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Lecture Outline • Huntington’s Chorea• Dystonia• Athetosis• Ballismus• Myoclonus• Wilson’s disease• Tardive dyskinesia• Essential Tremor• Tourette’s Syndrome (tics)• Exam prep-what to know!

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Movement Disorders•Chorea, athetosis, ballism & dystonia :Non-rhythmic involuntary movements may be combinations of fragments of purposeful movements & abnormal postures.

•All due to imbalance of activity in the complex basal ganglia circuits.

• Sometimes also known as

“ extrapyramidal disorders”

•Primarily conditions related to excessive dopaminergic activity in the basal ganglia.

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These should NOT be thought of as separate entities amenable to specific definition but rather as a SPECTRUM of movements that blend into one-another

WHY?

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They often co-exist Even neurologists may often not be able to agree as

to how a particular movement should be classified!

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Ballismus DystoniaChorea Athetosis

Movements become - Less violent / explosive / jerky

- Smoother and more flowing

- More sustained

They differ from tics in that they cannot be suppressed by voluntary control

Myoclonus

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Chorea(latin choreus, dance) • Jerky semi-purposive uncontrollable movements of limbs ,

face & trunk , increase with anxiety & disappear during sleep.

• In the limbs they resemble fidgety movements, & in the face, grimaces.

• Patients often attempt to conceal involuntary movements by superimposing voluntary movements onto them e.g. an involuntary movement of arm towards face may be adapted to look-like an attempt to look at watch

• Pathophysiology-Structural lesions putamen, globus pallidus and subthalamic nuclei-Balance is critical between the direct and indirect motor pathways to produce normal movement patterns.

HD Video:http://www.youtube.com/watch?v=OveGZdZ_sVs&feature=relahttp://www.youtube.com/watch?v=IjFWOJKRLQ0&feature=related

Chorea Video:http://www.youtube.com/watch?v=iKwRBVkEwkY&feature=relatedhttp://www.youtube.com/watch?v=xW6LciTLoEA&feature=related

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Huntington’s ChoreaClinical manifestations:Involuntary choreiformDiminished during sleepFacial tics/grimacingDementiaParanoia & hallucinationsAppetite

RavenousEmotions

Labile

George Huntington

He wrote this paper when he was 22, a year after receiving his medical degree from Columbia University in New York. He first read the paper before the Meigs and Mason Academy of Medicine in Middleport, Ohio on February 15, 1872 and then published it in the Medical and Surgical Reporter of Philadelphia on April 13, 1872.

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Huntington’s Chorea Prevalence 1 in 10000, average onset 40 and progresses over around 10-15

years.Etiology Autosomal Dominant inherited. Gene chromosome 4p. excess number of

CAG tri-nucleotide repeats (>35). Diagnosis-DNA testing. Mutant protein product called Huntington with 40-150 glutamine

residues. Usually manifests at middle age – severity related to the number of tri-

nucleotide repeats.

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Huntington’s Chorea pathology Grossly characterized as degeneration

of the cerebral cortex and the basal ganglia

Loss of GABAergic neurons in the striatum. Severe striatal atrophy with resulting enlargement of ventricles.

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Huntington’s Chorea TreatmentLoss of GABA mediated inhibition on Substantia Nigra causes:

hyperactivity of dopaminergic synapsesMedical management

No cureDopamine receptor blocking drugs (antipsychotics),

dopamine depleting drugs.Chlorpromazine (Thorazine)Haloperidol (Haldol)

Nursing ManagementFamily supportDietAmbulatorySafety

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The other most recognised chorea.Mainly children / adolescents patients 5-15 yo Etiology: Autoimmune response following infection with group A β-

hemolytic Streptococcal infectionRare in developed countries-antibiotics! Initially characterised by pharyngitis (sore throat) followed within

approx 1 to 5 weeks by the sudden onset of acute rheumatic ferver. Chorea usually only occurs in and usually 1-6 months after the onset of sore throat.

