MBB2 Flashcards
(287 cards)
1
Q
Describe pathophysiology of MG
A
Antibodies block AchR
Accelerated internalization and degradation of AchR
Complement-mediated lysis of post-synaptic membrane (see simplification of postsynaptic folds, this reduced number AchR)
2
Q
clinical features MG
A
Head drop (neck extensor weakness) Ocular: ptosis, binocular double vision Facial: hanging jaw sign, snarling smile Mouth: difficulty chewing, dysphagia, dysarthria, hypophonia Dyspnea (resp muscles) Proximal limb > distal
3
Q
What are sensation and reflexes like in MG?
A
Normal!
4
Q
MG weakness _____ with activity
A
increases
5
Q
MG most common presenting symptom is?
A
OCULAR - ptosis, double vision
(less commonly, oropharyngeal, limb muscles
rarely, head drop, SOB)
6
Q
MG age of onset?
A
Young Females 20-24
Older Males 70-74
7
Q
What is MG crisis
A
Respiratory Muscle Failure
& Upper Airway Compromise
leads to aspiration
8
Q
Describe basis and indication for Ice Test
A
indicated for ptosis
acetylcholinesterase enzyme has decreased activity at cold temp; ice pack will increase Ach availability and temporarily improve ptosis
9
Q
Describe Tensilon (edrophonium chloride) test
A
indicated for ptosis, ophthalmoplegia
Tensilon is a short-acting acetylcholinesterase inhibitor, causes transient increase in Ach availability at NMJ
in MG, transiently improves ptosis and diplopia
10
Q
Does serum titer of AchR antibody correlate with disease severity?
A
No
11
Q
Disorder associated with thymus problems (thymoma, thymic hyperplasia)
A
Myasthenia Gravis
70% of AchR-Ab positive patients have thymic hyperplasia
10% AchR-Ab MG have thymoma (hence must do chest CT to check for this)
12
Q
Treat Myasthenic crisis with?
A
PLEX or IVIG
may need mechanical respiratory support
13
Q
List some precipitation factors of Myasthenic crisis
A
Tapering rapidly immune modulators Aspiration Drugs Infection Surgery
14
Q
2 forms of LEMS
A
paraneoplastic primary autoimmune (no identified tumor)
15
Q
Most LEMS have antibodies against ______
A
P/Q type calcium channel
16
Q
Most common type of cancer associated w/ paraneoplastic LEMS?
A
Small Cell Lung Cancer
17
Q
Risk factors for paraneoplastic LEMS
A
median age 60
male
smoking
weight loss
18
Q
Non-tumor LEMS affects what age and gender?
A
30 & 60yo
female more
19
Q
What is the pathogenesis of LEMS?
A
P/Q VGCC antibody blocks Ca2+ influx
less Ach released at NMJ
muscle weakness
Ach is also neurotransmitter between pre- and post-ganglionic neurons so LEMS also results in autonomic dysfunction!
20
Q
3 clinical features of LEMS
A
proximal weakness (gradual onset) - can extend to bulbar and distally
Areflexia
*with post-exercise facilitation
Autonomic dysfunction (from decr Ach)
- dry mouth
- constipation
21
Q
What is motor facilitation? In what disease do you see it?
A
seen in LEMS
Exercise or HIGH-freq stimulation
keeps Ca channels in presynaptic membrane open longer, so more Ca influx, more Ach release –> transient amplification of muscle response
Contracting muscles transiently increases reflexes
22
Q
Describe cancer screening process for LEMS
A
Chest CT - for SCLC
if negative, PET scan for other cancers
if still negative, screen every 3 months for at least 2 years
23
Q
Treatments that can be used in LEMS (4)?
A
AchE inhibitors (less effective than in MG)
3,4-DAP
somehow increases Ca influx
Longterm immunsuppressants (prednisone, azathioprine)
IVIG/PLEX for severe or rapidly progressive LEMS
24
Q
Botulinum toxin works by?
A
Cleaves SNARE protein important for vesicle docking and fusion. –> no ACh released into NMJ
25
List 4 UMN signs
weakness
increased tone (spasticity)
hyperreflexia
pathological reflexes (babinksi & hoffman's)
26
List 4 LMN signs
atrophy
decreased tone
reduced reflexes
fasciculation
27
in a nerve conduction study, myelin corresponds to _______ and axon/cell body corresponds to _______
myelin - conduction speed
| axon/cell body - amplitude
28
Duchenne muscular dystrophy inheritance? mutation?
XLR
dystrophin gene mutation (most are due to deletions)
29
Two big causes of mortality in duchenne's
cardiomyopathy
| respiratory failure
30
duchenne's manifests at what age with what symptoms?
age 2
(before age 5)
proximal weakness
clumsiness
toe walking, waddling gait, can't run
Pseudohypertrophy of calves
31
3 potential treatments for duchenne's?
Supportive - PT, bracing, surgery
Prednisone
Gene therapy (not super effective)
32
What is difference between Duchenne and Becker muscular dystrophy?
both are XLR dystrophinopathies but Becker is less severe, later onset, cardiomyopathy less common
33
Fascioscapulohumeral muscular dystrophy inheritance pattern? mutation? hallmark symptom?
AD
DUX4 gene, chromosome 4q
weakness of FACE, neck, shoulder, (peroneal); prominent scapular winging
4 qute ADmiral DUX (ducks) can't move their face and wings
34
delay in relaxation after a muscle contracts is called ___
myotonia
ex: takes a while to relax after handshake
hatchet face
35
Emery-Dreifuss can be inherited as
XLR,
AD,
AR
36
Type 1 Myotonic Muscular Dystrophy inheritance pattern? mutation?
****
clinical signs?
AD
CTG repeat on chrom 19 (DMPK gene)
```
Respiratory insufficiency (diaphragm/intercostal weakness
Endocrine abnormalities
DISTAL muscle weakness
```
frontal Balding
Cardiac (1st degree heart block, sudden cardiac death)
Cataracts
Intellectual impairment
---------------------------------------------------------
19-year-old dumb RED balding CAT with a bad heart is gasping for air
37
Type 2 Myotonic Muscular Dystrophy inheritance pattern? mutation?
