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Flashcards in CN LANGE - Movement Disorders III Deck (55):

Wilson - The precise nature of the biochemical abnormality in Wilson disease is unknown - Its pathogenesis appears to involve?

Decreased binding of Cu to the transport protein ceruloplasmin.


Wilson - Studies suggest that what is important in the disease pathogenesis?

Studies of mitochondrial function and aconitase activity suggest that free radical formation and oxidative damage, perhaps through mitochondrial copper accumulation, are important in pathogenesis.


Wilson - Onset:

Approx. 11yr for patients presenting with hepatic dysfunction.
Approx. 19yr for those with initial neurologic manifestations.
--> The disease may begin as late as the 6th decade.


Wilson - Most prominent non-neurologic findings:

Ocular + Hepatic.


Wilson - Neurologic findings reflect:

Disproportionate involvement of the caudate nucleus, putamen, cortex, and cerebellum.


Wilson - Neurologic signs:

1. Resting or postural tremor.
2. Choreiform movements of the limbs.
3. Facial grimacing.
4. Rigidity.
5. Hypokinesia.
6. Dysarthria.
7. Dysphagia.
8. Abnormal (flexed) postures.
9. Ataxia.
--> Seizures may occur.


Wilson - Psychologic disorders:

1. Dementia - Characterized by mental slowness, poor concentration, and memory impairment.
2. Disorders of affect, behavior, or personality.
3. Rarely --> Psychosis with hallucinations.


Wilson - Difference of symptoms related to onset of disease:

1. When the disease begins before 20 --> Tendency for a dystonic or parkinsonian picture with hyperreflexia + extensor plantar responses to predominate.
2. Older patients --> Tendency for a wild tremor, chorea, or ballismus.


When Wilson disease presents as a neurologic disorder, other conditions that must be considered in the DDx include:

1. Other causes of movement disorders.
2. MS.
3. Juvenile-onset Huntington.


Wilson - Investigation may reveal ...?

Abnormal liver function blood tests + aminoaciduria as a result of renal tubular damage.


Wilson - Other studies:

1. Serum Cu + ceruloplasmin are LOW.
2. 24h urinary Cu excretion is INCREASED.
3. Liver biopsy shows huge excess of Cu --> Usually with cirrhosis.


Wilson - Imaging:

1. Brain CT/MRI --> Cortical atrophy + abnormalities in the basal ganglia.
2. The MRI abnormalities sometimes include --> "Face of the giant panda" sign in midbrain and sometimes a "face of the miniature panda" in the pontine tegmentum.


Side effects of penicillamine:

1. Nausea.
2. Nephrotic syndrome.
3. Myasthenia gravis.
4. Arthropathy.
5. Pemphigus.
6. Diverse blood dyscrasias.
7. Lupuslike syndrome.


Wilson - Prognosis:

Most patients treated early can expect a complete or nearly complete recovery.


Drug-induced parkinsonism - Risk groups:

Elderly + Women --> Somewhat increased risk.


Drug-induced movement disorders - Acute dystonia or dyskinesia:

Blepharospasm, torticollis, or facial grimacing is an occasional complication of dopamine receptor agonist treatment, generally occurring within 1 week, and often within 48h.


Drug-induced acute dystonia or dyskinesia - Who shows incr. susceptibility to this complication:

Men and younger patients.


Akathisia is a state ...?

Of motor restlessness characterized by an inability to sit or stand still, which is relieved by moving about.
--> It is a very common movement disorder induced by chronic treatment with antipsychotic drugs and occurs more often in WOMEN than in men.
--> May be seen as a tardive phenomenon after the discontinuation of neuroleptics.


Tardive dyskinesia:

1. May develop after long-term treatment with antipsychotic dopamine receptor antagonist drugs or with metoclopramide.
2. Common in chronically institutionalized psychiatric patients.


The risk of developing tardive dyskinesia appears to increase with ...?

Advancing age.


Tardive dyskinesia - Pathology:

No consistent pathologic features have been found in the brains of patients with tardive dyskinesia, although:
1. Inferior olive atrophy.
2. Degeneration of substantia nigra.
3. Swelling of large neurons in the caudate nucleus have been described in some cases.


Tardive dyskinesia - Clinical findings:

1. Abnormal choreoathetoid movements that are often especially conspicuous about the face and mouth in adults.
2. Tend to be more obvious in the limbs in children.


The onset of tardive dyskinesia is generally not until ...?

MONTHS or YEARS after the start of the treatment.


Tardive dyskinesia may be impossible to distinguish from such disorders as HD or isolated torsion dystonia unless a history of ...?

DRUG EXPOSURE is obtained.


Other tardive syndromes:

1. Tardive dystonia.
2. Tardive akathisia.
3. Tardive tic.
4. Tardive tremor.
5. Tardive myoclonus.


Tardive dystonia:

1. Usually segmental in distribution, affecting two or more contiguous body parts --> Face and neck or arm and trunk.
2. It is less often focal.
3. Blepharospasm, torticollis, or oromandibular dystonia.
4. Generalized dystonia is least common and tends to occur in younger patients.


Tardive tic:

Resembles Gilles de la Tourette syndrome --> Multifocal motor vocal tics.
--> Can be treated in the same manner as Gilles de la Tourette if symptoms do NOT remit spontaneously.


Rabbit syndrome:

Neuroleptic-induced disorder characterized by rhythmic vertical movements about the mouth, resembling the chewing movements of a rabbit --> The tongue is spared.


