Brigham and Women's Hospitals

Encephalitis

Encephalitis, myelitis case reports

Reference

Diagnosis

Clinical characteristics

Imaging

CSF characteristics

COVID-19 RT-PCR

Alternative etiologies tested

Moriguchi, Int J Inf Dis, 2020

Meningo-

encephalitis

24M with fever, AMS, headache, seizure, nuchal rigidity

MRI brain: R mesial temporal T2/FLAIR hyperintensity; R ventriculitis

-Elevated OP (32 cm H2O)

-Mononuclear pleocytosis (12 cells/ul)

CSF +

Pharynx -

Negative serum HSV1 Ab, VZV IgM

Duong, Brain Behav Immun, 2020; Hanna Huang, Brain Behav Immun, 2020

Meningo-

encephalitis

41F with headache, fever, nuchal rigidity, photophobia, seizure

CT head: normal

MRI brain not performed

-Elevated protein (100 mg/dL)

-Lymphocytic pleocytosis (70 cells/ul)

CSF + (in second article)

Pharynx +

None

Bernard-Valnet, Eur J Neurol, 2020

Meningo-

encephalitis

Case 1: 64F with flu-like sx developed psychosis, found to have focal nonconvulsive status epilepticus

Case 2: 67F 17d after COVID-19 dx with new headache, developed drowsiness and confusion. Found to have L hemianopia and sensory hemineglect

MRI brain normal in both cases

Case 1:

-Mildly elevated protein (46.6 mg/dL)

-Lymphocytic pleocytosis (17 cells/ul, 97% lymphs)

Case 2:

-Mildly elevated protein (46.1 mg/dL)

-Lymphocytic pleocytosis (21 cells/ul, 89% lymphs)

Both cases:

CSF -

Pharynx +

Both cases: CSF negative for bacterial pathogens (N meningitidis, L

monocytogenes, S pneumoniae, H influenza, E Coli K1, S agalactiae) and viral pathogens (Enterovirus,

HSV 1/2, VZV, CMV, HHV-6, Parechovirus)

Case 1: CSF negative for anti-neuronal Ab (NMDAR, CAPSR2, LGI1, DPPX, GABABR, AMPAR,

lgLON5, mGLUR5, GlyR)

Wong, Clin Med (Lond), 2020

Rhombencephalitis

40M with fever, dyspnea; 3-4 days after admission developed diplopia, oscillopsia, hiccups, ataxia, altered RUE sensation

MRI brain and C-spine: T2 hyperintensity of R cerebellar peduncle and upper cervical cord

Normal protein and cell count

CSF not performed

Pharynx +

Negative CSF bacterial culture

MOG and AQP4 Ab sent, results not reported

Xiang et al. unpublished, 2020

Encephalopathy

56M with fever and fatigue, developed facial and oral convulsions after sedation wean

Unknown

-Elevated OP (> 33 cm H2O)

-Normal cell count and chemistries

CSF +

Unknown

Poyiadji, Radiology, 2020

ANE

50F with cough, fever, AMS

MRI brain: hemorrhagic rim-enhancing lesions in bilateral thalami, medial temporal lobes, and subinsular regions

Reported as “limited secondary to traumatic puncture”

CSF not performed

Pharynx +

Negative CSF HSV 1 and 2, VZV, and WNV

Negative influenza nasal swab

Zhao, medRxiv, 2020

Myelitis

66M with fever, fatigue, rapidly progressive bilateral weakness and T10 sensory level, hyporeflexia, urinary/bowel incontinence

CT head: chronic strokes and atrophy, no acute abnormalities

Spine imaging not performed

Not performed

CSF not performed

Pharynx +

Negative serum: Chlamydia pneumoniae IgM, EBV Ab, influenza B, adenovirus, coxsackievirus, parainfluenza virus, Mycoplasma pneumoniae, CMV, RSV, T spot

Zanin, Acta Neurochir (Wien), 2020

CNS demyelinating lesions

54F found down, CXR suggestive of pneumonia, found to have seizures

MRI brain and spine: non-enhancing T2 hyperintensities in periventricular white matter and cervical spinal cord

“Normal”, reportedly not consistent with multiple sclerosis though specific testing unclear

