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Movement Disorders SAWA Summarizing Group

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Movement Disorders SAWA Summarizing Group Powered By Docstoc
					Movement Disorders




  Ali Alrefai, M.D
                 Objectives
•   Anatomy
•   Definitions
•   Clinical evaluation of movement disorders
•   ET & PD
•   Huntington’s chorea
•   Wilson’s disease
•   Drug-Induced movement disorders
    Anatomy & Physiology of Basal Ganglia
• Input zone (striatum: Putamen, caudate nucleus)
• Output zone (GPi, SNr)
• Intermediate zone (Gpe, STN)
• Input: Cerebral cortex, ventral midbrain
• Output: thalamusPremotor & prefrontal lobe;
  brainstem (SNr)
• Striatal neurons: 90% medium spiny neurons
  (GABA); Large spiny neurons (Ach); GABA
  interneurons
                                Cerebral Cortex
                 GLU                                                             +
                  +                                   + GLU
           -            GABA                                 GABA
                       D1>>D2        Striatum               D1>>D2
    DA

                  SNC                                              -               GLU

                                 -
                  SNR                               GPi
    SC     -
                   -     GABA                   -       GABA

                       Ventrolateral Thalamus


Direct pathway: + & - signs indicates Excitatory or Inhibitory nature of NT. Activated
pathways in large arrows. Inhibited pathways are shown in small arrows.
                           Cerebral Cortex
                                                                                    +
                                                    +GLU
       -                                                 ENK/GABA
               Striatum                                   D2>>D1
  DA

                                                                                     GLU
                                                 GABA-
                SNC                     STN                    GPe
                                                    GLU+
                                                                   GABA-


                SNR                                            GPi
                           +            GLU            +
           -
   SC
                -
                    GABA                                      -     GABA

                      Ventrolateral Thalamus

Indirect pathway: + & - signs indicates Excitatory or Inhibitory nature of NT. Activated
pathways in large arrows. Inhibited pathways are shown in small arrows.
   Symptoms of Movement Disorders
• Tremor: Rhythmic, mechanical oscillations
• Chorea: Abnormal involuntary purposeless
  brief dancing like movements, usually distal
• Dystonia: Involuntary sustained muscle
  contractions causing twisting movements or
  abnormal postures
• Ataxia: Disorganized poorly controlled
  movements
• Myoclonus; Tics; Ballism
    Clinical Evaluation of Movement
                Disorders
• History:
     Age of onset
     Mode of onset
     Course
     Drug history
     General medical background
     FH
                 Cont.

• Examination:
     MME
     Eye
     Focal motor or sensory loss
     Hepatic, vascular
• Investigations:
     Copper
     Electrolytes,LFT,CBC,ESR,ANA,TSH
     Genetic testing
     Imaging
                          Tremor


 Rest tremor                       Action tremor

PD                   Postural        Kinetic       Task-Specific
Tardive dyskinesia   Physiologic     Midbrain      Handwriting
Severe ET            ET              Cerebellar
                     PD
           Essential Tremor
• Bilateral action tremor of the hands and
  forearms
• Absence of other neurologic signs
• Long duration (>3 years)
• Family history
• Beneficial response to ethanol
            Genetics of ET

• FH of tremor in 17%-100%
• Bimodal distribution and autosomal
  dominant inheritance with nearly complete
  penetrance by the age of 65
• FET1 on chromosome 3q13 in 16 Islandic
  families
• ETM on chromosome 2p22-p25 in a large
  Czech-American family
             Treatment of ET

•   Beta-Blockers: Propranolol (Inderal)
•   Primidone (Mysoline)
•   Combination primidone/propranolol therapy
•   Calcium channel blockers
•   Carbonic anhydrase inhibitors
•   Botulinum toxin type A
•   Surgery: Ablative vs. DBS
          Parkinson’s Disease

•   Tremor, rigidity & bradykinesia
•   Stooped posture
•   Asymmetric onset
•   Response (>70%) to pharmacologic Rx
•   Dementia; Olfactory; Sleep;
    Autonomic; Depression
         Pathological Findings

• Neuronal loss: see figure
     Dopaminergic neurons in SNc




• Presence of ubiquitin + neuronal processes
  (Lewy bodies)
            Treatment of PD

•   Anticholinergics
•   Amantadine
•   Levodopa
•   Dopamine agonists
•   COMTi
•   Selegiline
•   Surgery
•   Symptomatic therapy
    Differential Diagnosis of PD

