Week 3 Flashcards
1
Q
***2 pathological hallmarks of alzeihmers
A
- amyloid plaques - accumulation of amyloid
- neurofibrillar tangles - accumulation of tau
*note - both can occur normally w/ageing … combo and amt distinguish AD
2
Q
episodic memory loss in alzeihmers occurs because of neurodegeneration of _____
T/F - memoyr loss is one of first symptoms
T/F - long term memory is usually normal in AD
A
-medial temporal lobe
- TRUE
- FALSE
3
Q
- perisylvian cortex degen in AD leads to ______
- topographic disorientation/inability to draw cube attributed to ______ lobe degen
A
- wordfinding/receptive language
- parietal lobe / cube = VISUAL SPATIAL
4
Q
- accumulation of tau leads to _______ pathology hallmark in ______ (2) dementia disease
- starts _____ and travels _____
A
NEUROFIBRILLARY FIBERS - ALZHEIMERS and LEWY
TAU - down in brainsteam and around hippocampus (memory probes) then go to frontal lobe and limbic cortexes then expands out to hemispheres
5
Q
- inflammation in AD is associated with _______(amyloid plaques, lewy bodies, rosettes or tau protein)
- leads to proliferation of _____ cells
A
AMYLOID PLAQUES –> proliferation of MICROGLIA –> release cytotoxic substances and cytokkines –> inflammation
6
Q
FDG-PET scan
- mech
- use
A
- metabolic scan (measuring glucose. uptake/use)
- used for alzeihmers and other neurodegenerative disorders
7
Q
- what cells are suseptible to degeneration in AD
- get loss of _____ (NT) leading to ______ (clinicacl problems)
A
-actecholine cells in basal forbrain (called nucleus basalis minor)
- loss of Ach –> loss of Ach throughout cortex
- key role in langugae, ED, receptive language etc
8
Q
- describe order of pathogenic mechanisms in AD
- is NF tangles or amyloid 1st?
- vascular fxn _____(dec/inc/no change)
A
- *IN ORDER:
- increased amyloid
- decreased vascular fxn
- inflammation
- dec glucose metabolism
- NF tangles
9
Q
APOE gene associated with risk of ______
A
Alzeihmers disease
and LBD
10
Q
T/F- early onset AD due to auto-dominant mutations. are 100% penetrant
- *what are the genes?
- -what are these genes fxn??
A
TRUE
-dominant mutations (100% penetrant)»_space; early onset = APP/PS1/PS2 »_space; these mutations lead to INC AMYLOID!!
APP = amyloid precursor protein»_space; expressed throught CNS»_space; cleaved / processed»_space; cleared (reduced clearance in AD)»_space; AMYLOID PLAQUES
early-onset = inc production late-onset = dec clearance
11
Q
- -difference between early and late onset AD
- what gene responsible?
A
EARLY = ADD mutations»_space; inc AMYLOID BETA peptides PRODUCTION
LATE = dec clearance of amyloid
12
Q
***what CSF biomarkers/values help dx alzeihmeres?
***are CSF tests more ______(sensitive or specific)
A
- Amyloid beta levels
- Tau / Phosphorylated Tau
***NOT very specific (lots of high levels in controls / false positive) ; but pretty SENSITIVE
NOTE - 100% sensitive for patients with mild cognitive impairment leading to AD
13
Q
- which would NOT be potential treatment for AD
- anti-tau
- anti-amyloid
- nasal insulin
- oral hypoglycemics
- NSAIDS
A
ALL ARE POTENTIAL TREATMENTS
14
Q
- 2 rx for treating symptoms of alzheimers
- Disease modifying rx?
