Green Neuro Upload Flashcards
what types of glutamate receptors are there
ionotropic (AMPA, NMDA, kainate) and metabotropic (quisqualate)
what types of GABA receptors are there
GABA A and GABA B: Gaba A is post synaptic and a Cl- channel; GABA B is pre-synaptic and is a K+ channel
where do benzos and barbiturates act
on GABA receptors
what are the cellular mechanisms of starting seizures?
too much exciting (inward Na and Ca channels); NT (glutamate, aspartate)
not enough inhibition (ionic 2/2 inward Cl- or outward K) or NT (GABA)
How are hyperexcitable networks formed? (i.e. seizure-generating networks)
excitatory neurons can have axonal sprouting (growth); there can be loss of inhibitory neurons; there can be loss of excitatory neurons that activate inhibitory neurons (loss of regulation)
how do we define epilepsy (ILAE definition)
- at least two unprovoked seizures > 24 hours apart OR one unprovoked seizure and 60% probability of seizure occuring in next 10 years OR diagnosis of epilepsy syndrome
what kinds of seizures may not need treatment long term?
generally, those with provoking cause- i.e. single seizure, febrile seizure, benign syndrome of childhood, simple partial seizure, impact seizure (TBI), provoked seizure
most common etiology of epilepsy?
unknown
common causes of seizures in children
febrile, congenitla, metabolic
common causes seizures in young adults
trauma and tumor
common causes seizure in elderly
stroke and degenerative changes
Absence (Generalized non motor) seizure features
school aged children; abrupt onset activity arrest and staring; brief, lasting 3-20 seconds bu return to normal abruptly. can happen many times throughout day.
EEG shows 3Hz spike wave, MRI usually will be normal. These tend to resolve by adolescence
General Motor (Myoclonic) Seizures
brief, shock like jerks of group of muscles;
these tend to be bilaterally synchronous, lasting < 1 second (hard to assess consciousness as a result).
repeat seizures can have impaired consciousness.
- these seizures are seen with other epilepsy syndromes and with progressive myoclonic epilepsy.
EEG will show 4-6 Hz polyspike wave
Generalized Motor- Tonic seizures
symmetric tonic muscle contraction- extremities and flexion of waist and neck; these will last 2-20 seconds (last longer than myoclonic).
on EEG- shows sudden attenuation with generalized, low voltage fast activity i.e. drop in EEG activity (common) or generalized polyspike wave.
Atonic (generalized onset) motor seizures
sudden loss postural tone–> two forms (severe- falls; mild head nods, jaw drops)
consciousness is typically impaired during this, lasting only seconds
general drug warnings with anti seizure meds
all anti seizure drugs have potential teratogenicity; all have high risk of suicide. Other genral risks incude eed to monitor blood and liver function (i.e. looking for anemia, increased LFTs). Can have cost issues and compliance issues
“old” anti seizure drugs include
phenobarbital, phenytoin, carbamazapine, and valproate; these generaly have higher side effects and require frug level monitoring
adverse effects seen with “old” anti seizure meds (phenobarbital, phenytoin, carbamazapine, and valproate) includes
bone marrow suppression, hepatic inflammation, rash, and SJS
what tests should be run to monitor if on an old anti seizure med
CBC (monitor for bone marrow suppression) , LFTs (Hepatic inflammation)
phenytoin MOA
blocks VG Na channels; aka Dilantin.
hepatic enzyme inducer
elderly individuals can’t tolerate as high a dose as adults
phenytoin side effects
gingical hyperplasia, hirsuitism, “coarsening” of featueres;
can have toxicity including cerebellar sx (ataxia, falls), cardiac arrythmia
Carbamazepine MOA
blocks VG Na channels; aka Tegretol
hepatic inducer
side effects of carbamazepine
can cause SIADH and hypOnatremia
toxic side effects of carbamazepine include
double vision and mental clouding
phenobarbital MOA
GABA-A inhibition; prolongs the duration of open Cl- channel (more inhibition)
good b/c inexpensive
phenobarbital side effects
sedation, respiratory depression, withdrawal sx
valproate MOA
multiple- Na channels, T type calcium channels, GABA
hepatic inducer
valproate SE
pancreatitis, thrombocytopenia, hyperammonemia
nausea, weight gain, hair loss;
toxic effects include tremor
valproate is CI in those with
urea cycle c/o, liver disease, mitochondrial disorders
which old anti seizure med is associated with NTD
valproate
anti seizure med used for absence seizure
ethosuximide
ethosuximide MOA
blocks T type calcium channels
which anti seizure med has risk of weight loss, kidney stones, and glaucoma (acute angle)
topiramate
which new anti seizure drug carries risk of rash and SJS
lamotrigine (lamictal); Na channel blocker that is hepatically metabolized
Keppra MOA
binds to SV2A (synaptic vesicle protein); decreases NT release
parampanel MOA
new anti seizure med - AMPA antagonist
Vigabatrin MOA
irreversible GABA transaminase inhibitor
Tiagabine MOA
new anti seizure med; binds to GABA; prevents re-uptake
drugs that can be used for focal onset seizures
anything except ethosuximide (this is only used for absence seizures)
drugs for generalized onset convulsive seizures
VLLTZ
valproate, lamotrigine, topriamate, levetriacetam, zonisamide
drugs for absence (generalized non motor) seizures
ethosuximide and valproate;
can use other drugs but less effective
when should anti seizure drugs be started?
after second unprovoked seizure, most would start; if only one seizure, consider risk for future seizures and can use MRI/ EEG
what can increase your risk of recurrent seizures
previous neuro insult, abnormal EEG, prior seizures, post-ictal paralysis, partial onset paralysis
first line anti seizure med for generalized onset motor seizure
valproic acid, lamotrigine, and topiramate
first line med for focal onset seizures
carbamazepine, oxycarbamazepine, phenytoin, lamotrigine, valproic
first line treatment for generalized nonmotor (absence) seizures
valproic acid, ethosuximide
treatment for status epilepticus
Ativan (lorazepam) IV; among other treatments (ABCs, thiamine, dextrose, IV anti seizure drug)
what is general mechanism for AMS
poorly understood, but thought to originate from changes to the reticular activating system or global cortical dysfx
in general, AcH plays a key role
the RF is a network of brainstem nerve fibers that extend to diencephalon and connects to centers of hypothalamus; serves to filter incoming informatio, also serves to arouse cerebral cortex into wakefulness
what kind of patient would have hypoglycemia encephalopathy?