• Parkinson plus syndromes:
     PSP, MSA, CBD, DLB
• HD
• Wilson’s disease
• Toxins: MPTP, CO, Cyanide
• Trauma
       Features suggestive of PD

•   Rest tremor
•   Bradykinesia
•   Rigidity
•   Asymmetric onset
Huntington’s Disease
              Clinical Presentation

•   3th-4th decade
•   Chorea; Cognitive decline; Psychiatric sx’s
•   Sleep disturbance
•   Duration: 15 years (10-30)
•   Juvenile HD:
    10%<20 years
    Father inheritance
    parkinsonism, dystonia, dementia, ataxia,
      Myoclonus, seizures etc.
        Genetics & Pathogenesis

• Unstable enlargement of CAG repeat in 5’
  (1st exon) IT15 (4p16.3)Huntingtin (Htt)
• CAGGlu
• Polyglutamine 6-34); HD >40
• Anticipation
• Htt widely distributed in CNS
• Function: ?
               Management
• Multidisciplinary approach
• Depression: SSRI, TCA…etc.
• Mania: VPA, CBZ
• Chorea; Neuroleptics, Reserpine,
  Tetrabenazine
• Sleep: Trazodone; benzodiazepines
• Nutrition:
• Behavioral management of caregiver(s)
            Wilson’s disease

• AR trait caused by mutation in copper-
  transporting P-type ATPase, causing abnormal
  copper accumulation in the liver, BG and other
  organs
• Liver disease (40%):
      Subclinical liver disease
      95% under age 20
      Acute hepatitis
      Fulminant hepatitis
      Cirrhosis
      Hemolysis
    Neurological Manifestations

•   40%
•   Invariably have liver dysfunction
•   Isolated tremor (50%)
•   Dysarthria
•   Drooling
•   Dysphagia
•   Gait abnormality, parkinsonian syndrome,
    generalized dystonic syndrome
                   Cont.
• Psychiatric (15%):
      Conduct disorder
      Cognitive impairment
      Psychosis
• Others (5%):
      Ocular:      Kayser-Fleisher ring

      Renal:      Aminoaciduria
                  RTA
                  Calculi
      Hematological       Hemolytic anemia
      Skeletal:   Osteomalacia and rickets
                             Dx & Rx
• Diagnosis:
  1. Low serum ceruloplasmin
  2. Raised 24 hr urinary copper excretion
  3. Raised liver copper concentration
  4. Kayser-Fleisher ring in virtually all patients with
  neurological presentation
  5. Brain MRI
• Treatment:
       1. D-Penicillamine
       2. Trientine
       3. Zinc
       4. Liver transplant
   Idiopathic Torsion Dystonia (Oppenheim’s
                   Dystonia)

• 8.2 years (6-9 years)
• Normal development, walk normally
• Symptoms start in legs in early onset and in arms
  and cranial structures in later onset
• Becomes generalized within one year of onset
• Intact mental function & no psychiatric illness
• + FH suggesting autosomal dominant inheritance
• Course is progressive in early stages followed by
  Spontaneous stabilization
               Genetics

• AD with reduced penetrance
• DYT1 gene is responsible for early-onset
  idiopathic torsion dystonia in Ashkenazi
  Jewish families, and in one large non-
  Jewish family
• Gene is mapped to chromosome 9q32-34
• Glycosaminoglycan (GAG) deletion
• Alteration of norepinephrine concentration
  in several areas of the brainstem
                   Diagnostic work up

• Typical history and pattern of onset with a positive family
• Secondary dystonia should be suspected if:
   (1) Adult-onset
  (2) Early cranial or bulbar involvement before the lower
  limbs
  (3) Hemidystonia
  (4) Pyramidal tract signs
  (5) Cerebellar tract signs
  (6) Peripheral neuropathy
  (7) Dementia
  (8) Seizures
  (9) Abnormal eye signs such as optic atrophy, retinitis
  pigmentosa, and Kaiser-Fleischer rings
  Treatment principles of dystonia

• Physical and supportive therapy
• Therapeutic trial of levodopa in all childhood
  dystonia
• Anticholinergics: Most useful in Rx
• Benzodiazepines
• Oral baclofen
• Botulinum toxin particularly for cervical and facial
  dystonias
• Surgery for those with disabling symptoms
  despite optimal medical therapy
Drug-Induced Movement Disorders

•   Parkinsonism
•   Acute dystonia
•   Tardive dyskinesia
•   Neuroleptic Malignant Syndrome
•   Other drug-induced movement disorders

				
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posted:3/5/2011
language:English
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