Usually generalized chorea that disappears with sleep

Usually remits spontaneously within 9 months (on average) to 2 yearsTreatment: Dopamine antagonists, valproic acid. SevereCases-immunosupression, plasmapheresis or immunoglobulin IV

Sydenham’s chorea Video:http://www.youtube.com/watch?v=RnxqqW_nH0k&feature=related

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Dystonia: Clinical featuresDystonias are sustained abnormal postures of limbs , neck , trunk, tongue

protrusion or fixed upward deviation of the eyes (occulgyric crisis). Due to co-contraction of agonist and antagonist muscles in part of body

Classification:Most common dystonias are focal (single body part); affect one part of the

body such as eyes, neck, arm or vocal cords. Usually idopahicMultifocal dystonia: affects many different parts of the body. Segmental dystonias affect two adjoining parts of the body usually

symptomatic: Hemidystonia affects an arm and a leg on one side of the body. Generalized dystonia affects most of the body, frequently involving the

legs and back.

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Blepharospasm means the involuntary contraction of the eyelids, leading to uncontrollable blinking and closure of the eyelids. Affects women> men

Torticollis, commonly called wry neck, is the condition of spasm affecting the muscles of the neck, causing the head to assume unnatural postures or turn uncontrollably. Spasmodic torticollis, also known as cervical dystonia, is the most common of the focal dystonias.

Writer’s cramp:- Dystonic posturing of arm when hand used to perform

specific tasks e.g. writing, playing piano

Dystonia Videos:http://www.youtube.com/watch?v=eKhOVaY-YNo&feature=relatedhttp://www.youtube.com/watch?v=EA2HU6rb9UM&feature=relatedhttp://www.youtube.com/watch?v=qpd1BxUxn8E&feature=related

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Anticholinergics (benzatropine), antihistamines (diphenhydramine), anti-Parkinsons agents (trihexyphenidyl), and muscle relaxers (diazepam) & GABAB receptor agonist (baclofen).

The drug resistant dystonias can be treated by botulinum toxin injection to the responsible muscles, to overcome the abnormal distribution of muscle activity for a period of time.

Dystonia Treatment:

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Dystonia-drug inducedAcute dystonic reaction- occulogyric crisis, sustained upward

deviation of the eyes +/- toricollis, jaw opening, tongue protrusion and anxiety.

Usually a result of administering dopamine receptor blocking drugs, generally metaclopramide (antiemetic and gastroprokinetic agent used to treat nausea and vomiting, and to facilitate gastric emptying) or prochlorperazine (neuroleptic; antiemetic) in young. 50% in 48hrs, 90% in 5 days.

Treatment anticholinergic drugs, usually benztropine 1-2mg IV

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Athetosis is a slow continuous stream of slow, sinuous, writhing movements, typically of the hands and feet.

Most commonly seen together with chorea in dyskinetic motor fluctuations in PD.Also in athetoid cerebral palsy where damage occurs in the basal ganglia.

Related to excessive dopaminergic activity. In PD reducing dopaminergic drugs alleviates.

If Athetosis becomes faster, it sometimes blends with chorea, ie choreoathetosis/ 'choreo-athetoid' movements. Can be thought of as an athetoid movement that “gets stuck” for a period of time; thus, a patient with choreoathetosis may perform an involuntary movement in which his hand and fingers are twisted behind his head. He may hold this position for a few moments before his hand moves back in front of his body. The part of the movement when the limb was held, unmoving, in an abnormal position would be considered a dystonia (may occur alone).

Athetosis

Athetosis Video: http://www.youtube.com/watch?v=J_wIDm1_ax4&feature=related

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Usually in elderly & ceases within few weeks usually self-limited, lasting 6 to 8 wk .

