Notes 2b Flashcards
Ataxia-telangiectasia
inheritance
mutation
features
lab thats high
AR
ATM gene on chromosome 11 → impaired DNA repair
- neuropathy, ataxia, and extraocular movement abnormalities (cannot move eyes without head thrusting)
- Telangiectasis in conjunctiva and other places
high serum alpha fetal protein
Spinocerebellar ataxia
inheritance
mutation
features
AD
CAG expansion on ataxin gene in chromosome 14
theres several types, like over 20. all have progressive truncal and limb ataxia, often associated with spasticity and other UMN findings
Most common type of spinocerebellar ataxia
SCA 3 (Machado-Joseph Disease)
Which SCA type is associated with retinopathy and vision loss
SCA 7
Cerebrotendinous xanthomatosis
inheritance
mutation
features
lab thats high
AR
defect in enzyme 27-sterol hydroxylase on chromosome 2
results in cholesterol deposits into various tissues, including the brain: neuropsych issues, ataxia, parkinsonism, neuropathy, tendon xanthomas especially in the Achilles tendon.
serum cholestanol is high
Orthostatic tremor: features
affects trunk and thighs, unsteadiness when standing with improvement when given physical support or with ambulation
Fahr’s Disease
features
- striopallidodentate calcinosis, benign hereditary calcification of the basal ganglia)
- CT finding of calcification most commonly in the caudate, putamen, thalamus and cerebellum
Profound hyperglycemia can cause what signs on MRI
T1 hyperintensity in the striatum
Most common gene mutation in hereditary Parkinson’s disease
LRRK 2
BUZZWORDS: Tongue protrusion dystonia, chorea, acanthocytes on wet most peripheral smear
Neuroacanthocytosis
BUZZWORDS: Huntington’s Dz- inheritance, chromosome abnormality
AD
CAG repeat chromosome 4
BUZZWORDS: primary generalized dystonia mutation?
Torsin A on chromosome 9
BUZZWORDS: filipino with generalized dystonia and parkinsonism
DYT3 Dystonia or Lubag’s Disease
X-linked dystonia and parkinsonism
BUZZWORDS: Dystonia in a young girl with diurnal variation
dopa responsive dystonia
BUZZWORDS: mutation in dopa-responsive dystonia
GTP cyclohydrolase (GCH1) on chromosome 14
BUZZWORDS: episodic ataxia with facial twitching
dx
gene
triggers
tx
Episodic ataxia type 1
KCN1A
exercise, startle
ASMs like CBZ
BUZZWORDS: episodic ataxia with nystagmus and dysarthria
dx
gene
triggers
tx
episodic ataxia type 2
CACN1A4
alcohol, fatigue, stress
acetazolamide
BUZZWORDS: NT implicated in familial hyperekplekia (exaggerated startle syndrome)
glycine
BUZZWORDS: ataxia with high serum AFP
Ataxia telangiectasia
BUZZWORDS: ataxia, parkinsonism in the grandfather of a patient with Fragile X syndrome
Whats the mutation?
FXTAS (fragile x tremor ataxia syndrome)
CGG repeat in FMR1 gene on X chromosome.
Imaging findings in FXTAS?
T2 hyperintensities in cerebellum and inferior cerebellar peduncle
BUZZWORDS: eye of the tiger sign on MRI
hyperintensity surrounded by hypointensity in BG, seen in PKAN (panthothenate-kinase-associated neurodegeneration)
BUZZWORDS: halo sign on MRI
hyperintense lesion on T1 in cerebral peduncles, seen in
BPAN (beta-propeller protein associated neurodegeneration
demyelinating plaques in MS consist mostly of
macrophages (in the core of the plaques) and glial cells
What are shadow plaques in MS
areas of remyelination where oligodendroglial cells are reduced in the plaque core and increased at the periphery
Black holes in MS are
lesions with reduced T1 signal: older plaques with significant axonal loss
Tumefactive MS sign on MRI
Tx
open ring sign (incomplete peripheral enhancement) with limited mass effect
PLEX/IVIG
ADEM (acute disseminated encephalomyelitis)
features
MRI
Tx
different entity from MS, presents with encephalopathy after an infection of vaccine.
