Week 2 - Neuro Diseases / Disorders Flashcards
tension-type headache
<40, more women, most common headache, episodic or chronic, 30 min - 7 days, bilateral headband pattern, may wake with it, phonophobia or photophobia, muscle tightness in scalp and neck, Tx stress reduction and tricyclic antidepressants (amitriptyline) and selective serotonin reuptake inhibitors (fluoxetine), acute Tx NSAIDs, tylenol, relaxation
cluster headache
20-30, more males, less common, episodic clusters, severe, unilateral, orbital, 15-180 min, lacrimation, congestion, sweating, eyelid edema, Tx verapamil, melatonin, prednisone; acute Tx oxygen, triptan injection; caused by dilation of vessels in dura (internal carotid artery in cavernous sinus)
migraine
<40, more adult females, more male children, intermittent, unilateral, crescendoing, lasts hours to days, possible preceding aura, Tx amitripyline, divalproex, propranolol, timolol; acute Tx triptans, DHE, perchlorperazine, metoclopramide, apap, ibu, naproxen, dexamethasone
subdural hematoma
hours to several weeks after head trauma, anticoagulant use
epidural hematoma
within hours of trauma, lucid period, associated with skull fractures
viral syndrome
flu-like, possible non-specific rash, contact with sick people with similar symptoms
glaucoma
severe, sudden onset, eye pain, vision loss, blurred vision, halos
meningitis
fever, stiff neck, photophobia, altered mental status
encephalitis
fever, stiff neck, photophobia, altered mental status
temporal arteritis
new onset of headaches, >50, high ESR, scalp tenderness
subarachnoid hemorrhage
sudden, sever headache, hypertension, smoker, alcohol, non-white, thunderclap headache
intracranial mass
gradual, focal neurologic deficits or symptoms
ruptured aneurysm
headache onset with exercise or sex, thunderclap headache - type of subarachnoid hemorrhage
environmental exposure
CO, new building, others at home or work with same symptoms
symptoms of cluster headache
pupil constriction, ptosis, lacrimation, diaphoresis, sharp frontotemporal pain
infection defense mechanisms
scalp / skull, meninges (dura, arachnoid, pia), blood-brain barrier
microbial invasion of brain
contiguous spread from previous infection, hematogenous spread, trauma or congenital lesion, viral infection
meningitis
infection in subarachnoid space
encephalitis
infection in brain parenchyma
abscess
focal infection in brain parenchyma
myelitis
spinal cord infection
shared symptoms of CNS infection
fever, headache, altered mental state; infectious - meningitis / encephalitis / abscess; noninfectious - subarachnoid hemorrhage, inflammatory disease (lupus), neoplasia, antimicrobial drugs
CNS infection acute Tx
H & P, blood culture –> empiric treatment, imaging (MRI/CT), lumbar puncture, ID organism, antibiotic susceptibility testing, switch to definitive Tx or supportive Tx (viral)
meningitis
headache, fever, altered mental status; plus nuchal rigidity, photophobia, rash, upper resp. symptoms; some with 3 symp.; most with 2 symp
aseptic meningitis syndrome
often viral, midler, less neck stiffness, has fever / headache / photophobia, more common in infants, CSF –> lymphocytes, monocytes, increased protein, normal glucose, PCR confirmation, Tx supportive therapy with recovery in two weeks
causes of viral meningitis
picornovirses (enteroviruses), poliovirus, coxsackievirus, echovirus; + sense s.s. RNA viruses
+ sense
can be immediately translated
- sense
must make a copy (transcription) before translating
picornavirus (enterovirus)
coxsackie, ECHOvirus, polio; 90% summer, oral - fecal or respiratory transmission, s.s., + sense, RNA, naked (no envelope), isohedral
septic meningits
bacterial, fever, stiff neck, irritability, neurologic dysfunction, CSF - PMNs, increased protein, decreased glucose, acute onset and progression, Tx empirically after samples taken
acute, purulent meningitis
H. influenza type b, N. meningiditis, and Strep. pneumonia - can follow viral infection, colonize mucosae of nasopharynx, invade and multiply in blood, cross blood-brain barrier by transcellular route, release cytokines in CSF, increased BBB permeability, diapedesis of leukocytes / edema / ICP –> neuronal injury