AD
CCTG repeat ZNF9 gene chromosome 3
proximal muscle involvement
cataracts
38
Myotonia Congenita is characterized by? Is due to mutation in ___gene.
generalized myotonia without weakness
CLCN1 gene
39
In myotonia congenita, muscles stiffness is worse with _____ and relieved with ____
cold, inactivity
relieved by exercise
40
AD myotonia congenita is called
Thomsen disease
41
AR myotonia congenita is called
Becker disease
42
Type II / Pompe disease = deficient ___
acid maltase
| muscle weakness, resp difficulty
43
Type III / Cori disease = deficient ___
| symptoms?
glycogen debranching enzyme
| myopathy
44
Type V / McArdle disease = deficient ___
| symptoms?
myophosphorylase deficiency
| exercise intolerance, rhabdomyolysis
45
Type VII / Tarui disease = deficient ___
| symptoms?
PFK deficiency
| exercise intolerance, muscle gramping
46
childhood onset lipid storage disease presents with
myopathy
encephalopathy
cardiomyopathy
hepatomegaly
47
adult onset lipid storage disease presents with
fatigability
muscle pain
myoglobinuria
48
in dermatomyositis, deposition of ____ leads to muscle ischemia
complement
49
25% of dermatomyositis associated with ___
malignancy
50
_____ is the most common myopathy in patients >50
inclusion body myositis
51
which inflammatory myopathy affects men more than women?
inclusion body myositis
52
which inflammatory myopathy does NOT respond to immunomodulating therapy (ie steroids)?
inclusion body myopathy
53
inflammatory myopathy with elevated CD8
what other marker?
what symptoms?
polymyositis
symmetric proximal weakness dev over weeks to months
bulbar symptoms
+ANA
54
symptoms of inclusion body myositis?
weak quads and finger flexors, ankle dorsiflexors (often asymmetric)
dysphagia, facial weakness
55
What do you expect to see in CSF with Guillaine Barre?
cyto-albumino dissociation (elevated protein without elevated WBC)
56
Describe symptoms and course of Guillaine Barre
```
subacute onset after GI or URI
ascending sensory symptoms
motor weakness
reduced reflex
symptoms worst within 4 weeks onset
```
57
GBS treatment
PLEX or IVIG
| most have good recovery
58
diagnostic indications for LP?
therapeutic indications for LP?
diagnostic:
- measure CSF pressure
- for lab studies
- inject dye/radioactive tracer to see if blockage in circulation
therapeutic:
- give anesthetics or chemo
- reduce CSF pressure
59
LP needle inserted between which vertebrae? ____ used as a landmark
L3-L4 interspace
iliac crest
60
acute indications for LP?
chronic/subacute indications for LP?
acute
- suspect meningitis or encephalitis
- suspect subarachnoid hemorrhage
- suspect demyelinating neuropathy like GBS
chronic
- eval chronic infection (neurosyphilis, CJD)
- suspect other meningial process (carcinomatous meningitis, neurosarcoid)
- evidence of Multiple Sclerosis
61
LP contraindications
- incr ICP due to mass lesion and/or edema
- obstruction hydrocephalus
- coagulopathy or therapeutic anticoagulation
- thrombocytopenia
- spinal epidural abscess
62
Normal opening pressure of CSF is
100-180 mmH20
63
normal CSF glucose is?
60
or ~2/3 of serum glucose
64
what is Xanthochromia?
yellow color in CSF due to bilirubin (lysed RBCs after SAH)
65
how to differentiate between Xanthochromia from SAH traumatic tap?
centrifuge it - if traumatic tap, CSF will become clear and colorless
66
ALS is due to loss of _____ (motor or sensory) neurons in _______ and ______
motor; brain and spinal cord
67
Does ALS have sensory symptoms?
no
68
Is most ALS sporadic or familial?
most is sporadic
5-10% familiali
SOD1
C9orf72
TDP43
69
EMG in ALS shows?
widespread denervation in multiple segments
70
ALS survival is ____(time) from time of onset. Most die from ____
2-4 years
| respiratory failure
71
Two medications for ALS and how they work
Rilutek
-block glutamatergic activation
Radicava (endaravone)
free radical scavenger, slows disease progression
72
_____ can mimic ALS
Cervical Disc Disease
73
Most of blood supply to spinal cord is provided by ___
anterior spinal artery
| posterior columns supplied by a pair of psosterior spinal arteries
74
Descending tracts are ______
motor
75
Ascending tracts are _______
sensory
76
Biceps and brachioradialis reflex mediated by ___ nerve root
C6
77
Triceps reflex mediated by ___ nerve root
C7
78
knee jerk reflex mediated by ___ nerve root
L3/L4
79
ankle jerk reflex mediated by _____ nerve root
S1
80
4 cardinal symptoms of Parkinson's
bradykinesia
resting tremor
rigidity
festinating gait (shortened accelerated steps)
81
Dopamine binding to D2 results in
inhibition of indirect pathway (more movement)
82
activation of _____ (in the nigrostriatial pathway) leads to inhibition of movement
subthalamic nucleus
SNr
GPi
83
Dopamine binding to D1 results in
stimulation of direct pathway (more movement)
84
Side effects of medical treatment of Parkinsons
- Dyskinesia
- On-Off response (abrupt transient fluctuations in severity of parkinsonism
- Psychosis (too much dopamine causes visual hallucinations)
- Orthostatic hypotension
- Nausea
- Somnolence
- Impulse control disorder (gambling, hypersexuality)
85
What is the on-off phenomenon in PD?
PD patients cycle between freezing (off), too much movement (on), and normal
86
Where can you put Deep Brain Stimulation to treat Parkinson's?
Advantages of each location?
STN - greater decr in medications
GPi is usually default
- less depression than STN
- better for cognition
- better for falls
87
Essential tremor is what type of tremor?
active
- holding a utensil, sipping or pouring from a cup
- writing
- fine motor tasks
- can also get tremor of head, voice, legs, or tongue
88
What is dystonia?