MRI with multifocal large lesions than can involve the BG
IV steroids
Balo’s concentric sclerosis
features
MRI
subset of MS: progressive demyelinating disorder in which concentric rings are seen on MRI
MRI with rounded lesions with alternating layers of high and low signal intensity
MOA of dimethyl fumarate (tecfidera)
anti-oxidant effect of NF2, unclear MOA
MOA of teriflunomide (aubagio)
okay in pregnancy?
inhibits dihydro-orate dehydrogenase (DHO-DH) involved in pyrimidine synthesis for SNA synthesis
TERATOGENIC
glatiramer is assoc with what SE?
okay in pregnancy?
lipoatrophy
safest in pregnancy
MOA of cladribine? (Mavenclad)
purine analog, B and T cell inhibitor
MOA of evobrutinib
Bruton-tyrosine kinase inhibitor, acts on B cells and macrophages
MOA of Natalizumab (Tysabri)
Side effect
Ab against alpha-4-integrin (cellular adhesion molecule). Binds to lymphocytes and prevents adherence at the endothelial surface of blood vessels.
1 in 1000 risk of PML
If patient on natalizumab (tysabri) begins to develop PML, what should you do?
stop tx and start PLEX
Mitoxantrone is assoc with
tx related leukemia and dose dependent cardiomyopathy
MOA of fingolimod (gilenya)
SE?
sphingosine-1-phosphate (causing uncoupling and internalization of this receptor)
bradycardia, macular degeneration, inc risk of VZV
MOA of alemuzimab (lemtrada)
SE?
selectively binds to CD52 on B and T cells, macrophages, and NK cells
hyperthyroidism and ITP
Dalfampridine MOA?
is used for?
SE
inhibitor of voltage sensitive potassium channels
helps with walking in MS patients
lowers sz threshold, insomnia, pain, nephrotoxic
Transverse myelitis
What is it
Caused by
term used for patients with subacute myelopathy which appears to have an immunologic bases
NMO, MS, viral illness, mycoplasma infection, vaccines, lupus, sarcoid
Uhthoff’s Phenomenon
transient worsening of a demyelinating disorder with heat of exercise
Lhermitte’s sign
electric shock like sensation down the body with neck flexion: suggest dural or meningeal irritation seen in transverse myelitis
Pulfrich’s sign
visual phenomenon in which patient has trouble following objects: 2D objects are perceived as moving 3 dimensionally
assoc with INO or demyelinating optic neuritis
MRI findings in astrocytomas?
T2 intense lesions without enhancement with gad
Pleomorphic xanthoastrocytoma: location and presentation
temporal lobe and presents with seizure
Treatment for leptomeningeal carcinomatosis
full body radiation and IV methotrexate
Batson’s plexus
network of valveless veins that connect pelvic veins with internal vertebral veins
main way that prostrate cancer can spread to the meninges
Neuroblastoma
presents with
tx
opsoclonus myoclonus syndrome, irregular high amplitude eye movements that occur in any direction, myoclonic jerks and ataxia
ACTH and resection
Opsoclonus myoclonus syndrome can also be seen in?
adults with Anti-Ri Ab (aka ANNA-2 Ab) which is associated with breast cancer as well as small cell lung cancer
most common primary brain tumor
glioma
Grade 1 gliomas are assoc with what mutation that improves prognosis
IDH1
Grade 3 (anaplastic) gliomas are assoc with what mutation
p53
Typical brain tumor that crosses the corpus callosum
GBM
butterfly lesion
GBM:
path
tx
prog
perinecrotic pseudopallsading nuclei
temozolamide, resection, radiotherapy
15 mo or less
Oligodendoglioma
path
deletion with better prog
“fried egg” and “chicken wire” appearance of capillaries
1p19q deletion has better prog
Ependymoma
path
what is assoc with worse prog
perivascular pseudorosette (in which the cells surround the blood vessels)
drop metastases (when brain tumors met to the spine)
Medulloblastoma
path
poor prognostic markers?
