Case-Based Presentation 21 February 2010. Monday AM, 05:05. On-call residents just saw this...
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Transcript of Case-Based Presentation 21 February 2010. Monday AM, 05:05. On-call residents just saw this...
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Case-Based Presentation21 February 2010
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Monday AM, 05:05. On-call residents just saw this
gentleman: 40- year old man encountered by police
on bench near the Olympic Cauldron. “Confused and belligerent” per EMS run
sheet. Brought to ER for “? Substance abuse” PMHx unremarkable aside from IV heroin
abuse, reportedly clean for a year.
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T= 38.8, HR 88 reg, BP 145/78, RR 16 unlabored. SpO2 98% on 3L O2 applied to the cheek.
Eyes open to painful stimulus, Disobeys commands, weakness to R arm/leg.
Labs: WBC 12, otherwise no red nor blue in screening labs…
Referred to CTU after CT brain ordered.
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CT brain suboptimal due to patient movement. Interpreted as “no obvious huge mass lesion” per radiology resident.
Referred to ICU due to concerns about airway protection in light of need for sedation for imaging.
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Resident asked for differential diagnosis of altered mental status with focal neurologic deficit, but stalls after “malignancy.”
Federico, could you help her out?
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Mortality 25%Morbidity 60%Fever, neck stiffness, altered mental
status (only 44%)95% has 2/4 symptoms33% focal neurologic deficit
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Altered mental statusFever, headache, myalgia, mild
respiratory infectionFocal neurologic deficitseizures
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Focal neurologic deficitNeck rigidity (associated meningitis)Seizures
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Cranial epidural abscessesSubdural empyemaVentriculitisStroke (arterial or venous)
Hypoglycemia Seizures (non-convulsive)
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Infections of CNS are neurologic emergencies
Early antibiotic therapy (in the emergency department, prior CT scan) is correlated with reduced mortality and morbidity
Early steroid therapy is recommended
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Meanwhile, the patient’s GCS has deteriorated to E1 V2 M5.
No response to painful stimulus on Right side.
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Any concerns about this man’s induction given your suspicion of an intracranial process? (Ibrahim)
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Suspect raised ICP: Headache, dec LOC (esp GCS <=8),
vomiting, blurred vision VI CN palsy Papilledema Spontaneous periorbital brusing (CVST) Cushing’s triad (constant inc BP, mainly
systolic, bradycardia, and resp depression)
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Herniation syndromes (subfalcine, entral and uncal transtentorial, upward and tonsillar/foramen magnum cerebellar, and transcalvarial)▪ Transtentorial: Altered LOC, ipsi- fixed mydriasis, III
CN, decerebrate, hemiparesis, bi dilated pupils, altered resp, brady, HTN, resp arrest
Kernohan notch phenomenon▪ Ipsi- hemiparesis + contralateral mydriasis secondary
to transtentorial herniation rather than loteralization
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Altered LOC and hemiparesis in our patient are enough concerns for increased ICP, requiring special considerations in positioning, sedation and paralytic agent selection pre intubation.▪ Inubation can increase ICP▪ Large shift of BP, esp with hypotension/hypoxemia, can
increase ICP. Idea is to keep CPP >60, use pressors if necessary
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30 degrees off bed (enhance VR from brain), minimize flexion, rotation, laryngial
manipulation with suctioning, gagging or coughing.
Good sedation will be required prior to intubation.
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Lidocaine 2mg/kg IV: ▪ sympatholytic (dec BP/HR raise), ▪ dec cough/gag (already avoided by NMB), ▪ dec cerebral metabolism and stabilizes brain cells
membranes (NA CB),▪ dec intraocular pressure
Systemic review found limited data in 6 small studies, with no neurological outcomes
Robinson, Emerg Med J, 2002
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Etomidate: 0.3mg/kg▪ Dec brain O2 consumption by 45%, and CBF by 34%--
>dec ICP, but maintain CPP▪ Maintain sympathetic and baroreceptor effects, so
maintain hemodynamics, but,▪ may be associated with inc BP, gag or cough which can
be minimized by NMB (or lidocaine)▪ Lack analgesic effect (Fentanyl)▪ Dose-dependent adrenal suppx, last 5-15hr reported▪ Lower seizure threshold
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Propofol: 2mg/kg, is alternative▪ Dec brain metabolism▪ Myocardial and dose-dependent resp
depressant, dec MAP, so cautious useAvoid Ketamine (inc BP, CBF, and
ICP)Caution with midazolam, mildly dec
CPP
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After an uneventful intubation, the patient is whisked off to CT for a non-contrast scan.
