Hyperkinetic movement disorders

Hyperkinetic movement disorders

• Hyperkinetic movement disorders

• Tremors

• Dystonia

• Tic

• Chorea

• Hemifacial spams

Task specific tremors:

• Task specific tremors:

• - Orthostatic tremor : when asked to stand in place for several seconds, they develop hard and cramping calves and thighs that shake uncontrollably. Although considered by

• - Primary writer’s tremor  only while writing. The handwriting becomes sloppy, shaky, and large.

• Cerebellar kinetic tremor “Intentional tremors”

• - Apparent during a goal-directed limb movement, e.g. finger-to-nose or

• - Patient’s greatest disability occurs at the “endpoint

• - Usually caused by a lesion in the cerebellar outflow (dentatorubral) tracts

• - Seen most typically in patients with multiple sclerosis, CVAs, or primary cerebellar disorders.

Life style

• Life style

• Medical management

• Botilinum toxin

• Surgical option

Avoid or minimize exacerbating factors (e.g. stress, tremogenic drugs).

• Avoid or minimize exacerbating factors (e.g. stress, tremogenic drugs).

• Limit Caffeine-containing beverages

• (although no clear convincing evidence)

• Alcohol reduce the ampl of ET in 2/3 of pts.

• Effective alcohol level can be as low as 0.03%
• Possible prophylactic treatment

The evidence concerning the risk of alcholism amont ET patients is contradictory.

• The evidence concerning the risk of alcholism amont ET patients is contradictory.

• Some investigators suggested that alcohol is a risk factor for ET.
• The regular use of alcohol to treat essential tremors is inadvisable.
• Mechanism of action is thought to be centrally by potentiating GABA receptor-mediated chloride influx and stabilizing neuronal membranes.

“Popranolol” (Inderal) non-selective.

• “Popranolol” (Inderal) non-selective.

• - most well-studied beta-blocker used in the treatment of ET.

• - 45% and 75% will show improvement in arm tremor compared with placebo.

• - Dosing “Standard” or “Long-acting” formulation

• - Initiated with 20 mg/d.

• - Titrated weekly to an effective dosage, typically 120 mg/d - as 320 mg/d.

• Side effects:

• - Elderly: may experience symptomatic hypotension or bradycardia.

• - Other side effects include impotence, drowsiness, confusion, headache, depression and exercise intolerance. (Benito-Leon et al, 2007b).

• If side effects develop, patients do not usually develop tolerance.

• Contraindicated: Asthma, COPD, 2nd degree heart block and Insulin dependent DM.

Mechanism of action:

• Mechanism of action:

• - Central mechanism of action has been suggested for β-adrenergic blockers, but they are not lipid soluble and hence do not cross the blood–brain barrier. -- This suggests that the therapeutic effect of β-adrenergic blockers might be mediated, at least in part, by the peripheral β-adrenergic receptors.

• Other selective beta-antagonists such as nadolol also appear to be effective but have not been as well studied compared with the nonselective beta-antagonist.

Propranolol and primidone Combination therapy

• Propranolol and primidone Combination therapy

• Greater relief in some patients

• Other less well-studied oral agents may be used to treat ET, including

• benzodiazepines, topiramate, and gabapentin.

• These medications have varying effectiveness.

“Topiramate” Topamax, Anticonvulsant

• “Topiramate” Topamax, Anticonvulsant

• - Shown effective anti-tremor drug in a multicentre, double-blind, placebo

• controlled trial of 208 patients with essential tremor. (Ondo WG et al,

• neurology 2006)

• - Addition to a significant decrease in the Fahn–Tolosa–Marin tremor

• rating scale scores.

• - Topiramate was associated with a greater improvement in function and

• disability than did placebo.

• Most common Side effects:

• paraesthesias (58 [28%]), weight loss (46 [22%]), and taste perversion (40 [19%]); other side-effects included nausea, difficulties in concentration and attention, and somnolence.

Gabapentin: Neurontin, anticonvulsant

• Gabapentin: Neurontin, anticonvulsant

• Mixed results from double-blind, placebo controlled studies in essential tremor have been reported. (Lyons KE et al, CNS drugs 2008)

• Levetiracetam, ‘Keppra” anticonvulsant

• Had a significant anti-tremor effect in one double-blind, placebo-controlled trial at a single dose of 1000 mg. (Bushara KO, Neurology 2005).

• Was not found to be effective in other studies. (Elble RJ, Clin Neuropharmacol 2007).