MRI will show changes similar to hypoxic/ ischemia (similar mechanism); most commonly will be found down and have been hypoglycemic for a while. DWI MRI is the test of choice
hyperglycemia associated seizure
epilepsia partialis continua, which is a form of focal motor seizure .
central pontine myelinolysis symptoms
AMS, quadriparesis, dysphagia
extrapontine myelinosis sx
behavioral disturbances, movement disorders, seizures
triphasic waves on EEG seen with
hepatic encephalopathy (seen with metabolic enceph but especially hepatic)
most common causes of hypercalcemia mediated AMS
primary hyperparathyroidism and cancer
who is at risk for B12 deficiency
pernicious anemia (IF binds B12); malabsorption; vegans
who is at risk for B1 (thiamine) deficiency
EtOH use d/o, bariatric surgery, anorexia
stages of B1 deficiency
Acute (Wernicke): encephalopathy presents with ataxia, oculomotor dysfunction (nystagmus, lateral rectus palsy, opthalmoplegia)
Chronic (Korsakoff): memory loss and confabulation
mammilary body dysfunction a/w what deficiency
B1 (thiamine)
vitamin E deficiency symptoms
leads to a slow progessing spinocerebellar syndrome; cerebellar symptoms include ataxia of trunk and limb and myelopathic features include upgoing toes, loss of vibration and proprioception
what kind of CNS damage do hydrocarbons and inhalants cause
white matter damage (toxic leukencephalopathy)
what region of brain classically injured in carbon monoxide poisoning
bilateral globus pallidus
toxic leukencephalopathy
white matter damage that is classically seen with toxin mediated damage to brain (i.e. hydrocarbons)
acute vs. chronic carbon monoxide poisnong
acute- HA, nausea, dizziness, malaise
chronic: cognitive changes, personality changes
hallmarks of CNS inflammation that occurs in MS (4 factors)
peripheral immune cells infiltrate, CNS immune cells are activated, BBB disrupted, IgG synthesis (intrathecal)
what kinds of peripheral immune cells infiltrate CNS in MS (perivascular, parenchymal, and meningeal)
perivascular = T and B cells, monocytes, macrophages
parenchymal: CD8 > CD4 T cells
meningeal: B cells, plasma, follicular cells
where do peripheral immune cells enter the CNS?
post capillary venules
what kinds of CNS immune cells are activated in MS
microglia are activated; can be shown in PET scan
astrocytes also become reactive
what does gadolinium infiltration on MRI indicate
BBB dysruption; seen in patients with MS over areas of ACTIVE lesions
what are the effects of BBB dysruption in MS
fibrin deposition, Ig deposition, complement activation
what role do fibrinogen/ fibrin entry into brain play in MS?
BBB dysruption leads to entry of these substances –> this can activate microlgia (CNS immune cell activation)
what is meant by dissemination in MS
pattern of active (gadolinium entry) and inactive lesions on MRI; indicates inflammatory activity of different acuity. characteristic of MS
dissemination is the basis of relapsing clinical course of MS
oligocloncal bands
IgG bands that indicate clonal proliferation of IgG by B cells in MS
(intrathecal synthesis of IgG)
adaptive immune system in MS
B cells produce oligoclonal IgG (intrathecal production) in a type of adaptive immunity that can then be used diagnostically
this is part of the CNS mediated immune response in MS (in addition to the peripheral immune cell response that occurs)
where do demyelinating lesions tend to occur in MS
periventricular lesions
what eye condition is closely associated with MS
optic neuritic (demyelinating lesions of CN II)
how do myelin and axonal damage in MS differ
myelin can be reformed (albeit incomplete) whereas axon damage is irreversible
optic neuritis and MS
typical clinical presentation = painful blurred vision
myelitis and MS
bilateral weakness and/ or numbness with bladder/bowel dysfunction
cerebellitis and MS
ataxia
brainstem syndrome
seen in MS; presents with double vision, vertigo, dysphagia, dysarthria, incoordination, numbness or weakness
hemispheric syndrome
hemiparesis, hemianesthesia, visual field cuts, word finding difficulty; clinically isolated syndrome seen with MS
periventricular lesions hint at
MS (prefers to localize to post capillary venules) where BBB is dysrupted
Natalizumab use and MOA
used to treat CNS indlammation in MS; MOA= blocks immune cell entry into CNS by binding to and blocking alpha4beta1 integrin, which mediates entry
Fingolimod
sphingosine 1 phosphate receptor modulator; used to treat MS
blocks leukocyte exit from lymph nodes
Ocrelizumab
CD20 Antibody used to treat MS; targets and depletes B cells and reduces CNS inflammation
B cells are part of peripheral inflammatory cells that enter CNS from perivascular and meningeal area
NMOSD
neuromyelitis optica spectrum disorder; an autoimmune demyelinating d/o that likes to target spinal cord and optic nerve, but generally spares brain. Results from anti aquaporin 4 aka anti NMO IgG
what are the core clinical syndromes a/w NMOSD
optic neuritis (similar to MS); myelitis (like MS); area postrema syndrome (NOT like MS), acute brainstem syndrome (like MS); acute diencephalic syndrome, symptomatic cerebral syndrome
what is area postrema syndrome
clinical syndrome that is strongly associated with NMOSD;
presents with intractable nausea, vomiting, and hiccups
how is NMOSD characteristically sen on imaging
MRI showing longitudinally extensive transverse myelitis (contiguous spinal cord lesion that extends > 3 vertebral segments)
MRI may also show lesions to the area postrema in the medulla; if there are lesions in hypothalamus may have autonomic dysfunction as well
how is NMOSD diagnosed
if anti AQP4 (NMO) IgG positive,must have also 1 or more core clinical syndrome (i.e. myelitis, area postrema syndrome, optic neuritis, etc) and other dx excluded
where are the aquaporins that area affected in NMOSD
on astrocyte end feet (part of BBB)
treatment options for NMOSD
Eculizumab (Ab vs. C5 antibody)- blocks complement activation in NMOSD; prevents clinical relapses
Inebilizumab (Ab vs. CD19)