- tx focal dystonia?
- tx generalized dystonia (5)?
movement disorder with involuntary contractions of opposing muscles --> stereotyped twisting movements and abnormal postures
focal dystonia: botulinum injections for
generalized dystonia:
- anti-cholinergics
- muscle relaxants
- benzos
- carbidopa/levo? (there's a rare form of dystonia b/c not enough dopamine, usu in kids)
- DBS
89
what is paratonia? what is it usually caused by?
unable to relax
| cause: frontal lobe lesion
90
what is tone?
List the 4P's of tone
resistance of muscle to PASSIVE movement of a joint
Position at rest
Palpation
Passive movement
Posture
91
what is weakness?
loss of muscle POWER (when testing muscle power, pt asked to resist)
92
What are two types of hypotonia? How are they different?
Spasticity - velocity dependent (the more you pull, the more resistance). HYPERACTIVE STRETCH REFLEX
Rigidity - equal resistance regardless of movement direction and velocity
93
spasticity caused by ____ lesions
UMN
loss of UMN suppression of spinal cord reflex
94
Charcot Marie Tooth affects ____ Nervous System.
-symptoms?
Peripheral
hereditary loss of myelin
--> FOOT DROP, atrophy, contracture, hammertoes, champagne neck legs, high foot arch (affects legs first)
negative sensory sxs - numbness, sensory ataxia, trouble w balance
affects distal more
95
Congenital causes of Cerebral Palsy?
Periventricular Leukomalacia (damage to white matter; maternal infection, fetus injury, unknown)
Cerebral dysgenesis (abnormal brain growth)
Intracranial hemorrhage
(fetal stroke, maternal HTN, maternal infection)
Hypoxic ischemic encephalopathy
96
Brown-Sequard syndrome leads to what deficits?
Loss of pain/temp on contralateral side
Ipsilateral Loss of motor (acutely flaccid paralysis, then spasticity/hyperreflexia)
Ipsilateral Loss of fine touch/ proprioception/vibration
97
cause of subacute combined degeneration + symptoms?
B12 deficiency
involves dorsal column and lateral corticospinal tract
dorsal column --> balance problems
lat corticospinal --> stiffness, spasticity
98
Causes of anterior spinal cord infarction + symptoms?
hypoperfusion or emboli
BL loss pain/temp
initial flaccid paralysis, then spasticity
vibratory sensation intact
99
VITAMIN D mnemonic for differentials
```
Vascular
Infections
Trauma/Toxic
Autoimmune
Metabolic
Inflammatory
Neoplastic
Dengenerative
```
100
Name gross and microscopic findings of ALS
Gross:
- shrunken/atrophic anterior nerve roots
- brain usu normal but may see atrophic precentral gyrus (dt disappearing UMN)
Microscopic
-degen of myelinated fibers in corticospinal tract
-loss of motor neurons w/ reactive astrogliosis
-cytoplasmic eosinophilic Bunina Bodies
affects motor cortex, brainstem, and spinal cord
101
Spinal Muscular Atrophies are due to degeneration of ____
LMNs
102
Spinal muscular atrophy inheritance pattern?
| Genetic mutation?
AR
SMN1, chromosome 5
103
Werdnig-Hoffmann Disease symptoms
aka SMA1, floppy baby syndrome
symptoms manifest abruptly in first months of life, quickly progress to respiratory failure
death within two years without mechanical vential
104
what is the most common genetic cause of infant death?
spinal muscular atrophy
105
two most common triggers of Guillain-Barre syndrome? (aka AIDP- acute inflammatory demyelinating polyneuropathy )
```
campylobacter jejuni (30%)
cytomegalovirus (10%)
```
106
poliomyelitis
- cause
- symptoms
- histo characteristics
- lytic infection of LMNs
- small RNA viruses in Enterovirus genus
- flaccid paralysis (usually temporary but can be permanent)
107
friedrich's ataxia
- inheritance pattern?
- mutation?
- age of onset
- symptoms
- associated conditions
childhood- toddlers/teens
AR, expansion of GAA in frataxin (FXN) gene, chromosome 9
degeneration of
- posterior column (vibratory sense, proprio)
- lateral corticospinal (spastic paralysis)
- spinocerebellar (ataxia)
assoc w/ DM and cardiomyopathy
Friedrich is Fratastic, he's your favorite frat brother, always staggering and falling but has a sweet big heart.
108
on histology, Chronic Inflammatory Demyelinating Polyneuropathy has __
recurrent demyelination and remyelination with onion bulb formation
109
cause of Charcot Marie Tooth type 1
duplication of a region on chrom 17 that includes peripheral myelin protein 22 (PMP22) gene
110
histology of CMT1
recurrent demyelination and remyelination with onion bulb formation (similar to CIDP)
111
what primary CNS neoplasm is classically seen at bottom of spinal cord
myxopapollary ependymoma
112
gene altered in tuberous sclerosis
TSC1 (hamartin)
113
gene altered in frontal lobar degeneration & ALS
TDP-43
114
Name 4 drugs/toxins can induce myopathies
steroids
statins
colchine
ethanol
115
List 5 non-movement symptoms of Parkinson's
```
memory problems/hallucinations
mood symptoms (depression, anxiety)
sleep problems
choking on food
dysautonomia (BP drops, ED, constipation, problems emtpying bladder, etc)
```
116
list three signs of bradykinesia
masked facies
decreased movement
soft voice
small handwriting
117
diagnostic criteria for Parkinson's?
Parkinsonism
+responds to Sinemet
+no evidence of PD mimics
*no labs or studies needed
118
carbidopa inhibits ____
DOPA decarboxylase in the periphery
119
List 3 medications for essential tremor
don't need to tx UNLESS it's bothering pt!!
