Transcript Sethalopathy - UBC Critical Care Medicine, Vancouver BC

Case-Based Presentation
21 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 symptoms
33% focal neurologic deficit
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Altered mental status
Fever, headache, myalgia, mild respiratory
infection
Focal neurologic deficit
seizures
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Focal neurologic deficit
Neck rigidity (associated meningitis)
Seizures
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Cranial epidural abscesses
Subdural empyema
Ventriculitis
Stroke (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,
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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
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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.
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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
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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 use
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Avoid 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 cm
Stat gram stain negative
WBC: 200, predominantly lymphocytes
Glucose 6
Total 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
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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 Herpessimplex-virus-encephalitis (GACHE): a
multicenter, multinational, randomized, doubleblind, 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
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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
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Reactivation leads to encephalitis with focal
neurologic deficits and seizures
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Dx:
 CSF PCR for VZV (sensitivity, 80%–95%, and specificity
>95% in immunocompromised person)
 CSF VZV IgM antibody
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Tx:
 Acyclovir, ganciclovir, steroids
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Evidence of widespread CMV disease (e.g.,
retinitis, pneumonitis, adrenalitis, myelitis,
polyradiculopathy)
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Dx:
 CSF PCR for CMV (for immunocompromised persons,
sensitivity, 82%–100%; specificity, 86%–100%)
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Tx:
 Ganciclovir and foscarnet
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Recent exantham, Seizures
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Dx
 Serologic testing; culture
 CSF PCR (sensitivity, > 95%); high rate of
detection in healthy adults (positive predictive
value, 30%)
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Tx:
 gancoclovir or foscarnet
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Abrupt onset of fever, headache, neck stiffness, and vomiting
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1 in 150 develop neuroinvasive disease (meningitis, encephalitis,
acute flaccid paralysis)
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Clinical features include tremors, myoclonus, parkinsonism, and
poliomyelitis-like flaccid paralysis (may be irreversible)
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Dx:
 CSF IgM (preferred)
 CSF PCR (<60% of results are positive)
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Tx:
 supportive
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Acute encephalopathy with seroconversion
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Most commonly presents as HIV dementia
(forgetfulness,loss of concentration, cognitive
dysfunction, psychomotor retardation)
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Dx:
 Serology + viral load
 CSF PCR
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Tx:
 HAART
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Cognitive dysfunction
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Limb weakness, gait disturbance, coordination difficulties
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Visual loss
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Focal neurologic findings, especially visual field cuts
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Dx:
 CSF PCR (for diagnosis of PML, sensitivity 50%–75%; specificity, 98%–
100%)
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Tx:
 Reversal of immunosuppression
 HAART in pts with AIDS
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Rhombencephalitis (ataxia, cranial nerve
deficits, nystagmus)
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Dx:
 Culture of blood specimens
 Culture of CSF specimens
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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
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Dx:
 Microorganism detection at sites outside CNS
 CSF AFB smear and culture
 CSF PCR has been reported to have a low sensitivity
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Tx:
 Isoniazid, rifampin, pyrazinamide, ethambutol
 Dexamethasone in patients with meningitis
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More commonly a chronic meningitis
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May present acutely as meningoencephalitis
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Dx:
 Blood fungal culture; serum cryptococcal antigen
 CSF fungal culture; CSF cryptococcal antigen
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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
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Approximately 50% of patients develop
disorientation, lethargy, confusion, or memory loss
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Dx:
 Serum complement fixing or immunodiffusion antibodies
 CSF complement fixing or immunodiffusion antibodies
 CSF culture
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Tx:
 Fluconazole, Itraconazole, VoriconazolE, Amphotericin B
(intravenous and intrathecal)
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More commonly a chronic meningitis; may present as acute encephalitis
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Isolated meningoencephalitis or associated with systemic findings
(hepatosplenomegaly, pneumonia, bone marrow suppression)
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Dx:
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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;
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Seizures, hemiparesis, and cranial nerve abnormalities common
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Convulsions and chorioretinitis in congenital toxoplasmosis
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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;
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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
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Cumulative risk at 5 yrs is 10% if no acute sz
vs 20% if acute sz present
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Respond to phenytoin and benzos
Pract Neurol 2007;285-302
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Most common deficits:
 Dysnomia
 Anterograde amnesia
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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
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Sense cam
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Seen after encephalitis caused by flavivirus
(Japanese encephalitis)
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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
Seizure
Pneumonia
Immunocompromised state
Hypotension (DBP < 60mmHg)
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MRI
CT
EEG
SPECT – single hemisphereic in viral enceph.