Movement Disorders Other Flashcards
What is episodic ataxia type 2? Mode of inheritance? Treatment? Gene?
Episodic ataxia type 2 is an autosomal dominant disorder characterized by recurrent attacks of unsteady gait, limb ataxia, and dysarthria lasting minutes to hours. Between attacks, patients may have nystagmus and mild gait ataxia, but the neurological examination is otherwise normal. Oral acetazolamide usually prevents or reduces the frequency of the attacks. It is associated with a mutation of the CACNA1A gene on chromosome 19.
Which drugs cause drug induced Parkinsonism?
This patient has drug-induced parkinsonism due to use of metoclopramide, a dopamine receptor antagonist. The other medications would not produce parkinsonism.This adverse effect is most likely to occur in younger patients within the first 48 hours of starting antidopaminergic medications. The appropriate therapy is an anticholinergic agent such as benztropine or diphenhydramine.”
Antipsychotic and antiemetics drugs (also known as neuroleptics) It may take up to one year to resolve; thus, the patient may not be on the offending drug at the time of the assessment Severity / Likelihood Antiemetics- Metoclopramide. Domperadone doesn’t cross blood brain barrier. Varying degree of EPSE from various antipsychotics: \+++ Fluphenazine Haloperidol Pimozide Thiothixene Trifluoperazine Paliperidone Risperidone \++ Loxapine Perphenazine Asenapine Cariprazine Lurasidone \+ Chlorpromazine Thioridazine Aripiprazole Brexpiprazole Olanzapine Ziprasidone
(least / none) Pimavanserin Quetiapine Clozapine Iloperidone
What is neuroacanthocytosis? What is the characteristic presentation? DDx? Ix
The onset of orofacial dyskinesias with lingual and oral dystonia in a 30-year-old patient is characteristic of neuroacanthocytosis, which may also be associated with chorea and peripheral polyneuropathy.
Neuroacanthocytosis is a group of neurological disorders that feature CNS degeneration, neuromuscular manifestations, and acanthocytosis on a peripheral blood smear. Generally neuroacanthocytosis can be categorised into abetalipoproteinemia, chorea-acanthocytosis, McLeod syndrome.
Abetalipoproteinemia: inability to absorb and transport Vitamin E – in early childhood get progressive ataxia, neuropathy, vision impairment. Fundoscopy shows retinitis pigmentosa. On bloods get very low triglyceries, acanthocytes, sensory NCS abnormalities (decreased absent SNAP), low vit E levels
Chorea acanthocytosis: AR disorder caused by mutations in VPS13A (CHAC) gene, which encodes a large protein called chorein. Young adulthood chorea, orolingual facial dystonias, parkinsonism, tics, seizures, areflexia, distal muscle wasting. Lab tests show acanthocytes, Elevated CK, MRI may show atrophy of the caudate head and dilatation of the anterior horns of the lateral ventricles, NCS often show sensory axonal neuropathy
McLeod Syndrome is clinically indistinguishable from chorea acanthocytosis but McLeod blood group phenotype differentiates it. X linked disorger caused by mutaton in the XK gene. Presents with chorea, sensory neuropathy, cognitive impairment and psychiatric sx. Bloods: acanthocytes, elevated CK, MR progressive atrophy of the caudate nucleus.
What is huntington disease – like 2
Huntington disease like 2 (HDL2) is a rare autosomal dominant disorder affecting CTG trinucleotide repeat mutations in the junctophilin-3 gene (JPH3). Mainly reported in patients with African Ancestry
Midlife presentation with progressive movement disorder along with dementia and psychiatric disturbance (depression, apathy, irritability). May be predominantly parkinsonian accompanied by rigidity, or chorea with abnormal eye movements.
Drug induced myoclonus:
This patient has multifocal myoclonus, which is most likely secondary to opioid therapy. Meperidine is particularly prone to produce neuro-excitatory effects due to the activity of the neurotoxic metabolite, normeperidine. For this reason, meperidine should be avoided as long-term analgesic therapy.