A
1-cholinesterase inhibitors (donepezil, galantamine, ribastigimine)
2-memantine (NMDA antagonist)
NO DISEASE-MODIFYING RX CURRENTLY (but in trials)
15
Q
Donepezil
- mech
- use
A
- cholinesterase inhibitors
- AD
16
Q
Possible FTD = must have ______ of the following
Early disinhibition
Early apathy or inertia
Early loss of sympathy or empathy
Early perseverative/ritualistic behavior
Hyperorality and dietary changes
Neuropsychological profile: executive/generation deficits with relative sparing of memory and visuospatial functions
A
3
17
Q
T/F - memory loss is not characteristic of frontal-temporal dimentia
T/F - poor personal regualation / judgement is one of first presenting symptoms
T/F - can see eating disorders in person with FTD
A
- FALSE (cann see in advanced)
- TRUE
- TRUE
18
Q
what are 3 “variants” (and their common chx) of FRONTO-TEMPORAL DEMENTIA
A
- BEHAVIOR - ED, disinhibition, poor judgement» cognitive problems
- NON-FLUENT PPA (primary progressive aphasia) - slowed speech/difficulty speaking (dysarthria, aaparaxia, agrammatism)»_space; mutism. worsening ED/memory
- FLUENT PPA - more of an issue with RECEPTIVE LANGUGAGE»_space; emotiona disturbances/eat/sleep»_space; disinhibition/emotional issues, compulsions, weight gain
19
Q
what type of FTD:
- apraxia with atrophy of area around lateral fissure and dilitation of ventricular system is chx of ______
- more temporal lobe involvement, word-finding difficulties
A
- non-fluent PPA (can’t speak)
- svPPA (can’t understand)
20
Q
Match FTD (behavior, nfPPA, svPPA) with:
- slowed speech, decreased word output, apraxia
- poor problem solving, sterotypies, eating disorder, difficulty in community affairs
- anomia, word finding difficulties
A
- nfPPA
- emotional
- svPPA
21
Q
T/F - word finding is generally more preserved in fluent PPA vs svPPA
A
TRUE
22
Q
***pick bodies and tauopathies chx of _____
A
FTD
23
Q
- neurofibrillary tangles are ______(extra or intracellular) accumulations of ________
- senile plaques are _______ (extra or intracellular) accumulations of ________
A
- NF tangles = Intracell, hyperphosphylated TAU
- PLAQUES = Extracell, B-amyloid core
24
Q
dx? 84 yo with poor memory and emotional problems, pathology lessions are TDP-43+
Dx? 62 year old with hallucinations and poor memory, cognitive decline. Pathology shows round eosinophilic intracell inclusions
A
–Frontotemporal dementia
–Lewy body dementia
25
***2 pathology hallmarks of FTD
- TDP-43 (~50%) >> more in SD, FTD-ALS subtypes
| - Tau (~45%) >> FTD-PSP /CB subtypes
26
--MAPT mutations assoc with ______ disease
--APP (amyloid precursor protein) mutations associated with ______ disease
--Auto-dom FTD (FTLD-Tau!)
--early-onset alzheimers
27
T/F - acetylcholinesterase inhibitors generally makes behaviors worse in behavioral FTD
T/F - anti-tau antibodies may be useful for AD and FTD
- TRUE
| - TRUE
28
*ubiquinated TDP-43 is associated with _______ disease
Frontotemporal dementia (FTD)
29
T/F - subtypes of frontaltemoral dementia have different areas of brain classically affected but aren't used to diagnose one over the other
TRUE! - there can be a lot of overlap so not diagnostic
- behavioral - symmetric or unilateral frontal lobe
- nfPPA - left frontal
- svPPA - parietal
**NOTE - there can be a lot of overlap so don't want to hang hat on just imaging for dx
30
- lewy body dementia has clinical characteristics of _______(AD, parkinsons, both)
- parkinssonisms occurs ______(early or late)
- both - CAUGHT IN MIDDLE
- dementia (>2 problems w/ : memory, learned motor behaviors, cognition etc)
- parkinsonism occur together w/ dementia as EARLY FEATURES
*1st Aid LBD = initially dementia and visual hallucinations followed by parkinsonian features
31
- psychiatric symptoms in LBD (4)
| - contrast with problems in AD / Parkinsons
- **hallucinations - seeing kids (in yard etc)
- delusional - paranoia (stealing from house)
- depression (more prominent than in AD)
- anxiety (overlap with FTD)
**hallucinations more unique to LBD** .. "LEWY" body = haLEWcinations
32
T/F- dementia with lewy body (DLB) make up majority of dementia cases
T/F - DLB has female predominance
- FALSE (10-20%)
| - FALSE (M dominant)
33
dx? 55 yo M present with gait instability, tremor at rest, worsening memory for 2 years and sleep problems (REM behavior/sleep walking) for 10 years. Has been depressed recently. Parnter says he has been furious for past 2 months because of "neighbor kids" playing in the yard but none of their neighbors have kids.
