Neurology UWorld Flashcards
Waterhouse-Friderichsen disease
Fulminant meningococcemia resulting in bilateral adrenal hemorrhage.
What does the internal capsule do?
Anterior limb: separates caudate nucleus from globus pallidus and carries some thalamocortical fibers
Genu: carries corticobulbar fibers
Posterior limb: separates thalamus from putamen and globus pallidus and carries corticospinal motor and sensory fibers, visual fibers and auditory fibers.
Genetic associations with Alzheimer’s disease
APP on chromosome 21 - Down’s syndrome
Presenelin 1 on chromosome 14 - early onset
Presenelin 2 on chromosome 1 - early onset
ApoE4 - late onset
Gabapentin mechanism of action in treatment of seizures
Inhibits pre-synaptic voltage-gated Ca2+ channel and prevents vesicle release
Levatiracetam mechanism of action in treatment of seizures
Disrupts neurotransmitter vesicle fusion
Phenytoin and carbamazepine mechanism of action in treatment of seizures
Prevent action potential generation in the axon hillock and propagation down the axon by inhibiting voltage-gated Na+ channels
A patient presents with mental retardation and low serum levels of serotonin and dopamine and high serum phenylalanine. How should you treat this patient?
Dihydropteridine reductase deficiency results in decreased synthesis of serotonin due to reduced conversion of BH2 to BH4 by dihydropteridine reductase for the enzyme tryptophan hydroxylase. There is also reduced dopamine because phenylalanine hydroxylase and tyrosine hydroxylase need BH4 to convert Phe to tyrosine and tyrosine to DOPA, respectively. This child should avoid Phe-containing foods and receive BH4 supplementation.
Enzyme involved in formation of GABA
Glutamate decarboxylase (from glutamate)
Enzyme involved in formation of glutamate
Glutaminase (from glutamine)
Superior vs. inferior gluteal nerve injuries
Superior = Trendelenberg gait from paralysis of medius and minimus
Inferior = difficulty rising from a chair or climbing stairs due to paralysis of gluteus maximus
Enzyme involved in joining Okazaki fragments on the lagging strand
DNA ligase
Lamotrigine side effect
SJS-TEN
How does toxin from Clostridium tetani cause unregulated firing of primary motor neurons?
Tetanospasmin migrates up motor neurons by retrograde axonal transport to the medulla and spinal cord where it is cleaved and inhibits inhibitory release of GABA and glycine from the spinal inhibitory neurons that results in increased activation of lower motor neurons.
A patient presents after head trauma, unable to grab something palpated by his left hand with his right hand. He is otherwise normal. What structure is most likely affected in this patient?
Corpus callosum lesions can cause split brain syndrome, as seen in this patient.
3 domains of frontal lobe syndrome
Disinhibition, apathy and disorganization
Microscopic features in a patient with Guillain-Barre
Segmental demyelination and endoneural inflammation with lymphocytes and macrophages.
Pathophysiology of Fragile X syndrome
Mutation of FMR1 gene on chromosome X -> 200 CGG repeats -> hypermethylation of DNA -> gene inactivation.
Use of edrophonium
Diagnosis of myasthenia gravis. Condition should improve immediately with this AChE inhibitor. Treat with neostigmine or physostigmine.
What would happen if there were CSF obstruction at the foramen of Monro?
Enlargement of only the one lateral ventricle that drains through that foramen
How does isoniazid cause peripheral neuropathy?
It competes with B6 (pyridoxine) for binding sites in synthesis of multiple neurotransmitters. It also increases excretion of B6, resulting in vitamin deficiency.
Carbamazepine side effects
Marrow suppression, hepatotoxicity and SIADH
Ethosuximide mechanism of action and use
Blocks T-type Ca2+ channels, 1st line for absence seizures.
Cholinergic agonist use in medicine
Bethanochol: used for post-operative ileus and urinary retention
Carbachol and pilocarpine: miosis causes the iris to move further from the cornea, used in treatment of glaucoma
Pupillary light reflex
Light -> CN II -> bilateral pretectal nuclei in superior colliculus of midbrain -> bilateral Edinger-Westphal nuclei -> pre-ganglionic parasympathetic fibers in CN III -> Ciliary ganglion -> post-gangiolonic parasympathetic fibers -> pupillary constriction
Fish toxins that inhibit voltage gated Na+ influx? Ones that keep voltage gated Na+ channels persistently open?
