neuro clinical Flashcards
(144 cards)
1
Q
Presentation of MS
A
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
2
Q
T1 and T2 MRI in MS
A
- T2 MRI: plaques are hyperintense
* T1 MRI: plaques are hypointense
3
Q
MS pathology
A
- 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
4
Q
marburg variant of MS
A
very aggressive, quickly progressive; severe axonal loss→death
5
Q
MS variant: Balo’s concentric sclerosis
A
alternating bands of demyelinated and myelinated white matter, forming concentric rings or stripes
6
Q
neuromyelitis optic (NMO)
A
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
7
Q
Acute Disseminated Encephalomyelitis
A
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
8
Q
Acute hemorrhagic leukoencephalitis/Hurst’s Disease
A
perivascular hemorrhage and severe brain edema
9
Q
progressive multifocal leukencephelopathy
A
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
10
Q
HIV encephalitis
A
subacute encephalitis involving white matter; direct invasion of neurons by virus
Headache, memory loss, language probs, movement d/o, sensory defecits
11
Q
subacute sclerosing panencephalitis
A
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
12
Q
demyelinating diseases
A
destruction of myelin MS Acute disseminated encephalomyelitis progressive multifocal leukencephalopathy HIV encephalitis subacute sclerosing panencephalitis
13
Q
dysmyelinating diseases
A
inherited disorders with abnormal myeline
metachromic leukodystrophy
globoid cell leukodystrophy
adrenoleukodystrophy
14
Q
Metachromic leukodystrophy
A
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
15
Q
Globoid cell leukodystrophy (Krabbe’s disease)
A
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
16
Q
Adrenoleukodystrophy
A
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)
17
Q
alexander disease
A
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
18
Q
central pontine myelinolysis
A
-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,
19
Q
canavan’s disease
A
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
20
Q
B12 deficiency
A
o Neuro sx
o Pernicious anemia (antibodies to intrinsic factor), dec absorption to GI pathology, dec. intake in strict vegans
21
Q
what is a seizure?
A
- 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)
22
Q
focal seizures vs generalized seizures
A
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
23
Q
tonic-clonic seizure
A
- 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
24
Q
absence seizure
A
- 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
25
myoclonic seizure
• Brief, lightning-like single contraction of a muscle or a group of muscles
26
atonic seizure
* Particularly devastating seizures where patient suddenly loses all muscle tone
* Common in retarded patients and may require wearing of a helmet
27
simple partial focal seizure
- NO change in level of awareness
- Aura type (subjective symptoms only)
- Focal motor seizure type (unilateral clonic or tonic)
28
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
29
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)
30
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
31
are focal epilepsy's symptomatic or idiopathic
symptomatic
32
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
33
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)
34
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
35
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)
36
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
37
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)
38
number one cause of symptomatic focal epilepsy in US?
cysticercosis (tanei solium=pork tapeworm)
39
defect in autosomal dominant nocturnal frontal lobe epilepsy
mutation in the ACh receptor
40
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)
41
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
42
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)
```
43
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
44
needle electromyography
evalutes NMJ and intrinsic muscle function
| -captures electrical signals from tested muscle
45
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
46
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)
47
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
48
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
49
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)
50
Mononeuropathy
* Single nerve
| * Include nerve entrapment neuropathies (e.g. carpal tunnel syndrome, ulnar tunnel syndrome)
51
multiple mononeuropathies
* Multiple nerves, asymmetric
* Associated with nerve infarction or inflammation (vasculitis-related neuropathies)
* Examples include lupus and polyarteritis nodosa
52
autonomic neuropathies
* Postural hypotension, abnormal HR variability, GI dysmotility, erectile dysfunction, urinary detention (detrusor dysfunction)
* Can be associated with amyloid neuropathy and diabetic neuropathy
53
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
54
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
55
what is wallerian degeneration?
-injury to axon-->progressive death of axon distal to injury site
56
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
57
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
58
parsonage-turner syndrome
- Brachial Plexus Neuritis or Amyotrophic Neuralgia
- due to diabetes (most common), lupus, vasculitis, hx of infection/vaccination
- Clinical: acute onset arm pain with patchy weakness/numbess; cannot form circle with indexu finger and thumb
59
Patient presents with painless proximal muscle weakness that is relieved with rest. He also reports bilateral ptosis that worsens throughout the day. What is the diagnosis? What would the diagnostic tests look like? treatment?