Satralizumaba (Ab vs. IL-6)
What is the ASIA Impairment Scale (AIS)
used to relay degree of sensory or motor function based on spinal cord injury
AIS A
highest level of impairment; leads to no motor/ sensory function below the level of injury
AIS B
no motor function below level of injury (sensation intact)
AIS C
> 50% of motor function below neuro level of ( less than 3/5 strength)
AIS D
more than 50% motor function below neuro level of injury (> 3/5 strength)
AIS E
full neuro recovery
What is the ambulation potential of people with AIS B
50%; better prognosis with sharp/ dull sensation
C3-C5 spinal cord injury
innervates diaphrag; impacts breathing without ventilatory support
C5 level spinal cord injury
C5- innervates elbow flexors/ biceps
self feeding with adaptive equipment/ setup
driving with chair independent
C7 level SCI abilities
elbow extensors (triceps);
this is a key muscle for independent activity- overhead reach, transfer ability, driving with basic hand controls
which UE muscle use/ spinal cord level is very important towards independent activity
C7- triceps (extensor);
this allows for more mobility and improves the ability of living independently with appropriate adaptive equipment
C8 level SCI
finger flexors- allows for gripping objects and turning knobs.
T1 level SCI
finger extensors- allows for full hand function
what role does muscular innervation level play in thoracic level SCI
plays a role in sitting balance and in cough (abdominal innervation required for)
T6 level SCI
an injury above this level increases risk of autonomic dysreflexia
what is autonomic dysreflexia- what can cause it
most commonly it is caused by bladder distension/ constipation/ etc in the context of someone with a SCI above the level of T6.
- signs include increased BP, bradycardia, flushing, sweating and goosebumps ABOVE LEVEL OF INJURY
how do you trea autonomic dysreflexia
control stimuli –> i.e. fix bladder distension/ constipation; can use medication temporarily as needed
what are some of the common complications to SCI?
bladder issues; such as detrusor/ sphincter dysynergia (i.e. bladder and the outlet sphincter don’t work in unison); risk for UTI, hydro, autonomic dysreflexia, UTI, stones
what kinds of force are responsible for TBI?
rapid acceleration/ deceleration 2/2 shear stress (SLOW COMPRESSION NOT AS IMPLICATED)
types of TBIs include
focal and generalized
focal is usually more related to acceleration/ deceleraton type injuries that lead to direct contact of brain and skull. i.e. SDH, epidural hematoma
generalized more related to shear/ tensile strength from acceleration/ deceleration injuries. includes diffuse axonal injury
GCS 13-15 =
mild TBI (includes concussion)
GCS 9-12=
moderate TBI
GCS of 8 or less =
severe TBI (threshold for intubation)
what regions of brain are most disposed to cortical contusions in TBI
anatioer inferior frontal lobes and temporal lobes
what are some biomarkers that can be used to demonstrate TBI
IL-1 beta, TNF alpha, Il-6, GFAP, UCHL-1
epidural hematoma
bleeding between dura mater skull
subdural hematoma
bleeding between arachnoid mater and dura mater
neuroexcitation in acute and chronic post TBI
- increased calcium entry
how does glycolysis change after TBI
there is early acute hyperglycolysis and later on develop hypoglycolysis
what is diffuse axonal injury
typically has little to no gross pathologic finaing but will see scattered damage to cerebral/ brainstem white matter –> especially corpus callosum
what imaging modality is most useful for detecting diffuse axonal injury
diffusion tensor imaging (DTI)
what factors influence the adverse complications of repeat TBI
how severe the concussion/ TBI is; how long between repeat events; how old you are when injury happens; what premorbid conditons you have
Intraparenchymal vs. extraparenchymal manifestations of neurocysticercosis
intraparenchymal symptoms = seizures, but can also be incidental finding. is MCC seizures in some endemic countries
extraparenchymal symptoms.= hydrocephalus; increased ICP with HA, AMS, n/v, death
what are the systemic symptoms of Lyme disease
affects skin (rash), joints (artharalgias), and nervous system changes
neurologic sx of Lyme disease
classic finding is bilateral Bell’s palsy (CN VII palsy);
can also cause radiculitis (mimics radiculopathy without any mechanically compressive symptoms)
meningtis- similar to viral meningitis (CSF and clinical profile)
“chronic” lyme disease canlead to pain, fatigue, and minor cognitive issues
what are the risk factors for PML
immunocompromise, treatment with Natalizumab (alpha4beta1 integrase blocker), infection with JC virus, hematologic malignancy,
radiographic findings a/w PML
unilateral or bilateral demyelinating foci (discrete foci); these do not cause mass effect and do not enhance contrast
tend to be located at the grey/ white junction in parieto-occipital and frontal lobes
vs. MS- small multifocal lesions that are ovoid and perpendicular to corpus callosum
toxoplasmosis infection routes
contaminated water/ soil from environment; can also get from eating meat that has been contaminated. latent infection from intracellular parasite toxoplasma gondii
toxoplasmosis MRI findings
toxo is the most common CNS infection in untreated AIDS –> leads to ringed lesions on MRI
clinically, presents with HA, confsuion, fever when reactivated infection. can also have focal neuro sx depending on location of lesion
what are unique features of cryptococcal meningitis
increased ICP (can be as high as 40, whereas normal = 10-20); can also see CN VI palsy (a/w increased ICP, not specific to crytpo)
who is at risk for cryptococcal meningitis
those with AIDS and CD4 < 100; if do not have HIV, may have chronic immunosuppressant use or hematologic malignancy
what is the mech of prion disease
exact MOA unknown, but originates from protein malformation info beta sheets (unlike typical alpha helices)
altered proteins convert normal prion proteins –> abnormal forms –> aggregate and can’t be degraded.
