neuro clinical Flashcards
Presentation of MS
o Young adults (20-50 yo), F>M
• initially focal neurologic deficit (optic neuritis, incomplete transverse myelitis, brainstem syndrome) which remits for a period of time and then comes back
• 10% have progressive course (primary progressive MS)
• spinal cord involvement=transverse myelitis (most plaques in cervical spine)—weakness/numbness in limbs and motor, sensory, sphincter deficits
T1 and T2 MRI in MS
- T2 MRI: plaques are hyperintense
* T1 MRI: plaques are hypointense
MS pathology
- Inflammation: upregulation of cytokines (IL-1,2,4,6,10,12, IFN-gamma, TNF-a, TGFb)
- Perivascular demyelination looks like a finger pointing down the axis of the vessel (Dawson’s fingers)
- Demyelination: acute loss of myelin, followed by Na channel redistribution and remyelination
- Axonal loss
- Chronic brain and spinal cord atrophy
marburg variant of MS
very aggressive, quickly progressive; severe axonal loss→death
MS variant: Balo’s concentric sclerosis
alternating bands of demyelinated and myelinated white matter, forming concentric rings or stripes
neuromyelitis optic (NMO)
variant of MS
• Sx of optic neuritis and myelitis develop rapidly often preceded by headache, nausea, somnolence, fever, malaise
• Bilateral optic neuritis
• Clinical course like MS
• Spinal cord lesions: acute and chronic; patchy or contiguous
Acute Disseminated Encephalomyelitis
o Monophasic illness, lasting 2-4wks
o Predominantly affects kids and young adults
o Follows infection or immunization (2-6wks)
o Acute onset of multifocal neurologic disturbances
• Most patients present with rapid onset headache, vomiting, pyrexia
• Can have spinal cord sx and widespread abnormalities (motor/sensory loss, ataxia, visual impairment, loss of consciousness, incontinence)
o Many patients recover (early recognition and steroid treatment)
o Perivenous and periarteriolar inflammation and demyelination, punctate to confluent, contemperaneous
Acute hemorrhagic leukoencephalitis/Hurst’s Disease
perivascular hemorrhage and severe brain edema
progressive multifocal leukencephelopathy
o Fatal subacute progressive demyelinating disease in persons with impaired cell-mediated immunity (AIDS, leukemia/lymphoma, transplant patients, immunodeficiency syndromes)
o 3 features: demyelination, enlarged nuclei or oligodendrocytes, bizarre astrocytes
o reactivation JC virus
HIV encephalitis
subacute encephalitis involving white matter; direct invasion of neurons by virus
Headache, memory loss, language probs, movement d/o, sensory defecits
subacute sclerosing panencephalitis
o Progressive neurologic d/o with encephalitis
o Measles virus, disease 2-10years after initial attack
o Initial sx: memory loss, irritability, seizures, involuntary muscle movements, behavioral changes→neuro deterioration
demyelinating diseases
destruction of myelin MS Acute disseminated encephalomyelitis progressive multifocal leukencephalopathy HIV encephalitis subacute sclerosing panencephalitis
dysmyelinating diseases
inherited disorders with abnormal myeline
metachromic leukodystrophy
globoid cell leukodystrophy
adrenoleukodystrophy
Metachromic leukodystrophy
o Deficiency of the lysosomal enzyme arylsulfatase A; autosomal recessive
o Late infantile form: most common, onset 1-2 years; progressive motor disability, intellectual decline, rapid demise
o “Metachromatic” deposits of sulfatide in CNS, PNS, and kidney
o Diagnosis made by measurement of enzyme activity, urinary sulfatide excretion; prenatal diagnosis is possible
Globoid cell leukodystrophy (Krabbe’s disease)
o Deficiency of the lysosomal enzyme beta-galactocerebrosidase; autosomal recessive
o Onset and symptoms:
• Late infancy most common (80%), usually before 6 months
• developmental arrest
