General Flashcards
Ramsay Hunt Syndrome
- caused by reactivation of VZV from the geniculate ganglion
- characterized by severe ear pain, ipsilateral facial nerve palsy, and herpetic rash of the external auditory meatus
Parkinson’s disease
- degeneration of dopaminergic neurons in substantia nigra pars compacta
- Lewy bodies: neuronal intracytoplasmic inclusions surrounded by halo
- alpha-synucleiopathy
Targets for DBS
- subthalamic nucleus
- globus pallidus interna
- ventral intermediate nucleus is especially useful for tremor
PSP
- tau-opathy
- gait & imbalance are prominent features; falling occurs 1.5 years after symptoms onset (unlike parkinson’s, when it occurs years after onset)
- vertical gaze abnormalities (restricted upward gaze making going down stairs difficult); can be overcome with oculocephalic maneuver
- square wave jerk and impaired optokinetic nystagmus
- MRI with hummingbird sign (atrophy of midbrain)
- PD features are less asymmetric and not levodopa responsive
- retrocollis: involuntary neck extension is present (vs antecollis in MSA)
- no autonomic features/ataxia (unlike MSA)
MSA
- alpha synnucleinopathy
- autonomic dysfunction: orthostatic hypotension w/o compensatory increase in HR; urinary incontinence, and impotence
- laryngeal dystonia –> potentially fatal
- 3 subtypes: signif autonomic dysfunction, signif parkinsonism, and signif cerebellar ataxia
- MRI with hyperintense rim around putamen & “hot cross bun sign” in pons
- poor response to levodopa
- antecollis (involuntary neck flexion)
Corticobasal Syndrome
- PD plus syndrome
- focal limb rigidity and/or dystonia, cortical myoclonus, and cortical sensory loss (asterognosis, agraphesthesia, and loss of two-point discrimination)
- other fx: frontal cognitive dysfunction, apraxia, alien limb
Secondary causes of Parkinson’s
- post-encephalitis (WNV, influenza)
- manganese toxicity, CO toxicity
- vascular (affects LE > UE); lacunes in BG
- drug-induced (typical antipsychotics)
- NPH and other hydrocephalus
Rubral tremor
- aka Holmes tremor
- low-frequency tremor present at rest, with posture, and with action
- lesions in dentate nucleus and superior cerebellar peduncle
- often seen in MS
Essential tremor treatments
- propranolol (Beta blocker)
- primidone (anticonvulsant which is converted into phenobarb and PEMA)
- 2nd line: atenolol, topiramate, gabapentin, benzo (clonazepam)
Tourette’s Syndrome
- at least one motor and one phonic tic at some time during illness (though not necessarily at the same time) before age 18
- comorbidities: OCD, ADHD, anxiety, depression
- dopaminergic hyperstimulation of ventral striatum + limbic system
- tx: haloperidol, pimozide, clonidine, habit reversal
Wilson’s Disease
- autosomal recessive dx of copper metabolism
- mutation in gene encoding copper transporting P-type ATPase (ATP7B) on chromosome 13 –> inability to excrete copper from liver into bile –> copper accumulation
- neurologic (PD, dystonia, tremor, ataxia), hepatic, and psychiatric features
- decreased serum ceroloplasmin and increased urinary excretion of copper
- MRI with T2 hyperintensities in caudate and putamen with sparing of red nucleus –> double panda sign
- tx: d-penicillamine, zinc supplementation, low copper diet
Lance-adams syndrome
- results from hypoxic-ischemic injury “cortical” myoclonus
- action myoclonus; gait may be affected with leg involvement
- may not be evident until a few months after injury
- Tx: clonazepam, piracetam, LEV, VPA
Huntington’s
- autosomal dominant, trinucleotide expansion of CAG on chromosome 4
- chorea, gait instability, dystonia, neuropsych
- motor impersistence (inability to maintain tongue protrusion)
- impaired saccades and pursuits, insuppressible head movements during eye movements
- MRI: caudate and putamen atrophy
- no cure; symptomatic tx with antidopaminergic (atypical antipsychotics and tetrabenazine)
Neuro-acanthocytosis
- mixed movement dx with chorea and dystonia
- acanthocytes (spiculated RBC) present in blood smear
- chorea-ancanthocytosis, Mcleod’s syndrome, abetalipoprotein are examples