describe the life cycle of tenia solium
parasitic infection that is endemic in areas including Mexico; lives in pork. pork eaten –> tapeworm in people; tapeworm makes eggs –> people poop out eggs –> eggs get eaten by others. larvae hatch and enter blood stream –> larvae enter other systems including brain (intra/extraparenchymal), eyes, and subcutaneous
how long does it take for infection –> symptom onset in cysticervosis life cycle (tenia solilum)
3.5 years = average incubation time
diagnosis and treatment for PML (progressive multifocal leukoencephalopathy)
dx= LP with JC virus serology
treatment: start ARD (if AIDS +), stop immunosuppression, stop natalizumab
poor prognosis- death within months
what condition can give you chronic meningitis?
crypto- fever, malaise and headache over several weeks/ months, associated with increased ICP (unique to crypto)
may also have vomiting and CN VI palsy (diplopia) 2/2 this
how do you evaluate creutzfeld jacob disease
presents as a rapidly progressive dementia; death within 1 year
symptoms of creutzfeld jacob disease
rapidly progressive dementia
90% have myoclonus (especially with startle)
can also present with cerebellar ataxia, UMN signs, Parkinsonism
How do you diagnose CJD
MRI is the best, most important test for this
can also use EEG (periodic sharp wave complexes) and CSF biomarkers (14-3-3 protein)
what does CJD + MRI show
hyperintense signal of cortex, caudate, and putamen on DWI sequence
(recall that hyperintensity also seen in stroke pathology)
causes of CJD
most cases are sporadic (85-95%); other cases can be caused by genetic mutations, mad cow disease, or iatrogenic (transplant, cadaveric grafts, HGH from cadavers, cadaver corneal transplant)
what structures sit medial to the putamen?
globus pallidus (internal and external segments);
structures involved in basal ganglia
corpus striatum, which includes the putamen and caudate nucleus; globus pallidus, and thalamus with subthalamic nuclei
what afferent input is sent to the caudate?
input from head and eye movement
what afferent input sent to the putamen?
limbs/ trunk movement
where is dopamine produced?
substantia nigra pars compacta (not the pars reticulata)
where is the superior colliculus and what function does it play?
in the midbrain, plays role in gaze
what are medium spiny neurons? where are they found,
these are found in corpus striatum; these are inhibitory neurons that are quiet at baseline. They receive input (glutamate) and send out inhibitory signals (GABA)
what is the function of the indirect pathway in basal ganglia? what structures are involved?
goal is to have multiple targets in motor/ pre motor cortex that are nearby direct pathway targets. Indirect pathway seeks to reinforce inhibition of neighboring cortex to create smooth movement. This is done by targeting MSN nearby. this will disinhibit the subthalamic nuclei, which then release glutamate to activate neighboring internal MSN –> MORE inhibitory tone blocking motor activation
D1 receptors
MSNs that target the GP internal express more of these. when there is more dopamine released, these D1 receptors activate more easily –> fire faster (faster motion)
D2 receptors
MSNs targeting the GP external express more of these; these are inhibitory in nature, when there’s more dopamine released there will be less activation of MSNs –> these
what causes Huntington’s disease
degeneration of the striatal neurons (MSNs expressing D2) to the globus pallidus external (indirect pathway loss); can result genetically from mutation in the HTT gene, with CAG repeats
vestibulocerebellum role
uses vestibular and visual input to regulate posture and balance as well we vestibulo-ocular reflex (i.e. maintaining fixed gaze)
Spinocerebellum function
receives spinal input and evaluates this input as well as desired motion. Main function is to predict and refine movement;
- this provides fast and precise feed forward execution of movement
Cerebrocerebellum function
input from cortical cognitive and motor centers;
refines complex behavioral responses via feedback. In particular, integrades complex spatial and temporal sequencing info. This is expanded in humans (compared to other vertebrates)
superior peduncle contents
white matter pathway that mostly contains efferent
middle peduncle contents
mostly afferent (from cortex)
inferior peduncle function
mostly afferent fibers
in addition to peduncle white matter tracts entering cerebellum, what other tracts enter?
mossy fibers (pontine) and climbing fibers from inferior olivary nucleus
where do mossy fibers enter the cerebellum
pontine enter via middle peduncle
proprioceptive information from spinocerebellar tract enter via inferior peduncle (along with climbing fibers)
where do climbing fibers enter the cerebellum
via inferior cerebellar peduncle
what kinds of cells are critical for calculating function in the cerebellum?
purkingje fibers; these receive input from both climbing fibers (inferior olivary nucleus, via inferior peduncle) and from mossy fibers (pontine enters via middle peduncle and spinocerebellum via inferior peduncle);
what information do mossy fibers carry?
generally, carry information about proprioception.
what information do climbing fibers carry?
carry information that determines if the body needs to make a correction (in position, etc); this is integrated with signal from the mossy fibers, which relay proprioceptive information
cerebellar lesions involving lower leg could result from damage to which vessels?
