived need to move)
               - Limited by a/bradykinesia
               - Festination – walk which is rapid & shuffling & difficult to stop
                   - Festinate Gait

Huntington’s Chorea
                 1/20,000
                 Currently incurable
                 Fatal within 15 years of onset
                 Progressive & difficult to control symptoms
                 Autosomal dominant genetic condition
                 Symptoms develop in adulthood (may already have children  issues of blame
                    may arise)
       What is it?
                 involves death of cholinergic & GABAergic neurones in BG & cerebral cortex
                 atrophy of the caudate and basal ganglia with hypertrophic enlargement of the
                 genetic defect of CAG trinucleotide repeats
                      number of repeats leads to worse HD (earlier onset, worse prognosis)
                 Chorea ( dopamine)
                 Dyskinesia ( dopamine)
                 Mental deterioration & dementia (cell death in cortex & BG)
                 Tranquilisers - diazepam (enhance GABA)
                 Neuroleptics & methlydopa ( dopaminergic influence)
                 Anti-epileptic drugs (enhance GABA)
                 Anti-cholinesterases – Physostigmine (block ACh b‟down  effect)
Wilson’s Disease
                    Recessive disease – rare
                    Common cause of liver cirrhosis & movement disorders in under 20‟s
                    Copper deposits in BG  cell death  Parkinsonian type movements &
                    Currently incurable but preventable if detected early (chelating agent – D-
                     penicillamine – to bind excess copper)
                    Prognosis depends on early detection

        Symptoms & Signs
                Mental deterioration & dementia
                Parkinsonian symptoms (tremors & dysarthria)
                Involuntary movements (flapping arm movement)
                Ataxia
                Kayser-Fleischer Rings – copper deposits in the cornea

        What is it?
                  Genetically controlled defect in the copper metabolism whereby the copper
                    reaches the liver normally but fails to bind to the caeruloplasmin (normally
                    transports copper around body & excreted in bile)
                  Copper is excreted in the urine
                  By age 5, the copper binding capacity of an individual has been exceeded &
                    copper begins to circulate unbound in plasma & deposits in tissues
                         BG – movement disorders & dementia
                         Liver - cirrhosis
                         Eyes – cataracts & Kayser-Fleischer rings (green/golden copper deposits
                        around cornea)
                  Diagnosis: serum caeruloplasmin low & urinary copper high
To be able to evaluate the response to drug treatment of a patient with Parkinson’s disease. (BCS)

Management involves assessment of disability and cognition regularly and objectively (e.g. time how
long to walk 20 yards; can he/she dress alone, and turn over in bed?). There are a few staging criteria
that can be used to determine the level of impairment objectively – see:

Choose the lowest dose of drug giving adequate symptom relief, without troublesome side-effects.

                      Gradual onset
                      Tests to grade extent of disease
                          1. Hoehn & Yahr scale (5 progressive stages)
                          2. North Western University Disability scale
                          3. Webster scale

Treatment of Parkinson's Disease.
There are five main mechanism of drug therapy in Parkinson's disease:
        1.       Dopamine Replacement – replacement therapy, aim to restore dopamine levels in
                 the basal ganglia. L-dopa is the principle drug.

         2.       Dopamine agonists – used as adjunct therapy in late stages to enhance dopamine
                  activity and overcome problems of therapeutic activity that arises in long term L-
                  dopa use (bromocriptine)

         3.       Drugs to promote dopamine release - amantidine

         4.       Anti metabolites – MAOB inhibiters that prevent metabolism of dopamine and hence
                  prolong its action

         5.       Anticholinergic drugs – relieve the effects of tremor and rigidity in early stages of

1) Dopamine Replacement (L-dopa)
     Dopamine cannot cross the BBB, hence L-dopa (precursor) is given instead
     L-dopa is converted to dopamine at the nigro-striatal neurones
     L-dopa is rapidly metabolised outside of the brain, and hence carbidopa is administered
       together to inhibit the extra-cerebral decarboxylases
     SINEMET = carbidopa + L-dopa in various ratios