Propranolol
Primidone (anti-sz med)
Topiramate (anti-sz med)
120
If meds don't work for a debilitating essential tremor, can place Deep Brain Stim in ____
Ventral intermediate nucleus of THALAMUS (which is relay point from cerebellum to rest of brain)
121
What are three antipsychotics that do NOT worsen parkinsonism
Quetiapine (seroquel)
Pimavanserin
Clozapine
122
What is Lewy Body Dementia
Parkinsonism
+ hallucinations
+dementia within ONE YEAR of onset of parkinsonism
123
what is multiple system atrophy
Parkinsonism and/or ataxia
+PROFOUND early dysautonomia (major orthostatic hypotension, urinary retention, ED, constipation, gastroparesis, severe peripheral neuropathy)
124
what drugs can induce parkinsonism?
antipsychotics or antiemetics that block dopamine
- risperidone
- haliperidol
- promethazine
125
what is progressive supranuclear palsy?
Parkinsonism
+early gait instability/falls
+limited vertical gaze
+frontal cognitive signs (cry or laugh randomly)
is a sporadic tauopathy
126
what is corticobasal degeneration?
Parkinsonism
+profound asymmetry
+weird stuff (alien limb, limb apraxia, rest AND action tremor, etc)
onset in 60s
127
list 6 drug classes that for parkinson's and an example of each
1. levodopa/carbidopa (sinement)
2. dopamine receptor agonists (pramiprexole, ropinirole, rotigotine, apomorphine, bromocriptine)
3. COMT inhibitors (entacapone)
- decreases peripheral metabolism of levodopa, making it last longer
4. MAO-B inhibitors (selegiline, rasagiline)
5. amantidine
- unclear moa
- just helps quiet dyskinesias
6. anti-cholinergics?
128
list 3 indications for DBS in parkinson's
must have previous good response to levodopa!!
current symptoms are limiting patient
failed all optimized med therapy
signific on-off fluctionations,
signific dyskinesias,
no significant cognitive/uncontrolled mood symptoms
129
Huntington's disease inheritance and genetic cause?
AD
CAG repeat, chromosome 4
shows anticipation- more repeats in subsequent generations which leads to earlier onset and more likely passed on
130
symptoms of Huntington's
- movement disorders - esp CHOREA- fidgety, wiggly
- psych issues
- cognitive decline
131
4 symptoms in ataxia
nystagmus
dysarthria
limb coord problems
wide based unstable gait
132
what is myoclonus
what part of brain can problem be in
first line tx?
second line tx?
quick shock-like jerks
cortex, brainstem, or spinal
first line: CLONAZEPAM
second line:
valproate (depakote)
levetiracetam (keppra)
133
what is a tic?
repetitive movements/sounds that interrupt normally activity
| have urge to do it, are uncomfortable until they do it
134
what are diagnostic criteria for Tourettes?
2 or more motor tics
AND
at least 1 vocal tic
beginning BEFORE age 18 and present for more than 1 YEAR
not due to other causes
135
treatment for Tourettes?
tx ONLY IF BOTHERSOME
- remove stimulants (like adderall)
- SSRIs
- alpha-2 agonists
- antipsychotics (risperidone)
- VMAT-2 inhibitors (tetrabenazine)
- behavior mod therapy
136
How are Functional Movement Disorders diagnosed?
H&P
totally variable, paroxysmal (goes away and comes back), distractible & not consistent with known movement disorders
Stress to pt that they are NOT CRAZY and NOT FAKING IT, symptoms are real and outside of their control
137
treatment for functional movement disorders?
no meds (unless for triggers)
treat triggers: psych/CBT/pain etc
retrain motor movements/brain (PT, OT, speech T)
138
what is vonsattel grading?
used for path staging of Huntington Disease
0-1: no gross changes but see microscopic changes
4: complete atrophy of caudate, putamen, globus pallidus
139
which movement disorders are Tau-opathies?
which are alpha-synuclein-opathies/?
tau:
Progressive Supranuclear Palsy and
Corticobasal degeneration
alpha synuclein:
parkinson's
multiple system atrophy
140
difference between Lewy Body Dementia and Parkinson's Disease dementia? similarity?
BOTH have lewy bodies on histology
pathologically look THE SAME
Lewy body dementia = dementia and movement disorder onset in the same year
Parkinson's disease dementia = have movement disease for a long time, then progress to dementia
141
how do COMT and MAO-B inhibitors work to treat parkinson's disease?
they inhibit dopamine degradatoin
142
why is dopamine not useful in treating parkinson's disease?
it does not cross the blood-brain barrier and generates peripheral side effects
143
difference between hypoxia and anoxia
hypoxia- deprivation of O2
anoxia- COMPLETE deprivation of O2
144
what is ischemia
inadequate blood flow
145
pale infarcts are due to ____ occlusion
thrombotic (from plaque rupture, which exposes subendothelial collagen leading to thrombus formation)
146
epidural hematoma etiology
trauma --> skull fracture --> lacerated middle meningeal artery which separates dura from skull and blood accumulates
147
etiology of subdural hematoma
damage to bridging veins going from cortex to venous sinuses
**brain moves differently than the surrounding skull, this movement can tear the bridging veins
148
Describe how an acute vs chronic subdural hematomas would present + possible causes
Acute
- present unconscious, NO lucid interval
- trauma
Chronic
- slow neurologic decline due to repeated bleeding and slow growth of hematoma
- elderly w/ brain atrophy _ GLF (can stretch and tear veins)
- minor trauma
149
etiology of amyloid angiopathy
amyloid deposits in blood vessel wall --> lobar hemorrhages
150
list three causes of intraparenchymal hemorrhage
- HTN
- amyloid angiopathy
- vascular lesions/malformations (ex AVM)
151
list and describe 4 types of edema in CNS
- vasogenic - BBB breakdown
- cytotoxic - cellular swelling
- interstitial- obstructive hydrocephalus
- osmotic - plasma too dilute
152
4 common signs of cerebellar tonsillar herniation
- intractable HA
- head tilt
- neck stiffness
153
uncal herniation results in what symptoms
- ipsilateral paralysis
- ipsilateral CN 3 compression --> pupil fixed and dilated, eye down and out
- posterior cerebral artery compression
154
central herniation / duret hemorrhage
downward herniation of bl temporal lobes
pons pushed down -> pressure on small vessels -> petechial hemorrhage in medial pons
fatal usu
155
enhancing mass crossing corpus callosum - what are 3 things on differential?