LEWY BODY DEMENTIA
-parkinonism occur with psychiatric probs / dimentia w/in 1st year
34
***Compare/contrast natural history of AD/PD/DLB
AD = cognitive dysfunction >> parkinson late
PD = motor signs (tremor/bradykinesia) >> dementia late
DLB = cognitive/motor features early on (parkinson motor signs w/in 1 year) >> FLUCTUATE >> get neuropsychiatrtic features (hallucinations, depression) later
35
DLB shares common risk gene with ______(alzheimer, parkinsons, both)
BOTH
- APOE = AD/DLB
- LRRK /synuclein = PD/DLB
36
what diseases (AD/DLB/PD) associated with:
- APOE mutations
- APP mutations
- LRRK2 mutations
- dec cortical acetylcholine
- dec striatal dopamine
```
APOE = AD/DLB
APP = AD/DLB
LRRK2 = DLB/PD
```
dec Ach = AD/DLB
dec dopamine = DLB/PD
37
dx?
- dementia with amyloid plaques and lewy bodies
- cognitive dysfunction with amyloid plaques and neurofibrillary tangles
- motor dysfunction and dementia with lewy bodies
- LBD
- AD
- PD
38
Lewy bodies seen in _____ dementia diseases
T/F - very specific for neurocognitive disorders (ie, not seen in normal adults)
- PD = widely distribted, mostly in neuromelanized regions (SN, dorsal motor vagus)
- AD = incidentally noted in large (66%) cases atautopsy
-Dystonia, RBD, NORMAL elderly (30%) etc ... FALSE
39
T/F - LEwy bodies are widespread in DLB but do NOT correlate with the of the dementia severity, and distinguish from other dementias
T/F - LB pathology involves cortical regions in DLB and uncommon in PD without cognitive impairment (no neuropathologic features distinguish PDD from DLB)
- FALSE
- TRUE
- TRUE
Cortical LB and Lewy neurites widespread in DLB, correlate with the of the dementia severity, and distinguish from other dementias
40
T/F - alpha-synuclein is major component of lew-boidies and is component of amyloid plaques in AD
T/F - lewy bodies seen in DLB and PD but not AD
TRUE
TRUE
41
-amyloid plaques are chx of ______ dementing disorders
T/F - Most DLB patients have amyloid plaques and tangle pathology
- AD and DLB
| * TRUE!
42
PD patients have which:
- amyloid plaques
- lewy bodies
- NF tangles
-LB only
43
which would/would not be rx for DLB:
- acteylcholinesterase inhibitors
- antidepressants
- antipsychiotics
ALL USED!
| -note - use antipsychotics sparingly and carefully) and atypical usually better
44
* could use acetylcholinesterase inhibitors for ________(AD, FTD, PD, DLB)
* could use dopamingergics for _______(AD, FTD, PD, DLB)
- FTD, DLB, AD
| - DLB, PD
45
Stopping anticholinergics would ______(help/hurt) patient with DLB
HELP .... they have low Ach... so stop antis or inhibit the inhibitor (cholinesterase inhibitors)
46
T/F - Hyperphosphorylated Tau leads to microtubule dysfunction
T/F - FTD and AD both have hyperphosphylated tau accumulations but have different tau isoforms
TRUE
| TRUE
47
PHF1 stain
- use?
- assoc dx?
- antibody against TAU
| - used for fronto-temp dementia (FTD) and AD
48
dx? pick bodies, PHF1+
dx? Lewy bodies, amyloid plaques, neurofibrillary tangles
dx? senile plaques, neurofibrillary tangles
- FTD-tau
- DLB
- AD
*pick bodies = round hyperphosphylated tau inclusions
49
delerium vs. dementia
- def
- what are criteria for DEMENTIA
def of praxis? assoc with delerium, dementia or both?
--DELERIUM = acute / transient change in ATTENTION/AWARENESS from patient baseline, fluctuates (worse at night)
--DEMENTIA = acquired COGNITIVE DECLINE FROM PERSONAL BASELINE, affect day-to-day function, with >2 more problems in .... memory, language, praxis, Visual-spatial, EF, personality / behavior
*praxis = learned motor activities (dressing, tying shoes)
50
- name some cognitive screening tests
- what tests are helpful to distinguish dementing disease
T/F - MRI is gold-standard for diagnosing different dementing diseases
SCREENS = MOCA; montreal ; mini-cog
TESTS = history (behavior - more FTD; parkinsonism + hallucinations = LBD); MRI (see what area affected); PATHOLOGY (look for plaques vs. neurofibrillary tangles vs. pick bodies vs. lewy bodies)
*FALSE - don't dx anything w/MRI alone, but can be highly supportive of a dx
51
* **altered mental status
- def; is _____(acute or chronic)
- ddx
-is it feature of dementia, delerium or both?
