hd-movemntdisdr

HD: The Movement Disorder

Involuntary Movements:

Chorea
Tics
Bradykinesia
Dystonia
Myoclonus
Tremor
Rigidity

Voluntary Movements:

Saccades
Smooth pursuit
Gait
Speech
Swallowing

Motor Disturbances: Involuntary

Chorea
Tics
Bradykinesia

Dystonia
Myoclonus
Tremor

Motor Disturbances: Voluntary

Incomplete chewing
Irregular respiratory rate
“Milkmaid grips”
Loss of postural reflexes
Variable stride length

Earliest Motor Signs of HD

Eye movements:
Delayed initiation
Slowed velocity
Jerky pursuit
Impaired blink suppression

Early Motor Signs of Adult Onset HD

Clumsiness
Restlessness
Exaggerated gestures
“Drunken” gait
Suppressible chorea

Consequences of Motor Impersistence in HD

Incomplete chewing -> choking on food
Irregular respiratory rate -> choking on food
“Milk-maid grips” -> dropping objects from hand
Loss of postural reflexes -> abrupt falls
Variable stride length -> abrupt falls

Early Motor Signs of Juvenile HD

School failure
Seizures
Rigidity
Bradykinesia
Tremor
Isolated myoclonic jerks

Akinetic Rigid Form (Westphal Variant)

Signs include: rigidity, bradykinesia, with or without tremor - occurs early in juvenile onset or late in adult onset

Patterns of Progression of HD

Stage	Early	Mid	Late
Chorea	+++	++	++
Bradykinesia	+	++	+++
Dystonia	+	++	+++
Decreased Voluntary Movements	+	++	+++

Chorea is the feature most often associated with HD, it may be one of the least disabling characteristics.
The voluntary movement abnormalities steadily worsen over the course of the illness, (15-20yrs), and are more strongly correlated with functional impairment than the involuntary movements.
Neuroleptics may worsen the voluntary movement abnormalities (gait & swallowing) and may cause additional movement disorders (parkinsonism, acute dystonia, tardive dyskinesia & dystonia, sedation and depression.

Strategies for the Treatment of the HD Movement Disorder:

Blockade of D2 receptors in the striatum
Replacement or restorative therapy
Neuroprotective strategies

Blocking the Nigrostriatal Pathway

Phenothiazines:- chlorpromazine,thioridazine
Butyrophenones:- haloperidol
Atypical neuroleptics:- clozapine
Dopamine depleting agents:- reserpine, tetrabenazine

Replacement or Restorative Therapy

Increase GABA:- isoniazid, muscimol
Decrease somatostatin:- cysteamine
Increase acetylcholine:- physostigmine
Decrease acetylcholine:- benztropine, scopolamine

Excitotoxic Hypothesis of HD

Glutamate released from corticostriatal terminals act through postsynaptic NMDA/AMPA receptors to kill striatal neurons

Decreasing Glutamate Transmission

Baclofen - GABA analog, but may inhibit release of glutamate and aspartate -double blind placebo controlled trial of baclofen 60mg in 60 patients for 30 months - non-significant worsening of TFC in active arm
Dextromethorphan - weak NMDA receptor blocker - open trial in 11 patients - no benefits with dose limiting side effects
Lamotrigine - Lamotrigine has glutamate release inhibiting properties. Therefore it may protect striatal neurons in HD patients. In a double blind placebo controlled study, including 63 patients with HD motor signs for less than 5 years, there was no benefit response based on TFC or secondary measures over a 2.5 year period.

Neuroprotective Strategies

Free radical scavengers
Opc-14117
D-alpha tocopherol ( vitamin E ) (3,000 IU)
Coenzyme Q10 plus remacemide

Coenzyme Q10 (coq)
-Shuttles electrons from complex II to complex III in the mitochondrial electron transport chain.
-Potent free radical scavenger
-MR spectroscopy demonstrated decrease in cortical lactate levels in 18 patients treated for 3 months with 360mg coq
Remacamide
-Noncompetitive NMDA ion channel blocker

General Principles of Treatment

Use the lowest possible dose of medication
Try non-pharmacologic treatment first
Re-evaluate need for medication frequently

Management of HD Movement Disorder

Haloperidol: begin 0.5-1.0mg and increase slowly, TID dosage, max 10mg side effects - tardive dyskinesia, acute dystonia, akathisia, swallowing & gait difficulties, parkinsonism
Perphenazine: begin 4mg qd. Increase slowly, TID dosage, max 24mg side effects - tardive dyskinesia, acute dystonia, akathisia, swallowing & gait difficulties, parkinsonism
Reserpine: begin 0.1mg qd, increase slowly, TID-QID dose, max 3mg side effects - parkinsonism, depression, drowsiness, hypotension
Tetrabenazine: begin 12.5 mg, increase slowly, TID-QID dose, max 200mg side effects - parkinsonism, depression, drowsiness, hypotension

Clozapine: 12.5-25mg qhs, increase slowly, QHS, max 150mg for chorea side effects - sedation, sialorrhea, weight gain, hypotension, seizures, agranulocytosis
Baclofen: 10mg, increase slowly, BID-TID, max 60-80mg side effects - drowsiness, dizziness, ataxia, GI distress, seizures

Gait Impairment in HD

Occurs in over 50% of people with HD in the first 3 years
Unrelated to chorea
Most common cause for institutionalization

Gait Characteristics in HD

Wide-based stance
Variable stride length with or without freezing
Variable speed
Postural instability

Gait Impairment in HD

Abnormalities include:
Imbalance / postural instability
Lateral swaying / wide based stance
Loss of associated arm movements
Variable walking speed
Irregular step length / invariable stride length with or without freezing
Difficulty turning

Physical Therapy for Gait in HD

Hold one hand -> let them lead you
Side by side -> one hand around waist, one hand held, hold a small waist belt
Stand in front, walk backwards -> hold both hands
Assess pattern of falls: if backwards -> add heel lifts if sitting -> use “touch-turn-sit” method if when rising from seated position -> teach “hands-on-knees, bend forward over feet, arise”