First Pass Miss Flashcards
What germ layer gives rise to the meninges? Include the two special terms for meninges.
Leptomeninges - pia / arachnoid mater - neural crest
Pachymeninges - dura mater - mesoderm
What is metabolic astrocytosis?
Proliferation of gray matter astrocytes in response to metabolic injury -> i.e. hepatic or renal failure
How does CSF compare to blood with regards to protein, chloride, glucose, and WBCs? Is it constant along the spinal cord?
Protein - increases towards lumbar cord (non-constant). Normal is <50 mg/dL
Chloride - Higher than blood
Glucose - comparable but slightly lower than blood
WBCs - very few 0-5 cells / mL, elevations suggest meningitis
Produced at a rate of 0.5 L/day
Normal pressure 50-200 mmHg
What is communicating hydrocephalus and what causes it? What will happen to ICP?
Impaired flow or resorption of CSF outside the ventricular system
- > i.e. scarring of arachnoid granulations post-meningitis
- > will increase ICP
What is vasogenic edema? Where does it especially affect?
“White matter edema” - Most pronounced in white matter. Increased interstitial fluid due to blood brain barrier breakdown secondary to inflammation, tumor, etc
Associated with increased protein in the interstitium
What is interstitial edema? Where does it especially affect?
Increased resistance to CSF outflow leads to increased intracranial pressure (obstructive or communicating hydrocephalus) and breakage of blood-CSF barrier, but will NOT cause a protein increase in the interstitium
Basically, edema caused by excess CSF
-> Affects predominantly the periventricular white matter (around where the CSF is)
What are the characteristic signs of increased ICP?
Headache
Papilledema
Vomiting
Cushing’s triad: Bradycardia, high blood pressure, Cheyne-Stokes breathing
Focal neurological signs and dilated / blown out pupils
Abnormal posturing / altered mental status
What is a cingulate herniation also called and what issue can it cause?
Subfalcine - displacement of cingulate gyrus under the falx cerebri
-> can cause compression of anterior cerebral artery, leading to infarction
What are the two types of transtentorial herniations? What might cause them?
These involve displacement of brain structures through tentorium cerebelli opening (incisure)
- Central - bilateral and symmetric, leading to caudal displacement and compression of entire brainstem -> i.e. due to diffuse brain swelling
- > causes fatal Duret hemorrhages (paramedian basilar pontine) - Uncal - unilateral, with herniation of medial temporal lobe into midbrain
- > i.e. due to supratentorial hemorrhage
- > can compress ipsilateral CN3, ipsilateral PCA, and contralateral crus cerebri (false localization sign via Kernohan notch)
What is a tonsillar herniation and what is the usual clinical result?
Herniation of cerebellar tonsils into foramen magnum
Compression of brain stem (medulla) leads to cardiopulmonary arrest
What are the clinical symptoms of most brain tumors?
Increased ICP -> headache, papilledema, due to mass effect
Local damage to structures -> focal neural deficits
Damage to cerebral cortex -> seizures
What molecular abnormalities characterize oligodendroglioma and what is its clinical presentation? What area of the brain is usually involved?
Codeletion of 1q and 19p chromosomes, and isocitrate DH
Clinical presentation - slow-growing tumor in young adults which may contain calcifications. Most often in frontal lobe, causing seizures
Fried egg appearance of oligodendrocytes
What is the most common CNS tumor in children and where does it tend to arise in adults and children? Include the disease association.
Pilocytic astrocytoma - low-grade astrocytoma which does not progress like diffuse gliomas
Children - cerebellum
Adults - cerebral cortex, spinal cord, or associated with optic nerve (optic glioma of NF-1!!!)
How does pilocytic astrocytoma appear grossly and microscopically?
Grossly - cystic lesion with nodular mass which grows adjacently on its wall.
Microscopically - Rosenthal fibers -> thick, eosinophilic aggregates of alpha-B-crystalline which accomulates in processes of astrocytes
What tumor is characterized by perivascular pseudorosettes? Why does it form this pattern, and who tends to get it?
Ependymoma - tumor of ependymal cells which form rosettes around vasculature -> similar to choroid-plexus type shape, which is made of specialized ependymal cells
Tends to be in children
-> causes obstructive hydrocephalus by blocking 4th ventricle
Who tends to get choroid plexus tumors and what is the major presenting symptom?
Tends to occur in children, even infants -> symptom is often congenital hydrocephalus (if in infants) -> overproduction of CSF, or blockade of outflow
papilloma vs carcinoma, only true primary brain tumor which is benign vs malignant
What is “drop metastasis”?