HUGE DDX - drugs, stroke, DEMENTIA AND DELERIUM, psychiatric illness
*anything that changes behavior, hallucination, disorientation etc ... can be ACUTE OR CHRONIC
52
disturbance in attention/awareness developing over short period of time is chx of _______
delerium
53
T/F- delerium affects attention and awareness but not cognition
T/F - delerium fluctuates and is often worse at night
FALSE
TRUE
54
reticular activating system
- location
- role?
- brainstem
- modulate awake/alertness and attention
*f'ed up in DELERIUM
55
***Delirium occurs with _____ (inc or dec) Ach and _____(inc or dec) NE
- -dec Ach
| - -inc NE
56
***List several major causes of delirium
- infection (esp UTI in elderly)
- withdrawl (benzos, etoh)
- electrolyte imbalance
- shock/stroke
- drugs / toxins
57
____ (anticholinergics or anticholinesterase) can cause delerium
anticholinergics (dec Ach)
58
2 tests to diagnose delerium?
-whats most important?
--Psychiatric Mental Status Examination - based of interview (apperance, behavior, speech, mood etc)
--Mini-Mental State Examination (MMSE)
--HISTORY !!! (most imp)
59
* **pathophys of delerium
- -disruption of _____ important for consciousness/attention
- -changes to _____ and ____ NTs
- -Disruption in the Reticular Activating System
| - -Delirium occurs with -- Ach and ++ NE
60
***criteria for delerium dx:
Criteria 1 AND 2, + 3 OR 4
1. Acute Onset and Fluctuating Course
2. Inattention
3. Disorganized Thinking
4. Altered Level of Consciousness
61
* **difference between delerium/dementia
- -onset / duration
- attention/language/speech
- hallucinations/tremor?
DELERIUM = acute/temporary, fluctuating, impaired attention/language, hallucinations, tremor
DEMENTIA = insidious/chronic, OK attention/language (unless severe), hallucinations/tremor uncommon
62
what should NOT be used to treat delerium:
Neuroleptics
BZD
Dexmedetomidine
*all may be used
BZD—only in sedative/hypnotic withdrawal
63
*visual hallucinations are more common in _____(delerium or dementia)
DELERIUM!
*uncommon in dementia except LEWY BODY DEM
64
which would meet criteria for coma?
- -Locked-in state
- -Persistent vegetative state
- -Minimally conscious state
- -Catatonia
NONE!
-COMA = total absence of awareness of self and environment even when externally stimulated, including the lack of sleep/wake cycles
(Lack of consciousness)
65
"locked-in state" from damage to _____ part of CNS
| --they are _____(awake/alert/both?)
- lower brainsteam (pointine stroke/hemorrhage)
| - awake and alert but can't move (except eyes)
66
T/F - persistent vegetative state has intact sleep/wake cycles
T/F - minimal conscious does NOT have intact sleep/wake
- TRUE
| - FALSE
67
Hypoxic-ischemic encephalopathy is one of the most common causes of ______(vegetative stake, locked in state, dementia, catatonia)
persistent vegetative state
68
dx?
-sleep/wake OK but not conscious; Neuropathology reveals diffuse laminar necrosis of the cerebral cortex with extensive involvement of the hippocampus
PVS
69
*how to distinguish between persistent vegetative state vs. minimally conscious state?
- PVS = not conscious (no cortical fxn) but have sleep/wake, may smile/cry/try to eat (BUT NO BRAIN FXN)
- MCS = severely altered conscious but SOME AWARENESS (may follow basic commands, some verbal, gesture etc)
70
Limited but clearly discernible evidence of self or environmental awareness is chx of ______(minimal conscious state; persistent vegetative state; coma)
MCS
71
T/F - persistent vegetative state has brainstem fxn but no cortical fxn, can have reflexes
T/F- people in coma may still have reflexes
- TRUE
| - TRUE
72
T/F - MCS can be a permanent or transitional state
T/F - sleep/wake cycle is present in locked in syndrome but absent in coma and minimally conscious state
- TRUE
| - FALSE ... present in veg/MCS/locked in
73
***how would you dx coma?
def = no sleep/wake, no consciousness, maybe some reflexes
- -neuro exam!!
- -EEG
- -Not usually by radiographic studies
74
- ____(Hyper/hypo) natremia can cause coma
| - ____(hypo/hyper) glycemia can cause coma
- both
| - both
75
*difference between vegetative state / minimally conscious state / coma
- consciousness?
- sleep/wake?
- motor fxn?