neonatal bacterial meningitis
Group B Strep. (received from birth, give mother penecillin before), Listeria monocytogenes, E. coli, maternal antibodies protect against H. influenza type B and Neisseria meningitids
over 65 bacterial meningitis
Listeria monocytogenes, Strep. pneumonia
late adolescent bacterial meningitis
Neisseria meningitids, college dorms
Neisseria meningitidis virulence factors
gram -, capsule, IgA protease, pili, endotoxin, outer membrane proteins
Haemophilus influenzae virulence factors
gram -, capsule, IgA protease, pili, endotoxin, outer membrane proteins
Streptococcus pneumoniae virulence factors
gram +, capsule, IgA protease, no - pili / endotoxin / outer membrane proteins
lipopolysaccharide
endotoxin, shed from Gram - bacteria, activates macrophages to release NO (hypotension) and IL-1 (fever), activates intravascular coagulation leading to purpuric skin rash
LOS - like lipopolysaccharide
endotoxin of Neisseria meningitides, mimic brain sphingolipids, recognized as self
pili
virulence factor, attachment to epithelial cells –> colonization of nasopharynx
IgA protease
cleaves IgA, found in mucosa, helps colonization of mucosa
capsule
virulence factor, acidic polysaccharides, protects from phagocytosis by PMN granulocytes
lumbar puncture
collect 10mL of CSF, focal lesion (abscess) suspected do not perform - may cause brain herniation
MRI
not useful for acute meningitis
CSF bacterial meningitis
high pressure, really high WBC - 80% PMN, really high protein, low glucose, gram stain
CSF viral meningitis
high WBC - 50% lymphocytes and 20% PMNs, high protein, normal glucose
CSF fungal meningitis
high pressure, high WBC - 50% lymphocytes, high protein, normal glucose
CSF tuberculous meningitis
high WBC - 80% lymphocytes, high protein, low glucose, gram stain
management of bacterial meningitis
empiric tx after lumbar puncture, bactericidal 10x min inhibitory concentration, BBB - give steroid so more drug gets through, antibiotic susceptibility testing
septic meningitis empiric Tx
ceftriaxone and vancomycin; if penicillin / cephalosporin allergy –> meropenem / aztreonam and vancomycin; add ampicillin if listeria suspected
septic meningitis empiric Tx
ceftriaxone and vancomycin; if penicillin / cephalosporin allergy –> meropenem / aztreonam and vancomycin; add ampicillin if listeria suspected
listeria suspected in septic meningitis
young, old, immunocompromised - add ampicillin
listeria suspected in septic meningitis
young, old, immunocompromised - add ampicillin
prophylactic Tx for septic meningitis
household contact, close exposures
prophylactic Tx for septic meningitis
household contact, close exposures
H. influenzae septic meningitis
Tx rifampin
H. influenzae septic meningitis
Tx rifampin
N. meningitidis septic meningitis
Tx ceftriaxone
N. meningitidis septic meningitis
Tx ceftriaxone
antibacterial actions of ceftriaxone
reaction involving transpeptidation
antibacterial actions of ceftriaxone
reaction involving transpeptidation
antibacterial actions of vancomycin
binds to transpeptidases, MRSA, given IV
antibacterial actions of vancomycin
binds to transpeptidases, MRSA, given IV
Neisseria meningiditis
meningococcal meningitis, gram -, diplococcus, pili, IgA protease, capsule, endotoxin, late winter / early spring, dorms, respiratory droplets, LOS endotoxin –> hemorrhagic rash, Tx ceftriaxone
resistance to rifampin
mutation of genes for DNA-dependent RNA polymerase
Streptococcus pneumonia
gram -, diplococci, lancet shape, pneumococcal pneumonia, respiratory droplets, meningitis secondary to sinus or ear infection, >2 mnths old, Tx penicillin or ceftriaxone add dexamethasone to reduce hearing loss, vaccine, capsular swelling
Hemophilus influenza type b
gram -, coccoid rod, unvac infacts and children, pili, membrane proteins, IgA protease, endotoxin, hearing loss, Hib vaccine, chocolate agar with V and X, Tx ceftriaxone and proph rifampin