the superior cerebellar or anterior inferior cerebellar artery
posterior inferior cerebellar lesion can affect what part of body
head
superior cerebellum fed mainly by which vessel
SCA (superior cerebellar)
where does AICA feed on cerebellum
inferior middle portion
where does PICA feed
inferior portion of cerebellum, from midline to lateral
how could PICA stroke effect cerebellar function? which parts would be involved?
could lead to damage to cerebrocerebellu, thereby affecting this tracts’ ability to aid in learning and fine tuning movements. This would affect contralateral side if affected
how do lesions to spinocerebellum and cerebrocerebellum differentially affect body function?
spinocerebellar lesions have ipsilateral effects to lesion
cerebrocerebellum has contralateral (crosses midline between the cerebellar cortex to VL complex in thalamus)
what cerebellar structures are involved in the learning process that improves coordination?
cerebellar cortex, deep cerebellar nuclei (dentate/ interposed nuclei), red nuclei, inferior olive, climbing tracts
fastigial nucleus of cerebellum involved in which portion of cerebellar function (movement)
spinocerebellar functionn- i.e. feed forward, predicting and refining movement.
where is the dentate nucleus located
lateral most nucleus on the cerebellum (would not be likely affected by central lesion)
lesion to vestibulocerebellum would cause what?
balance issues, postural issues, issues with vestibulooclear reflex
where do fibers from spinocerebellar deep cerebellar nuclei (fastigial nuclei) project to? what structures do they pass through?
pass through the inferior cerebellar nuclei to the superior and inferior colliculi
what causes intention tremors? what do they look like?
kinetic tremors that happen with goal oriented movemnet (i.e. pointing). These tremors are linked to spinocerebellar ysfunction. dyscuntion is related to spinocerebellar dysfunction (the cerebellum does not properly predict the extremity’s position in relation to goal)–> dysmetria
which part of cerebellum, if lesioned, could lead to dysarthria?
lateral cerebrocerebellum; the cerebellum plays a role in action sequencing, including speech. Speech would become chippy and deconstructed to syllabus, not fluent.
movement deficits associated with cerebellar lesion
ataxia (truncal, nystagmus, limb), dysmetria, intention tremor, dysarthria
vermis of spinocerebellum function role in movement and lesion effect
coordination of trunk movement; lesion would cause truncal ataxia
paravermis of spinocerebellum role in movement and lesion effect
limb movement coordination; limb ataxia
which part of cerebellum is involved in planning and sequencing of movement and speech?
cerebrocerebellum
which part of cerebellum involved in motor learning?
cerebrocerebellum
gait ataxia and balance dysfunction can result from lesions to
spinocerebellum and vestibulocerebellum
left limb dysmetric and tremor would result from lesions to which cerebellar structure?
cerebellar left hemisphere
loss of MSN in caudate that projct to the external globus pallidus seen in what disease
Huntington’s disease (leads to weakening of indirect pathway); loss of diffuse inhibition
symptoms seen with Huntington’s (from early to later stages)
involuntary mvmts, depression/ mood changes, clumsy, sexual dysfunction, trouble walking, delusions, speech difficulty
degernation of dopaminergic neurons in substantia nigra pars compacta
Parkinson’s disease
treatment for Huntington’s includes
dopamine antagonist (haloperidol)
what causes bradykinesia in Parkinsons?
over inhibited direct pathway, overactive indirect pathway limits movement and –> difficulty initiating/ slow movement. shuffled gait results from this, difficulty turning
what causes rigidity in parkinson’s
over sensitive indirect pathway –> stiff muscles that are resistant to stretch, contribues to postural deformities
what causes resting tremors in Parkinson’s disease?
synchrony of low frequency brain activity due to indirect pathway overactivity ; note that resting tremor often unilateral!
Hemiballism
hyperkinetic disorder resulting from lesion (stroke) to subthalamic nucleus; weakens the indirect pathway and leads to contralateral contractions of proximal limb muscles
Hypokinetic disorders
Parkinson’s disease, Parkinson’s plus disorders, Secondary Parkinsonism
Hyperkinetic disorders
tremor, dystonia, tics, chorea
what factors should you look at when evaluating tremor?
location of tremor, what makes tremor better/ worse, frequency of tremor, amplitude of tremor
low/ medium/ high frequency tremor
4 = low 4-7= high >7 = high
what is a resting tremor
tremor in a body part that is not being actively used; this must be totally supported against gravity! These tremors will increase with activation (mental i.e. math or motor i.e. moving different body part) and improve with voluntary action
what is an action tremor?
these are any tremor that occur with voluntary contraction of a muscle; several types including
postural, kinetic (simple vs. intention), task specific, and isometric
most common movement disorder
essential tremor
when do most essential tremors start? genetic linkage?
can occur at any age but mean onset betwen 35-45 y/o. In 60% of people, there is +FHx, other 40% have no family history
what kinds of tremors are involved in essential tremors?
typically ehse are posture and action tremors that progress over time. Sometimes can see resting tremors with this.
what locations most commonly affected with essential tremor?
bilateral hands> head > voice ; then leg, jaw, trunk and face less commonly affected.
first line treatment for essential tremor
beta blockers (propranolol is best); Primidone (anti seizure med)
propranolol side effects
first line treatment for essential tremor; generally well tolerated but can cause ED in men, depression, fatigue
primidone side effects
first line tx for essential tremor; SE can include dizziness and sedation (typically taken at night)
Second line essential tremor treatments (commonly used ones)
gabapentin and topiramate (others include alprazolam, atenolo, sotalol)
Surgical options for treating essential tremor
ablation and deep brain stimulator (typically into nucleus of thalamus)
average age onset PD
62; higher prevalence in men (estrogen = protective?)
early features of Parkinson’s disease include
resting tremor, muscle rigidity/ cogwheeling, bradykinesia/ akinesia
late features of parkinson’s disease
gait disorder, postural change (leaning forward), postural instability, freezing
diagnostic criteria for Parkinson’s disease
bradykinesia with at least one of the following: rigidity, 4-6 Hz (medium frequency) resting tremor, postural instability
alpha synuclein causes of parkinsonism
PD and multiple system atrophy
tau proteinopathies that can cause parkinsonism
progressive supranuclear palsy
corticobasal degeneration
alpha synuclein and Lewy body + is seen wtih
Parkinson’s disease
MSA-P
multiple system atrophy-P; this is glial cytoplasm inclusion of alpha synuclein. type of neurodegenerative d/o
rapidly progressive Parkinsonism that doesn’t respond to L-dopa.