VS = no consciousness, present sleep/wake, may respond to some stimuli but NO BRAIN FXN
MCS = partial conscious, present sleep/wake, can respond to stimuli
COMA = no consciousness, no sleep/wake, maybe reflex
76
higher glasgow conscious scale means _____(more or less) consciousness
higher score = higher consciousness
low = bad
77
* **patient that can flex both arms and extend the legs (decorticate posturing, a.k.a. flexor posturing) Indicates damage to _______
* **pt that can extend the arms and legs (decerebrate posturing, a.k.a. extensor posturing) indicates damage to ______
--flexor posture = upper midbrain
--extensor = LOWER midbrain/upper pons
78
* if patient is in coma and has assymetric motor/sensory findings what is most likely diagnoses:
- -drug overdose
- -stroke
- -tumor
-structural problem (stroke, brain tumor)
79
* COMA MOTOR RESPONSEs:
- -damage to upper pons
- -damage to lower midbrain
- -damage to uppermidbrain
- pons/lower midbrain >> extend the arms and legs (decerebrate posturing, a.k.a. extensor posturing)
- upper >> flexor posture
80
where is problem if coma patient is:
- chain-stokes respiration (fast then slow)
- cluster breathing
- constantly breathing
- ataxic breathing (all over the place)
- forebrain (hypoglycemia common)
- constant = low midbrain/upper pons
- cluster = lower pons
- ataxic = medulla
81
* pupil findings/causes in coma patient if:
- metabolic cause?
- no response?
- one crazy dilated?
- tiny pinpoints?
- metabolic - smaller pupils but equal/reactive
- loss = structural damage
- if one dilated and non reactive = blown pupil >> structural loss of CN3
- tiny pupils = pontine problems, opioids
82
oculocephalic vs. oculovestibular reflex?
-intact responses?
OCULOCEPHALIC reflex
--Eyes will conjugately rotate counter to the direction of the head movement
OCULOVESTIBULAR reflex
- -Cold water in the external ear canal will cause the eyes to conjugately deviate to the ipsilateral side
- -Cold water in both ears will cause the eyes do deviate downward, warm water will cause the eyes to deviate upward
83
- put cold water in R ear of non-responsive patient, if normal will get ______ response
- if NOT normal, then indicates ______ (problem/where?)
--BOTH eyes will have nystagmus (jerky movements) to RIGHT
--if anything else = structural problem in BRAINSTEM
84
* where/what (structural or metabolic) is injury?
- coma patient with decorticate/flexor posturing to pain, cold water in R ear illicites no eye movements
- coma patient with chyne-stokes respiration, normal but diminished pupillary response
- coma patient w/ loss of conjugate movements of both eyes ipselaterally, cluster breathing, abnormal oculocephalic reflex
- structural problem in upper midbrain
- metabolic damage to forebrain (ex - electrolyte prob)
- structural damage to pons
85
T/F - Loss of pupillary light responses almost always signifies structural damage in coma patient
TRUE!!!
86
**T/F - majority of coma patients will NOT stay in coma for more than a year
TRUE - w/in months (
87
***how to tell difference between structural vs. metabolic cause of coma?
STRUCTURAL:
- assymetry motor/sensory
- abnormal oculocephalic reflex (to brainstem)
- no pupil reflex
88
- -which defines "death":
(1) irreversible cessation of circulatory and respiratory functions
(2) irreversible cessation of all functions of the entire brain, including the brain stem is dead.
(1) & (2)
(1) or (2)
1 or 2
89
"brain death" def
T/F - may still have some reflexes (like in coma) even without brain fxn
-irreversible (w/ known cause!) loss of all brain/BS fxn (no reflexes, complete loss of consciousness (coma), apnea)
FALSE
90
T/F - needs to be clinical or imaging evidence of problem for dx of brain death
T/F - core temperature needs to be above 32C (90)F to dx
True
| True (cold temp will suppress brain fxn and reflexes)
91
clinical exam supporting "brain death"
-what BS reflexes are tested (4)
1 - Coma(pre-req)
2 - NO Brain stem reflexes
--Pupillary light reflex
--Ocular movements (cephalic and vestibular)
--Facial sensation and facial motor response
--Pharyngeal and tracheal reflexes
3 - Apnea test
92
* how to test for corneal reflexes in suspected brain dead patient?
- testing what 2 nerves?
- cotten swab on eye ball (not just water, like in coma)
| - tests afferent V and efferent VII
93
Grimacing to pain can be tested by ______ in potential brain dead pt
Grimacing to pain can be tested by application of deep pressure with a blunt object on the nail bed, pressure on the supraorbital ridge, and deep pressure on both condyles at the level of the temporomandibular joint
94
T/F - apnea test required for coma and brain death diagnosis
*how is apnea diagnosed?