• extreme irritability and crying followed by rigidity and spasms;
• frequent episodes of pyrexia
• death by 1-2 years with continued seizures and opisthotonus
o CNS pathology due to accumulation of psychosine
o May also affect the peripheral nervous system
o Globoid cells are monocyte derived
Adrenoleukodystrophy
o X-linked recessive (Xq28)o BIOCHEMICAL DEFECT: • Peroxisomal disorder • Accumulation of VLCFA (>C22:0) • due to defective beta-oxidation • Mutations in ALDP gene, an ABC transp
o Childhood cerebral (peak age of onset 4-8 years)
• Age of onset and extent of lesions at presentation (by MRI scans) are predictive of clinical course
o Adrenomyeloneuropathy (peak age of onset 20-30 years)
• slowly progressive (over decades) spastic paraparesis,
• sphincter disturbance due to spinal cord involvement;
• variable cerebral involvement
o Adult cerebral
• Cerebral symptoms after age 21, no spinal involvement
o Adrenal insufficiency only (“Addison disease” in men)
o Symptomatic ALD Heterozygotes (women age 25-55 years)
alexander disease
hypomyelinating disease
o Most often presents in infancy with increased head size,
o psychomotor retardation, spasticity; rapidly progressive
o widespread demyelination in CNS with Rosenthal fibers in astrocytic processes
o usually sporadic; autosomal recessive
o majority of patients have mutations in glial fibrillary acidic protein encoded on 17p21
o 63% present by 6 months of age; 24% between 3-10 years
central pontine myelinolysis
-myelinolytic disease
-noninflammatory, demyelinating condition common assoc. w/ rapid correction of hyponatremia
o pt presents with spastic quadraparesis, pseudobulbar palsy, acute changes in mental status,
canavan’s disease
o Deficiency of the lysosomal enzyme aspartoacylase; N-acetyl-aspartic acid accumulates in brain
o Autosomal recessive; most common in Ashkenazi Jews
o Presents at 2-6 months of age with psychomotor retardation, hypotonia; blindness, megalencephaly, seizures occur
o Vacuolar change (“spongy”) in CNS due to intramyelinic edema in white matter of cerebrum and cerebellum
B12 deficiency
o Neuro sx
o Pernicious anemia (antibodies to intrinsic factor), dec absorption to GI pathology, dec. intake in strict vegans
what is a seizure?
- sudden, rhythmic change in cortical electrical activity
- almost always accompanied by a change in behavior (sometimes only a subjective one)
- abnormal synchronous firing of neurons in the cortex (doesn’t happen in other areas of the brain)
focal seizures vs generalized seizures
Focal (partial) seizures
• Starts in one hemisphere and then spreads (it could end up spreading to both hemispheres, or not)
• Can start anywhere in the cortex
Generalized seizures
• Starts in both hemispheres simultaneously
• This is able to occur due to thalamo-cortical interactions
tonic-clonic seizure
- lasts ~1 minute
- 1st tonic phase: generalized stiffening
- 2nd is clonic phase: back and forth generalized shaking +/- tongue biting or incontinence
- can have post-ictal confusion or loss of consciousness
absence seizure
- lasts a few seconds
- abrupt loss of awareness
- sometimes eye fluttering or automatisms
- occurs mostly in children
- no post-ictal confusion or loss of consciousness
- atypical absence: same but lasts longer
myoclonic seizure
• Brief, lightning-like single contraction of a muscle or a group of muscles
atonic seizure
- Particularly devastating seizures where patient suddenly loses all muscle tone
- Common in retarded patients and may require wearing of a helmet
simple partial focal seizure
- NO change in level of awareness
- Aura type (subjective symptoms only)
- Focal motor seizure type (unilateral clonic or tonic)
complex partial focal seizure
- alteration of awareness
- Often preceded by an aura (subjective symptoms)