Diazepam, lorazepam, clonazepam, alprazolam,

• Diazepam, lorazepam, clonazepam, alprazolam,

• Ameliorating effects on essential tremors. (Lyons KE, CNS Drugs 2008).

Definition:

• Definition:

• - Dystonia is a neurologic disorder dominated by involuntary, stereotyped, patterned (sustained or spasmodic) contractions of muscles. These movements frequently cause twisting and other abnormal movements or postures.

• - Causes involuntary simultaneous co-contraction of both agonist and antagonist muscles, resulting in the ‘‘twisted’’ Movements.

• - Dystonic contractions are usually sustained at the peak of the movement, differentiating dystonic contractions from the brief contractions seen in chorea or myoclonus.

Childhood-/Adolescent-Onset

• Childhood-/Adolescent-Onset

• - The average age of onset is around 9 years.

• - A GAG deletion mution in DYT1 gene in Chromosome 9q lead to failure of

• protein torsin A production.

• - Autosomal dominant condition has only a 30% penetration rate

• - More common among Ashkenazi Jews

• - Usually begins with symptoms in a limb, most commonly a leg, during

• activities such as running or walking.

• - The dystonia often spreads to other body regions, including the other leg,

• trunk, and arms within 5 years.

Adult onset

• Adult onset

• - Prevalence 3.4 to 6.2 per 100,000.

• - Commonly 4th – 5th decade of life

• - Women: Men 3 : 1

• - It often begins as a focal dystonia in the upper body, Symptoms may

• worsen over time and spread  segmental  rarely generalize.

In general, these are rare disorders that are different from heredodegenerative disorders or other secondary dystonias since they are not associated with known neuropathologic findings (Fahn et al, 1998).

• In general, these are rare disorders that are different from heredodegenerative disorders or other secondary dystonias since they are not associated with known neuropathologic findings (Fahn et al, 1998).

• 1) Myoclonus-dystonia, 2) Rapid-onset dystonia-parkinsonism

• 3) Dopa-responsive dystonia (DRD, DYT5, Segawa disease)

• Presents in normal children
• Typically begins with foot dystonia, gait abnormalities, and hyperreflexia, progressing to generalized dystonia.
• Maybe confused with the distonia seen in cerebral palsy.
• A unique feature of DRD is its diurnal fluctuation, with worsening of symptoms late in the day.
• autosomal dominant (“point” mutation in the gene for GTP cyclohydrolase 1 “GCH1”(synthesis of tetrahydrobiopterin, a cofactor in dopamine synthesis). May also occur in autosomal recessive forms due to a mutation in the tyrosine hydroxylase gene.
• DRD is extremely sensitive to treatment with levodopa, and the effect is sustained over time.
• Most reliable diagnostic test is: response to dopamine

Medical management

• Medical management

• Botilinum toxin

• Surgical option

Primary dystonia:

• Primary dystonia:

• - Is only symptomatic, not neuroprotective, with the goal to: - relieve involuntary movements,

• - correct abnormal posture,

• - prevent contracture,

• - reduce pain and embarrassment, and improve function.

• Secondary dystonia with an identifiable etiology

• - respond to specific treatments,e.g.:

• - Levodopa in dopa-responsive dystonia

• - Withdrawal of the causative treatment in drug-induced

• - Copper chelation in Wilson’s disease.

Tics are sudden, repetitive, rapid, involuntary movements or vocalizations with differing degrees of intensity and frequency and unpredictable durations. They usually involve the eyes, face, shoulders, neck, and vocal apparatus more than the rest of the body.

• Tics are sudden, repetitive, rapid, involuntary movements or vocalizations with differing degrees of intensity and frequency and unpredictable durations. They usually involve the eyes, face, shoulders, neck, and vocal apparatus more than the rest of the body.

• Motor tics:

• - Simple: brief, sudden, meaningless movements such as eye blinking, shoulder shrugging, and head turning.

• - Complex: involve a variety of muscle groups, can appear to be purposeful

• (touching, jumping, body contortions, copropraxia), or involve the prolonged maintenance of a posture (dystonic tic).

• Vocal (Phonic)

• - Simple: e.g. throat clearing, grunting, barking, or sniffing

• - complex: the use of words—ie, echolalia, palilalia, or coprolalia. It is important to note, that coprolalia occurs in only about 10–19% of patients.

Medical management

• Medical management

• Botilinum toxin

• Surgical option

First step is “education”

• First step is “education”

• Most patients do not require pharmacological

• therapy.