T/F- apnea test is temperature dependent
FALSE! - just brain death
DX = absence of respiration at a CO2 levels > 60 mm Hg (or > 20 mm Hg above baseline) as measured by ABG
***disconnect ventilator...watch for 8-10 min for CO2 to build up (if complications but still 36.5
95
*complications of apnea test?
- -Pneumothorax, pneumoperitoneum
| - -Cardiac arrythmias, hypotension and desaturation can occur
96
T/F- Electroencephalography (EEG)
is gold standard for diagnosis of brain death
T/F - Tests like transcranial doppler ultrasonography are required prior to dx of brain death
FALSE .... there are false positives so only use these as CONFIRMATORY (after PE and repeated PE)
FALSE, but can be done
97
T/F - There should be no EEG reactivity to intense somatosensory, auditory or visual stimuli
T/F - Most patients meeting clinical criteria for brain death will have isoelectric EEGs, but persistent EEG activity may occur
True
| True (never gonna be completely flat)
98
* **pitfalls for brain death dx***
- pts with ____ dx can't undergo testing
- -_____ or _____ conditions can mimic brain death
- -Massive facial trauma, spinal cord injury, etc.
| - -HYPOTHERMIA, barbiturate coma, etc
99
T/F - if patients have spontaneous movements (jerking, coughing) after ventilator removed then they were NOT brain dead
-T/F - EEG will NOT record any brain fxn during these movements
- FALSE (40% of brain dead will have spontaneous or reflex movements) usually triggered by tactile stimuli
- TRUE
100
- spasticity/hyperreflex = ______(UMN / LMN)
- decreased reflex/atrophy = _____ (UMN/LMN)
**myopathies will ahve ______(inc/dec/normal) deep-tendon reflexes
- UMN
- LMN (peripheral nerve from inteerneruon in horn out to muscle)
myopathia/myasthenia = NORMAL
101
myopathies from steroid predominantly lose type _______ fibers
-steroid myopathy = lose type 2 fibers (fast-twitch)( >> lose highE/bursts (body building)
aerobic (type 1) OK
102
T/F - weakness, atrophy and fatigue are ALL common symptoms in most myopathies
Give a dx if pt presents with all of the above +
- cramps / tired
- exercise intolerance
- myalgia/SLE
- calf hypertrphy / boy
TRUE so not that specific, more specifics:
- cramps (hypothyroid)
- exercise intolerance (mcardle)
- myalgia (polymyositis)
- FH/hypertrophy (duchenne)
103
dx (lipid pathway problem or glycolysis pathway problem)
- kid is very tired after starting exercise but gets "second wind" 30 min later
- kid who is fine in the beginning but poops out after 30 min
**which would be more chx of "MCARDLE"??
start exercise = use glycolysis, then use lipids after 20-30 minutes
```
#1 = glycolysis pathay (MCARDLE)
#2 = lipid pathway problem (acyl transferase?)
```
104
inheritance pattern:
- beckers
- LGMD type 1
- LGMD type 2
- mitochrondrial problem (MELAS)
- X-linked
- auto-dom
- auto-rec.
- maternal transmission
105
* *MATCH MYOPATHY W/ UNIQUE SYMPTOM**
- carnitine palmitoyltransferase deficiency myopathy associated with _______(cold temp, fever, exercise, cramps)
- hypothyroidism associated with _____
- mcardle associated with _____
- paramyotonia congenita w/ _______
- CPD (or other mitochondrial / lipid storage) = fever
- hypothyroid = cramps
- mcardle = exercise
- paramyotonia = cold
106
*if babinski sign is + that is sign of ____(UMN/LMN)
-UMN! ("hyperreflexia")
107
dx?
- 55 yo w/ assymetric weakness in prox arm/leg, slowly progressive
- wing scapula and foot drop, popeye arms
- droopy eyes, double vision, VARIABLE
- 45 yo F w/ acute onset symmetric limb/girdle weakness (trouble getting out of chair) w/ diffuse myalgia
```
#1 - IBM (inc body myositis)
#2 - facialscalpular humoral myositis (FSH)
#3 - thinking neuromusc junction dx (like myasthenia gravis)
#4 - polymyositis
```
108
*common muscular findings in ALS?
- weakness in neck
- weakness in tongue/dysarthria (bulbar)
**pathopneumonic = fasiculations in tongue **
***BUT very variable - may be dysarthric, may be parapalegic but fine speech, maybe both
109
***T/F - immunotherapies generally more effective in acquired myopathies (ex - dermatomyositis) compared to inherited myopathies (duchennes etc)
TRUE !