1. glioblastoma
2. CNS lymphoma
3. really really bad MS
156
difference between stroke and TIA
acute loss of focal brain or monocular function
stroke symptoms >24h
TIA symptoms <24h with NO ischemic changes on imaging
157
role of adenosine in sleep/wake
adenosine inhibits activity in basal forebrain --> sleep homeostatic drive
158
how does caffeine work to keep us awake?
is an adenosine receptor antagonist
159
sleep onset occurs with ___ Core Body Temp
lower
160
what time is CBT at a minimum
2 hours before waking
161
what type of light has greatest phase shifting effect
short wavelength (~460nm) blue light
162
to cause a phase delay, how should you time light exposure?
to cause phase advance?
phase delay- light 3-4h after CBT minumum
phase advance- light 2-4h before CBT min
*light in middle of day has relatively little effect
163
what part of the brain is "pacemaker" of the entire circadian system?
suprachiasmatic nucleus (SCN)
164
melatonin is secreted by
pineal gland
165
what is process C?
what is process S?
process C = circadian ALERTING signal
process S = homeostatic drive for sleep
166
moa Ramelteon, Tasimelteon
MT1 and MT2 receptor agonists
approved for treating insomnia (Ramelteon) and non-24h sleep/wake disorder (Tasimelteon)
167
when are melatonin levels high? low?
high at night (dim light melatonin onset is 2-3h before bedtime)
low during daylight
168
describe pathway of how light reduces melatonin secretion
light stimulates MERGs which has axons to SCN via RetinoHhypothalamic tract. ERGs release glutamate which stimulates the SCN to release GABA.
GABA inhibits PVN (paraventricular nucleus) of hypothalamus, shutting down pathway that makes melatonin.
169
what is the molecular basis of endogenous circardian rhythms?
clock and bmal1 are transcribed in the AM. the proteins form hetermodimers (CLOCK-BMAL1) that bind promoter regions of per and cry genes --> stim PER and CRY productino.
Per and Cry proteins get broken down but so much is made that they accumulate and form heterodimers, which go into the nucleus. There, PER-CRY inhibits CLOCK-BMAL1 --> negative feedback; reduces PER and CRY production in the PM
as PER and CRY levels get very low, per and cry gene activation begins again in AM and repeat
170
describe pathway by which melatonin increases in absence of light
without light, no MERG stimulation, no SCN stimulation. PVN disinhibited --> stimulate intermedioalateral cell column (ICC), which releases Ach --> stim superior cervical ganglion, which releases NE --> stimulate pineal gland.
171
what is sundowning?
- patient population
- timing
- symptoms
- cause
institutionalized pts w/ dementia
agitation in late afternoon/early evening
- anxiety
- confusion
- pacing, wandering
- visual and auditory hallucinations
due to DEGENERATION of SCN
tx include late afternoon/evening bright light exposure , avoid daytime napping with planned activities, scheduled daytime routines. antipsychotics
172
what is Free Running Sleep Disorder
what pt population is it often seen in
two possible treatments
```
sleep progressively delayed each day
blind individuals (no MERG cells); free running rhythm in absence of light entrainment
```
Melatonin before desired bedtime
Tasimelteon
173
Two explanations for why headaches with brain tumors?
1. Mass pressing on dura, which is innervated by trigeminal nerve
2. Mass causing obstructive hydrocephalus
174
genetic factors affecting survival in oligodendrogliomas
1p and 19q deletion
175
genetic factors affecting survival in gliomas
MGMT methylation in tumor
| silences MGMT, which repairs DNA damaged by chemo, thus conferring chemo resistance
176
which brain tumors can NOT just be observed?
High/Low Grade Gliomas
Metastatic Carcinoma
Cerebral Lymphoma
these are the same ones that can't undergo stereotactic radiosurgery bc no focal target
177
whic brain tumor can't be surgically resected
cerebral lymphoma
178
which brain tumors can't be biopsied
Pilocytic Astrocytoma (usu locations not suitable for bx ex optic chiasm/tract, posterior fossa)
Metastatic Carcinoma (surg removal preferred)
pituitary adenoma (location not amenable)
179
which brain tumors CAN undergo chemo
High/Low Grade Glioma
| Cerebral Lymphoma
180
classic tetrad symptoms of meningitis
fever
AMS
headache
nuchal rigidity
181
bacterial meningitis - what type of WBC in CSF
how about viral
bacterial- PMNS (ex neutrophils)
viral - mononuclear
182
Which drug is particularly useful for treating acute episodes of akinesia in a Parkinson’s
patient and should be co-administered with an anti-emetic?
apomorphine
183
Huntington Disease
(3) meds to minimize movement disorder symptoms?
(3) meds to treat psychosis/disruptive behavior?
movement:
- VMAT inhibitor (tetrabenazine)
- Ach precursor (choline, lecithin; not super effective)
- Antipsychotics (D2 receptor antagonists- Haloperidol, Quetiapine)
Psychosis
-Atypical antipsychotics (quetiapine, olanzapine, risperidone)
Depression- SSRIs - anitdepressants that DO not have anti-muscarinic activity (don't wan't to decrease cholinergic tone!)
184
Tetrabenazine
- what used for
- MOA
- side effects
Huntington's
reversible VMAT-2 inhibitor (to decr dopaminergic tone)
side effects: depression, incr suicide risk!
185
2 meds to chelate Cu in Wilson's disease
Penicillamine
- potential cross-reactivity for penicillin
- SE: marrow suppression, N/V
Trientine
- if can't tolerate penicillamine
- side effects: Fe deficiency, muscle spasms, rash
186
Benzodiazepines and Baclofen act on which receptor types, to reduce muscle spasms and spasticity?