Neuroleptic malignant syndrome:

Rare complication of treatment with antipsychotic drugs (neuroleptics) manifested by:
1. Rigidity.
2. Fever.
3. Altered mental status.
4. Autonomic dysfunction.


NMS - Symptoms develop ...?

Over 1 to 3 days and can occur at any time during the course of treatment.


NMS - DDx:

1. Infection - must be excluded in any febrile patient.
2. Malignant hyperthermia.


NMS from malignant hyperthermia:

Malignant hyperthermia develops over minutes to hours rather than days and is associated with the administration of inhalational anesthetics or neuromuscular blocking agents rather than antipsychotics.


Rx of NMS:

1. Withdrawal of antipsychotic drugs, Li, and anticholinergics.
2. Reduction of body temp with antipyretics and artificial cooling.
3. Rehydration.
4. Dantrolene may be beneficial, as may dopamine agonists, levodopa preparations, or amantadine.
5. Mortality rate is as high as 20%.


Other drug-induced movement disorders:

1. Levodopa --> Wide variety of abnormal movements as dose-related phenomenon.
2. Chorea may develop in patients receiving a variety of other medications (dopa agonists, anticholinergic drugs, buspirone, phenytoin, carbamazepine, OCPs etc.).
3. Dystonia may develop in patients taking dopa agonists, Li, SSRIs, carbamazepine, and metoclopramide.
4. Postural tremor from theophylline, caffeine, Li, thyroid hormones, TCAs, valproate, isoproterenol.


Gilles de la Tourette:

Chronic, typically lifelong, multiple motor and verbal tics.
--> Unknown cause and does NOT relate to social class, ethnic group, perinatal abnormalities, birth trauma, or birth order.


Tourette - Symptoms begin before ...?

21yr, most often by age 11 and the course is one of remission and relapse.


Tourette - Prevalence:

0.05% (USA) --> More common in males than females.


Tourette - Pathogenesis:

1. Corticostriatothalamocortical pathways seem to be involved.
2. Dopaminergic excess has been postulated.


Tourette - Genetics:

Analysis of linkage in a 2-generation pedigree has led to the identification of a rare mutation in the HDC gene encoding histidine decarboxylase --> Rate-limiting enzyme in histamine biosynthesis.
--> Such finding suggest a role for histaminergic neurotransmission in the pathogenesis.


Tourette - Clinical findings - The first signs:

Consists of motor tics in 80% of cases and vocal tics in 20%.
--> Either single or multiple tics.


When the initial sign is a motor tic, it commonly ...?

Involves the face, as in sniffing, blinking, or forced eye closure.
--> Generally not possible to make the diagnosis at this stage.


Tourette - All patients ultimately ...?

Develop a number of different motor tics and involuntary vocal tics, the latter commonly consisting of grunts, barks, hisses, throat-clearing or coughing, and the like.


Tourette - Vocal tics sometimes take the form of verbal utterances including:

1. Coprolalia (vulgar or obscene speech).
2. Echolalia (parroting the speech of others).
3. Echopraxia (imitation of others' movements).
4. Palilalia (repetition of words and phrases).


Tourette - Sensory tics:

Consists of pressure, tickling, and warm or cold sensations, also occur.


Tourette DDx:

1. Various movement disorders that can present in childhood.
2. Wilson can simulate Tourette.
3. Sydenham chorea can be difficult if there is no history of rheumatic fever.
4. Bobble-head syndrome.


Bobble-head syndrome:

Which can be difficult to distinguish from Tourette --> Characterized by rapid, rhythmic bobbing of the head in children with progressive hydrocephalus.


Tourette - Complications:

1. Often unrecognized for years.
2. Tics being attributed to psychiatric illness or attention-seeking behavior.
3. Tics may be mistaken for allergies, as when sniffing and throat clearing.
4. In many cases the correct diagnosis is finally made by the family rather than the physician.
5. Psychiatric disturbances, sometimes culminating in SUICIDE, may occur because of the cosmetic and social embarrassment produced by the tics.


Drugs for Tourette:

1. Clonidine.
2. Guanfacine.
3. Atypical antipsychotics --> Risperidone, aripiprazole + Haloperidol when required.
4. Botox.


Acquired hepatocerebral degeneration:

Neurologic disorder associated with extrapyramidal, cerebellar, and pyramidal signs as well as dementia.


Restless legs syndrome:

Unpleasant creeping discomfort that is perceived as arising deep within the legs and occasionally in the arms as well.


Restless legs syndrome - The disorder seems especially common ...?

Among PREGNANT women and is NOT uncommon among uremic or diabetic patients with neuropathy.
--> MOST patients, however, have no obvious predisposing cause.


Restless legs syndrome - Symptoms sometimes resolve after ...?

Correction of coexisting iron-deficiency anemia, and they may respond to treatment with drugs such as dopamine agonists, levodopa, gabapentin, pregabalin, or opiates.
--> Benzodiazepines are also sometimes helpful.


Restless legs syndrome - Dopaminergic therapy is the ...?

Treatment of choice, BUT carries the risk of AUGMENTATION.


The term augmentation refers to ...?

1. The earlier onset or greater intensity of symptoms.
2. A reduced latency to symptom onset when at rest.
3. A briefer response to medication.


Wilson - The affected gene ATP7B codes for ...?

The beta polypeptide of Cu-transporting ATPase.