Movement Disorders Flashcards
What are abnormal movements?
Involuntary contractions of voluntary muscles
Name the systems in the basal ganglia?
• Nigro-striatal dopaminergic system
• Intra-striatal cholinergic system
• GABAergic system from the striatum to the GP and SN
Name hyperkinetic abnormal movement disorders?
• Hyperkinetic
• Tremor
• Chorea
• Dystonia
• Myoclonus
• Hemiballism
• Tics
• Dyskinesias
• Akathisia
• Restless Leg Syndrome
Name hypokinetic movement disorders?
Parkinsonism
Describe the epidemiology of Parkinsonism?
• Occurs in all ethnic groups
• Prevalence is 1-2/1000
• Males = Females
Describe the Etiology of Parkinsonism?
- Idiopathic Parkinson Disease (most common)
- Encephalitis Lethargica
- Familial
- Drug or Toxin-Induced
- Manganese and carbon disulfide.
- MPTP
> Meperidine analogue
- Therapeutic drugs (Dopamine depleting agents and dopamine antagonists) - Parkinson-plus Syndromes
Describe the pathology of Parkinsonism?
• Loss of pigmentation in substantia nigra
• Cell loss in globus pallidus and putamen
• Lewy bodies (alpha-synuclein) in basal ganglia
Describe the pathogenesis of Parkinsonism?
• Depletion of dopamine
•Disorder of balance of excitation and inhibition within the basal ganglia connections
What are the major clinical features of Parkinsonism?
- Resting tremor
- Rigidity
- Bradykinesia
- Gait and Postural instability
State additional features of Parkinsonism?
• Sialorrhea
• Dysphagia
• Myerson sign
• Depression
• Visual hallucinations
• Autonomic dysfunction
• Dementia
• REM sleep behavior disorder
What are the differential diagnoses of Parkinsonism?
• Depression
• Essential Tremor
• Wilson’s disease
• Huntington’s disease
• Creutzfeld-Jakob disease
• Normal Pressure Hydrocephalus
• Parkinson Plus Syndromes
> Diffuse Lewy Body disease
> Multiple System Atrophy
> Progressive Supranuclear Palsy
> Corticobasal Degeneration
Describe the use of anticholinergic drugs in the management of Parkinsonism?
• Most helpful in treating tremor and rigidity,
> Trihexyphenidyl (Artane)
> Benztropine (Cogentin)
Describe the use of amantadine in the management of Parkinsonism?
Used in mild disease
Reduces dyskinesias in advanced disease
Describe the use of Carbidopa/Levodopa in the management of Parkinsonism?
• Levodopa converted to dopamine via dopa decarboxylase
• Carbidopa inhibits dopa decarboxylase, prevents conversion of levodopa to dopamine in the periphery
• Dopamine unable to cross BBB, but levodopa does cross BBB
What are the side effects and complications of levodopa?
Side-effects of levodopa
• Nausea/vomiting, Gl upset
• Orthostatic Hypotension
• Dyskinesias
• Confusion/hallucinations
Other complications of levodopa
• Wearing-off
• On-off phenomenon
Describe the use of dopamine agonists in the management of Parkinsonism?
• Bromocriptine (Parlodel)
• Pramipexole (Mirapex)
• Ropinirole (Requip)
• Similar side-effects as levodopa, increased hallucinations, sleepiness
• Less likely to cause dyskinesias or on-off phenomenon
Describe the use of catechol-o-methyltransferase inhibitors?
• Talcapone and Entacapone
• Reduce dose requirements and decrease fluctuations
• More sustained plasma levels of levodopa
Describe the use of monoamine oxidase type B inhibitors in treatment of Parkinsonism?
• Selegiline and Rasagiline
• Inhibits metabolic breakdown of dopamine
• ?Neuroprotective
Describe other treatment considerations for Parkinsonism?
- Surgery
- Thalamotomy - tremor
- Pallidotomy - Bradykinesia - Deep Brain Stimulation
- Globus pallidus and subthalamic nucleus - Cellular Therapies
- Protective Therapies (?)
- MAO B inhibitors
- Coenzyme Q10 - Physical Therapy/Aids for Daily Living
Describe symptoms of progressive supranuclear palsy?
Gait instability (early falls)
Supranuclear opthalmoplegia
Describe multiple system atrophy?
Autonomic dysfunction (orthostatic hypotension)
Cerebellar dysfunction
Describe symptoms of corticobasal degeneration?