        Short term side effects (which can be reduced by  carbidopa, or  L-dopa) include:
             o Nausea and vomiting
             o Psychic events – hallucinations, vivid dreams, confusion
             o Postural hypotension
             o L-dopa induced dyskinesia

    Long term side effects (over approximately 5 years, reduced by use of adjunct drugs):
            o Progressive disease and wearing off effect: L-dopa does not alter the course of the
                 disease   dosage required to prevent Parkinson symptoms (Tolerance)
            o On-Off effect: Rapid oscillations between controlled movement and severe
                 dyskinesia related to plasma levels of the drug and can be extremely debilitating due
                 to unpredictability and severity.

2) Dopamine Agonists
    Bromocriptine, D2 agonists
       Acts directly on dopamine receptors to promote normal actions in control of movement
       Given as adjunct therapy in the emergences of long term side effects of L-dopa, OR given
       early in the disease to promote the activity or remaining natural dopamine.
       Side effects similar to L-dopa
3) Dopamine Releasers
     Acts to stimulate dopamine release/ blocks reuptake in early mild Parkinson‟s.
     E.g. Amantadine – modest efficacy, few side effects, but tolerance develops quickly.

4) MAOB Inhibitors
     Preserves dopamine activity by inhibiting metabolism of dopamine by MAO B
     Used as adjunct therapy, and does not slow progression of the disease
     E.g. Selegiline – allows L-dopa dosage to be dropped to 1/3, but also  side effects of L-dopa

5) Anticholinergics (Muscarinic Antagonists)
     Muscarinic acetylcholine receptors exert an excitatory effect, opposite to that of dopamine, on
        striatal neurons and also exert a presynaptic inhibitory effect on dopaminergic nerve terminals.
     Suppression of these effects thus make up, in part, for a lack of dopamine.
     Diminish tremor more than rigidity or hypokinesia, and their side effects (dry mouth,
        constipation, impaired vision, urinary retention) are often troublesome.
             o Elderly males with prostatism with  micturition
To be aware of the effects of long term treatment with levodopa-containing preparations. (BCS)

Problems with therapy
       1. Wearing off effect (End of dose effect)
            - Combated by smaller doses more frequently
       2. On / Off Effect
            - Appears after a couple of years of Tx
            - Loss of symptom control
            - Characterised by acute rigidity & loss of mvt NOT assoc with the end of dose
                decrease in plasma L-DOPA levels
            - Probably due to a reduced capacity of the striatum (C.N. & Put) to buffer fluctuating
                levels of L-DOPA
            - The OFF episodes can occur several times a day & cause great distress to the effected
            -  L-DOPA may help initially
            - Use apomorphine (dopamine agonist) later stage
To be aware of intellectual changes that occur in the later stages of Parkinson’s disease (BCS)

       About 10 to 15% of patients with idiopathic Parkinson‟s disease develop dementia.
             o  Age   Incidence
       The dementia is attributed to widely disseminated Lewy bodies, particularly in the cerebral
        cortex, but also involving the amygdala and brain stem neurons
       Lewy bodies are single or multiple, intracytoplasmic, eosinophilic, round to elongated
        inclusions that often have a dense core surrounded by a pale halo.
       Lewy bodies are composed of fine filaments, with neurofilament antigens, -synuclein and
        ubiquitin embedded within.