More dramatic ballistic movements of of the arms & legs on one side of the body (unilateral) and therefore

use term “ HEMIBALLISMUS”.Treatment with antipsychotics is often effective.Usually due to a CVA in contralateral subthalamic nucleus

Hemiballismus video:http://www.youtube.com/watch?v=hqg2GTUq1k4&feature=related

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Structural lesions (subthalamic nucleus)-

Hereditary Huntington's disease /Wilson's/Neuroacanthocytosis Porphyria Paroxysmal choreoathetosis Cerebral birth injury (including kernicterus); Static Encephalopathy (Cerebral Palsy ) Cerebral trauma Cerebrovascular ( ischaemia, haemorrhage ) Drugs Levodopa /Dopamine agonists /Phenothiazines /Tricyclics Oral contraceptive Pregnancy Endocrine: Thyrotoxicosis /Hypoparathyroidism /Hypoglycaemia Infective/inflammatory Post-streptococcal (Sydenham's chorea) Henoch-Schönlein purpura Creutzfeldt-Jakob disease Antiphospholipid antibody syndrome SLE Vascular: Lacunar infarction /Arteriovenous malformation

Extra material to read latter-Causes of Chorea, Dystonia and athetosis

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Causes:Primary dystonia refers to the situation where dystonia is the only sign and there is no identifiable cause or structural abnormality in the central nervous system. Although the causes of dystonia are not fully known it is currently thought that the condition results from a malfunction in a part of the brain called the basal ganglia. The problem may mainly lie in an area of the basal ganglia called the globus pallidus. If this area of the brain is not functioning correctly then the control of another structure in the brain called the thalamus is affected. The thalamus controls the planning and execution of movement and sends nerves to muscles via the spinal cord. The end result is that muscle co-ordination is not regulated properly. The wrong muscles will contract on movement or all muscles will contract unnecessarily causing abnormal movement and posture.

Secondary dystonia implies there is a clear cause, such as a change in the structure of the brain, an environmental cause, as part of an inherited or acquired neurological disease or due to drugs or toxins. Environmental causes include head trauma, stroke, a tumour, multiple sclerosis, infections in the brain, injury to the spinal cord, or after chemotherapy, drugs (neuroleptics-Tardive dystonia) or toxins that affect the basal ganglia, thalamus or brain stem. They may be associated with other hereditary neurological syndromes. Dystonia may be the first sign in a patient with Huntington's disease, and is secondary to many other neurological diseases including Parkinson's disease, Wilson's disease and Ataxia telangiectasia.

Extra material to read latter-Dystonia: Etiology

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Brief, isolated, random, non-purposeful jerks of muscle groups in the limbs, may occur normally at the onset of sleep (hypnic jerks).

May be caused by active muscle contraction - positive myoclonus

May be caused by inhibition of ongoing muscle activity- negative myoclonus ( eg. Asterixis )

Generalised - widespread throughout body Focal / segmental – restricted to particular part of body

Treatment:Valproic acid is drug of choice May respond to benzodiazepines e.g. clonazepam

Myoclonus video: http://www.youtube.com/watch?v=HeOn99vJ8s0&NR=1 21

Physiologic - Nocturnal ( usually on falling asleep )- Hiccups

Essential - Occurs in the absence of other abnormality

- Benign and sometimes inheritedEpileptic - Demonstrable cortical sourceSymptomatic i.e secondary to disease process

- Neurodegenerative eg. Wilson’s disease- Infectious e.g CJD, Viral encephalitis- Toxic e.g. penicillin, antidepressants- Metabolic - anoxic brain damage

- hypoglycemia- hepatic failure ( “ asterixis” )- renal failure- hyponatremia

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Wilson’s diseaseAutosomal recessive defect of copper excretion in which there is

defective copper-binding to ceruloplasminClinical presentation: bradykinesia, dysphagia,dysarth ria, dystonia.Leads to copper deposition in:

- liver causing cirrhosis- brain ( especially basal ganglia ) leading

to movement disorders and other abnormalities- Cornea leading to the appearance of rusty brown “ Kayser-Fleischer rings” around cornea (yellow-brown pigment at the limbus of the cornea ).

Diagnosis is via low serum ceruloplasmin, increased urinary Cu, liver biopsy ( excessive Cu) and brain MRI changes

Although it is rare it is very important to think-of and diagnose as it is TREATABLE:- Penicillamine is given to chelate the copper and promote excretion.

Video WD:http://www.youtube.com/watch?v=JgDvQUwUOo0

Wilson’s disease Hand Dystonia

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Involuntary movements as facial grimacing , chewing movements, tongue movements (oro-bucco-mandibular dyskinesia).

