Case-Based Presentation21 February 2010

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.

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.

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.

Resident asked for differential diagnosis of altered mental status with focal neurologic deficit, but stalls after “malignancy.”

Federico, could you help her out?

Mortality 25%Morbidity 60%Fever, neck stiffness, altered mental

status (only 44%)95% has 2/4 symptoms33% focal neurologic deficit

Altered mental statusFever, headache, myalgia, mild

respiratory infectionFocal neurologic deficitseizures

Focal neurologic deficitNeck rigidity (associated meningitis)Seizures

Cranial epidural abscessesSubdural empyemaVentriculitisStroke (arterial or venous)

Hypoglycemia Seizures (non-convulsive)

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

Meanwhile, the patient’s GCS has deteriorated to E1 V2 M5.

No response to painful stimulus on Right side.

Any concerns about this man’s induction given your suspicion of an intracranial process? (Ibrahim)

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)

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

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

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.

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

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

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

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

What are the key CSF findings in infectous causes of encephalopathy? (Ibrahim)

Opening pressure: 18 cmStat gram stain negativeWBC: 200, predominantly

lymphocytesGlucose 6Total protein 0.5 g/L

How is it managed?What if you had to drive past a

suspicious number of dead birds on your way into the hospital? (Omar)

Herpes Simplex Virus

Acyclovir Inhibits viral DNA polymerase, thereby

inhibiting viral replication Decreases mortality from 70% to 20% if

started within 48hours of presentation 10mg/kg Q8H

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?

Valacyclovir?? Pro-drug of Acyclovir Initiate after discontinuing Acyclovir?

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

• 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

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)

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

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…

What are some infectious causes of encephalitis in immunocompromised (particularly AIDS) patients? (Marios)

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

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

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

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

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

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

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

Rhombencephalitis (ataxia, cranial nerve deficits, nystagmus)

Dx: Culture of blood specimens Culture of CSF specimens

Tx: Ampicillin plus gentamicin TMP-SMX if pen allergic

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

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

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)

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

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

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:

(Noemie)

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

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

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

Neuro page

Sense cam

Seen after encephalitis caused by flavivirus (Japanese encephalitis)

dull, flat, mask-like faces with unblinking eyes, tremor, and cogwheel rigidity

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

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)

S. pneumonia vs. N. meningitidis - odds of an unfavorable outcome was six times as high (95% CI, 2.61- 13.91; P<0.001)

Symptom onset < 24 hrs prior to admission

SeizurePneumonia Immunocompromised stateHypotension (DBP < 60mmHg)

MRI CTEEG SPECT – single hemisphereic in viral

enceph.