       Lewy Body Dementia
        - Shares features of cortical and subcortical dementia.
        - Relatively new entity that may account for up to 20% of cases formerly diagnosed as having
        - Rapidly progressive dementia with combined features of Alzheimer‟s Disease and
        Parkinson‟s Disease
        - A strong propensity to produce hallucinations and delusions.
        - Histopathology shows the Lewy bodies that are characteristic of Parkinson „s disease present
        in both the cortex and the basal ganglia.
The physical and psychosocial consequences of Parkinson's disease to patients, their families and
carers, and the community. (PPH)

To develop skills in (ICSCRP):
     Neurological history taking to allow diagnosis of extrapyramidal disorders (ICS/CRP)
     Neurological examination to allow diagnosis, and assessment of the severity of,
        extrapyramidal disorders (ICS/CRP)
     Neurological history and examination taking to allow assessment of intellectual function

When taking a neurological history to diagnose, and assess the severity of extrapyramidal disorders the
questions about the following areas can be asked:
     Speech – ability to put intelligible words together with minimal effort
     Salivation – does the patient drool?
     Swallowing – does the patient have difficulties swallowing? Does the patient only have soft
         food? Choking?
     Handwriting – size, time it requires to write, legibility
     Cutting food/ Handling utensils – does patient feed him/herself?
     Dressing – does the patient need help? Slow?
     Hygiene – does the patient need help to shower? Brush teeth? Go to toilet?
     Falling (unrelated to freezing) – frequency, when walking/ standing?
     Tremor – frequency, resting/ postural/ action/ intention, impairment of activities, bothersome-
     Walking – difficulty, leg dragging, shuffling, start/stop difficulties
     Involuntary movements – type? Frequency?
     Drug history (Phenothiazines, methyldopa), Medical history (post-encephalitis), Family
More specific signs and symptoms can often be obtained from the neurological examination
Neurological Examination in Parkinson’s and Other Extrapyramidal Disorders
            o     Lack of facial expression (Mask-like facies)
            o     Flexed posture, few spontaneous movements

              o   Ask patient to rise from a chair, walk, turn quickly, stop and start
              o   Characteristic gait  shuffling (small steps, feet hardly leaves ground)
              o   Difficulty in initiating walking, but once begins, the patient hurries (festination) and has difficulty stopping
              o   Lack of normal arm swing

           o      Look for a resting tremor
           o      “Pill-rolling” – movenet of the fingers at the MCP combined with the movements of the thumb at 4 to 8
              o   On finger-nose testing the tremor decreases, but a faster action remor may supervene
              o   Tremor may be facilitated by getting patient to perform „serial 7s‟ or moving the contralateral limb

              o   Test tone at both wrists
              o   Characteristic cogwheel rigidity – tone  with an interrupted nature, giving way with a series of jerks
              o   If not obvious, obtain reinforcement by asking patient to turn head from side to side or wave the
                  contralateral arm
              o   May be asymmetrical early in the course of Parkinson‟s disease
              o   Titubation (tremor) of the head
              o   Absence of blinking
              o   Dribbling of saliva
              o   Lack of facial expression
              o   Test glabellar tap – sign is positive when patient continues to blink as long as the examiner taps. Normal
                  people only blink a couple of times then stop
              o   Assess speech – usually monotonous, soft, faint, lacking intonation, sometimes palilalia (repetition of the
                  end of a word) is present.
              o   Ocular movements – weakness of upward gaze (isolated failure is characteristic of Parkinson‟s.)
              o   Feel brow for greasiness (seborrhoea) or sweatiness, due to associated autonomic dysfunction
              o   Orthostatic hypotension may be present for the same reason.

            o     Ask patient to write his or her name and address
            o     Micrographia (small writing) is characteristic
            o     May also be unable to do this because of the development of dementia

       Other Extrapyramidal Movement Disorders
            o     Chorea – Shake hands. May be tremor and dystonia superimposed on lack of sustained hand grip
                  “milkmaid‟s grip”. Ask the patient to hold out hands, look for a choreic posture, involving finger and
                  thumb hyperextension and wrist flexion.
            o     Look at eyes for exophthalmos (thyrotoxicosis), Kayser-Fleischer rings (Wilson‟s disease) and
                  conjunctival injection (polycythaemia
            o     Ask patient to poke out tongue and note serpentine movements
            o     Skin rashes (SLE, vasculitis)
            o     Test reflexes  tendon reflexes may be reduced and may be pendular due to hypotonia
            o     Assess higher centres for dementia (Huntington‟s chorea)
            o     Dystonia – involuntary abnormal posture with excessive co-contraction of antagonist muscles
Assessment of Intellectual Functions (Mini-mental State Examination)

