Sethalopathy

1
Sethalopathy

• Case-Based Presentation
• 21 February 2010

2
Good Morning

• Monday AM, 0505.
• 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.

3
In Emergency Department

• 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.

4
Nice Try

• 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.

5
Differential Diagnosis

• Resident asked for differential diagnosis of
  altered mental status with focal neurologic
  deficit, but stalls after malignancy.
• Federico, could you help her out?

6
Differential Diagnosis
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Acute septic meningitis

• Mortality 25
• Morbidity 60
• Fever, neck stiffness, altered mental status
  (only 44)
• 95 has 2/4 symptoms
• 33 focal neurologic deficit

8
Encephalitis

• Altered mental status
• Fever, headache, myalgia, mild respiratory
  infection
• Focal neurologic deficit
• seizures

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Brain abscesses

• Focal neurologic deficit
• Neck rigidity (associated meningitis)
• Seizures

10
Others

• Cranial epidural abscesses
• Subdural empyema
• Ventriculitis
• Stroke (arterial or venous)
• Hypoglycemia
• Seizures (non-convulsive)

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Emergency treatment

• 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

12
Does someone need to know about this?

• Meanwhile, the patients GCS has deteriorated to
  E1 V2 M5.
• No response to painful stimulus on Right side.

NOT COOL !
13
Before we get too carried away

• Any concerns about this mans induction given
  your suspicion of an intracranial process?
  (Ibrahim)

14

• Suspect raised ICP
• Headache, dec LOC (esp GCS lt8), vomiting,
  blurred vision
• VI CN palsy
• Papilledema
• Spontaneous periorbital brusing (CVST)
• Cushings triad (constant inc BP, mainly
  systolic, bradycardia, and resp depression)

15

• 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

16

• 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 gt60, use
  pressors if necessary

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Position in increased ICP

• 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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Pretreatment RSI

• 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

19
Induction

• Etomidate 0.3mg/kg
• Dec brain O2 consumption by 45, and CBF by
  34--gtdec 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

20

• Propofol 2mg/kg, is alternative
• Dec brain metabolism
• Myocardial and dose-dependent resp depressant,
  dec MAP, so cautious use
• Avoid Ketamine (inc BP, CBF, and ICP)
• Caution with midazolam, mildly dec CPP

21
Back to business

• 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

22
Time for a lumbar puncture

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

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(No Transcript)
24
LP

• Opening pressure 18 cm
• Stat gram stain negative
• WBC 200, predominantly lymphocytes
• Glucose 6
• Total protein 0.5 g/L

25
What is the most common cause of viral
encephalitis in North America?

• 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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HSVE

• Herpes Simplex Virus

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HSV Treatment

• 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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HSV Treatment

• 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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HSV Treatment

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

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HSV Treatment

• 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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HSV Treatment

• 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 200576(11)1544-9
• Non blinded, retrospective analysis in 45
  patients with HSVE
• Suggested improved outcomes in those treated with
  steroids

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HSV Treatment

• 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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HSV Treatment

• 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.
  2008840

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(No Transcript)
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West Nile Virus
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Whatever Omar says, well do.

• The patients 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 mans
  abstinence from IV drug use may not be complete

37
Does this change the game?

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

38
Causes of infectious encephalitis in the
immunocompromized

• 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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VZV

• 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, 8095, and
  specificity gt95 in immunocompromised person)
• CSF VZV IgM antibody
• Tx
• Acyclovir, ganciclovir, steroids

40
CMV

• Evidence of widespread CMV disease (e.g.,
  retinitis, pneumonitis, adrenalitis, myelitis,
  polyradiculopathy)
• Dx
• CSF PCR for CMV (for immunocompromised persons,
  sensitivity, 82100 specificity, 86100)
• Tx
• Ganciclovir and foscarnet

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HHV-6

• Recent exantham, Seizures
• Dx
• Serologic testing culture
• CSF PCR (sensitivity, gt 95) high rate of
  detection in healthy adults (positive predictive
  value, 30)
• Tx
• gancoclovir or foscarnet

42
West Nile virus

• 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 (lt60 of results are positive)
• Tx
• supportive

43
HIV

• 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

44
JC Virus

• 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
  5075 specificity, 98100)
• Tx
• Reversal of immunosuppression
• HAART in pts with AIDS

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Listeria

• Rhombencephalitis (ataxia, cranial nerve
  deficits, nystagmus)
• Dx
• Culture of blood specimens
• Culture of CSF specimens
• Tx
• Ampicillin plus gentamicin
• TMP-SMX if pen allergic

46
M. tuberculosis

• 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

47
Cryptococcus

• 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 610 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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Coccidioides

• 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)

49
Histoplasma

• 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 46 weeks, followed
  by itraconazole for at least 1 year and until
  resolution of CSF abnormalities

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Toxoplasma

• 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

51
The results are in

• The patients 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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What are some complications of viral encephalitis?

• (Noemie)

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Complications

• 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 2007285-302
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Seizures

• 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 2007285-302
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Memory impairments

• 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 1990,47646-647
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Memory impairment

• Neuro page
• Sense cam

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Post-encephalitic parkinsonism

• Seen after encephalitis caused by flavivirus
  (Japanese encephalitis)
• dull, flat, mask-like faces with unblinking eyes,
  tremor, and cogwheel rigidity

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Poliomyelitis-like flaccid paralysis

• 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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When you have a second

• The patients extended family all show up
  simultaneously and want to meet with you at
  1645. They are most interested in his prognosis
  for neurologic recovery.
• What can you tell them? (Erik)

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Predictors of unfavorable outcome
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as well as
62
as well as

• S. pneumonia vs. N. meningitidis - odds of an
  unfavorable outcome was six times as high (95
  CI, 2.61- 13.91 Plt0.001)

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Trends, though no statistically sig.

• Symptom onset lt 24 hrs prior to admission
• Seizure
• Pneumonia
• Immunocompromised state
• Hypotension (DBP lt 60mmHg)

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Neuroimaging

• MRI
• CT
• EEG
• SPECT single hemisphereic in viral enceph.