Result: Not much to write home about, according to the radiology resident.
If you want an MRI, do the following: Wait until the day call person arrives Put the req in PCIS Talk to the neuroradiology fellow Run 3 laps around the VGH campus
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What are the key CSF findings in infectous causes of encephalopathy? (Ibrahim)
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Opening pressure: 18 cmStat gram stain negativeWBC: 200, predominantly
lymphocytesGlucose 6Total protein 0.5 g/L
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How is it managed?What if you had to drive past a
suspicious number of dead birds on your way into the hospital? (Omar)
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Herpes Simplex Virus
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Acyclovir Inhibits viral DNA polymerase, thereby
inhibiting viral replication Decreases mortality from 70% to 20% if
started within 48hours of presentation 10mg/kg Q8H
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Acyclovir Duration of therapy unclear 10 (minimum) – 21 days Increased relapse rate after 10 days
therapy (10%) Repeat CSF PCR for HSV at 10 days?
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Valacyclovir?? Pro-drug of Acyclovir Initiate after discontinuing Acyclovir?
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Valacyclovir?? National Institute of Allergy and Infectious
Diseases (NIAID): Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valacyclovir
Randomised, Multicenter, placebo controlled trial
90 days of Valacyclovir vs placebo, after IV treatment with Acyclovir
Primary outcome: Neurological recovery 2000 – 2011
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• Steroids– Controversial– Kamei S, et al Evaluation of combination
therapy using aciclovir and corticosteroid in adult patients with herpes simplex virus encephalitis. J Neurol Neurosurg Psychiatry. Nov 2005;76(11):1544-9
– Non blinded, retrospective analysis in 45 patients with HSVE
– Suggested improved outcomes in those treated with steroids
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Steroids Dosages, in Prednisolone equivalents,
was 40.0 mg/day to 96.0 mg/day (mean 64.6 mg/day)
2 days to 6 weeks of treatment (mean 13.6 days)
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Steroids Martinez-Torres F, et al. Protocol for
German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE): a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933]. BMC Neurol. 2008;8:40
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The patient’s old chart materializes.During previous admissions there
are references to a need for HIV testing, but no results are noted.
There are repeated suggestions that this man’s abstinence from IV drug use may not be complete…
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What are some infectious causes of encephalitis in immunocompromised (particularly AIDS) patients? (Marios)
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Varicella zoster virus
Cytomegalovirus Human
herpesvirus 6 West Nile virus HIV JC virus
L. monocytogenes M. tuberculosis C. neoformans Coccidioides
species Histoplasma Toxoplasma gondii
IDSA Encephalitis Guidelines 2008
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Can occur in patients without rash, especially if immunocompromised
Reactivation leads to encephalitis with focal neurologic deficits and seizures
Dx: CSF PCR for VZV (sensitivity, 80%–95%, and
specificity >95% in immunocompromised person)
CSF VZV IgM antibody
Tx: Acyclovir, ganciclovir, steroids
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Evidence of widespread CMV disease (e.g., retinitis, pneumonitis, adrenalitis, myelitis, polyradiculopathy)
Dx: CSF PCR for CMV (for immunocompromised
persons, sensitivity, 82%–100%; specificity, 86%–100%)
Tx: Ganciclovir and foscarnet
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Recent exantham, Seizures
Dx Serologic testing; culture CSF PCR (sensitivity, > 95%); high rate
of detection in healthy adults (positive predictive value, 30%)
Tx: gancoclovir or foscarnet
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Abrupt onset of fever, headache, neck stiffness, and vomiting
1 in 150 develop neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis)
Clinical features include tremors, myoclonus, parkinsonism, and poliomyelitis-like flaccid paralysis (may be irreversible)
Dx: CSF IgM (preferred) CSF PCR (<60% of results are positive)
Tx: supportive
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Acute encephalopathy with seroconversion
Most commonly presents as HIV dementia (forgetfulness,loss of concentration, cognitive dysfunction, psychomotor retardation)
Dx: Serology + viral load CSF PCR
Tx: HAART
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Cognitive dysfunction
Limb weakness, gait disturbance, coordination difficulties
Visual loss
Focal neurologic findings, especially visual field cuts
Dx: CSF PCR (for diagnosis of PML, sensitivity 50%–75%;
specificity, 98%–100%)