Inhibit influx: tetrodotoxin (pufferfish) and saxitoxin (red tide)
Persistently open: ciguatoxin (eels) and batrachotoxin (frogs)
Valproic acid mechanism of action in seizure treatment
Blocks NMDA receptors, increases K+ efflux, blocks Na+ channels and potentiates GABA receptors.
How does a globus pallidus externus lesion differ from an internus lesion?
In normal physiology, DA binding to D2 -> inhibition of GPe -> disinhibits STN -> GPi stimulation -> thalamic inhibition. A GPe lesion would cause bradykinesia because the STN would never be inhibited -> GPi constitutively activated -> constant thalamic inhibition.
In normal physiology, DA binding to D1 -> inhibition of GPi -> disinhibition of thalamus. A GPi lesion would result in continuous thalamus activation and increased movement.
Symptoms of internal capsular stroke
Contralateral pure facial, UE and LE weakness with UMN lesion signs
What is responsible for the majority of side effects associated with 1st generation anti-histamines?
Anticholinergic, anti-serotonergic and alpha-blocking effects
Microscopy of the temporal lobe of a patient who died of HSV encephalitis
Cowrdry A intracytosplasmic inclusion bodies in glial cells.
Multi-nucleated giant cells.
Most common cause of viral meningitis
Enterovirus (coxsackie, echo and polio)
Inherited disorders caused by mutations in DNA repair enzymes
Ataxia-Telangiectasia: DNA hypersensitivity to radiation -> cerebellar atrophy, recurrent sinopulmonary infections, occult telangectasias and cancer
Xeroderma pigmentosum: DNA hypersensitivity to UV radiation -> early malignant melanoma and squamous cell skin cancer.
Fanconi anemia: DNA hypersensitivity to cross-linking agents
Bloom syndrome: generalized chromosome instability and increased cancer
HNPCC: DNA mismatch-repair enzyme defect -> colon cancer
Histology of prion disease
Vacuoles in neurons and PMNs that results in spongiform encephalopathy
CSF analysis in patients with narcolepsy
Absence of hypocretin-1 and 2. These neuropeptides are produced in the lateral hypothalamus, an area that promotes wakefulness.
Amino acids to avoid in a child with propionic acidemia
They have a deficiency in the conversion of propionic acid to methylmalonic acid by propionic acid decarboxylase + biotin. Branched chain amino acids like leucine, valine, isoleucine, threonine and methionine need this enzyme for catabolism to succinyl CoA and entry to the TCA cycle.
Why does L-asparaginase work as an antineoplastic agent in leukemia?
Leukemic cells loose the ability to synthesize asparagine and must collect it from circulating plasma. L-asparaginase increases catabolism of asparagine to aspartate, limiting the neoplastic cells’ ability to recover adequate asparagine to continue protein synthesis.
Why is too much IgA a bad think in patients with Neisseria meningitis?
It coats the bacteria to prevent it from attaching to mucus membranes; however, this prevents IgM and IgG attachment and activation of complement.
When would you expect to see astrocytes, neutrophils and microglia in a cerebral infarct?
PMN’s: 1-3 days
Microglia: 3-5 days
Astrocytes: 2 weeks
Mode of inheritance for diseases like MERRF (seizures and myopathy), Leber optic neuropathy (vision loss) and MELAS (stroke, lactic acidosis)?
Maternal, via mtDNA. Males cannot transmit these diseases
Phenytoin side effects
1) Induces P450 metabolism and decreases drug levels
2) PDGF increases, leading to gingival hyperplasia
3) Fetal hydantoin syndrome if taken when pregnant
4) Megaloblastic anemia due to interference with folic acid metabolism
5) Ataxia and nystagmus from cerebellar and vestibular system involvement
Methimazole mechanism of action
Suppresses thyroid hormone synthesis by preventing the iodination and coupling of tyrosine.
Quadrangular space
Teres minor, humerus, long head of triceps and teres major. Axillary nerve exits here and innervates the deltoid and teres minor muscles.