Levodopa
●Psychiatric medications (eg, tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, lithium)
●Antibiotics (eg, penicillins, cephalosporins, quinolones)
●Narcotics (particularly meperidine and morphine)
●Anticonvulsants
●Anesthetics
●Contrast media
●Cardiac medications (eg, calcium channel blockers, antiarrhythmic agents)
●Drug withdrawal from certain agents (eg, sedatives)
Toxins associated with myoclonus include the following:
●Bismuth
●Heavy metals
●Methyl bromide
●Dichlorodiphenyltrichloroethane (DDT)
What is myoclonus? What are the causes? What are the Ix?
What is myoclonus?
Myoclonus is a brief, shock-like, involuntary movement caused by muscular contractions or inhibitions.
Muscular contractions produce positive myoclonus,
Muscular inhibitions produce negative myoclonus (asterixis)
The four major subgroups are physiologic, essential, epileptic, symptomatic (secondary). Secondary myoclonus is the most common.
Physiologic: often during sleep transition, can be anxiety or exercise induced.
Essential (primary symptoms, non progressive history). Hereditary AD, sporadic
Epileptic (in the setting of epilepsy). Etiology may be idiopathic, genetic or a static encephalopathy.
Symptomatic myoclonus: progressive myoclonic epilepsy, storage diseases, neurodegenerative diseases (CBD, CJD, Alzheimer’s, HD, PD), infective / postinfectious, autoimmune, metabolic, drug induced, encephalopathies, focal nerve damage, peripheral (hemifacial spasm)
Simultaneous electroencephalography-electromyography polygraphy is the most important clinical neurophysiology study, since it can show the approximate relationship of electroencephalography activity with myoclonus, and determine which muscles are most frequently involved with the myoclonic jerks.
What are the manifestations of whipple’s disease?
This patient most likely has Whipple disease, a rare multisystem disorder secondary to infection by Tropheryma whipplei, a Gram-positive, non-acid-fast, periodic acid-Schiff (PAS) positive bacillus.
four cardinal manifestations (arthralgias, diarrhea, abdominal pain, and weight loss).
CNS manifestations: Cognitive dysfunction, including dementia, other memory impairment, and confusion, is also a common abnormality among those with CNS involvement. Isolated involvement of other organs, most prominently CNS and heart valves, can also occur in the absence of the classic findings of Whipple’s disease.
What is FXTAS? how is it distinguished from other syndromes?
FXTAS (Fragile X associated tremor ataxia syndrome) occurs in older men who carry the permutation in the fragile X intellectual disability 1 gene. Fragile X syndrome is caused by CGC expansion of >200 in the FMR1 gene and causes intellectual disability in males. Carriers of the permutation with lengths 55-200 have FXTAS. They can present with premature ovarian failure, fragile X associated tremor ataxia syndrome (ataxia and postural tremor), mild cognitive and behavioural deficits on the spectrum of those seen in fragile X syndrome. FMR1 should be tested for in unexplained cerebellar ataxia in men older than 50.
This patient most likely has fragile X-associated tremor ataxia syndrome (FXTAS). He is not likely to have Friedreich ataxia, dentatorubral-pallidoluysian atrophy, or spinocerebellar ataxia type 3 given his age, absence of other clinical features, and the history of mental retardation in his daughters son.
What is restless leg syndrome?
Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a disorder characterized by an unpleasant sensation in the legs (and occasionally the arms), accompanied by an urge to move, that emerges during periods of inactivity, is most prominent in the evening, and is transiently relieved by movement. (
RLS/WED is common, affecting 5 to 15 percent of adults in studies that include primarily Caucasian populations.
The diagnosis is made by history and does not require additional testing, except for an assessment of iron stores in all patients and blood urea nitrogen and creatinine if uremia is suspected.