group B streptococcal (GBS) - Streptococcus agalactiae
gram +, diplcocci, noraml flora, to infant during birth, sight / hearing loss, more African Americans, pregnant women screened and given penicillin G proph to prevent in first week, hemolysis of RBC by phospholipase
Listeria monocytogenes
gram +, rod, intracellular, neonatal meningitis via mother, no nuchal rigidity, milk and deli meat, phospholipase and listeriolysin O = escape from vacuole, actin tails = pseudopod spread, Tx ampicillin and gentamicin
action of ampicillin
weakens membrane
action of gentamicin
ribosomal inhibitor
Escherichia coli K1 strain
gram -, rod, enteric, transcellular across BBB, LPS prevents fusion with lysosome, beta-lactamase strains ceftriaxone and carbapenem
Klebsiella pneumoniae
gram -, normal flora, enteric, lactose fermenters, healthcare acquired, Tx ceftriaxone, resistant strain with carbapenemase
chronic meningitis
weeks, mycobacterium tuberculosis and spirochetes and fungi, base of brain (not dorsum), HIV/AIDS, Tx isoniazid, rifampin, ethambutol, pyrazinamide
action of isoniazid
inhibits mycolic acid in mycobacterial cell wall, acetylated in liver faster in Asians and Native Americans
action if rifampin
inhibits DNA-dependent RNA polymerase, induces formation of drug metabolizing enzyme P450
action of ethambutol
inhibits cell wall synthesis by binding arabinosyl transferase in mycobacterium
protozoa caused meningitis
Naegleria flwleri and Acanthamoeba, swimming in warm infected water, into nose –> olfactory necrosis, altered smell, Tx cephtriasone and metronitisol
encephalitis
fever, headache, altered mental status, motor / sensory deficits, seizures, speech problems, lethargy, coma, empiric Tx acyclovir until HSV ruled out, previous infection, travel, tick bites
viral encephalitis
enterovirus, arbovirus, herpes virus, rabies
nonviral encephalitis
rickettsia, mycoplasma, ADEM
encephalopathy
diffuse, toxin, metabolic dysfunction, steady mental status decline, unlike encephalitis
encephalitis Dx
CSF - lymphocytes predominant, normal glucose, elevated proteins, negative culture, focal lesions on MRI, serum PCR and antibodies, EEG abnormal
viral causes of encephalitis
HSV, mumps, varicella, rabies, HIV, polio, rubella, measles
+ strand, RNA, isohedral viruses
picorniviridae (enterovirus), togaviridae (rubella), flaviviridae (WNV)
- strand, RNA, helical viruses
rhabdoviridae (rabies), paramyxoviridae (measles, mumps)
segmented, - strand, RNA, helical virus
Bunyaviridae (LaCrosse strain of California virus)
DNA viruses isohedral
adenoviridae (adenovirus), herpesviridae (HHV)
herpes virus (HSV1, HSV2, VZV, CMV)
linear DNA, icosahedral, enveloped, human to human
HSV1
acute sporadic encephalitis, respiratory secretions, reactivated in trigeminal ganlia, bilateral temporal lobe on MRI, necrotizing, hemorrhagic, RBC in CSF, IV acyclovir
HSV2
neonatal encephalitis via mother during birth, STD, can cause encephalitis in adults, IV acyclovir
fusion of viral envelop (nucleocapsid) with plasma membrane
paramyxovirus, retrovirus, herpesvirus
fusion of viral envelop with endocytic membrane
togavirus, rhabdovirus, coronavirus, orthomuxovirus
immediate early genes (lytic cycle)
produce viral RNAs needed for early gene expression
early genes (lytic cycle)
thymidine kinase, ribonucleotide reductase, DNA polymerase –> DNA replication
late genes (lytic cycle)
capsid protein, envelope glycoproteins, tegumental proteins (exocytosis, creates viruses)
tegumental protein VP16
recruits host cell transcription machinery
Oct1
key for early gene expression, RNA Pol II to viral promoters
HSV1 latency in trigeminal ganglion
axon terminal of sensory neuron, capsids retrograde to cell body, enter nucleus, reactivated when VP16 and HCF-1 enter nucleus = transcription, new virion anteretrograde back to axon terminal
action of acyclovir and ganciclovir for HSV1
inhibits viral DNA polymerase, terminates chain by replacing sugar on guanine, only active against dividing virus, suppresses bone marrow, resistance via loss of thymidine kinase