Dx: myasthenia gravis (autoantibodies target post-synaptic Ach-R)
Tests:
-electrodiagnostic: repetitive nerve stimulation causes decremental response (reflects fatigability), singler fiber EMG shows inc. jitter
-Erdophonium (tensilon test): improvement with injection
Labs: Anti-Ach antibodies (if anti-AchR negative, may have anti-MuSK)
-Ice pack test: improvement ptossis
Tx: Achesterase inhibitors (pyridogstigmine); thymectomy (may cure), immunotherapy (IVIG, plasma exchange, steroids)
60
What may be associated with myasthenia gravis?
1. thymoma or thymic hyperplasia
| 2. other autoimmune diseases
61
neonatal myasthenia gravis (floppy infant)
- neonates of myasthenic mothers: passive transfer of maternal Ach-R antibodies
- transient disease lasts a few weeks
62
congenital myasthenic syndromes
- autosoal recessive
- present similarly to neonatal myasthenia gravis but myasthenic sx persist for life
- can be presynaptic, postsynaptic or affect Achesterase
63
Lambert Eaton syndrome
- acquired autoimmune d/o; paraneoplastic assoc/ w/ small cell lung carcinoma
- antibody binds voltage-gated Ca channels-->dec. Ach released into synaptic cleft
- weakness/diminished reflexes that improve w/ repeated contraction
- anticholinergic sx: dry mouth/eyes, impotence
- EMG: rapid, repetitive stimulation results in incremental response
64
botulism
- clostridium botulinum neurotoxin (from contaminated foods, IV drugs, wound infection)
- impaired Ach vesicle docking, fusion and release from presynaptic nerve terminal
- GI sx (constipation), generalized weakness, extra-ocular muscle weakness, difficulty swallowing/breathing
65
duchenne muscular dystrophy
- X-linked inherited mutation in dystrophin gene-->absent dystrophin protein
- muscle fiber breakdown and regeneration
- Clinical: proximal m. weakness by age 3, Gower's sign, pseudohypertrophy of calf, dec. reflexes, toe walking, mental retardiation, cardiomyopathy
- Tx: supportive, steroids
66
what diagnostic tests are useful to investigate myopathies
EMG: small amplitude, short duration motor unit action potential with early recruitment
Muscle enzymes: serum CK and aldolase elevated
muscle biopsy
67
Do you see sensory changes in myopathies?
No
68
Becker's muscular dystrophy
- X-linked inherited mutation in dystrophin-->low levels of protein
- like duchenne's but later onset and milder disease
69
myotonic dystrophy
-most common muscular dystrophy in adults
-unstable trinucleotide repeate in DMK gene
Clinical:
-distal m. weakness, myotonia,, heart arrhythmias
-ptosis, frontal balding, temporalis and masseter muscle atrophy
-sleep apnea, personality d/o, gastroparesis, impaired cognition
70
polymyositis
- myalgia, pharyngeal involvement
- biopsy shows endomysial infiltrate
- Tx: steroids, immunosuppresssion
71
dermatomyositis
- myalgias, rash
- can be paraneoplastic
- biopsy shows perifascicular atrophy
- Tx: steroids, immunosuppression
72
inclusion body myositis
- specific m. groups are weak (quads, deep finger flexors)
- biopsy show's inlcusion bodies and beta-amyloid
- refractive to treatment
- most common myopathy in older adults
73
Which drug can cause myalgia?
statins
74
which drug can cause mitochondrial dysfx?
zidovudine (antiretroviral)
75
metabolic myopathies
- exercise-induced cramps, pain, weakness, stiffness
- myoglobinuria
- acid-maltase deficiency (Pompes)
- myophosphorylase deficiency (McArdles)
- Phosphofructokinase def
- Carnitine def
76
mitochondrial myopathies
-progressive or static weakness
-extra-ocular muscle involvement
-assoc/ w/ diabetes, short stature, seizures, deafness
-biopsy show's ragged red fibers
o Myoclonic Epilepsy with Ragged Red Fibers (MERRF)
o Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke (MELAS)
o Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE)
77
Hypokalemic Periodic Paralysis
* Results from Ca2+ channel abnormality
* Attacks last from hours to days
* Treatment: acetazolamide
78
Hyperkalemic Periodic Paralysis
* Results from Na+ (that’s right, Na+, not K+) channel abnormality
* Attacks last from minutes to hours
79
When would you use an EEG?
looking for seziures
| BUT can have negative EEG and still have seizures, as it is a clinical diagnosis
80
When would you perform electromyelography?