Metastasis to cauda equina -> lower spinal cord
- > spread of medulloblastoma thru CSF
- > medullablastoma can also cause obstructive hydrocephalus by compressing 4th ventricle
- > homer-wright rosettes around pink neuritic cell process (neuropil), grows in cerebellum
What is the most common benign CNS tumor in adults and who tends to get it? What is the cell of origin?
Meningiomas - more commonly seen in women because it expresses the estrogen receptor
Cell of origin - arachnoid cells (neural crest derived)
- > associated with chromosome 22 deletions (think meningiomas in NF-2)
- > form calcified psammoma bodies
How is a Schwannoma different from a neurofibroma, and what genetic disease is associated with each?
Schwannoma - generally grow as solid masses - often associated with NF-2 (bilateral acoustic Schwannoma)
Neurofibromas - infiltrative growth pattern in nerve - associated with NF-1 - unable to resect without nerve damage
What is Leptomeningeal carcinomatosis? What does it mimic?
Spread of tumor cells into subarachnoid space and through CSF
-> mimics acute or chronic leptomeningitis due to high CSF protein, hydrocephalus, and involvement of multiple cranial and spinal nerve roots
What are Brudzinski’s and Kernig’s signs and what are they indicative of?
Indicative of acute meningeal irritation
Brudzinski - “B”ringing the neck forward in flexion -> observe for any flexing of hips and knees
Kernig sign - Starting from flexed hip / knee - extension of knee is resisted
How does the clinical syndrome of aseptic meningitis differ from acute purulent meningitis?
Systemic signs of fever / headache are still there, but it is generally milder and does not cause significant alteration in levels of consciousness. Mild and self-limiting.
-> usually caused by enteroviruses, but may be caused by carcinomatous meningitis, or chemicals / drugs
-> acute purulent often causes focal CNS signs, seizures, and alteration of consciousness
What is chronic meningitis and what is it caused by?
Chronic inflammatory process of leptomeninges
- > relatively persistent or indolent agents
- > TB, sarcoidosis, meningovascular syphilis, etc
How is chronic meningitis diagnosed? CSF characteristics?
Non-specific findings of slowly evolving headache, low-grade fevers, rarely seizures / cognitive dysfunction. Difficult to diagnose.
CSF - increased pressure due to blockage of CSF flow
Increased protein
Decreased glucose, but not as much as acute
Leukocytosis - predominantly lymphocytes and monocytes (forming granulomas)
What cells does Rabies affect?
Pyramidal cells of the hippocampus (think of pyramid in boat with seahorse) + Purkinje cells of cerebellum (think of bungee cords from tree (folia of cerebellum)
Cytoplasmic inclusions = Negri bodies
How does virus usually spread to the brain, and how is encephalitis diagnosed?
Sometimes by axonal transport, but usually hematogenous spread
- > Diagnosed via index of suspicion especially following aseptic CSF findings
- > can do PCR assay for virus (HSV1 most common)
What are a few examples of agents causing chronic “slow” viral hepatitis?
HIV - AIDS dementia
JC virus - PML
Measles - SSPE
HTLV-1 - tropical spastic paraparesis
What is the pathogenesis of meningitis in HIV?
Acute - can cause acute aseptic meningitis during primary infection
Chronic HIV encephalitis - progressive dementia and infected monocytes / T cells cross BBB and infect microglia / damage white matter -> progressive demyelination like PML
What are the Tauopathies?
Disorders of tau protein accumulation
Alzheimer’s, Pick disease, progressive supranuclear palsy
What are three other common changes seen in elderly patients with or without diagnosis of Alzheimer’s disease?
- Hirano bodies - crystalloid, rod-like structures made of actin alongside hippocampal neurons
- Granulovacuolar degeneration - intracytoplasmic vesicles with tau core
- Amyloid angiopathy - deposition of beta-amyloid in walls of leptomeningeal and intracortical blood vessels
How is A-beta amyloid formed? How is it usually cleared?
APP is normally cut by alpha-secretases
If APP is cut by beta-secretases -> this is further processed by gamma secretase and forms I-40 and I-42 beta-amyloid.
It is neurotoxic and usually degraded and cleared by proteosomes of astrocytes
What is Pick disease? What are the symptoms?
Frontotemporal dementia
Frontal lobe effects - behavioral symptoms, especially disinhibition
Temporal lobe - aphasia (language effects)
-> associated with 3R tau accumulation
Microscopic - “Pick bodies” - round aggregates of tau protein in neurons of the cortex
What drives amyloid formation in sporadic vs familial forms of Alzheimer’s?
Sporadic - environmental factors such as metal ions, free radicals, and oxidative stress
-> antioxidants may be of some benefit
Familial - mutations induce misfolding of amyloid
What are the characteristic physical exam findings and EEG findings of CJD? CSF?