action of foscarnet for HSV1
pyrophosphate analog, blocks chain elongation by DNA polymerase
HHV-3 varcella zoster virus
rare immunocompromised encephalitis, lytic in epithelial cells, latent in trigeminal and dorsal root ganglia, reactivation, vaccine, Tx acyclovir
Zoster pain
peripheral pain –> rash –> acute pain –> rash healed (30 days) –> chronic pain (post-herpetic neuralgia)
cytomegalovirus (HHV5)
tropic to polymorphonuclear leukocytes, slight elevation in CSF protein, HIV/AIDS, organ transplant, congenital, paraventricular subependymal cells –> hemorrhagic necrotizing ventriculoencephalitis, Tx ganciclovir (organ transplant) add foscarnet (neuroinvasion)
arboviruses
transmitted by arthropods
flavivirus / togavirus
s.s., +, RNA, icosahebral, enveloped
West Nile Virus
crows, jays, mosquito bite / breast feeding / blood transfusion, >60, mid-late summer, CSF normal glucose and protein, lymphocytic leukoctosis, IgM
Powassan encephalitis
tick flavivirus, WNV related, ticks with lyme in <15 minutes of bite, May-Oct
bunyaviridae (LaCrosse / California encephalitis)
<16, circular segmented genome, helical capsid, chipmunks/squirrels, mosquitos to humans
rabies (encephalomyelitis)
saliva / aerosals from dogs / foxes / raccoons / bats, binds nicotinic ACh receptors, retrograde into CNS, replicates in grey matter, to saliva glands, bite irritation, sore throat, headache, fever, muscle spasms, convulsions, paralysis, Negri bodies with ribonucleoproteins in Purkinje cells of cerebellum, active and passive vaccines, rhabodoviridae, bullet shaped capsid, -, RNA
progressive multifocal leukoencephalopathy (PML)
John Cunningham (JC) polyomavirus, d.s., circular, no envelope, infect oligodendrocytes, demyelination, inhaled to tonsils, latent in kidneys and bone marrow, reactivated in blood, neuroinvasion
Rickettsia rickettsii
rocky mountain spotted fever, gram -, intracellular (need CoA and NAD+), pleomorphic, bacteria, headache, fever, petechia rash, endothelial cells, Tx doxycycline
acute disseminated encephalomyelitis
inflammatory demyelination following infection or vaccination
brain abscess
fever, headache, seizure, focal infection of parenchyma, acute - oropharyngeal / streptococci, chronic - mycobacterium tuberculosis / cryptococcus neoformans, poor teeth, ear infection, trauma, immunosuppressed, surgery, embolism, CT or MRI, Tx ceftriaxone and metronidazole (parasites) and surgery
suspected ICP
get MRI first, then CSF sample, otherwise could cause herniation
Toxoplasma gondii
protozoan, trachyzoite, immunocompromised, pregnant women, reactivation of latent infection, fever, headache, focal deficits due to intracranial calcification, schizophrenia?, uncooked meat and cat feces, Tx pyrimethamine (blocks dihydrofolate reductase) and sulfadiazine (blocks pteridine synthetase)
myelitis
herpes, motor and sensory loss, polio / coxsackie / WNV attack ventral horn motor cells = paralysis, chronic Tropical Spastic Paraparesis caused by human T-lymphotropic retrovirus (s.s. RNA + linear diploid icosahedral), long latency in lymphocytes
poliomyelitis (enterovirus)
headache, sore throat, vomiting, paralysis, brain invasion = encephalomyelitis, Tx pain killers, moist heat, PT, vaccine
post-polio syndrome
muscle weakness, 30 years after disease, fecal-oral to throat to intestines to bloostream to CNS, degeneration of lower motor neurons in anterior spinal cord, Tx pain killers, moist heat, PT
immunocompromised
bacterial meningitis (listeria, klebsiella), toxoplasmosis, fungal meningoencephalitis (candida, cryptococcus), encephalitis (CMV, HHV6, JC virus), AIDS subacute encephalitis with dementia
perinatal infections
meningitis (strep group B, E. coli, listeria), toxoplasmosis, syphillis, varicella-zoster, parvovirus, rubella, cytomegalovirus, herpes
inflammation
acute vs chronic
acute inflammation
happens fast, lasts few days, neutrophil response, vessels dilate and leak so neutrophils (segmented nuclei) can get out and make pus, looks busy - black dots
chronic inflammation