    What day of the week is it? (1pt)
    What is today‟s date (d/m/y)? (3pt)
    Where are we now/ What country are we in? (1pt)
    Name of this town (1pt)
    What are two main streets nearby (1pt)
    What floor of the building are we on? (1pt)
    What is the name of this place/ address? (1pt)
    Read three consecutive instructions and ask to follow (3pt)
    Show pencil and ask what it is called (1pt)
    Show wristwatch and ask what it is called (1pt)
    Ask to repeat “no ifs, ands or buts” (ask only once) (1pt)
    Write on a piece of paper “close your eyes” – ask to read paper + perform action (1pt)
    Ask patient to write a complete sentence (1pt)
    Ask patient to copy two intersecting pentagons (1pt)
    Name three objects, ask patient to remember and repeat each word until learnt (3pt)
    Serial 7‟s – ask patient to take 7 away from 100, and then take 7 away from the result etc. Five
    rounds for 5 pts.
    Recall of three objects (3pts)

Maximum score is 30; 28-30 does not support the diagnosis of dementia. Score of 25-27 is borderline;
<25 suggests dementia, but also consider acute confusional state and depression.
                                        Learning Objectives

Dom               LO Title                                              LO Detail
BCS   Diagnosis of meningitis         1. To be able to develop a differential diagnosis for the febrile child.
                                      2. To be able to recognize the clinical syndrome of bacterial meningitis.
                                      3. To be aware of the various CSF profiles in different types of meningitis.
                                      4. To describe the types of investigations and their role in evaluating
BCS   Pathophysiology of meningitis   1. To discuss the pathophysiology of meningitis and the changes that occur
                                      in the blood brain barrier in meningitis.
                                      2. To outline the common organisms causing meningitis, including parasitic
BCS   Treatment of meningitis         1. To be aware of the current treatment guidelines for meningitis in children
                                      and the pharmacology of those drugs.
EPPD Immunisation issues              1. Describe the related ethical issues in maintaining adequate infant
                                      immunisation rates.
ICCP Clinical examination             1. Perform a focussed central nervous system examination for:
                                      (a) Cranial nerves (including ophthalmoscopy)
                                      (b) Upper or lower limb (power and sensation)
                                      (c) Cerebellar function
                                      (d) Locomotion.
ICCP Clinical examination             1. Perform ear nose and throat examination on an adult.
                                      2. Discuss differences in ENT examination between children and adults.
PPH   Infectious disease outbreak;    1. Document the public health implications of a disease outbreak such as
      Child care centres (Public      bacterial meningitis.
      Health)                         2. What general public health measures are recommended for child care
                                      centres to minimise the occurrence of infectious disease outbreaks?
                                      3. Be able to discuss with a parent, the possible reasons why his/her toddler
                                      has developed several infectious illnesses since enrolling in a childcare
                                      centre 6 months previously.
PPH   Immunisation (Public Health)    1. Describe the related public health and policy issues in maintaining
                                      adequate infant immunisation rates
A Febrile Irritable Baby - Bacterial Meningitis

Meningitis – An inflammatory process of the leptomeninges/CSF within the subarachnoid space 
usually caused by infection.

Differential Diagnosis – The Febrile Child
Fever – the most common A&E presentation in paediatrics.
All febrile neonates < 2 months  full septic workup.

Cultures of:
         - Blood
         - Urine
         - CSF

1) In most the cause is:
    Viral infection
    Otitis media
    Pharyngitis/tonsillitis
    All have good prognosis and the fever has beneficial effects.