```
Nerve conduction study: sensory nerve or muscle
Needle electromyelography (EMG): electrical activity of a muscle at rest and after activation
```
indications:
- peripheral neuropathy
- motor neuron disease
- myositis
- muscular dystrophy
81
What is an evoked potential test?
* Assess sensory pathways in both the peripheral AND central nervous systems simultaneously
* Provide a peripheral stimulus and then measure the action potential as it reaches the CNS
* Extremely sensitive to artifact, which is overcome with the use of “averaging” (shock many times and average evoked potentials)
82
when would you perform a somatosensory evoked potential?
• Suspected lesion within the long tract sensory pathways in the spinal cord (e.g. demyelinating disease, trauma, tumor)
o Combining upper and lower extremities is helpful for localization within the spinal cord
83
When would you perform a visual evoked potential?
* Multiple sclerosis (and similar diseases)
| * Assess for organic lesion in patients with vision loss or decreased acuity
84
When would you perform an auditory evoked potential?
* Auditory nerve tumors
* Demyelinating disease
* Vertigo
* Brain death (to prove that the brainstem is not functioning)
85
When would you use angiography?
What are the potential risks?
* Assess for arterial problems (e.g. aneurysms, AV malformations, atherosclerosis)
* Assess for tumors (some tumors are highly vascularized and may require embolization prior to removal)
* Assess for venous problems (e.g. dural venous thrombosis)
risks:
• Hemorrhage
• Ischemic or hemorrhagic stroke
• Allergic contrast reaction
86
when would you use a CT scan?
* Emergent scan (e.g. acute head trauma, acute stroke, meningitis)
* Acute bleeding (e.g. suspected hemorrhage)
ADV: fast, widely available, ideal for detecting acute blood flow (bright)
DISADV: radiation, poor differentiation b/t gray and white matter
87
T1 MRI
fluid is back
88
T2 MRI
fluid is white
89
What is the most sensitive diagnostic test for multiple sclerosis?
MRI
90
Where do you insert the needle for lumbar puncture?
one of 3 spaces:
- between L3-L4
- between L4-L5
- between L5-S1
91
When would you perform a lumbar puncture?
if you suspect....
o CNS infection (meningitis, encephalitis)
o Inflammatory disorder (MS, Guillain-Barre, vasculitis)
o Subarachnoid hemorrhage (if CT is negative, but it is still suspected)
o CNS neoplasm (neoplastic meningitis, medulloblastoma)
92
What are the possible complications of LP?
headache! (Tx w/ lying down, fluids, caffeine)
- injury to nerve root
- hemorrhage (epidural)
- infection
93
overexpression of the direct pathway in basal ganglia leads to....
hyperkinetic d/o
94
overexpresssion of indirect pathway in basal ganglia leads to...
hypokinetic disorders
95
hypokinetic movement disorders
Parkinson's disease
parkinson's plus syndrome
secondary parkinsonism
96
hyperkinetic movement disorders
```
restless legs syndrome
tremor
Tics (including tourette's syndrome)
chorea (Huntington's and tardive dyskinesia)
myoclonus
dystonia
```
97
4 cardinal features of parkinson's disease?
Supportive features?