Chorea-acanthocytosis
- orolingual dystonia (tongue-protrusion dystonia particularly while eating), self mutilating behavior, cognitive decline with dementia, dysarthria, opthalmoplegia, PD, seizures, and behavioral problems
- chorea and athetosis (slow form of chorea) also occur
- autosommal recessive; VPS13A gene Chr 9 (chorein protein)
Lesch-Nyhan
x-linked recessive from mutation in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) –> abnormal purine metabolism –> hyperuricemia
- self mutilation
- nephrolithiasis, neuropsych sx, chorea, athetosis, and rigidity occur
Hemiballism
- lesions in contralateral STN
- also occur with contralateral parietal or thalamic lesions
- often responds to antidopaminergic therapy
Tardive Dyskinesia
- more common with typical antipsychotics (haloperidol, fluphenazine b/c of > D2 antagonism)
- can also occur with Reglan (metoclopramide)
- also associated atypical antipsychotics ie risperidone (clozapine and quetiapine least likely to cause it)
- oro-bucco-lingual movements, akathisia (inner restlessness), dystonia (usu neck), tremor, parkinsonism
- tx: clonazepam and tetrabenazine (dopamine-depleting agent)
Primary generalized dystonia
- autosomal dominant
- mutation in torsin A gene, Chr 9 (DYT1)
- generally starts in one limb, then spreads to trunk and other limbs
- poor response to levodopa; tx = anticholinergics, benzodiapines, and DBS of GpInterna
Segawa’s Syndrome (Dopa-responsive dystonia)
- more common in females
- diurnal variation (worse in afternoon and evening)
- mild parkinsonism present on exam
- typically presents in childhood
- response to low-dose levodopa
- MC form: autosomal dominant mutation in GCH1 on CHr 4 (involved in dopamine synthesis)
AEDs in breast milk
Valproate, phenobarbital, phenytoin, and carbamazepine are not excreted in breast milk to the extent of lamotrigine, gabapentin, levetiracetam, and topiramate
Physiologic Changes in Pregnancy
Some of the physiologic changes that may alter AED levels include major hormonal shifts, changes in body mass, increased renal blood flow, hepatic enzyme induction, decreased albumin levels, and decreased absorption
Hypercoagulability in pregnancy
- multiple hematologic changes occur –> hypercoag state
- Fibrin generation is increased & fibrinolytic activity is decreased.
- Levels of factors II, VII, VIII, and X are all increased. Protein S and acquired resistance to activated protein C also occur. Also elevation in D-dimer
- hypercoagulable state is most pronounced near the end of the third trimester and postpartum.
Reversible Cerebral Vasospasm Syndrome (RCVS)
- presents with a thunderclap headache
- pathophys: related to endothelial dysfunction –> hypertension and vasospasm
- ddx: SAH and CVT
- MRA shows vessel beading similar to that seen in vasculitis, but with a very different presentation.
- Tx: BP control, seizures (AED), antianalgesic (HA), and nimodipine
Palatal myoclonus
- rhythmic palatal movements –> audible clicks due to eustachian tube contractions
- may be primary or secondary ( to brainstem lesion interupting the guillain-mollaret triangle inv dentate nucleus, inferior olive, and red nucleus)
- may persist during sleep
- MRI may demonstrate HYPERTROPHY of inf olive
Paroxysmal Dyskinesias
3 types: kinesogenic, non kinesogenic, and exertional (what triggers the episode)
- kinesogenic: episodes last seconds to 5 mins. triggered by sudden movement, including startle and hyperventilation. genetic component. responds well to AEDs
- nonkinesogenic: 2 mins - hours. no clear triggers. do not respond to AEDs
- exertional: triggered by prolonged exercise, last 5-30 mins. tx inlcudes ketogenic diet
Stiff Person Syndrome
- begins in 4th/5th decade of life
- increased tone affecting predominantly axial muscles (paraspinals –> lumbar lordosis, and abdominal muscles –> “board like” abdomen)
- limbs can be involved
- muscle spasms can be triggered by movement, touch, emotion, and startle
- anti-GAD antibodies (autoimmune)
- GAD = glutamic acid decarboxylase (involved in GABA synthesis, which is an inhib neurotransmitter)