2) Bacteraemia
    In 4% of febrile children
    If no focus can be found a CXR, LP, urine MCS should be carried out.
    Blind AB treatment should cover S. pneumoniae, H. influenzae, N. meningitidis (i.e. a third
       generation cephalosporin)

3) Encephalitis
    Rarer than bacteraemia
    Clouding of consciousness, odd behaviour, seizures

4) UTI

5) Malaria

6) Endocarditis/malignancy if prolonged
Bacterial Meningitis
Clinical syndrome – The Meningitic syndrome
    - headache
    - neck stiffness
    - fever
    - +/- photophobia
    - +/- vomiting

Intense malaise, fever, rigors, severe headache, photophobia and vomiting developing within hours or

NB: Petechial rash = meningococcus (rash appears violaceous and is macular)
As a rule, neonates and young infants have minimal findings on examination, which makes early
diagnosis difficult.
- Convulsions 40%
- Bulging fontanelle 30% - late sign

Neonates/Young infants                               Older than 3-6 months
Fever                                                Fever
Lethargy                                             Headache
Respiratory distress                                 Nuchal rigidity
Poor feeding                                         Seizures
Vomiting and Diarrhoea                               Photophobia
Increased irritability                               Vomiting
Poor muscle tone                                     Cutaneous lesions (meningococcaemia)
Changed level of consciousness                       Kernig sign positive

Untreated – mortality 70%
With AB’s – mortality < 10% (neonates 20- 50%)

Brain and SC
- Very well protected and isolated by skull/BBB
- Very vulnerable
- In a limited space, effects of infections tend to be magnified – even minor swelling/inflammation
     damage (due to pressure effects in the constrained vault)
- BBB inhibits passage of micro-organisms and toxic substances into brain/CSF but also impedes
    passage of humoral and cellular defence from blood.
- BBB also hinders passage of AB‟s.

Causative agents
Bacteria (90% occurs in 0-5yo)
- Neisseria meningitidis
- Haemophilus influenzae (B)
- Streptococcus pneumoniae
- Group B Streptococci
- Escherichia coli
- Chronic meningitis:
         - Mycobacterium tuberculosis
         - Cryptococcus neoformans
         - Other fungi
- Mumps
- Enteroviruses

- Toxoplasmosis (HIV)
- Amoebic

Malignant cells
Drugs and contrast media

Age                        Pathogen (bacterial)
                           Most common                            Other
Birth – 2 months           Streptococcus agalactiae               E. coli
                           (group B  haemolytic Strep.)          L. monocytogenes
2 months – 5 yrs           H. influenzae B                        N. meningitidis
                                                                  S. pneumoniae
> 5 yrs                    S. pneumoniae                          N. meningitidis
Elderly                    S. pneumoniae                          L. monocytogenes

Virulence factors – big 3 (HiB, Strep, Neisseria)
All 3 have:
- capsule
- IgA protease
These permit survival and colonisation in the blood.
S. pneumoniae lacks pili, endotoxin (gram +ve), outer membrane proteins which the other 2 have.
Pathologic Sequence
- Nasopharyngeal colonisation
- Local invasion
- Bacteraemia
- Meningeal invasion
- Subarachnoid inflammation
        1) Increased BBB permeability
               Vasogenic cerebral oedema
        2) Blockage of normal CSF pathways
               Interstitial cerebral oedema
        3) Toxic factors from macrophages and or bacteria
               Cytotoxic cerebral oedema
        4) Cerebral vasculitis
               Cerebral infarction
- These lead to decreased cerebral blood flow either directly (4) or due to increased intracranial
- Cerebral hypoxia
- CSF acidosis
- Encephalopathy
- Death