Benzos - GABA-A agonist
Baclofen- GABA-B agonist
187
Tizanidine
- usage
- drug type
- side effects
- drug interactions
reduces spasticity (ex MS, cerebrovascular lesions)
alpha-2 agonist (unclear MOA, other a2 agonists don't work as well)
SE: drowsiness, hypotension, dry mouth, muscle weakness
metabolized by CYP1A2
fluroquinolones inhibt CYP1A2, would increase Tizanidine levels
188
Dantrolene
- usages
- MOA
- side effects
spasticity, MS, spinal cord trauma, Malignant Hyperthermia
RyR antagonist- inhibits Ca induced CA released from SR
specific for skeletal muscle
SE: generalized muscle weakness, sedation, hepatotoxicity, hepatitis
189
What is status epilepticus?
How should you intervene?
At what time point can it lead to long-term consequences (inclu neuronal death, injury)
Seizures for more than 5 minutes
INTERVENE! initiral tx w/ IV Lorazepam is key
More than 30 minutes will have long term consequences
190
most common cause of status epilepticus in cihldren?
in adults?
children- fever/infection
adults - stroke
(other: metabolic abnml, TBI, brain neoplasm, withdrawal, cerebral anoxia)
191
3 ways hyperexcitable networks are generated?
excitatory axonal sprouting
loss of inhibitory neurons
loss of excitatory neurons that drive inhibitory neurons
192
what is the most imp study for diagnosis, prognosis and treatment of epilepsy
EEG
193
what is the Kindling model
in mice- repeated subthreshold stimuli over time leads to abnormal neuronal pathway in which subthreshold stimulus leads to spontaneous seizures
posisble mechanism of epileptogenesis (unclear applicability to humans)
194
highest incidence of seizures occurs when
early childhood & late adulthood
195
what is a seizure
clinical manifestation of abnormal, excessive excitation and synchornization of a population of cortical neurons
196
what is epilepsy
tendency toward UNPROVOKED recurrent seizures
197
what is epileptogenesis
sequence of events that converts normal neuronal network into hyperexcitable network
198
common causes of epilepsy in
- children
- young adults
- elderly
children- fever, metabolic, congenital
young adults - trauma, tumor
elderly- stroke, tumor, degenerative
199
carbidopa improves peripheral side effects of levodopa, but exacerbates ____
psychiatric symptoms
200
which drug for parkinsonism can cause hepatic failure
Tolcapone
201
what two drug classes can be used as monotherapy in parkinson's early on?
Dopamine agonists (bromocroptine, ropinarole, pramipexole, rotigotine)
MAO-B inhibitors (selegeline, rasageline)
202
what type of ionic currents are excitatory?
inhibitory?
excitation:
-inward Na+, Ca2+
inhibition
- inward Cl- (GABA-A receptor)
- outward K+ (GABA-B receptor)
203
pathophysiology of MS
peripheral immune cell infiltration
- -> CNS immune cell activation
- -> BBB disruption
- -> intrathecal IgG synthesis
204
how is MS defined pathologically?
presence of inflammatory demyelination in CNS in the absence of infection
is an immune-mediated inflammation targeting OLIGODENDROCYTES
demyelination w/ incomplete remyelination
205
MS demyelination has predilection for what location? why?
periventricular regions
| -there is a confluence of veins here; lesions start here in the post-capillary venules and spread out
206
what are meningeal lymphoid follicles
areas of B cell activation in MS
207
CNS capillaries have tight junctions. So where can immune cells from blood enter the CNS
via CNS perivascular space (in the post-capillary venules)
208
TWO key features of MS?
- lesional inflammatory activity / simultaneous presence of active and inactive lesions
- relapsing remitting clinical course
209
what are oligoclonal bands in CSF and what is their significance?
indicates intrathecal synthesis of IgG - clonal proliferation of B cells and establishment of an adaptive immune response in CNS
210
What does gadolinium contrast enhancement indicate?
gadolinium contrast leaking into brain parenchyma means BBB compromised.
gadolinium enhancement of an MS lesion indicates ACTIVE INFLAMMATION
211
how is MS diagnosed?
NO single test.
based on presence of CNS lesions disseminated in SPACE and TIME
+typical clinical presentation
+excluded alt diagnoses
212
List (7) clinical presentations of MS
- optic neuritis (painful blurred vision)
- myelitis (BL weakness/numbness, urinary dysfunction)
- cerebellitis (ataxia)
- brainstem syndrome (diplopia, vertigo, dysphagia, dysarthria, incoord, n/wk)
- hemisphereic snydrome (hemoparesis, hemianesthesia, visual field cut, word finding diff)
- syndrome duration >24h in ABSENCE of fever or infection
typically followed by remission regardless of treatment
213
(3) medications for MS and their MOA?
1. Fingolimid is a sphingosine-1-phosphate receptor modulator that prevents immune cell egress from lymph nodes (must have S1P chemotactic gradient)
2. Natalizumab is an antibody against alpha4 integrin (needed for immune cells to migrate to CNS)
3. Ocrelizumab is a CD20 antibody, depletes all B cells
214
What locations does neuromyelitis optica affect?
what is the cause?
-spinal cord ("myelitis")
-optic nerves
LIMITED brain involvement
NMO IgG - a pathogenic antibody that targets aquaporin 4 --> loss of aquaporin 4 on astrocyte endfeet
215
how is Neuromyelitis Optica diagnosed
relapsing optic neuritis & acute myelitis
at least 2 of the following:
- contigous spinal cord MRI lesion extending down 3 or more vertebral segments
- brain MRI does not meet criteria for MS
- NMO IgG (aquaporin 4) seropositivity
216
4 core clinical criteria for lewy body dementia
- fluctuating attention/concentration
- recurrent, detailed visual hallucinations
- REM sleep disorder
- Parkinsonism
217
indicative biomarker for lewy bdoy dementia
reduced dopamine transporter uptake in basal ganglia
218
Triad of Normal Pressure Hydrocephalus
Wet (incontinence)
Wacky (dementia)
Wobbly (gait)
219
cause of normal pressure hydrocephalus? how is diagnosis confirmed?