- tx: benzo and baclofen (GABA effect); if doesn’t respond, can then consider IVIG
Alcoholic Ataxia
- alcohol is toxic to cerebellum
- predom affects midline structures (vermis) –> truncal ataxia with sparing of limbs
- wide-based, “lurching” gait
- can also lead to eventual hemispheric atrophy with limb involvement
Causes of acquired cerebellar ataxia
- hypothyroidism
- chemotherapy (5-FU, cytarabine)
- metals (mercury, bismuth salicylate, toulene)
- chronic use of phenytoin (damage to purkinje cells)
- HIV, whipple’s disease
- millerfisher variant GBS
Friedrich’s Ataxia
Autosomal recessive; trinucleotide repeat expansion of GAA on frataxin gene on Ch 9
- cerebellar dysfunction, neuropathy, UMN findings
- high arched feet, spinal deformities, cardiac (conduction blocks, cardiomyopathy)
Ataxia-telangiectasia
- autosomal recessive dx, presents in childhood
- neuropathy, ataxia, EOM abnormalities (inability to move eyes without head thrusting)
- telangiectasias present in oral mucosa and conjunctiva
- increased risk of hematologic malignancies and prone to infections due to immunodeficiency
- mutation in ATM gene on Ch 11 –>impaired DNA repair
Fragile X Syndrome
- CGG repeat in FMR1 gene on chr X
- tremor, ataxia, parkinsonism, dysautonomia, cognitive decline
- men > women
- MRI: T2 hyperintensities in cerebellum and inferior cerebellar peduncle
Fahr’s disease
BL calcification of BG and cerebellum
“striopallidodentate calcinosis”;
parkinsonism (rigidity, bradykinesia, dysarthria)
ataxia, dystonia, chorea, cognitive impairment
age of onset 20-60
various modes of inheritance
Synucleinopathies
- parkinsons
- LBD
- MSA
Tauopathies
PSP
Frontotemporal dementia
CBD
Anti-Hu AB
- usu in setting of small cell lung CA
- associated with peripheral neuropathy and sensory neuropathy
Anti-voltage gated calcium channel AB
- associated with small cell lung CA
- Lambert Eaton syndrome
Anti-Yo AB
- associated with ovarian and breast CA
- manifests with cerebellar degeneration
Anti-Ri AB
- asso with lung/breast CA, gynecologic
- opsoclonus myoclonus with or w/o ataxia
Anti-MAG AB
- target myelin-associated glycoprotein
- associated with MGUS
- causes demyelinating neuropathy
Meralgia paresthetica
- mononeuropathy of lateral femoral cutaneous nerve
- purely sensory nerve (L2, L3)
- numbness, paresthesias, pain in anterolateral thigh worse with standing and walking, better with flexion at hip/sitting
- due to compression or trauma to nerve
Lheber’s Hereditary Optic Neuropathy (LHON)
- mitochondrial dx
- produces bilateral optic neuropathy
- age of onset 15-35 years; painless central vision loss which is permanent
- exam: hyperemia of optic head with edema and focal hemorrhages
Fatal Familial Insomnia
- prion disease
- characterized by progressive worsening insomnia, impaired autonomic and motor functions, dementia, and death
Pharmacologic etiologies of painless myopathies
- corticosteroids
- antibiotics
- D- penicillamine
- colchicine
- beta-blocker
- chloroquine/hydroxychloroquine
Paramyotonia Congenita
myopathic channelopathy
autosomal dominant Na channel mutation
presents in first decade of life with stiffness/weakness worsened by exercise and cold exposure
Mononeuritis multiplex
- asymmetric weakness, beginning distally in hands without sensory involvement
- motor involvement in at least 2 nerve distributions
- immune mediated disorder; tx of IVIG
- EMG with “pseudo-conduction block” , evolves towards axonal neuropathy
- associated with ANCA-vasculitis, HIV, Churg-strauss, sarcoid, lyme, DM, lymphoma, RA, sjogren’s, cryoglob
CADASIL
- cerebral autosomal dominant associated with subcortical infarcts and leukoencephalopathy
- Notch 3 mutation –> vasculopathy in small to medium cerebral arteries
- onset in adulthood, usually with migraine with aura
- mood dx, ischemic strokes, gait disorder, dementia
- MRI: WM hyperintensities (frontal, temporal, subinsular) with sparing of U fibers; microbleeds common
Hemiballismus
usually due to lesion in contralateral subthalamic nucleus