MSA-P clinical presentation
rapidly progressive postural instability and or dysphagia within few years; can present wiht gait/ limb ataxia, autonomic dysfunction (rare in PD)
putamen discolaration can be seen in
MSA-P
glial alpha synuclein seen in
MSA-P (multiple system atrophy- Parkinsonism)
progressive supranuclear palsy aka
Steel Richardson Olszewski syndrome
progressive supranuclear palsy clinical presentation
Parkinsonism with extrapyramidal sx; can present with supranuclear opthalmoplegia (vertical gaze palsy). can have cognitive problems including dementia, nuchal/ truncal dystonia
PSP sex and age average
2:1 male to female; avg age 50-70
what regions of the brain are affected in PSP?
substantia nigra, CN X and XII, globus pallidus, hippocampus, dentate nucleus of cerebellum, locus ceruleus, subthalamic nucleus, CN II, IV nuclei, red nucleis, colliculus, periaqueductal cord grey matter
phases of corticobasa degeneration (CBD)
phase 1- asymmetric clumsiness
phase 2- Parkinsonism (akinetic, rigid), “alien hand”, sensory cortical dysfunctions,
phase 3: cognitive decline
what is difference between motor unit and motor neuron pool
motor unit is made of single motor neuron and all of the muscle fibers that it innervates. Size of motor unit proportional to size of motor neuron (large = innervate lots of muscle fibers, generate lots of force. Small motor unit = innervates fewer fibers, does finer movement i.e. eye movement)
motor neuron pool = a group of motor neurons that innervate fibers in the same muscle. These can come from multiple spinal cord levels.
what are the three types of motor units, how do they differ
three types- slow, fast fatiguable, and fast fatigue resistant
slow = slowly contracting muscle fibers that generate low force but don’t get tired easily
fast fatigue resistant= contract with intermediate speed. generate intermediate force but will lost some of max force with repeat stimulation
fast fatiguable= contract rapidly and generate max force but get tired fastest
how is graded muscle force developed
partially based on the three different types of muscle fibers but also based on recruitment
overall, force is based on the number of active motor units
size principle= recruitment will occur accoridng to size of motor unit! i.e. smaller recruited first
how do intra and extrafusal muscle fibers differ
extrafusal muscle fibers are those that general force
intrafusal muscle fibers are included in the muscle spindle apparatus and include nuclear bag and chain fibers; these are in parallel with extrafusal fibers and detect changes in length
how does the muscle spindle regulate muscle length
muscle spindle contains fibersr that respond to changes in muscle length (this includes Ia and II afferent fibers)
Ia respond to dynamic changes in muscle length (i.e. upon tap with reflex hammer); linear stretch = increased firing, release = stop diring
II respond to the degree of stretch/ static response
what is the role of the gamma fiber in muscle spindle function
motor fiber that attaches to the ends of the spindle and helps to maintain contracted tone and responsiveness to stretch in the muscle spindle unit
Stretch reflex
monosynaptic; afferent fibers= Ia, efferent = alpha motor; responds to changes in muscle length (contract synergist, relax antagonist)
Golgi reflex
disynaptic; afferent = Ib, efferent = alpha motor; responds to changes in muscle tension. leads to relaxation of synergist, contraction of antagonist
flexor withdrawal reflexes
afferent= II, C (pain), and A delta; multiple interneurons/ polysynaptic; efferent = bilateral alpha motor neurons. Ipsilaterla will lead to flexion (withdraw from pain); contralateral = extension, stabiliize
what are UMN- function, location, and signs of damage?
UMN- modulate activity of LMN to control movement; send descening projections to LMNs
located in motor cortex (precentral and paracentral lobules) and brainstem (vestibular nuclei, reticular formation, etc)
symptoms include: spastic paresis, hyperreflexia, hypertonia, upgoing Babinski
what are LMN- function, location, and signs of damage?
LMN- final common pathway for initiating movement; project axons directly to skeletal muscle
located in spinal cord (ventral aka anterior horn) and brainstem (cranial nerve motor nuclei)
LMN symptoms include: paralysis or weakness (paresis), loss of reflexes or decreased reflexes, flaccidity/ loss of tone, muscle atrophy/ wasting, fibrillations/ fasciculations
structures involves in corticospinal tract
UMN in layer 5 of motor cortex –> posterior internal capsule –> midbrain crus cerebri/ cerebral peduncle –> basilar pons –> medullary pyramids –> decussasion at the pyramidal decussation of medulla –> lateral cortical spinal tract in spinal cord (laterla white matter) –> synapses along ventral/ anterior horn with LMN
structures involved in corticobulbar tract
ventrolateral precentral gyrus of motor cortex (layer 5 pyramidal neurons) –> internal capsule genu –> crus cerebri (midbrain) –> bilateral termination along CN nuclei (general rule) in brainstem
exception: hypoglossal innervates contralateral and lower facial = only crossed innervation
how is posture controlled (feedforward/ feedback mechanisms)
feedforward mech via reticulospinal tract; feedback via vestibulospinal tract. There is also some input from rubrospinal tract, which arises from red nucleus and innervates UE extensors
what kind of neurons project from LMNs?