Can be idiopathic or secondary - iron deficiency, renal failure, pregnancy
Treatment:
Iron stores should be evaluated in all patients
Nonpharmacologic therapy options include avoidance of aggravating drugs and substances such as caffeine, mental alerting activities, short daily hemodialysis for patients in renal failure, exercise, leg massage, and applied heat.
In patients with chronic persistent RLS despite nonpharmacologic therapies, we recommend pharmacologic therapy with a non-ergot dopamine agonist or an alpha-2-delta calcium channel ligand. The choice between the two classes of drugs is based on symptom severity, patient age and comorbidities, drug side effect profiles, and patient preferences
For patients with very severe RLS, comorbid depression, or obesity/metabolic syndrome, we suggest initial therapy with a dopamine agonist (pramipexole, ropinirole, or rotigotine) rather than an alpha-2-delta calcium channel ligand (Grade 2C).
For patients with comorbid pain, anxiety, or insomnia or a history of impulse control disorder or addiction associated with use of a dopamine agonist, we suggest starting with an alpha-2-delta calcium channel ligand (gabapentin enacarbil, gabapentin, or pregabalin)
Augmentation, which refers to an overall worsening of RLS/WED symptom severity, with earlier onset of symptoms, shorter symptom latency with rest, shorter duration of action of drugs, or spread of symptoms to trunk or arms, is the most common complication of long-term dopaminergic therapy
Huntington’s Disease? Essentials.
Huntington disease (HD) is inherited as an autosomal dominant trait (AD), causing an abnormal CAG expansion. While greater than 36 repeats are considered disease-causing, greater than 40 repeats are needed to be fully penetrant.
The phenomenon of anticipation, whereby offspring of a parent with an intermediate number of repeats manifests disease while the carrier parent does not, may be caused by an expanding number of repeats in the offspring during meiosis. This results in children potentially manifesting a genetic disease before the affected parent, obscuring the AD mode of inheritance.
Huntington disease is an autosomal dominant movement disorder characterized by chorea, dementia and behavioral disturbances. The pathologic hallmark of Huntington disease is atrophy of the caudate and this can be visualized with an MRI of the head.
Sydenham chorea - what is it?
The patient has Sydenham chorea, a poststreptococcal autoimmune disorder which typically begins within 2 to 6 months of group A beta-hemolytic streptococcal pharyngitis. Most patients recover within 6 months, though some have a more prolonged course. Girls who recover from Sydenham may present years later, during pregnancy or while on hormonal (estrogen) or contraceptive therapy, with recurrent chorea.
What is dopa responsive dystonia?
Dopa-responsive dystonia (DRD) presents in childhood as a progressive dystonia in children without a history of cerebral palsy or cognitive delay.
It typically starts in a foot and progresses to become generalized; the most common inheritance pattern is autosomal dominant.
The disease is unique for its robust and sustained response to low doses of levodopa. Its most notable characteristic is a diurnal variation, with symptoms usually more severe towards the end of the day and improved in the morning.
What are the clinical manifestations of manganese toxicity
The main site of disposal of manganese in the body is biliary excretion. Patients with biliary atresia, chronic liver disease, or exposure to high dose of manganese during prolonged parenteral nutrition, are prone to develop manganese intoxication. Clinically, it is characterized by parkinsonism and dystonia, which do not respond to levodopa. T1-weighted MRI shows hyperintensity in the globus pallidus, striatum, and midbrain. The primary site of damage is the globus pallidus.
What is paroxysmal kinesigenic dyskinesia?
Paroxysmal kinesigenic dyskinesia may be sporadic or inherited in an autosomal dominant fashion. It responds well to low-dose anticonvulsants.
Opsoclonus myoclonus ataxia syndrome - Presentation?
The darting random eye movements are consistent with opsoclonus, and the rapid presentation and symptom complex is most consistent with opsoclonus-myoclonus-ataxia syndrome.