*is due to failure of CSF drainage system
confirmed w/ imaging and LP
may reverse with shunt
220
what is pseudodementia?
| -signs?
severe depression that resembles dementia
fhx, prior hx, subacute onset likely precipants, depressive sxs
AMOTIVATIONAL exam
221
What kind of necrosis does cortex undergo?
which cortical layers are most vulnerable
laminar necrosis
layers 3, 4, 5
222
when does anoxic-ischemic encephalopathy occur?
what three clinical syndromes can result?
cardiopulm arrest
- man in the barrel syndrome
- parkinsonism
- action myoclonus
223
what is one cause of Osmotic Demyelination Syndrome?
rapid correction / overcorrection of chronic hyponatremia
- causes water to leave brain
- corticospinal tracts become demyelinated
224
CO toxicity causes necrosis where?
globus pallidus
225
Methanol toxicity affects?
retina (degen retinal ganglion cells)
if severe- BL putamen necrosis, focal WM necrosis
226
Neuro symptoms of vit B12 deficiency
- ataxia
- LE n/t
- progression to LE spastic weakness
- complete paraplegia may occur later on in course - if reaches this point, recovery is poor
227
what 2 marine toxins can cause temperature reversal
brevetoxin
ciguatoxin
228
what marine toxins inhibit Na+ channel
which ones activate Na+ channel
inhibit
- tetrodotoxin (puffer fish)
- saxitoxin (dinoflagellates)
activate:
- brevetoxin
- ciguatera
229
what does domoic acid act on
glutamate receptor agonist
| -GI -> neuro -> memory impairment, can last years
230
CT/MRI imaging not indicated in recurrent migraines unless??
- recent substantial change in HA pattern
- hx seizures
- focal neuro signs/symptoms
231
what is most dangerous, primary or secondary HA?
secondary
232
dull, achy, BL, nonpulsating pain
episodic
sensation of pressing/tightening
not worse with physical activity
no N/V
may have photophobia OR phonophobia (noth both)
no prodrome or aura
msk component
tension HA
233
criteria for chronic Tension Type Headache
- occurs at least 15 days/month for more than 3 months
- lasts hours or may be continous
at least TWO of following:
- BL
- pressing/tight (nonpulsating) quality
- mild.mod intensity
- not aggravated by routine phys activity
AND
- no more than one of photophobia, phonophobia, or mild nausea
- no mod or severe nausea, no vomiting
- not due to another disorder
234
Tension HA pathophys
a manifestation of abnormal neuronal sensitivity and pain facilitation
posisble hypersnesitivity of myofascial nociceptors
or neurons in trigeminal nucleaus
235
TTH treatment
OTC analgesics
but if freq or chronic, consider preventatives:
- SSRI
- tricyclic antidepressant
- muscle relaxant
nonmedication
- manage stress
- biofeedback to promote muscle relaxation
236
Cluster HA
```
Men
Genetic
Circadian and annual periodicity
1 every other day - 8 daily
clusters lasting 2wks - 3 months
```
Severe unilateral pain
Autonomic features - ex Horner's, congestion/rhinorrhea, lacrimation, sweating, ptosis, conj injection
237
Tx for acute cluster HA
O2 mask
| inject sumatriptan
238
Cluster headache - pathophysiology
- activ of posterior hypothalamic grey matter
- parasympathetic overacvitiy
- sympt dysfunction, secondary to activation of trigeminal-parasymp reflex
239
diagnostic criteria of trigeminal neuralgia
Paraoxysmal attacks of pain lasting seconds-2 min affecting at least one div of CN V
-pain intense, sharp, superficial or stabbing and/or precipitated from trigger areas or by trigger factors (talking, eating, brushing teeth - anything that involves face movement)
Attacks are sterotyped in each patient
No neuro deficity
Not attributed to another disorder
240
what workup should be done in trigeminal neuralgia?
what treatments
MRI to look for lesion impinging on trigeminal nerve
Preventive Meds (carbamazepine, gabapentin most common)
Surgery
- decompression (in applicable)
- ABLATION on trigeminal ganglion! face all numb
241
recurrent attacks lasting 4-72 hours
unilateral, pulsating pain
aggravated by routine activity
n/v
photphobia/phonophobia
migraine without aura
242
how does migraine prevalence change with age
most common in teens/20s
worsen in 30s/40s
improve later in life
243
migraine
- risk factors?
- protective factors
risk
- hormones
- chronobiologic changes
- drugs
- diet (tyramine, smoked foods, red wine)
- sensory input
- stress, trauma
protective
- healthy lifestyle
- hydrated
244
Describe the pathway of a migrainte
1. originates deep in brain
2. electrical impulses spread
3. changes in nerve cell activity and blood flow --> symptoms like visual disturbance, n/t, dizziness
4. chemicals in brain (CGRP, substance P, NKA) cause blood vessel DILATION and INFLAMMATION of surrounding tissue
5. inflammation irritates the TRIGEMINAL NERVE, resulting in severe or throbbing pain
245
list three specific migraine treatments
Dihydroergotamine (DHE)
Triptans
CGRP inhibitors (preventive)
246
Triptans
- mechanism
- site of action
- what can they be used for
5HT-1 (serotonin) receptor AGONIST
works at interface between trigeminal nerve endings and blood vessel walls
migraines
cluster headaches
247
most common cause of nonepidemic fatal encephalitis in US
HSV1
most pts who get CNS complications are actually in good health!
248
HSV encephalitis affects what part of brain
fronto-temporal lobe(s)
249
diabetic acidosis is strong risk factor for what fungus
rhinocerebral mucormycosis
250
what 3 fungal infections often seen in untreated HIV infection
- cryptococcus
- coccidiodes
- histoplasma
251
CSF findings in fungal meningitis
lymphocytic pleocytosis, elevated protein,
| mildly depressed glucose
252
what is most common helminithis CSN infection?
what is it caused by?
what is the presentation?