-very important to distinguish between inherited vs. aquired becuase immunotherapies very helpful for aquired, but very harmful if inherited
110
**what laboratory tests would you need to order to dx if patient comes in w/ muscle weakness and muscle pain and want to dx myopathy:
- CBC/CMP
- inflammatory markers (skeletal muscle enzymes)
* needle EMG
* muscle biopsy
*gold-standard / required usually
111
dx?
- symmetric axial muscle weakness esp in in arms, improved w rest, have dyarthria/dysphagia
- symmetric axial muscle weakness but more in legs compared to arms, relieved temporarly by exertion, worse in heat
- arm and leg weakness, worse w exercise and in cold weather
- MG
- Lambert-eaton
- Paramyotonia
112
dx? 45 yo M w HIV presents with ascending muscle weakness/paralysis, had viral illness a few weeks ago, weakness has gotten worse, no sensory problems
guillan-barre
113
dx? 45 yo with painless assymetric weakness in R leg and arm, hyperreflexia in both legs, difficulty swallowing over past yer, ocular movements normal
ALS
114
* most common causes of peripheral neuropathy?
| - median age of onset is ____() 50
- DIABETES! (25-50%)
- Etoh
- idiopathic
- genetic
**majority are older (>55)
115
clinical exam findings to distinguish between CNS vs. PNS problem if present with weakness/numbess?
```
CNS = UMN = hyperreflexia, BABINSKI+, hypertrophy., spasticity
PNS = LMN = dec reflex, babinski neg, atrophy,
```
116
- -fasiculations chx of ____(UMN/LMN)
| - -spasticity chx of _____(UMN/LMN/both)
- LMN
| - UMN
117
small or large fiber neuropathy
- -pain, sensitive, normal DTR
- -numbness, ataxia, dec DTR
- -small
| - -large
118
* compare large vs large fiber periph neuropathy
- -numbness / pain
- -autonomic dysfunction
- -weakness / ataxia
***how does diabetes present?
* SMALL = pain, autonomic dysfxn (sweaty), no ataxia/weakness
* LARGE = numbness, no auto, ataxia/weak
***DIABETES = mostly pain, autodysfxn
119
decreased pinprick but ok vibration is chx of ____(small or large) fiber periph neuropathy
dec vibration but ok pinprick/temp is chx of ______ (small or large)
- small
| - large
120
where might problem be if patient:
- just weakness
- weakness and numbness
- weakness only (ventral nerve cell or dorsal nerve root or jxn?)
- weakness and numbness (mixed nerve root)
121
--fast progressing weakness more likely to be _____(inherited/aquired) where as slowly progressing more likely to be _____
--fast progressing numbness +/- weakness more likely to be _____ where as slow progressing numbness
WEAK = MYOPATHY
- fast = aquired (give steroids/immunospression)
- slow = inherited (do NOT give ^^)
NUMB/WEAK = PERIPHERAL NERUOPATHY
- fast = BAD/red flag
- slow = good
122
dx?
Symmetric proximal and distal weakness with sensory loss
Examples: ____
Symmetric distal sensory loss with/without distal weakness
Examples: _______
- -GBS/CIDP (slow progressive)
| - -diabetes
123
- single Asymmetric distal weakness with sensory loss
- multiple asymmetric distal weakness with sensory loss
- Asymmetric proximal and distal weakness with sensory loss
***should these be treated with STEROID/IMMUNOSPRESSANTS??***
--Asymmetric distal weakness with sensory loss= If single: radiculopathy, mononeuropathy. If multiple: vasculitis
Asymmetric proximal and distal weakness with sensory loss = Radiculopathy, plexopathy
***NO - ASYMMETRIC = RED FLAG***
124
*dx?
--Asymmetric distal weakness without sensory loss
--Symmetric sensory loss and upper motor neuron signs
- -Asymmetric distal weakness without sensory loss = ALS!!!
| - -Symmetric sensory loss and upper motor neuron signs = B12 deficiency!!!
125
***which are "red" flags in pt with neuropathy (weak/numb) that WOULD NOT be as likely to respond to immunosupression:
- young or old
- start in feet or hand
- symmetric or asymmetric
- rapid or slow onset
- young
- starts in hands
- asymmetric
- rapid onset
126
***MOST peripheral neuriopathies are _____(quick or slowly) progressing and _____(should or should NOT) be treated with steroids/immunosepressants
-most are slow, and can be treated with steroids (esp if later onset, start in feet, symmetric etc)
127
T/F - GBS, MG, and LE are all auto-immune releated peripheral neuropathies and may therefore respond to immunotherapies
*are each symmetric or assymetric?