most common genetic defect
Findings on MRS
Homer Wright rosettes
onset <3yo, N-mc transcription factor amplification
most common genetic defect on chromosome 17
high choline peak, high taurine peak, low N-acteylaspartate
Pilocytic astrocytoma
path
associated with
Rosenthal fibers
NF-1
Meningioma
path
sign on MRI
assoc with (3)
monomorphic cells with psamomma bodies
dural tail on MRI, isointense to grey matter on T1/T2 with homogenous enhancement
assoc with NF-2, previous radiation and breast cancer
Pleomorphic xanthoastrocytoma (PXA)
path
location
MRI
prognosis
can see rosenthal fibers
well demarcated tumor usually in temporal lobe
enhancing moral nodule on MRI
good prog can be resected
Subependymal Giant cell Astrocytoma (SEGA)
location
assoc with
Seen in 3rd or lateral ventricles
assoc with TSC
Most common primary cerebellar tumor in adults
hemangioblastoma (benign vascular tumors)
Hemangioblastoma
MRI
secretes?
assoc with
demarcated and cystic cyst with an enhancing mural nodule
erythropoetin-like substance is secreted, causes secondary polycythemia
Von Hippel-Lindau mutation on chromosome 3
Ganglioglioma
location
MRI
path
markers
temporal lobe, presents with seizures
cyst with enhancing mural nodule
eosinophilic granular bodies
GFAP+ and synoptophysin +
Neurocytoma
location
marker
lateral or 3rd ventricle
synoptophysin +, GFAP (-)
Dysembryoplastic neuroepithelial tumor (DNET)
path
location
MRI
“floating neurons” which are mucinous cysts around neurons
temporal lobe
nodular or cystic lesion that is hyperintense on T2 and does not enhance
CNS Lymphoma
path
patient pop
assoc with
MRI
prog
tx
hyperplastic cells around vessels
immunocompromised
EBV
T2 hyperintensity, edema and contrast enhancement
poor prog
steroid responsive, (avoid before bx)
Craniopharyngioma
originates from
MRI
path
remnants of Rathke’s pouch in the sellar region
cystic tumor that causes mass effect on the optic chiasm, pituitary, ventricular system, that area
mix of solid and cystic componenets on path
Choroid plexus papilloma: population and location
childhood, lateral ventricle and resectable.
Chordoma
what is it
arises from
presents with what based on loc
invasive osseodesctructive tumor
remnant of primitive notochord
- If in the clivus: headache, neck pain, multiple CN neuropathies (due to brainstem compression)
- If in sacral area: sphincter dysfunction and pain
Vestibular schwannoma
common loc
presents with
MRI
path
marker
cerebellopontine angle tumor from CN8: can compress the brainstem/internal auditory meatus
hearing loss, tinnitus, cerebellar findings
isointense tumors with contrast enhancement
Verocay body: cells and nuclei tend to be elongated, sometimes in pallisade configuration
Most common CNS tumors in children (3)
- pilocytic astrocytoma
- medulloblastoma
- ependymoma
Most metastatic CNS tumors are supra or infratentorial
supra
Most common source of mets to brain?
- lung
- breast
- melanoma
- colon
- kidneys
Colon and pelvis cancers, if they do metastasize tend to go where?
posterior fossa
MRI findings that indicate mets
round, well demarcated, located in grey-white junction and hyperintense on T2 with significant gad enhancement and vasogenic edema
Paraneoplastic cerebellar degeneration
assoc with what cancers
Ab assoc (3)?
ovarian and breast
Anti-Yo Ab (antibody to Purkinje cells) assoc with ovarian cancer
Anti-Hu assoc with small cell lung cancer
Anti-Tr9 assoc with lymphoma
Limbic encephalitis
assoc with what Abs
Anti-Hu (small cell lung ca)
Anti-Ma (testicular germ cell tumors)
Anti-VGKC (voltage gated K channels)
Dermatomyositis assoc with what cancers?