```
do not need all 4 to make diagnosis
• Tremor (3-6 Hz rest tremor)
• Bradykinesia (slowness)
• Rigidity (cogwheeling)
• Postural instability
```
supportive: Hypomimia and hypophonia, Micrographia, Stooped-flexed posture, Shuffling gait and festination, Constipation, Anosmia, Mood disorders, Sleep disorders, Masked facies
98
pathophysiology of PD
loss of doapminergic neurons in pars compacta substantia nigra-->disinhibition of indirect pathway and decreased activation direct pathway-->increased inhibition of cortical motor areas
-lewy bodies: cytoplasmic nuclear inclusion bodies containing alpha synuclein
99
etiologies of secondary parkinsonism
drug-induced (neuroleptics)
cerebrovascular disease
toxic (MPTP, lytico-Bodig)
dementia pugilistica (repeated head injury)
100
Progressive supranuclear palsy
```
parkinson's plus syndrome
o Gaze palsy (“deer in a headlights” look)
o Nuchal rigidity
o Early gait disorder
o Falls
o Speech disorder
o Dementia
```
101
dementia with lewy bodies
parkinson's plus syndromes:
o Early dementia
o Hallucinations
o Cognitive fluctuations
102
multiple system atrophy
parkinson's plus syndrome
o Autonomic insufficiency (eg. Passing out)
o Early incontinence
o Cerebellar ataxia
103
corticobasal degeneration
parkinson's plus syndrome
o Asymmetric limb apraxia (“alien limb phenomenon”, one limb seems to just do what it wants)
o Rigidity
o Dementia
104
restless leg syndrome
- most cases idiopathic but secondary causes are iron deficiency, pregnancy, end-stage renal disease
- subjective disorder in which pt experiences restless sensation in legs at night that improves with moving around
- tx: dopamine agonist (ropinirole, pramipexole)
105
essential tremor
-most common movement disorder, 50% AD inherited
• Postural and kinetic tremor
• Bilateral and symmetric
• Affects the upper extremities +/- voice +/- head
• Improves with alcohol
• Worsens with stress and stimulants (e.g. caffeine)
• Remainder of physical exam is normal
-tx: beta-blockers (propanolol)
106
Essential tremor vs parkinson's tremor
* Essential tremor is 4-12 Hz, while Parkinson’s tremor is 3-5 Hz
* Essential tremor is associated with sustained posture (postural) and movement while Parkinson’s tremor occurs at rest
* Essential tremor tends to be hereditary while Parkinson’s tremor is NOT
* Essential tremor begins and stays bilateral and symmetric while Parkinson’s tremor begins unilateral and asymmetric
* Essential tremor is made better (reduced) by alcohol while Parkinson’s tremor is not affected by alcohol
* Essential tremor is NOT associated with any other neurological signs while Parkinson’s tremor is (see above)
107
What is a tic?
-brief, involuntary, repetitive, rapid and non-rhythmic movements (motor tics) or sounds (vocal tics)
o Tic is preceded by overwhelming urge to perform the tic activity
o Exacerbated by stress
o Relieved by concentration
o CAN be suppressed (usually)
o Often migrate to different parts of the body and tend to relapse-and-remit
108
Gille's de la tourette's syndrome
Most severe form of tic disorders
Diagnostic criteria
o Multiple motor tics + one or more vocal tics occurring for > 1 year without a period of 3 months in which tics are absent
o Onset before age 21
o No other medical etiology (e.g. infection, HIV, amphetamines) responsible for the tics
Management
o Treatment depends on whether the tics are interfering with patient’s life
o If tics are debilitating → dopamine antagonist (fluphenazine, pimozide or haloperidol)
o If associated OCD issues → SSRI (fluoxetine)
109
myoclonus
o Fast, jerk-like movements due to muscle contractions
o Random and irregular, but generally more abrupt than chorea
o May resemble tics, but are different in that they can NOT be suppressed and they are not associated with any “urge”
-can be focal, segmental or generalized
Tx: GABAergic medications
• Benzodiazepines (clonazepam)
• Valproic acid
110
What are the clinical features of chorea?