- TRUE!!
| - symmetric!!
128
**symptomatic (PAIN) treatment of peripheral neuropathies?
Pain management with antiepileptic drugs, antidepressants, tramadol and local agents such as capsaicin or lidocaine
129
CIDP
- symptoms
- treatment
- dx
Chronic inflammatory demyelinating polyneuropathy (CIDP)
- -relapsing symptoms
- -Symmetric proximal and distal weakness with sensory loss (like GBS)
- -immunotherapy
- - inc IgM on IFE, +anti-MAG
130
autonomic testings in peripheral neuropathy?
- -Sympathetic skin response (SSR)
- -Quantitative sudomotor axon reflex testing (QSART)
- -Thermoregulatory sweat testing (TST)
- -R-R variability during deep breathing (HRDB), Valsava and tilt
131
work-up of peripheral neuropathy
- -B12, if > if IgM, then anti-MAG
| - -Electrodiagnostic testing
132
dx? 21 yo F with discoid (skin) lupus, present with swollen joints, fatigue, fever (systemic lupus), 3 weeks ago had symmetric paralysis proximal and distal (couldn't walk) and numb, low reflexes, high IgM band on electrophoresis
- PNS or CNS
- nerve or neruomusc jxn
- length dependent or non-length dependent
- dx?
- CSF findings?
- PNS (LMN signs - low reflex)
- nerve (not length dependent since quick progressing and motor/sensory)
- guillen-barre syndrome!
- high protein in CSF, normal cells
133
symptoms of "length dependent" problem in peripheral neuropathy?
length dependent = SLOW PROGRESSION ... sensory presents worse and is WORSE than motor)
134
Describe the clinical features and gene mutation for Kennedy’s disease
--CLINICAL = Lower motor neuron disease- bulbar dysfunction and PROXIMAL weakness; androgen sensitivity (GYNOCOMAST, INFERTILITY etc); Mean age of onset 40s in men, SLOW progression
--GENE = X linked mutation of androgen receptor
135
UMN or LMN/both/neither:
- -fasiculations
- -weakness
- -spasticity
- -urinary incontinence
- -LMN (invol muscle twitches)
- -both
- -UMN (inc tone)
- -neither
136
**is numbness a UMN or LMN problem?
NEITHER ... don't expect numbness in pure "motor neuron diseases" (ALS, Kennedy, SMA)
137
**Jaw jerk reflex is ____(UMN or LMN)
**hoffman's sign is ____(UMN 0r LMN)
--UMN (above neck)
--UMN - hyperreflexia in fingers (like babinski of the hand)
138
**Dysarthria seen in ___ (UMN or LMN)
both
- LMN - weakness/wasting of muscles
- UMN - spastic
139
T/F - dementia is UMN problem seen in subset of ALS patients
FALSE not a UMN or LMN but is in about 10% of ALS get FTD / ED)
140
distinguish progressive muscular atrophy (PMA), ALS and PLS (primary lateral)
```
PMA = LMN
ALS = both
PLS = UMN
```
*diseases linked though, think of continum
141
pseudo bulbar affect
- def
- seen in ____ disease
- laughing and crying inappropriately
| - ALS
142
* **how is ALS diagnosed?
- MRI findings?
- acetecholine receptor antibodies ___(+ or -)
- neuro exam?
* **DIAGNOSED CLINICALLY (def = UMN and LMN findings in 3 regions)***
- normal
- negative (+ = MG)
- UMN (spastic/high reflex) and LMN (tongue atrophy/ fasciculation's)
143
which is/are NOT seen in ALS:
- -jaw jerk reflex
- -hoffman sign
- -opthalmoparesis
- -spasticity
- -numbness
- -opthalmoparesis (abnormal eye movements)
| - -numbness
144
***Spinal Muscular Atrophy clinical / genetics
CLINICAL = PURE LMN ; Progressive diseases of anterior horn cells and select motor cranial nerve nuclei but phenotypically heterogeneous (different age of onsets/progression)
GENETICS = Autosomal recessive; Survival motor neuron (SMN) 1 gene on the long arm of chromosome 5 (Severity of SMA with SMN1 mutation depends on number of SMN2 copies)
145
T/F - Survival motor neuron (SMN) 1 gene is associated with Kennedy disease
FALSE - assoc with SMA
-kennedy = x-link of androgen receptor
146
T/F - In healthy people, SMN2 produces little functional SMN protein; however if SMN1 is mutated SMN2 copies is very important for clinical phenotype
TRUE