Physical exam - rapidly progressive dementia with startle myoclonus
-> MRI enhances in basal ganglia
EEG findings - periodic sharp waves
CSF - elevated levels of 14-3-3 protein
What does the pathology of CJD look like?
- Spongiform degeneration -
Represents intracellular vacuoles filled with abnormal PrPsc protein -> tends to be in gray matter areas where there its lots of neuropil (vacuolated cytoplasmic processes) - Gliosis - extensive astrocyte hyperplasia and activation of microglial cells (beyond what would be normally expecting)
- Neuronal loss - apoptosis with activation of microglial cells, but minimal inflammation and minimal atrophy (since so rapid)
- Amyloid plaques - in various places depending on exact type of CJD
Susceptibility determined by codon 129 on chromosome 20
Define anomia, anosognosia, neglect
Anomia - difficulty finding words - (without name)
Anosognosia - difficulty to recognize illness / lack of awareness of one’s disability
(without-disease-knowledge, nosos = disease)
Neglect - Inattention to stimuli from one side of the visuospatial environment
How do transcortical motor / transcortical sensory aphasia differ from other aphasias?
Transcortical motor - affects frontal lobe around Broca’s area. Similar symptoms except repetition is intact (Broca’s area not affected)
Transcortical sensory - affects temporal lobe around Wernicke’s area. Similar symptoms except repetition is intact (Wernicke’s area not affected)
Transcortical mixed aphasia = echolalia
What does a dominant parietal lobe lesion cause?
Gerstmann’s syndrome
- think of someone trying to count their fingers
Tetrad:
-Finger agnosia - cannot identify finger named by examiner or recognize which finger has been touched / moved
-Left-right disorientation
-Acalculia
-Agraphia - writing impairment
What will lesion of the nondominant parietal lobule cause?
Contralateral neglect, often with anosognosia of the issue.
If it affects more superior portion can cause constructional apraxia (difficulty drawing objects like clockface) or dressing apraxia (poor processing of spatial information so cannot put clothing on well)
What is Balint’s syndrome? What is notably preserved?
Triad:
1. Oculomotor apraxia - cannot gaze effectively via saccadic eye movements
- Optic ataxia - can’t reach out to a visual target accurately (i.e. finger to nose on someone else, but could do on themselves easily since proprioception is intact)
- Simultanagnosia - visual inattention, can’tt ell whole from the parts. Often associated with prosopagnosia.
Basically similar in reasoning to Anton syndrome, and Anton may recover thru Balint’s.
Color vision is notably preserved. -> loss would occur in achromatopsia due to inferior occipital lobe lesions
What is visual agnosia?
Ability to see and describe an object’s features without being able to recognize / name it, as well as associate it with its function
Patient does not have anomia - i.e. they can tell you what a glove is
They can even draw the object and match it to a drawing or picture
i.e. man who took his wife for a hat
What are the portions of the brain responsible for each type of memory?
Working memory / attention span - frontal cortex
Short-term memory and longterm memory - hippocampus and neocortex
Motor skills / conditioned reflexes - cerebellum / neocortex
What are the symptoms of amnestic syndrome?
Mixture of anterograde and retrograde amnesia which will improve as the lesion resolves
-> patient will be left with a memory gap
What is transient global amnesia?
An acute onset transient anterograde amnesia which is usually benign, but leaves a permanent memory gap during that period
There will be a full recovery of anterograde memory
What are the symptoms of dissociative amnesia?
Inability to recall DISTANT memories -> personal information, with intact recent memory for recent events (how it is differentiated from other amnesias, violates Ribot’s law)
- > usually occurs secondary to longterm trauma or stress
- > may be accompanied by dissociative fugue (wandering)
What scale helps distinguish vascular dementia from other kinds of dementia? How does it work / what is it looking for?
Modified Hachinski Ischemic Score. Score >7 = vascular dementia
-> Asks about abruptness of onset, stepwise deterioriation, presence of risk factors for CVAs, and focal neurologic signs which would not be present in other causes of dementia
What are the clinical features of Lewy body dementia? What precipitates symptoms?
Changes in attention and alertness that fluctuate greatly
Frequent visual hallucinations
Parkinsonism within 1 year of dementia onset
Symptoms precipitated by antipsychotics and antinausea drugs (metoclopramide) which are D2 receptor antagonists -> worsen parkinsonism
What are a few routine tests which should be done to rule out other causes of dementias?
Serum B12, LFTs (hepatic encephalopathy), thyroid function tests, depression screenings (pseudodementia), BUN/creatinine (metabolic encephalopathy), etc
What is mild neurocognitive disorder define? “pre-dementia”
Modest cognitive decline in one or more cognitive domains: Complex attention Executive function Learning and memory Language Perceptual-motor Social cognition
Range of 1-2 standard deviations below normal, but do not interfere with function and are not due to another mental disorder or delirium
How does vasogenic vs cytotoxic edema appear differently via imaging?