Tx: Reversal of immunosuppression HAART in pts with AIDS
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Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)
Dx: Culture of blood specimens Culture of CSF specimens
Tx: Ampicillin plus gentamicin TMP-SMX if pen allergic
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Patients more commonly present with basilar meningitis followed by lacunar infarctions and hydrocephalus
Dx: Microorganism detection at sites outside CNS CSF AFB smear and culture CSF PCR has been reported to have a low
sensitivity
Tx: Isoniazid, rifampin, pyrazinamide, ethambutol Dexamethasone in patients with meningitis
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More commonly a chronic meningitis
May present acutely as meningoencephalitis
Dx: Blood fungal culture; serum cryptococcal antigen CSF fungal culture; CSF cryptococcal antigen
Tx: Amphotericin B plus flucytosine for 2 weeks, followed by
fluconazole for 8 weeks Liposomal amphotericin B plus flucytosine for 2 weeks, followed
by fluconazole for 8 weeks Amphotericin B plus flucytosine for 6–10 weeks (in HIV-infected
patients) Reduction of increased intracranial pressure by lumbar
puncture; may need to consider placement of lumbar drain or VP shunt
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Usually a subacute or chronic meningitis
Approximately 50% of patients develop disorientation, lethargy, confusion, or memory loss
Dx: Serum complement fixing or immunodiffusion
antibodies CSF complement fixing or immunodiffusion antibodies CSF culture
Tx: Fluconazole, Itraconazole, VoriconazolE, Amphotericin
B (intravenous and intrathecal)
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More commonly a chronic meningitis; may present as acute encephalitis
Isolated meningoencephalitis or associated with systemic findings (hepatosplenomegaly, pneumonia, bone marrow suppression)
Dx: Urine for Histoplasma antigen Visualization of yeast in sputum or blood by special stains Yeast in CSF visualized by special stains CSF Histoplasma antigen CSF Histoplasma antibody
Tx: Liposomal amphotericin B for 4–6 weeks, followed by
itraconazole for at least 1 year and until resolution of CSF abnormalities
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Extrapyramidal symptoms and signs;
Seizures, hemiparesis, and cranial nerve abnormalities common
Convulsions and chorioretinitis in congenital toxoplasmosis
Dx: Serum IgG may define those at risk for reactivation disease CSF PCR has lack of sensitivity and standardization MRI shows multiple ring-enhancing lesions in patients with
AIDS;
Tx: Pyrimethamine plus either sulfadiazine or clindamycin Trimethoprim-sulfamethoxazole Pyrimethamine plus either atovaqone, clarithromycin,
azithromycin, or dapsone
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The patient’s family consents to HIV serology, which is negative.
CSF data: HSV PCR positive. CRAG negative. No growth of bacteria nor fungi.
MRI is performed:
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(Noemie)
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2/3 of survivors have longterm neuropsychiatric sequelae Memory impairment in 69% Personality and behavior changes in
45%▪ Depression and dishinibition
Dysphagia in 41% Epilepsy in 25%
Pract Neurol 2007;285-302
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Greatest risk of longterm seizures if had sz during acute illness
Cumulative risk at 5 yrs is 10% if no acute sz vs 20% if acute sz present
Respond to phenytoin and benzos
Pract Neurol 2007;285-302
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Most common deficits: Dysnomia Anterograde amnesia
Also have impairment with calculations, visuo-constructional abilities and facial recognition
Consistent with temporal lobe localization of HSV encephalitis
Arch Neurol 1990,47:646-647
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Neuro page
Sense cam
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Seen after encephalitis caused by flavivirus (Japanese encephalitis)
dull, flat, mask-like faces with unblinking eyes, tremor, and cogwheel rigidity
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Seen in Japanese and Tickborne encephalitis
paralysis occurs in 1 limbs, usually asymmetric
More common in the LE than UE In these patients encephalitis
develops subsequently in about 30 percent
Affects the ant horn cell on EMG
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The patient’s extended family all show up simultaneously and want to meet with you at 16:45. They are most interested in his prognosis for neurologic recovery.
What can you tell them? (Erik)
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S. pneumonia vs. N. meningitidis - odds of an unfavorable outcome was six times as high (95% CI, 2.61- 13.91; P<0.001)
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Symptom onset < 24 hrs prior to admission
SeizurePneumonia Immunocompromised stateHypotension (DBP < 60mmHg)
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MRI CTEEG SPECT – single hemisphereic in viral
enceph.