Dorsal scapular nerve innervation
Rhomboids and levator scapulae
CN IX innervation
Somatic: stylopharyngeus
Parasympathetic: inferior salivatory nucleus -> CN IX -> otic ganglion -> travel along auriculotemporal nerve -> parotid
Sensory: eustachian tube, inner TM, posterior 1/3 of tongue, tonsils, upper pharynx (gag afferent), carotid body and carotid sinus
Taste: posterior 1/3 of tongue
Taste and sensation of anterior 2/3 of tongue
Taste: chorda tympani (CN VII)
Sensation: CN V
How do you treat a patient with orotic aciduria?
Supplement with UMP because they are deficient in the enzyme that converts orotic acid to UMP. Supplementation also inhibits carbamoyl phosphate synthase II, reducing the overall production of orotic acid.
Enzyme involved in the conversion of methylmalonyl CoA to succinyl CoA
Methylmalonyl CoA mutase + B12
Well known hydrolysis reaction in urea cycle
Conversion of arginine to ornithine by arginase.
An 3 year has progressive neurodegeneration, no liver enlargement, cherry-red macular spot, macrocephaly, enlarged neuronal cytoplasm and lysosomal onion-skin lamellar lipid rings on electron microscopy. What is causing his condition
Tay-Sachs disease is an AR mutation in beta-hexosaminidase A resulting in accumulation of GM2 ganglioside within lysosomes.
A child presents with painful peripheral neuropathy, angiokeratomas, heart and kidney problems. What lysosomal storage disease is causing his symptoms?
Fabry disease is an X-linked recessive mutation in ceramide trihexoside resulting in accumulation of alpha-galactosidase in lysosomes.
A child presents with hepatosplenomegaly, pancytopenia, severe bone and joint pain. Biopsy reveals macrophages that look like crumpled tissue paper. What lysosomal storage disease is causing his condition?
Gaucher disease is an AR mutation in beta-glucocerebrosidase resulting in accumulation of glucocerebroside within lysosomes.
A child presents with gargoylism, corneal clouding, hepatosplenomegaly and developmental delay. What lysosomal storage disease is causing his condition?
Hurler disease is an AR mutation in L-iduronidase resulting in accumulation of dermatan and heparin sulfate within lysosomes.
A child presents with mild gargoylism, no corneal clouding, mild hepatsplenomegaly and mild developmental delay. What lysosomal storage disease is causing his condition?
Hunter disease in an X-linked recessive mutation in iduronate sulfatase resulting in accumulation of dermatan and heparin sulfate within lysosomes.
A child presents with progressive neurodegeneration, a cherry red macular spot and hepatosplenomegaly. Biopsy reveals foam cells. What lysosomal storage disease is causing his condition?
Niemann-Pick disease is an AR mutation in sphingomyelinase resulting in accumulation of sphingomyelin within lysosomes.
A child presents with progressive neurodegeneration and optic atrophy. What lysosomal storage disease is causing his condition?
Krabbe disease is an AR mutation in galactocerebrosidase resulting in accumulation of galactocerebroside and galactosyl-sphingosine.
A child presents with muscle wasting, dementia and ataxia. What lysosomal storage disease is causing his condition?
Metachromatic leukodystrophy is an AR mutation in arylsulfatase A resulting in accumulation of cerebroside sulfate within lysosomes.
What disease causes cystic degeneration of the putamen
Wilson’s
A patient with HIV presents with seizures. MRI shows multiple ring-enhancing lesions. What is the first line treatment for this patient?
This patient has toxo. 1st line treatment is pyrimethamine and sulfadiazine + leucovorin. If the patient does not respond to this treatment, suspect primary CNS lymphoma due to diffuse large B-cell lymphoma from EBV infection.
Special features of phenytoin metabolism
1) Dose-dependent metabolism resulting in toxicity even with small increases above the hepatic saturation level
2) Phenytoin induces P450 and decreases concentration of other drugs (especially note OCPs)
P450 inducers and inhibitors
Inducers: barbiturates, rifampin, carbamazepine, phenytoin, griseofulvin and chronic alcohol use.
Inhibitors: INH, cimetidine, macrolides, ciprofloxacin, grapefruit juice, ritanovir and azole antifungals.
What is responsible for the “on-off phenomenon” in patients being treated with levodopa for Parkinson’s disease?
Progressive nigrostriatal degeneration leads to a more narrow therapeutic window.