Apraxia/clumsiness
Neglect
Alien hand syndrome
Myoclonus
Describe dementia and Lewy bodies?
Fluctuating dementia and psychosis
Dementia appears before or within one year of Parkinsonism
What is a tremor?
Involuntary relatively rhythmic purposeless oscillatory movements with alternating contraction of opposing groups of muscles
How can tremors be classified by?
• Rate (Slow = 3-5 Hz OR Fast = 10-20 Hz)
• Location (Arms, feet, tongue, jaw, head, voice)
• Amplitude (Coarse, medium, fine)
• Rhythmicity (Rhythmic or non-rhythmic)
• Relationship to rest and movement (Rest, action, postural, intention)
• Etiology
• Underlying pathologic change
Name the types of tremors?
• Physiologic
• Rest
• Postural
• Intention
• Rubral
• Psychogenic
What causes drug induced tremors?
• Theophylline
• Caffeine
• Lithium
• Valproic Acid
• Tricyclic Antidepressants
• Isoproterenol
• Thyroid hormone
Describe an essential tremor?
Typically a postural tremor, may worsen with goal-directed activity
• Familial in ~50%
Hands, head, voice, trunk
• Alcohol improves
Describe the treatment for an essential tremor?
• Propranolol
• Primidone
• Gabapentin
• Topiramate
• Deep Brain Stimulation
Describe an intention tremor?
• Localizes to Cerebellum
• Occurs with deliberate movement
• Tremor worsens as the target is approached
• Can occur in
extremities, head or entire body
Describe chorea?
• Involuntary, irregular, purposeless, asymmetric, non-rhythmic movements
• Abrupt, brief, rapid, jerky, non-sustained, and explosive in character
• Worse with activity
• Usually involves distal upper extremities
• Associated with motor impersistence - “milkmaid grip” due to contractions alternating with relaxation of grip
• Associated with cell loss in striatum (caudate and putamen)
Describe the etiology of chorea?
• Etiology
• Hereditary
• Huntington
• Wilson
• Sydenham Chorea
• Chorea Gravidarum
• Drug Toxicity
• Levodopa (dopaminergic drugs)
• Antipsychotics
• Lithium
• Phenytoin
• Oral contraceptives
What medical disorders cause chorea?
• Etiology
• Cerebrovascular Disorders
• Medical Disorders
• Thyroid
• SLE, lupus anticoagulant
• Encephalitis
• AIDS
• Hypocalcemia, hypomagnesemia, hypernatremia
Hyper-/Hypoglycemia
• Hepatic Cirrhosis
Describe Huntington disease?
• Autosomal dominant with complete penetrance
• Mutation of huntingtin gene on chromosome 4
• Expansion of CAG trinucleotide repeat
• Cell loss in cortex and striatum
• MRI shows atrophy of caudate
• Genetic testing available - Genetic counseling.
Describe the clinical presentation of Huntington disease?
• Clinical
• Dementia
• Chorea,difficulty initiating saccadic eye movements
• Psychiatric
• Depression
• OCD
What is the prognosis of Huntington disease?
Progressive to death within 10 to 20 years
Describe hemiballism?
• Unilateral choreiform movements, more violent and rapid compared to typical
chorea
• Involves proximal muscles
• Lesion of contralateral subthalamic nucleus (usually vascular)
Describe dystonia?
• Slow, bizarre, may be grotesque in type, and writhing, twisting, and turning character
• Characterized by repetitive muscle contractions that are sustained at peak
• Muscles often in constant state of hypertonicity, may be associated with severe pain
• Eventually postures become fixed by contractures and deformities develop
Describe how dystopia is classified?
• According to the site of involvement, dystonia is classified as:
1)Focal - One body part involved
2)Segmental - Two or more contiguous parts involved
3) Multifocal - Two or more noncontiguous parts involved
4)Hemidystonia - One side of the body affected
5)Generalized
Describe causes of dystonia?
• Many recognized hereditary dystonias
• Other causes of dystonias include:
• Parkinson’s/Parkinson-plus syndromes
• Huntington Disease
• Wilson disease
• Drugs
• Dopamine receptor antagonists
• Chronic levodopa therapy,
• AEDs
• SSRIs
• Stroke
What is the treatment of dystonia?
• Treatment
• Medications frequently not helpful
• Anticholinergics
• Benzodiazepines
• AEDs
• Levodopa
• Baclofen
• Botox for focal dystonia/writer’s
cramp
Describe myoclonus?