> few days, lymphocytes (mononuclear cells), macrophages, plasma cells, uniform round nuclei, seen with viral meningitis
bacterial meningitis
neutrophils make pus, engorged cerebral vessels
abcess
after acute inflammation, circumscribed collection of pus, can persist beyond few days, neutrophils, looks busy - segmented nuclei, necrotic tissue, compressed brain tissue with engorged vessels
gliosis
astrocyte reaction to injury, scar, large pink processes
microglial nodule
microglial proliferation around dying tissue
hydrocephalus
block in CSF circulation, noncommunicating = block in ventricular system, communicating = block in CSF resorbption (sinus), can get due to meningitis, ex: as it healed it blocked arachnoid granulations causing communicating hyrocephalus and entire ventricular system is enlarged
case - encephalitis (Rickettsia)
confused, lethargy, two weeks, unsteady gait, falls, high resp, high pulse, fever, mild nuchal rigidity, non-blanching macular rash knees to ankles (gram - endotoxin), CSF - slightly low glucose, high proteins, somewhat high WBC (neutrophils - PMNs = bacterial), not on gram stain - intracellular organism, serum platelet count low, season and location
encephalitis
brain inflammation, seizures, stupor, coma, headache, fever, not as sick as meningitis, commonly viral or Rickettsial
rocky mountain spotted fever
gram -, coccobacillus, intracellular (endothelial), tick-borne, death or serious sequelae, May - Aug, cases increases, deaths decreasing, small mammal in cycle, 2-14 days after bite, fever, rash (2-5 days after fever), headache - possible nausea, vomiting, abdominal pain, conjunctivitis, labs - low platelets, low serum sodium, high liver function, skin biopsy of vasculitis, Tx doxycycline (caution on kids and pregnant - ribosome inhibitor)
anaplasmosis
tick-borne, fever and rash, no headache
case - Neisseria meningitides meningitis
headache, 19, top of head, blurry vision, vomited, nausea, dull / pressure pain, dorm, lethargic, neck pain, photophobia, petechiae rash on arms and trunk, fever, high HR, CBC - high WBC (80% granulocytes / PMNs / neutrophils = bacterial) and platelets low, CSF - color abnormal, culture abnormal, glucose low, gram neg stain with diplococci, high proteins, high RBC, high WBC (mostly granulocytes = bacterial)
normal CSF glucose
greater then 1/2 serum glucose
CSF sample contraindicated by CT findings of ICP
examples - cerebral infarction (sharp white point on CT), hydrocephalus (enlarged ventricles), cerebral abscess (clearly demarkated circle), diffuse brain edema (gyri not clear - no dark / light contract on brain surface)
<1 month
group B strep meningitis
1-23 months
streptococcus pneumoniae
2-18 years
neisseria meningitidis
19-59 years
streptococcus pneumoniae
> 60 years
streptococcus pneumoniae and listeria meningitidis
case - bacterial meningitis Neisseria meningitidis
hematogenous, naspharyngeal -> blood -> crosses BBB to subarachnoid space, possible extension of nearby infection, fever, headache, stiff neck, vomiting, sleepy, seizures (but not confused - encephalitis), CT then lumbar puncture CSF, Tx IV fluids + immediate antibiotics (age 2-50 vancomycin + ceftriaxone, age > 50 ampicillin + vancomycin + ceftriaxone), prophylaxis for close contacts, immunization age 11-12
Neisseria meningitidis
gram -, aerobic, encapsulated, colonize nasopharynx, crowded conditions - dorms, 40% of pop asymptomatic carries
bacterial meningitis process
bacteraemia -> endothelial damage -> bacteri in CSF -> inflammatory cytokines -> increased BBB permeability + WBC infiltration + cerebral vasculitis -> edema + ischaemia -> ICP -> neuronal injury
bacterial meningitis gross findings
pus (neutrophils in CSF), engorged veins, basal - H. influenza / TB / cryptococcus, cortical or basal - S. pneumoniae, basal is pus in cistera magna, dense over blood vessels, “organized” pus = late stage and likely hydrocephalus
bacterial meningitis microscopic findings