ovarian, lung, colorectal and pancreatic
Polymyositis is assoc with what cancers
Non-Hodgkin lymphoma, lung, bladder cancer
Ab assoc with poly/dermatomyositis
Anti-Jo
Antibody assoc with paraneoplastic optic neuropathy
anti-CRMP5 (lung cancer)
Antibody assoc with paraneoplastic retinal degeneration?
anti-recoverin Ab (small cell lung cancer, thymoma)
Antibody assoc with paraneoplastic subacute sensory neuropathy?
anti-Yo (ovarian cancer)
Antibody assoc with paraneoplastic LEMS?
anti-voltage gated Ca channels of P/Q type
Antibody assoc with paraneoplastic chorea?
anti-Hu and anti-CRMP5 Ab (lung cancer)
colloid cysts commonly arise in?
foramen of monro
Colloid cysts on MRI
inc T1 signal with no enhancement
How to differentiate epidermoid cysts from arachnoid cysts on MR
epidermoid cysts have restricted diffusion on DWI
BUZZWORDS: marker of nuclear proliferation
Ki-67
BUZZWORDS: marker for T cells
CD3
BUZZWORDS: marker for B cells
CD20
BUZZWORDS: chromosome 1p and 19q deletion is good prog for?
oligodendoglioma
BUZZWORDS: SEGAs are assoc with
Tuberous sclerosis
BUZZWORDS: Ab assoc with small cell lung ca, paraneoplastic sensory neuropathy,
Anti-Hu (ANNA-1)
BUZZWORDS: Ab assoc with opsoclonus myoclonus, breast cancer and ovarian cancer
Anti-Ri (ANNA-2)
BUZZWORDS: opsoclonus myoclonus in children
Neuroblastoma
Paraneoplastic encephalitis assoc with ovarian teratoma?
anti-NMDA
BUZZWORDS: stiff person syndrome: paraneoplastic Ab vs nonparaneoplastic?
para: anti-amphiphysin
nonpara: Anti-GAD
Giant axonal neuropathy
inheritance
mutation
features
pathognomonic pathology
prog
AR
mutation in GAN gene (gigaxonin)
sensorimotor polyneuropathy, UMN, optic atrophy, tightly curled hair, characteristic gait walking on inner edges of feet
large focal axonal swelling that contain tightly packed disorganized neurofilaments.
poor- die by adolesence
Refsum Disease
inheritance
mutation
features
tx
AD
defect in fatty acid metabolism leading to accumulation of phytanic acid
retinitis pigments, cardiomyopathy, neuropathy (large fiber sensorimotor), hearing loss, anosmia, cerebellar signs
diet low in phytanic acid
EMG evidence of axonal loss
reduction in action potential amplitude, tend to have preserved or mildly reduced conduction velocities.
Sensory NCS measures?
SNAP amplitude
sensory latency
conduction velocity
what is the SNAP
measure of the number of axons conduction between the stim site and the recording site.
what is sensory latency
time it takes for the action potential to travel between the stim site and the recording site of the nerve
conduction velocity
obtained by dividing the distance between the stim site and the recording site by the latency
Motor NCS measures?
CMAP
motor latency
conduction velocity
CMAP is a measure of
the status of neuromuscular junction and muscle fibers
what findings correlate with axon loss vs demyelination
decreased amplitudes = axon
prolonged latency/slow velocity = demyelinating
chronic alcoholism leads to what findings in the brain
atrophy of the cerebellar vermis and truncal ataxia
LGI1 encephalitis
cell surface protein associated antibody syndrome characterized by faciobrachial dystonic seizures
Encephalitis + seizures ^ and behavioral/memory changes.
Does not respond to ASMs but does respond to immune therapy.
diffuse astrocytomas can be divided into?
fibrillary, gemistocytic, protoplasmic, small cell, giant cell, epithelioid, granular cell, glioblastoma with oligodendroglioma component
astrocytoma
anaplastic astrocytoma
glioblastoma
WHO grades?
2
3
4
SEGA: WHO grade?
1