Vasogenic - extracellular edema due to BBB breakdown, follows white matter tracts in FINGER-LIKE projections - “white matter edema”
Cytotoxic - intracellular edema from disruption of Na/K pump - involves both gray and white matter (seen in acute stroke from ischemia) - no finger-like projections, involves large areas, MOSTLY gray matter involvement
What contrast type is used for CT and for MRI? What are the risks for each?
CT - iodine-based -> may cause nephropathy
MRI - gadolinium-based -> may cause nephrogenic systemic fibrosis, a scleroderma-like syndrome. Happens less now that we do MRIs less.
What are normal X-rays / radiographs still important for in spine evaluation? Where have they been supplanted?
Important in LIGAMENTOUS instability with flexion / extension films
-> very cheap and easy to use. Can see bony fractures, deformities, and osteophytes
Also okay for evaluation of radiculopathy (spinal nerve root impingement)
Have been supplanted in evaluation of trauma -> CT shows improved fracture detection.
-> Fractures are only thing which CT is better than MRI for
What is the only thing which CT has no efficacy in at all and cannot be done for?
Cord signal abnormalities -> cannot detect demyelinating diseases of the cord via CT
What is the best way to workup arthritis / degenerative disc disease in imaging?
Best: MRI if patient able
Best alternative: CT / CT myelography if patient is not MRI compatible
How is epilepsy defined? Three definitions.
- At least two unprovoked seizures occurring more than 24 hours apart (could be 60 years).
- One unprovoked seizure and a probability of further seizures (i.e. tumor was due to a tumor, trauma, or stroke and will likely recur)
- Diagnosis of an epilepsy syndrome
When does Todd’s paralysis occur and what is it?
When there is a seizure of the premotor cortex
- > post-ictal paresis contralateral to seizure side
- > occurs due to depletion of glutamate during seizure
Where do partial vs generalized seizures generally start?
Partial - Medial temporal lobes
Generalized - Thalamus
What else is on the differential diagnosis of seizures?
- Movement disorders
- REM sleep behavior disorder (may be mistaken for frontal lobe epilepsy)
- Migraines with auras (vs simple partial seizures)
- Limb-shaking transient ischemic attacks
- Syncope
- Hyperventilation syndrome
- Psychogenic non-epileptic spells
What type of syncope mimics seizures? How is it told apart?
Convulsive syncope where patient can have myoclonus, hallucinations, automatisms, etc
Syncope is precipitated by postural changes, has a long prodrome, is precipitated by emotion, pain, heat, is not associated with post-ictal confusion, and is commonly associated with cardiovascular signs
What is the most common epilepsy syndrome and what is the most common neuropathologic finding in patients when it is medically refractive?
Temporal lobe epilepsy
- > commonly caused by hippocampal sclerosis / mesial temporal sclerosis
- > neuronal loss and gliosis in CA1/3 of ammon’s horn, dentate gyrus, subiculum, and entorhinal cortex
What is Benign Epilepsy with CentroTemporal Spikes (BECTS) and what is the prognosis?
Focal epilepsy syndrome characterized by epileptiform spikes on EEG
Occurs in children age 3-13 years, can have hemifacial motor seizures and facial twitching which usually occurs at night -> may progress to bilateral tonic clonic
No treatment is generally required because there will be remission by mid-teens
What seizures characterize juvenile myoclonic epilepsy (JME)? What precipitates them?
- Myoclonic jerks of arms (usually early morning)
- Generalized tonic-clonic
- Behavioral arrest / staring spells
Precipitated by sleep deprivation, alcohol use, and stress
4-6 Hz spike and wave, seizures controlled by meds for life
What is the diagnostic triad of Lennox Gastaut syndrome? Prognosis?
- Multiple seizure types (atonic, absence, tonic, generalized tonic-clonic)
- Developmental delay
- Slow 1-2.5 spike and wave on EEG as a baseline (not just during seizures)
-> patient will have static encephalopathy with poor prognosis
What is EEG actually recording? And what is the gold standard for seizure diagnosis?
Summation of excitatory or inhibitory post synaptic potentials -> NOT action potentials (dendritic processes of outer cortex have EPSP and IPSP)
Gold standard: Epilepsy monitoring unit -> video recording of seizure with EEG
What are the non-pharmacologic treatment options for focal seizures? Generalized?
- Resective surgery
- Vagus nerve stimulator
- Responsive neurostimulator device (i.e. deep brain stimulation) -> implanted near brain foci to terminate seizure
Generalized - vagus nerve stimulator and corpus callosectomy
