Movement Disorders Flashcards
DYT1 DYSTONIA
AD DUE TO GAG DELETION IN TOR1A GENE
increased prevalence in Ashkenazi Jews
Inversion of foot is first sign, occurs around 10 yo.
DYT 5 (Dopa-Responsive) Dystonia
Gait dysfunction in childhood
Symptoms have diurnal variation: worsen as day goes on and Improve after nap
Multiple etiologies:
- GTP Cyclohydrolase 1 deficiency from mutations on GCH1 gene; AD
- tyrosine hydroxylase deficiency from mutation in TH gene; AR. (Tyrosine hydroxylase catalyzes the rate limiting step of dopamine synthesis , the conversion of tyrosine to levodopa)
DYT 11 (Myoclonus-Dystonia)
AS
mutation in epsilon-sarcoglycan gene on chrom 7q
presents in child hood. Myoclonus primarily in neck, trunk and arms
Dystonia usually involves the arm or neck
DYT 12 (Rapid Onset Dystonia-Parkinsonism)
dystonia and parkinsonism develop over days to weeks
mutation in ATP1A3
Abetalipoproteinemia/Bassen Kornsweig Syndrome
Progressive ataxia due to vitamin E deficiency Also with retinitis pigmentosa, steatorrhea, acanthocytosis and low triglyceride and cholesterol levels NO CARDIOMYOPATHY (how to differ from Friedreich's Ataxia)
Ataxia with Isolated Vitamin E Deficiency (AVED)
aka Friedreich-like Ataxia bc phenotype similar.
Vitamin E deficiency due to mutation in gene encoding ATTP on chrom 8q
Ataxia Telangiectasia
ATM gene on chrom 11q-DS DNA repair defect Truncal ataxia eye telangiectasia at ~3-5 yo skin telangiectasias recurrent simupulmonary infections Abnormal movements: athetosis, tremor, myoclonus can dev polyneuropathy cancer risk
dentatorubral-pallidoluysian atrophy (DRPLA)
AD ataxia
found primarily in Japan, in US, found in North Carolina
expansion of CAG repeat in ATN1 on chrom 12
Age <20: present as progressive myoclonic epilepsy
age >20 yo: ataxia, choreoathetosis, dementia, psychosis
Episodic ataxia 1 vs Episodic ataxia 2
EA1: KCNA1 gene on chrom 12; myokymia, attacks last minutes
EA2: CACNA1A gene on chrom 19; nystagmus, acetazolamide responsive; starts in childhood or adolescence; attacks last min to days (hours on avg)
Friedreich’s Ataxia
AR due to GAA expansion in GXC gene on chrom 9q, encodes frataxin, a mitochondrial protein
Starts with gait ataxia during puberty
Dysarthria, hyporeflexia, upgoing toes, scoliosis, pes cavus, loss of proprioception
Cardiomyopathy, arrhythmias, DM
Glutaric Acidemia Type 1
AR due to deficiency of glutaryl-coenzyme A dehydrogenase that causes an extrapyramidal syndrome in infancy
-dystonia, dyskinesias, dev delay, hypotonia, opisthotonus
MRI: frontotemporal atrophy with prominent Sylvian fissures (batwing appearance)
HARP Syndrome
Hypobetaliporoteinemia
Acanthocytosis
Retinitis pigmentosa
Pallidal degeneration
Some have PANK2 gene mutation
Huntington Disease
AD, due to expanded CAG repeat in HD gene on chrom 4p, encodes huntingtin
Change in saccadic eye movements, clumsiness and fidgeting, followed by chorea and later bradykinesia and dystonia
Irritability, mood changes and later, apathy
Tx for chorea: tetrabenazine
Meige Syndrome
Mandibular dystonia Eyelid muscle spasm Involuntary eyelid closure Excessive blinking Occasionally tongue protrusion/tongue spasms and cervical dystonia
Tx: botox
Alpha Synucleinopathies
think "Palm Synday" Parkinson's Disease Alzheimer's (both alpha-synuclein AND tau-opathy) Lewy Body Dementia Multiple Systems Atrophy
Hot Cross Bun sign on MRI
MSA
due to degeneration of pontocerebellar fibers
Shy Drager Syndrome
Parkinsonism and dysautonomia (impotence in men, orthostatic hypotension, decreased sweating, difficulties with urination)
Cell loss in putamen, substantia nigra, locus ceruleus, Onuf’s nucleus, and intermediolateral cell column)
Neuroacanthocytosis
presents ~30 yo
Associated with behavior and cognitive changes
chorea, dystonia, tics, parkinsonism
Orofacial dystonia–patients accidentally bite tongue and lips, dysarthria and interference with eating
AR form-gene chorein
X-linked form=McLeod Syndrome
Causes of acanthocytosis
Neuroacanthocytosis Wolman disease (acid lipase deficiency) abetalipoproteinemia vitamin E deficiency Ataxia-telangiectasia McLeod syndrome HARP syndrome
Bromocriptine, pergolide, pramipexole, ropinirole, apomorphine
Dopamine agonists used to treat PD
Associated with sudden attacks of sleepiness
Pergolide and bromocriptine may cause pulmonary fibrosis, hallucinations, seizures, syncope or erythromelalgia
Selegiline, rasagiline
MAO-B inhibitors used to treat PD
Selegiline is metabolized into L-methamphetamine and L-amphetamine–>may have +UDS for methamphetamines
MAO breaks down dopamine
Amantadine
Indirect dopamine agonist
can cause CHF, cardiac arrhythmias, bone marrow toxicity
Tolcapone, entacapone
COMT inhibitors
COMT breaks down dopamine
Tolcaphone associated with liver toxicity
Trihexyphenidyl, benztropine
anticholinergics used to treat tremor and rigidity in PD
Pelizaeus-Merzbacher
Classic phenotype (X-linked recessive): presents in infancy with abnormal eye movements, such as pendular nystagmus or roving eye movements
Head tremor/nodding and later spasticity, ataxia and optic atrophy
MRI with symmetric dysmyelination. A tigroid appearance due to small regions of normal neurons and myelin in midst of abnormal white matter
Classic form: PLP1 mutation on Xq X-linked spastic paraplegic type 2: PLP1 mutation Connatal form (absence of myelin): presents earlier and progresses faster: AR or X-linked
Periodic Limb Movement Disorder
Dx: >5 PLMs per hour of sleep
PLMs: involuntary, stereotyped movements that meet criteria on polysomnography: Movements last 0.5-10 seconds and occur in a cluster of at least 4 movements
Occur in light sleep
Causes of secondary: uremia, DM, spinal cord injury, abnormalities of iron, calcium, potassium, or magnesium
Worsened by antidepressants and caffeine
Tx: pramipexole, pergolide, sinemet, clonazepam, carbamazepine, clonidine, opiates
Pathology in Corticobasal Ganglionic Degeneration
Astrocytic plaques–immunoreactive for tau
Ballooned neurons
Coiled atrophy, especially of the parietal and frontal lobes and Coiled bodies of tau in oligodendrocytes
Degeneration of the substantia nigra and striatum
Chorea gravidarum needs eval for
Rheumatic fever
Antiphospholipid antibody syndrome
SLE