o Rapid, predictable, non-rhythmic movements that tend to flow from joint-to-joint, often appearing as “fidgety” movements
o Often try to incorporate the movements into a purposeful movement
o Dance-like gait
o Accompanied by motor impersistence (inability to continue and ongoing movement)
111
tardive dyskinesea
- chronic dopamine blockade assoc w/ typical antipsychotics, anti-emetic -metoclopramide
- stereotyped movements that involve orobuccolingual movements resembling chewing and tongue thrusting
- Tx: stopping the medication and switching to an atypical antipsychotic (can still cause TD)
112
dystonia
: involuntary, sustained muscle contractions causing abnormal repetitive twisting postures, frequently accompanied by pain
- temporary relief with specific sensory stimulation "geste antagonist"
- general, segmental or focal (eg. writer's cramp, blepharospasm, cervical dystonia)
- tx of focal dystonia: botox
- tx of general dystonia: benzo's anticholinergics
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ataxia
- patients look like they're drunk: lack of coordination with voluntary movement, wide-based gait and “scanning” speech
- cerebellar or sensory (damage to afferent proprioceptive system)
- hereditary: spinocerebellar ataxia
- acquired: antiepileptic drugs, alcohol, hypothyroid, vit B12, B6, thiamine deficieincy, lesions (stroke, tumor etc), paraneoplastic syndrome
- tx is supportive or reversal of underlying condition
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psychogenic movement disorder
o Suggested by variability and distractibility
o This is NOT usually do to malingering (the movements are usually NOT voluntary)
o Often associated with some traumatic experience in past (e.g. rape, abuse)
o This is a diagnosis of exclusion
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migraine
o More common in females
o Unilateral pulsating pain lasting from several hours to 3 days
o Very commonly accompanied by nausea, vomiting, photophobia, phonophobia and worsening of symptoms with movement
o Often preceded by visual or sensory aura (e.g. visual scintillating scotomata) and/or an excitatory or inhibitory prodrome
o Pathophysiological features include brain hyperexcitability, trigeminal nerve inflammation and central sensitization resulting in allodynia
o Overuse of headache-relieving medications can transform episodic migraine into chronic migraine
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tension headache
o No gender predominance
o Bilateral tightening-pressure (NOT pulsating) quality lasting from 30 minutes to 1 week
o NOT accompanied by nausea-vomiting, NOT exacerbated by movement and may have photophobia or phonophobia, but NOT both
o Overuse of headache-relieving medications can transform episodic tension-type headache into chronic tension-type headache
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cluster headache
o More common in males
o Unilateral extreme pain centered at or around the eye, usually lasting around 1 hour
o Always accompanied by a triad of unilateral autonomic symptoms: tearing, rhinorrhea and periorbital edema
o Often accompanied by increased movement (e.g. pacing), which is in stark contrast to migraine attacks
o May occur several times per day (commonly at the same time every night) in cycles that last several weeks and repeat a few times a year
o Transformation to chronicity is NOT associated with overuse of headache-relieving medications
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trigeminal neuralgia
- middle aged to older persons
- o Stabbing, intense paroxysms of pain in the mandibular, maxillary and (rarely) ophthalmic division of the trigeminal nerve (CN 5)
- Usually lasts seconds
- May be initiated by light touch in a “trigger zone” on the face
Primary: not assoc w/ other neurologic findings (idiopathic, vascular loop impinging on CN5)
Secondary: assoc. w/ some neuologic findings (tumor/mass, or MS)
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headache red flags
```
"SNOOP"
S: systemic sx, secondary risk factors
N: neurlogic sx or abnormal signs
O: sudden onset
O: older persons with new onset
4P: prior history, positional change, papilledema, preciptants
```
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definition of dementia
* Dementia is a chronic and progressive decline in the cognitive ability of a patient that leads to a decline in their activities of daily living
* Dementia can ONLY be diagnosed if cognitive problems have a direct impact on a patient’s daily life (especially if they lead to loss of independence)
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major causes of dementia
* Alzheimer’s disease (most common, 70%) and other neurodegenerative processes
* Vascular dementia (15%)
* Multiple strokes, vitamin deficiencies, chronic alcohol abuse, chronic infection, trauma, paraneoplastic, hydrocephalus, prion disease (~5%)
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diagnostic criteria of alzheimer's disease
• Anterograde amnesia (impaired ability to learn new information)
* At least one of the following
* Aphasia (language disturbance)
* Apraxia (impaired ability to carry out motor activities despite intact motor function)
* Agnosia (failure to recognize or identify objects despite intact sensory function)
* Disturbance in executive functioning (planning, organizing, sequencing, abstracting)
* Course is characterized by gradual continued cognitive and functional decline (i.e. NOT waxing-and-waning)
* Deficits sufficient to interfere significantly with social and occupational functions and are decline from past functioning
* Other causes of dementia have been excluded
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histo features of alzheimer's
* Extracellular amyloid plaques
* Intracellular neurofibrillary tangles (intracytoplasmic paired helical filaments of B-amyloid and hyperphosphorylated tau protein)
* Loss of pyramidal cells
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MRI features of alzheimer's brain
* Generalized atrophy
* Hippocampal atrophy
* Hydrocephalus ex vacuo: ventricles appear enlarged (because of atrophy of surrounding cortex)
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explain the amyloid hypothesis of alzheimers disease
* Inappropriate deposition of amyloid beta protein (Aβ protein), particularly the toxic Aβ42 amyloid
* Aβ42 aggregates and deposits as plaques → triggers inflammatory and oxidative response
* Inflammatory and oxidative response → hyperphosphorylation of tau (microtubule-associated protein)
* Hyperphosphorylation of tau → renders tau insoluble
* Insolubility of tau→ tau precipitates in the form of paired helical filaments (neurofibrillary tangles)
* This cascade and polymerization is toxic to neurons → death of neurons that produce neurotransmitters
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genetics of alzheimer's disease
* Apolipoprotein E (Apo-E, e4 allele), from chromosome 19, accounts for the majority of sporadic, late-onset Alzheimer’s
* Most patients with Down’s syndrome (trisomy 21) develop features of alzheimer’s disease if they survive into their 40’s
* Familial forms are associated with chromosome 14 (presenilin 1 protein)
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what meds can you use in alzheimer's
* Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
* Improve memory and function
* Slow cognitive decline
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dianostic criteria for vascular dementia
all must be present
• Presence of dementia
• Evidence of cerebrovascular disease
• Temporal relation between the vascular changes and the dementia
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What are the clinical features of dementia with Lewy bodies?