alpha motor neurons; project directly via ventral root via spinal nerve to peripheral nerves
lateral vs. medial ventral horn difference
lateral anterior/ ventral horn contains cell bodies of distal muscles (fine motor fx)
media anterior/ ventral horn cell bodies contain proximal muscle (posture, balance)
nucleus ambiguus
nucleus of CN IX and X; controls pharynx/ larynx muscles
how do golgi fibers and muscle spindles respond differently to stretch and tension/ force
muscle spindles are responsive to stretch; golgi fibers are responsive to tension;
when a muscle contracts you see increased afferent Golgi activity whereas you have decreased muslce spindle activity
difference between fasciculations and fibrillations
both involve spontaneous electrical activity of muslce fibers that are denervated in cases of LMN symptoms.
fibrillations = need EMG to detect
fasciculations= can be seen with naked eye (i.e tongue fasciculations)
acute poliomyelitis
fecal orally spread viral infection that can cause initial phase of fever, fatigue, nausea, HA, URI/ GI sx, neck stffness and limb myalgia
most severe symptoms present when there is virus attack of LMB in ventral horn (spinal polio); this leads to irreversible flaccid paralysis of limbs. if it involves the brainstem/ bulbar muscles can lead to respiratory failure (bulbar polio)
LMN syndrome and will therefore expect decraeased reflexes but intact sensation
Treatment: NONE; supportive. best = polio vaccine. eradicated most of the world except still endemic in Pakistan and Afghanistan
what is the function of the precentral cortex
part of primary motor cortex; serves to aid in anticipatory/ feedforward motor action planning (not actually initiation of movement)
positive shar waves and fibrillation potential on EMG
sing of inflammation and necrosis; seen with spontaneous EMG (i.e. without contractile effort)
myotonic discharged on EMG
sign of pompe’s disease, toxic myopathy (i.e statins, colchicine), myotonic d/o, periodic paralysis
seen with spontaneous EMG (i.e. without contractile effort)
nerve conduction studies typical findings with myopathy
typically these are normal, unless there is myopathy affecting distal muscles (may see low CMAP amplitude)
angualted atrophic fibers on muscle biopsy
indicate neurogenic changes
rounded atrophic fibers on muscle biopdy
indicate myopathic changes
which myopathies are associated with asymmetric muscle findings
FSH-D (facioscapulohumorla dystrophy) and inclusion body myositis
asymmetric winged scapula
can be seen with FSH-D or with inclusion body myositis
pectoral creases
seen with FSH-D
physical exam findings characteristic of FSH-D
asymmetric winged scapula and pectoral creases
inclusion body myositis
knee extensor weakness, hand/ wrist flexor weakness. most common muscle disorder in those > 50 y/o. ASYMMETRIC muscle weakness.
can also present with asymmetric winged scapula (like FSH-D)
rimmed vacuole seen on biopsy with
inclusion body myositis
myotonic dystrophy subtypes and differences
both result in fixed weakness/ myotonia of mucles. forms = DM1 and DM2
a. DM1= more common, results from CTG repeat, defect in DMPK on chromosome 19q; presents with distal weakness, myotonia bifacial weakness, temporal wasting, frontal balding, ptosis.It is also often a/w cardiac problems, respiratory failure, OSA, cataracts, and endocrine dysfunction.
b. DM2= results from CCCG repeat in ZFN9 on chromosome 3
1. presents with calf hypertrophy and symptoms similar to DM1, but less CNS sx. Proximal muscle weakness/ atrophy
Duchenne Muscular Dystrophy
A. caused by deletion of dystrophin gene; presents around age 3 with proximal > distal weakness that is symmetric in arms and legs. Tend to lose ability to ambulate by adolescence (9-13); Can have pseudohypertrophy of calves (fat buildup, not muscle). Commonly see contractures (esp at ankles) and scoliosis, especially after loss of ambulatory ability.
a. diagnostic labs include: high CK and ALT/ AST.
b. other disease risks = cardiomyopathy and MR
Dermatomyositis
inflammatory disorder that presents with relatively acute onset proximal muscle weakness plus limb and facial rash. in adults, considered possible paraneoplastic syndrome –> cancer screening done. treatment = steroids, followed by steroid sparing agent.
McArdle’s Disease
dz with glycogen phosphorylase with typical onset < 15. presents with exercise and fatigue and can have second wind phenom. Myoglobinuria common (50%). EMG can can show myopathic changes. Testing includes non-ischemic forearm test –> reduced lactate rpoduction with normal ammonia increase. Can also genetically test. On histo- glycogen filled vacuoles in muscle stores. Will also show deficiency myophosphorylase
CPT2 deficiency
can lead to exercise intolerance 2/2 defect with FA metabolism. leads to weakness –> tends to occur with longer periods of exercise than in Mcardles
A alpha fiber
skeletal muscle efferent
IB fiber
skeletel muscle efferent (muscle spindle)
IA fiber
skeletal muscle efferent (stretch)
A delta fibers
skin afferents (temp and fast pain)
C fibers
skin afferents for slow pain and SNS post gang afferents
B fibers
SNS pregang visceral afferents
A gamma fibers
muscle spindle efferent fibers (keep muscle spindle tone appropriate)
what kind of neuropathy follows stocking glove distribution pattern
polyneuropathy
describe the clinical presentation of guillain barre syndrome
tends to present ~2 weeks after a GI or respiratory illness with acute onset proximal and distal weakness that is rapidly progressive and ASCENDING (distal to proximal)
areflexia is common, as is respiratory impairment (can require intubation) and autonomic dysfunction
most common agent = campylobacter jejuni –> molecular mimicry
what kind of damage does GBS cause?
demyelinating polyradiculopathy
how is GBS diagnosed
mostly a clinical diagnosis based on history and exam!!
CSF and EMG studies may be early normal early on, but eventually can show
CSF: cytoalbuminologic dissociation
electrical studies- acquired demyelinating polyneuropathy
MRI can show hypertrophc, contrast enhancing nerve roots
hypertrophc, contrast enhancing nerve roots on MRI can be indicative of what?