- May secondarily generalize (e.g. may turn into a generalize tonic-clonic seizure)
- Post-ictal confusion/lethargy (alteration of awareness)
- Doesn’t have to be complete loss of consciousness to be considered complex partial
definition of epilepsy
> 1 spontaneous seizure
- spontaneous means not provoked by acute disturbance of brain (no cerebral injury, drugs, infection, metabolic disturbance)
- predisposition (potential for spontaneous seizures)
idiopathic generalized epilepsy vs symptomatic
idiopathic:
• Nothing else wrong with the brain other than a predisposition to spontaneous seizures
• Normal “background” activity on EEG, normal intelligence
symptomatic:
• Generalized epilepsy that results from some insult to the brain
• These patients tend to be neurologically retarded or abnormal and have abnormal background EEG
are focal epilepsy’s symptomatic or idiopathic
symptomatic
Childhood Absence (“Petit mal”) Epilepsy
- Onset between ages 4-8
- May have dozens of them in a day
- 3 Hz spike-wave discharges (while seizure is occurring and sometimes in between seizures)
- May rarely also have generalized tonic-clonic seizures
- They are idiopathic (no other associated neurologic problems)
- Normal intellectual function
- Responds well to medication
- Always resolves by puberty
Juvenile (Adolescent) Myoclonic Epilepsy
- Onset between ages 12-18
- Always occurs early in the AM (e.g. during brushing teeth)
- On “bad days”, a cluster of myoclonic seizures culminates in a generalized tonic-clonic seizure
- 10-20% also have absence seizures
- Responds well to medication
- Lasts for the rest of the patient’s life (after onset in adolescence)
benign rolandic epilepsy
- Onset between ages 5-9
- Focal motor seizures consisting of unilateral facial twitching
- May occasionally get generalized tonic-clonic seizures, but ONLY at night
- Idiopathic (no other associated neurologic problems)
- An example of an idiopathic partial epilepsy (there are very few examples of these)
- NO treatment required (because the generalized tonic-clonic seizures are rare and only occur at night)
- Always resolves by puberty
mesial temporal lobe epilepsy
- Onset of seizures childhood or adolescence
- Usually there is a history of a predisposing “hit” in childhood (e.g. prolonged seizure with high fever, infection of CNS, head injury)
- Patient has one or a few generalized tonic-clonic seizures early on in disease course, then they stop and focal seizures start
The focal seizures are preceded by an aura characterized by any of the following:
• Nausea (“rising epigastric sensation”) – most common
• Autonomic abnormalities (e.g. flushing, tachycardia)
• Déjà vu
• Olfactory hallucinations (foul smell)
• Perceptual distortions (micropsia or macropsia – everything looks big or small)
temporal lobe complex partial seizure
• 1st there is aura
• 2nd there are automatisms
o Automatic, quasi-purposeful movements that people make in normal life, but which are out of context here
o Oral-related automatisms include repetitive lip-smacking and swallowing
o Manual automatisms include fumbling and picking at clothes
- Often there is also dystonic posturing
- There is a post-ictal period of confusion
- Secondary generalization is rare
frontal lobe epilepsy
- Characterized by seizures that occur during sleep
- Strange noises
- Weird postures
- Bizarre and complex automatisms
- Fencer’s posture: head turning, extension of one arm, flexion of the other arm
- Patient may remain responsive during seizure (usually not though)
- NO post-ictal confusion
- No aura (usually)
number one cause of symptomatic focal epilepsy in US?
cysticercosis (tanei solium=pork tapeworm)
defect in autosomal dominant nocturnal frontal lobe epilepsy
mutation in the ACh receptor
what is hippocampal sclerosis? Which type of epilepsy is it associated with?