Pathogenic sequence of bacterial neurotropism
Stage                                      Host Defence                     Strategy
1       Colonisation or mucosal invasion   Serum IgA                        sIgA protease
                                           Ciliary activity                 Ciliostasis
                                           Mucosal epithelium               Adhesive pili/fimbriae
2       Intravascular survival             Complement                       Evasion of alternative pathway by
                                                                            polysaccharide CAPSULE
3       Crossing the BBB                   Cerebral endothelium             Adhesive pili
4       Survival in the CSF                Poor opsonic activity            Bacterial replication

-   NB: Initiation of AB treatment results in rapid lysis of bacteria within and around the subarachnoid
    space with the release of large concentrations of bacterial products which in turn stimulate release
    of local pro-inflammatory mediators from endothelial cells and macrophages, allowing further
    penetration of bacteria through the BBB.

The development of sustained, high grade bacteraemia is suggested as an important factor in the
development of CNS infections.
The choroid plexus is the most common site of entry.
Ways through the BBB:
1) Invasion engineered by pathogen
    Pathogen signals the cell to take it from the blood and discharge it in the CSF
         L. monocytogenes, H. influenzae B.
2) Paracellular transmigration
         H. influenzae B
3) Enhanced vesicular transport
         Meningococcus
4) Receptor mediated uptake
         pneumococcus + PAF-receptor, malaria +ICAM-1

Spread and multiplication
CNS – sequestered compartment with not many defence mechanisms
- complement levels are low
- lysis and phagocytosis are low except by microglia
    CSF = an excellent culture medium and rapid means of dissemination

Damage to Host
Death of host cells may be due to:
     Direct action of the bacterial toxins
     Lytic cycles of viral replication
     The result of intracellular growth of bacteria/fungi
     The hosts own inflammatory reaction (most)
          Inflammatory mediators, pressure

Characteristics of inflammation of the CNS are:
- Infiltration of microglia
- Proliferation of astrocytes (astrocytosis)
- Humoral component evident first:
       - Oedema due to increased capillary permeability
       - Neutrophil/macrophage infiltration and phagocytosis
       - Neutrophils often lyse  digestive enzymes

-   Oedema may:
    - Produce symptoms from decreased capillary perfusion
    - Cause herniation of the temporal lobe through the falx/foramen magnum.

Acute bacterial meningitis – cerebral oedema common
     Pia-arachnoid is congested with polymorphs
     Layer of pus forms that may:
         Organise to form adhesions
         Cause cranial nerve palsies (deafness is a common adverse outcome due to damage of CN
         Cause hydrocephalus

Chronic meningitis (eg TB)
    Brain is covered in a viscous greyish/green exudate.
    Numerous meningeal tubercles
    Adhesions are typically seen
    Cerebral oedema common

Viral meningitis
     Predominantly lymphocytic inflammatory reaction
     No pus/adhesions
     No cerebral oedema unless viral encephalitis develops.

CSF Changes in Meningitis
                             Normal               Viral               Pyogenic                TB
Appearance           Crystal clear         Clear/turbid         Turbid/Purulent      Turbid/viscous
Total WCC            <5/mm3                        -                 -                 
Mononuclear          <5/mm3                        -                                    - 
Polymorphs           Nil                   Nil                          -              N - 
Protein              0.2 – 0.4 g/L                                      -                - 
                     1 2
Glucose               /2- /3 BSL           > 1/2 BSL            < 1/2 BSL            < 1/3 BSL

CSF Pressure is characteristically elevated in meningitis.