* Visual hallucinations
| * Fluctuating cognition (pronounced variation in attention and alertness)
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compare dementia with lewy bodies to parkinson's disease
* IN PD, the movement d/o is profound with relative sparing of cognition
* In DLB, cognition is severely affected but movement d/o is milder
both have lewy bodies (alpha-synuclein) but in PD, lewy bodies are in midbrain substantia nigra and in DLB they are in the cortex
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treatment of dementia with lewy bodies?
* Acetylcholinesterase inhibitors (help cognitive aspects)
* Dopaminergic medications (improve parkinsonism, but often worsen hallucinations)
* Neuroleptics (help with hallucinations by blocking dopamine, but markedly worsen the parkinson’s symptoms)
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where do you see “Knife edge” gyral atrophy of the frontal and temporal lobes?
frontotemporal degeneration
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What are pick bodies?
seen in frontotemporal degeneration.
• Intraneuronal inclusions containing abnormal tau proteins, composed of straight filaments
• Swollen, achromatic neurons (aka “ballooned neurons” aka “Pick cells”)
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frontotemporal dementia clinical features
• Onset in late 50s (younger than dementia)
• Common clinical features
o Personality change
o Impaired social conduct
o Emotional blunting
o Loss of insight (don’t understand why things are inappropriate)
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clinical features of primary progressive aphasia
subtype of frontotemporal degeneration
• Effortful, non-fluent agrammatical speech, often void of any meaningful content
• Preserved understanding of language
• Difficulty understanding individual word meaning
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wobbly, wacky, wet
- classic triad of normal pressure hydrocephalus
- ventricular enlargement (seen on imaging)
- support diagnosis w/ lumbar tap (sx should improve)
- tx: CSF shunting
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Cretuzfeld-Jacob disease
- rare disease, usually affects older patients
- most cases are sporadic
- familial form: mutations in human prion protein PrPC on chr20
- very small number of cases iatrogenic
- clinical: rapidly progressive dementia and startle myoclonus
- rapidly fatal (within months)
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nvCJD
- patients usually younger
- consumption of cow meat from animals with BSE
- clinical: first see neuropsychiatric sx, ataxia, pyramidal sx then later see dementia
- death in 1 year
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Gerstmann-Sträussler-Scheinker syndrome
* Features prominent ataxia with later onset of dementia
* Typical onset is between age 20-40
* Death occurs in about 5 years
* Inherited autosomal dominant
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fatal familial insomnia
* Features progressive insomnia, neuropsychiatric symptoms, dysautonomia, weight loss
* Eventual results in “total insomnia” (patient NEVER sleeps) and dementia
* Death occurs in about a year and a half (18 months)
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kuru
* Rare and fatal brain disorder, caused by ritualistic cannibalism among the Fore
* Mainly affected the cerebellum
* Features unsteady gait, tremors and slurred speech
* Dementia was either minimal or completely absent
* Mood changes were often present and patients would often laugh uncontrollably
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pathology of prion diseases
* Change in conformation of prion proteins, from a-helical to B-pleated sheet → catalyzes PrPC to PrPSC
* PrPSC is protease-resistant and accumulates in the brain, resulting in toxic plaques and spongiform changes
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tx of prion diseases
NONE!
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other common causes of dementia that are not neurodenerative or vascular
o B12 deficiency
o Hypothyroidism
o Neuro-syphilis