• Abrupt, brief, rapid, jerky, arrhythmic, involuntary contractions involving portions of muscles, entire muscles, or groups of
muscles
• Seen primarily in muscles of the extremities and trunk, but involvement may be diffuse and widespread
• Occur at a rate of ~ 10-15/minute, usually at irregular intervals
• May be decreased by voluntary movement and increased during stimulation
• May be focal, segmental, multifocal, or generalized
• Asterixis - Negative myoclonus
Describe the etiology of myoclonus?
• Physiologic
• Essential Myoclonus
• Epileptic
• IME
• Progressive myoclonic epilepsy syndromes
• Drug-Induced
• symptomatic
What are the drug induced causes of myoclonus?
• SSRIs
• TCAs
• Lithium
• Levodopa
• Opiates
What are the symptomatic causes of myoclonus?
• Etiology
• Symptomatic
• CID
• SSPE
• Metabolic disorders
• Vascular lesions
• Neoplasms
• Spinal cord lesions
• Wilson disease/ degenerative disorders
What is the treatment of myoclonus?
• Difficult to treat
• Valproic acid
• Benzodiazepines
What is TICs?
• Brief, involuntary, rapid, recurrent, non-rhythmic movements (motor tics) or sounds (vocal tics)
• Worsened by stress, anxiety, and fatigue
• Relieved by concentrating on a task or absorbing activities such as reading
• Frequently involves face, neck and shoulders
• Irresistible urge to move before the tic, relieved with execution of the tic
• Can be voluntarily suppressed for short period, but leads to build-up of tension and rebound exacerbation
Describe Tourette syndrome?
• Multiple (at least two) motor and vocal tics
• 3x more common in males
• Associated with OCD,ADHD, depression
Describe the treatment for Tourette syndrome?
• Treatment
• Clonidine
• Low dose, high potency antipsychotics
• Haloperidol (Haldol)
• Dopamine agonists
• ?Botox
What is a acute dystonia?
• Acute athetosis or dystonia of midline structures (torticollis, oculogyrus, opisthotonus)
• Usually occurs within hours to one week of starting a dopamine receptor antagonist treatment
What is the treatment of acute dystonia?
• IM/IV Diphenhydramine (Benadryl) or Benztropine (Cogentin)
What is tardive dyskinesia?
• Bizarre movements commonly of mouth, face, jaw, and tongue that consists of grimacing, pursing of the mouth and lips, and writhing movements of the tongue
• Often develop after prolonged use (months to years) of dopamine blocking agents, but may occur shortly after they are started
• May also be associated with levodopa and dopamine agonists in a dose-related fashion
What is the treatment for tardive dyskinesia?
• Treatment
• Discontinue use of medication
• Switch to atypical antipsychotic
• Riserpine and tetrabenazine
• Lithium
• Baclofen
• Benzodiazepines
Describe neuroleptic malignant syndrome?
• Caused by decreased dopaminergic transmission
• Associated with treatment with neuroleptics, abrupt withdrawal of dopamine
• Clinical
• Altered mental status, autonomic dysfunction, rigidity, fever
• CK markedly elevated (> 1000)
• Treatment
• Withdrawal of medication
• Reduction of body temperature
• Dantrolene and/or bromocriptine
• ECT for refractory cases
Describe Wilson disease?
• Autosomal recessive
• Impairment of ceruloplasmin synthesis with excessive copper deposition
• Clinical features
• Acute/chronic hepatitis
• Movement disorders
• Chorea, tremor (wing-beating), rigidity, bradykinesia, ataxia, dystonia
• Kayser-Fleischer rings
• Psychiatric
• Psychosis, dementia, depression
What are the lab results in Wilson disease?
• Labs
• Abnormal liver function
• Low serum copper and ceruloplasmin
• Increased urinary copper excretion
• High copper in liver biopsy
Describe the treatment of Wilson disease?
• Reduction of dietary copper
• Penicillamine (copper-chelating agent)
• Pyridoxine to prevent anemia
• Liver transplantation
What is restless leg syndrome?
• Unpleasant, creeping discomfort
• Usually legs, can involve trunk and arms
• Worse at rest (lying down or sitting), improves with activity
• Worse in evening or at night
• Associated with:
• Pregnancy
• Iron Deficiency Anemia
• Renal failure
What is the treatment of restless leg syndrome?
• Dopamine agonists
• Carbidopa/levodopa
• Benzodiazepines
• Opiates
• Gabapentin
• Carbamazepine