Diagnosis of meningitis
Recognition and immediate treatment of acute meningitis is vital  mortality is around 15% even with
- Immediate parenteral AB treatment should be given before any investigations.
        1) LP
              Should follow if it is deemed safe
              Reasons to delay /withhold LP:
                  Clinically significant cardiorespiratory compromise
                  Signs of increased ICP
                      Decreased LOC
                      Decreased HR
                      Increased BP
                      Vomiting
                      Tonic seizure with ceberebrate/decorticate posture
                      Irregular breathing
                      focal neurological signs
                      papilledema
                      abnormal pupil size/reaction
                  Infection in area where spinal needle will pass
                  History or signs of bleeding disorders
        2) Bloods
              Culture, glucose and FBC
        3) Urine
              Culture
        4) Chest and skull films
        5) Throat swabs
              Culture

Treatment guidelines in children
- AB‟s
- Fluids
- Observations – HR, RR, BP, LOC, head circumference (in infants)

             Age                                               Treatment
Neonates < 1 month              Ampicillin + (cefotaxime or gentamycin)
Infant 1 – 3 months             Ampicillin + cefotaxime
Infant 3 months – Adult         Cefotaxime or Ceftriaxone

Chemoprophylaxis of rifampicin or minocycline eradicates nasopharyngeal carriage in 90% recipients.
Recommended for all primary contacts (household and day-care) of kids with H. influenzae B and N.
No chemoprophylaxis is recommended for S. pneumoniae.

Complications of meningitis
- Convulsions (20-30% prior to hospital admission)
- Cerebral oedema
- Shock – 5 – 10%
- Neurological lesions (10 –20%) including:
        - Hemiparesis
        - Persistent hypotonia
        - Ataxia
        - Isolated CN palsies
-   Subdural effusions - ? surgical drainage
-   Persistent or secondary fever

Outcomes in meningitis
Mortality – 20-50% neonates + 1 –5 % infants/young kids.
Morbidity – 1 in 8 survivors have adverse outcomes including:
- intellectual disability
- spasticity
- paresis
- deafness
- seizures
1 in 4 survivors have disabling sequelae/functional behaviour disorder or auditory dysfunction 
decreased school performance.

Long term management
Complete neurological examination at the time of discharge including vision, hearing and formal
developmental assessment.
Regular review for at least 2 years consisting of:
- Hearing tests
- Assessment of neurological functioning
- Behavioural and school performance
- Developmental assessment

Paediatric History

Presenting complaint – record mother’s and child’s own words.
- When and how did it start?
- Was the child well beforehand?
- How did it develop?
- What aggravates/relieves it?
- Has there been any contact with infections? (school, day-care, family)
- Has the child been overseas recently?
- In infants – feeding/excretion/alertness/weight gain

Past Health
- In utero – toxaemia, Rubella, Rh disease
- At birth – prematurity, duration of labour, type of delivery, birth weight, birth injury,
- Neonate – jaundice, fits, fevers, bleeding, feeding problems,
- Later  illnesses, operations, accidents, screening tests, drugs, allergies, immunisation status,

- Assess milestones with Denver II chart

Family History
- Are all siblings alive and well?
- Stillbirths, TB, DM, renal disease, seizures, jaundice, malformation, other…

Social History
- Location of both parents
- Play, eating, sleeping, school
- Who minds the child if the parents work.
- What work do they do?

-   Growth
-   Weight
-   Failure to thrive
-   Fatigue
-   Lumps
-   Itch
-   Fevers
-   Bleeding
-   Family interaction questions

Is this child seriously ill?
- Agitation or coma
- Unreactive/unequal pupils
- Laboured breathing/hyperventilation
- Stridor/wheeze/apnoea/Cheyne-Stokes respiration
- Ashen, blue or mottled complexion (peripheral stigmata of meningococcosis)
- Weak/absent peripheral pulses/poor capillary refill (norm < 2 secs)
- Decorticate (flexed arms, extended legs)
- Decerebrate (arms and legs extended)
- Opisthotonus (head extended, back arched)

      Age (years)                  RR (/min)             PR (/min)             Systolic BP (mmHg)
          <1                        30 - 40              110 - 160                    70 - 90
        2–5                         20 - 30               95 - 140                   80 - 100
        5 – 12                      15 - 20               80 - 120                   90 - 110
         > 12                       12 - 16               60 - 100                  100 - 120

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