neutrophils (busy - lumpy nuclei) in subarachnoid space, gram stain bacteria, phlebitis (neutrophils in wall of vessels), cerebritis (neutrophils in surface parenchyma), pink stringy fibrin organization of exudate -> healing and possible communicating hydrocephalus
TB meningitis gross findings
basal gelatinous exudate in cisterns that encases cranial nerves and forms organized adhesions, tuberculomas (collection of mycobacterium and granuloma), more chronic presentation,
TB meningitis microscopic findings
lymphcytes (mononuclear cells), caseating granulomas (central necrosis and pallisading histiocytes), obliterative endarteritis, positive acid fast stain
pathology of viral meningitis
gross - swelling, microscopic - no findings, mildly lymphocytic meninges (mononuclear cells, small round dark nucleus)
fungal meningitis outbreak
contaminated epidural injections with methyl prednisolone for back pain, no preservatives, clean room problems, large batches, bad sterilization, main causative agent Exserohilum rostratum (dead leaves, grass), steriods reduced immune system, filaments penetrate dura, warm for yeast form, injection site abscess or septic arthritis too, Tx voriconazole for 3 months or liposomal amphotericin B
Dx fungal meningitis
lumbar puncture CSF - low glucose, high proteins, high lymphoctyes (mononuclear), visualize with KOH, stain, culture - low/high temp or high glucose agar, sequence 28S rDNA, not contagious, spores inhaled from environment
fungi
heterotroph, saprophytic, eukaryotic
yeast
Candida, Cryptococcus, single cell, warm environment
mold
Aspergillus, Fusarium, Scedosporium, Zygomycete, mutlicellular, form hyphae, cold environment
dimorphic fungi
Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, converts between mold (cold) and yeast (heat)
Tx fungal meningitis
usually self-limiting, antifungals are very toxic, drugs work on cell membrane or cell wall
systemic mycoses
dimorphic, endemic, inhaled spores, bat dropping -> pneumonia, meningitis, Tx mostly resolve on own, liposomal amphotericin 1 month, itraconazole 3-12 months, add amphotericin B if meningitis; caused by Histoplasma, Blastomyces, Coccidioides, Paracoccidioides
opportunistic mycoses
environment or human flora, infect immunocompromised
Cryptococcus neoformans
opportunistic fungi, encapsulated yeast - inhibits phagocytosis, meningitis and pneumonia in immunicompromised, india ink, soap bubbles in brain, Tx amphotericin B + Flucytosine + Fluconazole (following)
Candidiasis
opportunistic fungi, yeast, communicable, diaper rash, thrush, vaginal, systemic (catheter, skin breaks), seeds after antibiotic Tx, immunocompromised, Tx clotrimazole (azoles) or amphotericin / echinocandins
Aspergillus fumigatus, Zygomycosis mucor
opportunistic mold, soil, pulmonary, sinusistis, otitis externa, CNS abscess, immunocompromised, tissue biopsy - 45 degree angles = Aspergillus, no angles = Zygomycosis, Tx voriconazole or amphotericin / echinocandins
superficial mycoses
dematophyte, skin lesion, ringworm, athlete’s foot, Tx terbinafine or -azole
subcutaneous mycoses
through skin, subcutaneous or lymphatic spread, Sporothrix, Tx itraconazole 6 months
Horner Syndrome
interruption of sympathetic trunk on ipsilateral side at cervical sympathetic trunk or sympathetic fibers in brain stem / spinal cord, ptosis (drooping of eyelid - superior tarsal muscle), miosis (pupil constriction), anhidrosis (absence of sweat), flushed face (red/vasodilation)
eye can’t adduct
medial rectus deficit, CN III oculomotor
eye can’t look down
superior oblique deficit, CN IV trochlear nerve
eye can’t abduct
lateral rectus deficit, CN VI abducens
eye can’t look up
inferior oblique or superior rectus deficit, CN III oculomotor
Bell’s Palsy
acute peripheral nerve palsy, CN VII, taste to ant ipsilateral tongue, general touch / pain sensory around ipsilateral ear, motor to facial expression ipsilateral, stapedius muscle in ear (dampens sound), dryness in ipsilateral eye (parasympathetic to lacrimal gland)
case - HSV1 encephalitis
19, memory and behavior changes, coma, death, necrotizing hemorrhagic inflammation, perivascular infilatrate, Cowdry A inculsions