Urea cycle abnormality to rule out before diagnosing someone with cerebral palsy?
Arginase deficiency. It looks like cerebral palsy, but can be easily treated by only eating essential amino acids to minimize nitrogen load that needs to be excreted in the urea cycle.
Major amino acid found in blood
Glutamine, it transports ammonia from peripheral tissue to the kidney where it is hydrolyzes by glutaminase to form glutamate and free ammonium that will be excreted in the urine.
What other molecules have a similar origin as beta-endorphin does?
ACTH and MSH are also derived from POMC.
Serotonin syndrome antidote mechanism
Cyproheptadine is an anti-histamine with non-specific 5-HT1 and 5-HT2 antagonism
A patient is weed whacking his new yard and develops tachycardia, flushed skin, constipation, improved asthmatic symptoms, urinary retention, anhydrosis, mydriasis, agitation and delirium. How should you treat this patient?
He has Jimson weed poisoning from inhaling belladonna alkaloid toxin resulting in anticholinergic toxicity (like atropine overdose). Treat with pyridostigmine to increase ACh at synaptic cleft.
“Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, bowel/bladder lose their tone and the heart runs alone”
What is contained in the femoral sheath
The femoral artery and vein, not the nerve.
Corneal reflex
Nasociliary nerve (branch of V1) and temporal branch of CN VII.
Structures that enter the superior orbital fissure
CN III, IV, V1, VI, sympathetic fibers and superior ophthalmic vein.
Structures that enter the optic canal
CNII, central retinal vein and ophthalmic artery
Structure that enters the foramen rotundum
CN V2 -> pterygopalatine fossa -> inferior orbital fissure -> infraorbital foramen -> infraorbital nerve
Structure that enters the foramen ovale
CN V3
GABA-A mechanism of action
Stimulation open Cl- channels and hyper polarizes the membrane.
Cellular receptors that allow entry of CMV, EBV, HIV, rabies and rhinovirus
CMV = cellular integrins EBV = CR2 (CD21) HIV = CD4 and CCR5/CXCR4 Rabies = nAChR Rhinovirus = ICAM1 (CD54)
3 dopaminergic systems and what goes wrong with each when they are out of whack.
Mesocorticolimbic = schizophrenia Tuberoinfundibular = hyperprolactinemia Nigrostriatal = Parkinson's
Structure that enters foramen spinosum
Middle meningeal artery and vein
Structures that enter the internal acoustic meatus
CN VII and VIII
Structures that enter the jugular foramen
CN IX, X, XI and jugular vein
Structure that enters the hypoglossal canal
CN XII
Structures that enter the foramen magnum
Spinal cord, medulla, CN XI roots and vertebral arteries
A patient opens his mouth and his jaw deviates to the right on opening. Which side does he have a cranial nerve lesion on?
Right CN V3 lesion due to unopposed action of the left lateral pterygoid
Wilson disease mutation
AR ATP7B mutation leads to poor hepatocyte copper transport and decreased ceruloplasmin
Vision changes that may follow a lesion in the temporal lobe
Contralateral quadrantanopia due to disruption of Meyer’s loop that swings through the temporal lobe.
A patient presents with difficulty releasing the doorknob after grabbing it, cataracts, frontal balding and gonadal atrophy. He got the symptoms earlier than his dad who got symptoms earlier than his dad. What is causing his condition? What would light microscopy show?
AD myotonic muscular dystrophy is due to CTG trinucleotide repeats in the gene encoding for myotonia-protein kinase. Light microscopy would show degeneration of type 1 fibers without fibrofatty infiltrate.
Fetal malformations, disruptions, deformations and sequences.
Malformation = primary fetal defect (holoprosencephaly) Disruptions = normal tissue breakdown due to secondary cause (amniotic banding) Deformation = defect of normal tissue due to extrinsic mechanical force (clubbed feet) Sequence = a number of abnormalities result from a single primary defect (renal agenesis -> Potter sequence)
Pathophysiology behind subacute sclerosing panencephalities.
Measles infection by virions without protein matrix or envelope evade immune system and camp out in CNS. The viruses continue to replicate intracellularly and nucleocapsids accumulate within the neurons resulting in damage and gliosis. High measles antibody titers exist in CSF and patients may have oligoclonal bands.