• Councilling, Relaxation training, Cognitive

• behavioral therapy and Habit reversal training

• might be enough.

Neuroleptic drugs

• Neuroleptic drugs

• Dopamine receptor blocker
• Fluphenazine “less sedating”
• Resperidone
• Pimozide Less sedating (FDA approved)
• Haloperidol (FDA approved)

• Side effects: sedation, depression, weight gain, and school phobia (separation anxiety), tardive stereotype and tardive dystonia. Prololned QT interval, Neuroleptic malignant syndrome, Akathisia

Neuroleptic drugs

• Neuroleptic drugs

• Monoamine-depleting drug
• Tetrabenazine (Nitoman)
• Side effect: Dizziness, Depression, Akathisia and parkinsonism, not known for Tardive dyskinesia, less wt gain.

Localized motor tics

• Localized motor tics

• Life threatening tics e.g. dystonic cervical tics

Chorea consists of irregular, purposeless, abrupt, rapid, brief, jerky, unsustained movements that flow randomly from one part of the body to another.

• Chorea consists of irregular, purposeless, abrupt, rapid, brief, jerky, unsustained movements that flow randomly from one part of the body to another.

• The term “choreoathetosis” describes the combination of chorea and athetosis, a slow form of chorea manifested by writhing movements predominantly involving distal extremities.

• Ballism, a severe form of chorea, comprises wide amplitude, flinging movements, usually involves the proximal limbs and most often affects only one side of the body (hemiballism).

• Ballism is typically caused by a lesion in the contralateral subthalamic nucleus

A primary neurodegenerative disease

• A primary neurodegenerative disease

• Autosomal dominant

• Mutation in Chromosome 4, causing between 37 and 86 CAG repeats. Leading to intranuclear inclusions.

• Prevalence 5 to 10 per 100,000 in the US

• Gradual onset of chorea, dementia, and behavioral abnormalities in a young or middle-aged adult should suggest the possibility of HD

• In the terminal phases of HD, dysarthria, dysphagia, and respiratory difficulties become the most disabling and life-threatening problems

Targeting the chorea

• Targeting the chorea

• 1) DA receptor-blocking agents

• e.g., haloperidol and fluphenazine
• Side effects

• 2) Dopamine-depleting agents (less side effects)

• e.g., tetrabenazine
• Side effect: Dizziness, Depression, Akathisia and parkinsonism, not known for Tardive dyskinesia, less wt gain.

Despite advances in treatment, this disorder results in progressive functional decline and eventual death, usually within 12 to 15 years of onset.

• Despite advances in treatment, this disorder results in progressive functional decline and eventual death, usually within 12 to 15 years of onset.

• Neural transplantation with fetal striatal or other cell sources may become experimental options in the future.

Definition: intermittent twitching of the muscles supplied by one facial nerve.

• Definition: intermittent twitching of the muscles supplied by one facial nerve.

• Incidence 0.78 per 100,000, F : M 2 : 1

• Average age at onset being 45 to 51 years.

• Etiology: compression of the facial nerve at its junction with the brain stem by an aberrant or ectopic posterior fossa artery. 90% of cases; other: tumors and bony or other abnormalities.

Begin in the periorbital region and spread to the ipsilateral facial muscles during the next few months.

• Begin in the periorbital region and spread to the ipsilateral facial muscles during the next few months.

• Spasm occurs spontaneously, is almost always unilateral, and is exacerbated by voluntary facial movements such as lip pursing, stress, fatigue, anxiety, or a change in head position.

• The movements often persist during sleep.

• Ipsilateral tinnitus Stapedius muscle contraction

Clonazepam

• Clonazepam

• botulinum toxin injection to the involved muscles is now the treatment of choice

• Endoscopic surgical correction may offer a permanent treatment.

Bhidayasiri R. Differential diagnosis of common tremor syndromes. Postgrad Med J. 2005 Dec;81(962):756-62.

• Bhidayasiri R. Differential diagnosis of common tremor syndromes. Postgrad Med J. 2005 Dec;81(962):756-62.

• Joseph Jankovic, Treatment oh hyperkinetic movement disorders. Lancet Neurol 2009; 8: 844–56

• Harvey S.Singer, Treatment of Tics and Tourette Syndrome. Current Treatment Options in Neurology (2010) 12:539–561

• Jill L. Ostrem, Nicholas B. Galifianakis, Overview of common movement disorders. Continuum Lifelong Learning Neurol 2010;16(1):13–48.

• Joseph Jankovic, Chapter 30 “Movement disorders”