GBS
how is GBS treated?
IV Ig or plasma exchange
also need to monitor respiratory function and for signs of autonomic dysfunction. send to rehab!
common causative agents of GBS
campylobacter jejuni = most common cause (30%); 10% caused by CMV
what are some common histologic findings a/w GBS?
perivenular and endoneurial inflammatory infiltrates such as histiocytes, plasma cells along with segmental demyelination
Chronic Inflammatory Demyelinating Polyradiculopathy
onion skinning changes on biopsy secondary relapsing and remission pattern of disease (like chronic GBS)
Charcot Marie Tooth Disease
inherited demyelinating disorder that is most commonly AD form; can also be AR.
treatment is supportive and involves bracing
most commonly inherited neurologic disorder
charcot marie tooth disease
CMT1 genetic cause
duplicaion of PMP22 gene (peripheral myelin protein 22); located on chromosome 17
classic initial symptom of charcot marie tooth disorder
foot drop and foot deformities; can be followd by distal muscle atrophy and sensory loss
when do symptoms of charcot marie tooth disease typically start
early childhood to early adulthood
signs of axonal damage on nerve studies include
decreased signal amplitude; CV should be normal to slightly decreased (not less < 75% normal); latency should be normal to slightly prolonged
signs of demyelination on nerve study include
decrased conduction velocity, prolonged latency, conduction block
median mononeuropathy etiology and sympptoms
caused by compression of median nerve along passage through carpal tunnel; pain, paresthesias along median nerve course.
recurrent thenar motor branch of medina nerve supplies
thenar eminnnce- opponens, abductor pollicis brevis, superficial head of flexor pollicis previs
motor division of median nerve innervates
first and second lumbricals
palmar cutaneous sensory branch of median nerve innervates
thenar eminence- note that this branches before carpal tunnel, so could be spared in compressive mononeuropathy
management of ulnar nerve entrapment
generally conservative, splinting and avoiding prolonged flexion of elbow. if sx last > 6 months –> consider surgery
where does ulnar nerve originate from (spinal levels)
C8-T1; continues along lower trunk to medial cord and continues along medial elbow
fibular nerve spinal level derivation
L4-S1
where does fibular nerve bifurcate
popliteal fossa into common fibular nerve and lateral cutaneous branch.
lateral cutaneous nerve of knee
branches of the common fibular nerve near the popliteal fossa and supplies sensory innervation of lateral knee
branches of common fibular nerve
deep and superficial branch
deep fibular nerve innervation pattern
toe extensors (i.e. extensor digitorum longus, hallicus longus, digitorum brevis)
superficial fibular nerve innervation includes
mid to lower calf sensation; this will also divide into the medial and intermediate dorsal cutaneous nerves, which supply dorsum of foot and dorsal medial 3-4 toes
common causes of fibular neuropathy
prolonged surgery, leg crossing, squatting, casting
fibular neuropathy symptoms include
foot drop, weak eversion (weak fibularis longus), and weak toe extension
what sensory pattern follows with fibular neuropathy
along superficial/ deep fibular nerve distribution –> mid to lower calf, dorsum of foot, dorsal medial 3-4 toes
which muscles are typically spared in ALS
extraocular muslces, sphincters, sensory nerves
painless weakness = hallmark of which disease
ALS
symptoms seen with ALS
UMN = spasticity, hyperreflexia; LMN = atrophy and fasciculations,
pseudobulbar affect (labile), frontotemporal dementia, cognitive changes
mutations seen in familial forms of ALS
10% of cases are familial –> 40-50% have c90rf mutation, 10% have SOD1 mutation
disease modifying drugs in ALS
riluzole and edavarone
edavarone use and MOA
used to modify ALS; MOA not fully known but thought to be antioxidant
Riluzone use and MOA
used to modify ALS; MOA = blocks glutamatergic NT
Spinal muscular atrophy inheritance pattern and mutation
autosomal recessive 2/2 mutation in survival motor neuron gene (SMN1)
SMN1 mutation
seen in SMA
most common fatal genetic disease in infants
SMA (spinal muscular atrophy)
anterior horn degeneration –> weakness and muscle atrophy describes what condition
spinal muscular atrophy; AR disease 2/2 mutation in SMN1 (survival motor neuron gene)
baby with decreased muscle tone (hypotonia)
SMA (spinal muscular atrophy)
most common type of spinal muscular atrophy
type 1, infant onset (sx onset between 0-6 months); these babies have progressive proximal muscle weakness, hypotonia, loss of reflexes;
on exam can have bell shaped chest (poor chest wall expansion with preserved diaphragm)
cognition in SMA1
usually normal
TDP-43 inclusions seen in which disease
implicated in ALS (amyotrophic lateral sclerosis); presents wiht protein rich inclusions of TDP_43(TAR DNA binding protein 43)
also seen in tau and alpha synuclein negative frontotemporal lobar degeneration
what segments of spinal cord will show demyelination in ALS
lateral and anterior corticospinal tracts
Bunina body
seen in ALS; cytoplasmic feature seen in motor neurons
characteristics of Werndig Hoffman Disease
affects nervous system and skeletal muscle; grossly will present with shrunken anterior nerve roots and skeletal muscle atrophy
nerve conduction studies are useful for what disease
peripheral nerve disease
EMG is useful for what types of diseaes
anterior horn syndromes
diabetic neuropathy
generally motor sparing; affects sensation. But can have different forms –> mononeuropathy, autonomic neuropathy, etc.
cytoalbuminologic dissociation
elevated protein and normal WBC count on CSF analysis = sign of GBS
benign peripheral nerve sheath tumors
Schwannoma and neurofibroma
malignant peripheral nerve sheave tumor
malignant peripheral nerve sheath tumor (MPNST)