Appear after weeks, generally years of exposure to dopamine receptor blocking drugs. Older or classical ‘typical’ antipsychotics e.g. chlorpromazine, haloperidol

With typical antipsychotics prevalence around 20%Thought to be due to receptors super sensitivity to these drugs .

Changes in synapse number and dendrite arborisation also occur.

Tardive dyskinesia

TD Video:http://www.youtube.com/watch?v=FUr8ltXh1Pc&feature=related

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Tardive dyskinesiaNewer ‘atypical’ drugs (e.g. clozapine, quetiapine,

aripiprazole)Atypical antipsychotics

5-HT1A receptor partial/full agonists. Antagonist activity at D2 receptor mainly in limbic system rather than striatum.

Treatment is difficult but withdrawal of the causative drug. Withdrawal often worsens symptoms.

Tardive dykinesia disappears with time in 1/3 (generally mild cases). Permanent in 2/3s.

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•Probably the most common movement disorder.

•Hallmark: postural and action tremor affecting the hands, head and/or voice. Presents as a rhythmic tremor (4–12 Hz). Typically bilateral, accentuated with goal-directed movement (Action tremor) as opposed to rest tremor (PD)

•Often, it is inherited as an autosomal dominant trait with the tremor becoming apparent by middle age and sometimes as early as childhood.

•Diagnosis-Clinical grounds; No gene or identifiable pathology has been identified for essential tremor. Abnormalities of the basal ganglia, the cerebellum, the thalamus, the connections between these structures, or a combination of factors may be causative.

•Treatment: First line- beta-blockers (propranolol 30-240 mg/d), or anticonvulsants primadone (50-1000 mg/d). Second line-benzodiazepines and methazolamide (Carbonic Anhydrase Inhibitor. Finally if all else fails- Botox or Surgical therapies such as electronic stimulation of the VIM nucleus of the thalamus or ablation of this structure (thalamotomy), can be effective treatments for those refractory to drug therapy.

Can be confused with:•Physiologic tremor -physical exertion, hyperthyroidism, acute hypoglycemia, and other physical and metabolic stressors.•Induced tremor -Stimulant drugs (including caffeine and the amphetamines), antidepressants, Depakote, and agonist drugs (used to treat asthma).

Katherine Hepburn

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•Neuropsychiatric condition characterized by the childhood onset of multiple motor and vocal tics-Repetitive semi-purposeful movements as blinking, winking, grinning or screwing up of the eyes. Coprolalia (the inadvertent utterance of obscenities), echolalia (involuntary repetition of other's phrases), palilalia (involuntary repetition of one's own utterances) and echopraxia (involuntary mimicking of the action of others). Worsen under stress!

•Distinguished from other involuntary movements by the ability of the patient to suppress their occurrence, at least for a short time.

•Often-times, affected individuals have co-existing obsessive-compulsive disorder, learning disabilities, hyperactivity/attention deficit disorder and behavioral problems.

•Although the pathogenic basis is not understood, Tics are believed to result from dysfunction in the thalamus, basal ganglia, and frontal cortex of the brain, involving abnormal activity of the brain chemical, or neurotransmitter, dopamine therefore Tics can be treated with dopamine receptor blocking or dopamine depleting drugs such as neuroleptics.

•Treatment of tics is symptomatic with haloperidol and other neuroleptics. •Some patients benefit from clonidine, an -2 agonist, or with benzodiazepines. •May be transmitted as an autosomal dominant trait 27

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Exam prep-what to know!• Learn the basic terms used to describe abnormal movements (chorea, tremor,

athetosis, ballismus, dystonia, tics).

• Understand the connections of the basal ganglia and their influence on movement.

• Recognize the clinical features of the following movement disorders and be familiar with the appropriate pharmacologic interventions for each condition:

• Chorea- Huntington’s; Sydenham’s.• Essential tremor.• Tourette’s syndrome.• Dystonia.• Myoclonus.• Wilson’s disease.• Tardive Dyskinesia.

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