- mesial temporal lobe epilepsy
- Affected hippocampus appears atrophic (small) and sclerotic (bright) on MRI
- The most common cause of medically refractory epilepsy
- history of precipitating event (meningitis, head trauma, febrile seizure)
- 2 hit hypothesis (genetic susceptibility + precipitating event)
mechanism of absence seizures
- 3Hz spike and wave on EEG
- reticular nucleus of the thalamus (NRT) has inhibitory (GABA) connections onto both the cortex and thalamic relay
- 1st: GABAB-mediated hyperpolarization → leads to opening to T-type (transient) Ca2+ channel opening
- 2nd: T-type Ca2+ channel opening causes depolarization
- A recurrent cycle of this hyperpolarization-depolarization process continues for about 300msec (3 seconds)
- Anti-absence drugs (ethosuximide) block the T-type Ca2+ channels, thereby interrupting the circuit
consequences of epilepsy
o Self-injury
• Drowning
• Automobile accidents
• Falls, lacerations, intracerebral bleeds
o Memory impairment
• Occurs in focal epilepsy only (especially temporal)
• Almost certainly due to progressive hippocampal cell loss with seizures
o Status epilepticus o Cognitive impairment, death o Psychosocial maladjustment o Employment discrimination o Sudden unexplained death (SUDEP)
nerve conduction studies
assess large nerve fibers (amplitude, latency, duration, conduction velocity)
-can help diagnose neuropathy or radiculopathy, but results can be normaly in myopathies
needle electromyography
evalutes NMJ and intrinsic muscle function
-captures electrical signals from tested muscle
amyotrophic lateral sclerosis (ALS)
- progressive degeneration of both upper AND lower motor neurons due to death of anterior horn cells
- LMN findings: muscle twitching/fasciculations, weakness, limb and tongue atrophy, dysphagia, dysarthria
- UMN findings: hyperreflexia, babinski
- normal sensory function, normal eye movements
Tx: riluzole, non-invasive ventilaiton, supportive care
-sporadic or assoc/ w/ SOD-1 mutation
spinal muscular atrophy type 1 disease
werdnig-hoffman syndrome
floppy baby
- due to deletion of SMN-1 gene (survivial motor neuron-1); AR inheritance
- clinical: areflexia, tongue fasiculations, normal IQ, normal sensory
- Tx: supportive (prognosis depends on ventilatory status)
spinobulbar muscular atrophy (kennedy disease)
- CAG repeat expansion causes defects in androgen receptor (X-linked, anticipation)
- Clinical: muscle cramps, fasciculations, limb weakness, dysphagia, dysartheria (LMN); +/- gynecomastia
- slowly progressive disease, nl lifespan
Etiologies of peripheral neuropathy: DANG THE RAPIST
o Diabetes, Alcohol, Nutritional, GBS
o Trauma, Hereditary, Environmental toxins
o Rheumatologic, Amyloid, Paraneoplastic, Infectious, Systemic disease, Tumor
distal symmetric polyneuropathy
“stocking glove neuropathy”
• Length-dependent sensory loss (more deficits distally)
• Diabetes is the most common cause (other causes include hypothyroidism, alcohol, chemotherapy, vitamin B12 deficiency)
Mononeuropathy
- Single nerve
* Include nerve entrapment neuropathies (e.g. carpal tunnel syndrome, ulnar tunnel syndrome)
multiple mononeuropathies
- Multiple nerves, asymmetric
- Associated with nerve infarction or inflammation (vasculitis-related neuropathies)
- Examples include lupus and polyarteritis nodosa
autonomic neuropathies
- Postural hypotension, abnormal HR variability, GI dysmotility, erectile dysfunction, urinary detention (detrusor dysfunction)
- Can be associated with amyloid neuropathy and diabetic neuropathy
small fiber sensory neuropathy
- Characterized by numbness, paresthesias, burning pain
- Length-dependent pattern (distal deficits)
- EMG and NCS will be normal, because they only test for large nerve fibers
- Diagnosis may be confirmed by epidermal nerve fiber density assessment of a skin biopsy
charcot-marie-tooth disease
- most common inherited neurologic disorder; autosomal dominant; duplication or mutation in PMP-22
- disturbance of peripheral myelin–>uniform demyelination
- Clinical: distal>proximal, weakness, atrophy, numbness
- NCS: homogeneously reduced conduction velocities
what is wallerian degeneration?
-injury to axon–>progressive death of axon distal to injury site
Guillain Barre syndrome
- acquired autoimmune acute demyelinating disorder most commonly after infection
- ascending weakness of lower and upper limbs; areflexia
- High protein count in CSF (but normal cell count)
- symptoms peak in 3 weeks and resolve in 4-5wks
- Tx: IVIG, plasma exchange, mechanical ventilation, NOT steroids
chronic inflammatory demyelinating polyradiculoneuropathy
- proximal and distal weakness
- high protein in CSF
- electrodiagnostic studies show acquired demyelination (conduction block, temporal dispersion)
- lasts ~2months
- Tx: steroids, IVIG, plasma exchange