CSN Cysticercosis
ingestion of larvae of pork tapeworm Taenia solium
chronic or acute HA, seizures, focal neuro deficits, subacute meningitis, or hydrocephalus
CT/MRI scan with cysts
CSF may have EOSINOPHILS
253
CSF with eosinophils should make you think?
parasites
254
treating parasitic CNS infections?
supportive
- anti seizure meds
- steroids if needed
- shunting for mass effect and hydrocephalus if needed
255
HIV dementia cause?
what does endstage look like
viral invasion of parencyhmal cells. secondary neuronal loss
akinetic mute with fetal posturing
256
PML (Progressive Multifocal Leukoencephalopathy)
- cause
- what increases risk
- what can it resemeble
- CSF findings
- treatment
- JC virus
- immunsuppression (virus normally contained) & use of monoclonal Ab therapies like Natalizumab (MS, crohn's)
- virus reactivates and infects oligodendrocytes --> multifocal areas of demyelination = resembles MS
CSF
- mild lymphocytic pleocytosis
- eleva protein
- normal glucose
- JC virus+
No treatment except for underlying immunosuppression
257
list at least four meds that can prevent migraines
- anticonvulsants
- antidepressants
- beta blockers- Propranolol, Timolol
- CCBs
- NSAIDs
258
CGRP inhibitors
are monoclonal antbodies, prevent migraines
Fremanezumab - bind CGRP
Erenumab - bind CVRP receptor
259
definition chronic migraine
headache at least 15 days/month, symptoms meet criteria for migraine on 8 or more of those days
preventive meds
Botox
wean off prn analgesics
260
gross anatomical changes in aging brain
- overall reduced weight
- narrowing gyri, widening sulci
- ventricle dilation
- widening subarachnoid space
leads to memory impairments common with normal aging
261
role of microglia and neuroinflammation on normal aging of CNS
normally microglia switch between resting surveillance / activated state
in older brain, once activated, harder to switch back to surveillance state. stays in an intermediate "primed" state. once there is a trigger, become SUPER-activated --> amplified cytokine production
- -> elevated ROS prod
- -> prolonged inflamm state
neurotoxic!!
262
why is the nervous system uniquely vulnerable to aging?
-nervous tissue does NOT divide!
263
describe the type of neuron loss in aging / histo changes
NOT just a generalized loss of neurons
instead, atrophy or loss of larger neurons that have high energy requirements - soma and dendrites shrink back; reduced complexity of the dendritic tree, decreased spine density, reduced excitatory input
264
which neurons are uniquely susceptible in aging?
| why? (4 reasons)
dopaminergic neurons
- dopamine gets oxidized to ROS
- neuromelanin (responsible for the pigment) sequesters Fe, which generates ROS
- mitochondrial DNA deletion levels highest
- local microglial activation
265
where are reductions in white matter most common in aging?
prefrontal
| temporal
266
three sources of ROS production
how are ROS inactivated?
leaked from cell respiration in mitochondria
made by phagocytes
degradation of dopamine
inactivated by:
- antioxidants (dietary)
- superoxide dismutase, catalase
267
reason why brain is uniquely susceptible to ROS damage?
- high energy demand, high O2 consumption
- abundant peroxidizable FAs
- high Fe levels (potent ROS catalyst)
- low levels of antioxidants and related enzymes
- dopamine oxidation
268
harmful effects of ROS?
lipids: lipid peroxidation makes toxic aldehydes
DNA: causes double strand breaks, base mod, alter gene expression
protein: oxidation causes loss of function, misfolding, aggregation
269
GCS Eye
4 - spontaneous
3 - voice
2 - stimulation
1 - no opening
270
GCS Verbal
```
5 - oriented
4 - confused
3 - inappropriate
2 - incomprehensible
1 - none
```
271
GCS Motor
```
6 - obeys commands
5 - localizes
4 - withdraws to pain
3 - decorticate posturing
2 - decerebrate posturing
1 - none
```
272
Injury where increases risk of Autonomic dysreflexia?
abovce T6
273
what is autonomic dysreflexia
what is most common cause
what is treatment
life threatening reaction to noxious stimuli below level of injury
- elevated BP
- bradycardia
- flushing/sweating above level of injury
- goosebumps below level of injury
Bladder distention
(also: constipation, fecal impaction, fractures, pressure injury)
Treatment: remove stimulus!!!
can temporarily tx with meds if needed
274
upper trunk lesionn
- location
- symptoms
Cf, C6
- prox arm muscles
- infraspinatus
- deltoid
- biceps
- supinator (waiter's tip)
sensory deficit over lateral arm (C5, C6 dermatome)
275
lower trunk lesion
- location
- symptoms
C8, T1
- hand muscles (of median, ulnar and radial innervation)
- interossei, thenar, hypothenar, EIP
sensory deficit over medial arm r
276
how is lateral cord lesion diff from upper trunk lesion
similar to upper trunk lesion but spares the deltoid
277
medial cord plexopathy
ulnar N
| extended sensory deficit
278
posterior cord affects what nerves
axillary nerve
| radial nerve
279
acute brachial plexus neuritis (parsonage-turner syndrome)
- cause
- symptoms
autoimmun
subacute severe shoulder/arm pain, followed by weakness
can affect any portion or individual proximal branches
280
Erb palsy
neck lateral traction - affects upper trunk
281
Klumpke palsy
arm upward extension - affects lower trunk
282
thoracic outlet syndrome
compression of subclavian artery and lower trunk
--> hand munscle atrophy
283
radiculopathy
- sensory symptoms
- motor symptoms
- how to confirm
radiating pain
numbness in dermatome
weakness in muscles of myotome
reduced reflex at affected level
EMG and MRI
284
Anti-epileptics that are hepatic inducers?
PCBOT
Phenytoin
Carbamazepine
Barbiturates
Topiramate
285
Anti-epileptics that are mainly renally excreted?
Gabapentin
Levetiracetam
Topiramate (lesser extent)
286
if you rly suscpet a subarachnoid hemorrhage but CT is negative, what next
LP
287
familial intracranial aneurysm syndrome (FIA)
two first thru thirddegree relatives have intracranial aneurysms