CSF -

Pharynx +

Negative “CSF analysis for neurotropic viruses”, but not listed

Dogan, Brain Behav Immun, 2020

Autoimmune meningo-

encephalitis

6 intubated COVID-19 patients (age 22-59) with impaired consciousness or agitated delirium

MRI brain normal in 3/6 cases, abnormal in 3/6 cases (cortical or white matter hyperintensities, contrast enhancement, or sulcal hemorrhagic features)

-Variably elevated protein in all 6 cases (37.6-131 mg/dL)

-No pleocytosis (6/6)

-Negative oligoclonal bands (5/5)

-1/5 cases had increased IgG index

All cases:

CSF -

Pharynx +

CSF negative for SARS-CoV-2 and “common seasonal viruses” (not specified)

Encephalitis and Myelitis work-up and management

  1. Work-up
  1. Encephalitis/meningitis:
  1. Screen for suggestive clinical features: Severe headache, nuchal rigidity, photophobia, altered level of consciousness, seizure, focal neurological deficits (e.g. cranial nerve palsy, focal/hemi-weakness or sensory loss, aphasia)
  2. Serum laboratory evaluation: CBC with differential, BMP, magnesium, LFTs, lactate, ABG/VBG, urine tox, serum tox, UA/UCx, BCx, ESR, CRP, ammonia, TSH, treponemal Ab, HIV, T spot.
  1. If subacute headache, consider serum cryptococcal antigen (especially if immunocompromised patient)
  1. Test for other respiratory viral infections if not already done (e.g. influenza, parainfluenza)
  2. Imaging
  1. Urgent CT/CTA head and neck to evaluate for structural etiologies or vessel occlusion (given hypercoagulable state associated with COVID-19). Also consider CTV if concern for elevated intracranial pressure.
  2. MRI brain with contrast (discuss with neurology re: urgency and prioritization of LP vs MRI)
  1. LP: opening pressure, bacterial culture and smear, cell count (tubes 1 & 4), glucose, protein, HSV PCR, VZV PCR and IgM, enterovirus PCR, oligoclonal bands, save extra CSF for additional studies.
  1. Consider: CSF meningitis/encephalitis panel (biofire), cryptococcal antigen, fungal cultures based on OP and imaging. CSF next generation sequencing or RT-PCR for SARS-CoV-2. Consider serum anti-aquaporin-4 (AQP4) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies if imaging concerning for demyelinating lesions.
  1. Consider EEG in consultation with neurology
  1. Myelitis:
  1. Screen for suggestive clinical features: Rapid onset of weakness, sensory alterations(especially sensory level), +/- bowel or bladder dysfunction
  2. Exam: strength, sensation (including assessment for sensory level, saddle anesthesia), reflexes, Babinski, rectal tone
  3. Serum laboratory evaluation: CBC with differential, BMP, magnesium, LFTs, vitamin B12, MMA, copper, ceruloplasmin, treponemal Ab, HIV, T spot, ANA, ds-DNA, SS-A/SS-B. Consider serum anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies if clinical picture is appropriate, other viral testing in discussion with infectious disease, neurology.
  4. Urgent MRI whole spine with and without contrast (discuss with neurology if particular segments should be prioritized or performed with more detail). If MRI is delayed, order CT spine as first pass to rule out compressive lesions.
  5. Non-urgent MRI brain with and without contrast to evaluate for concurrent brain lesions
  6. LP: bacterial culture and smear, glucose, protein, cell count (tubes 1 & 4), HSV PCR, VZV PCR and IgM, oligoclonal bands, IgG index, save extra fluid for additional studies.
  1. Management
  1. For all suspected cases of a CNS inflammatory process:
  1. Initiate empiric anti-infectives (should not be delayed for imaging or LP). These can be discontinued once HSV/VZV and bacterial processes are exonerated during work-up. Dosing should be adjusted for renal function. Anti-bacterials can be deferred if the clinical presentation is not consistent with a bacterial process (discuss with neurology).
  1. Ceftriaxone 2 g IV Q12H
  2. Vancomycin 20 mg/kg initial load, 15 mg/kg Q8H
  3. Ampicillin 2 g IV Q4H (if patient is immunocompromised, >50 years old, or pregnant)
  4. Acyclovir 10-15 mg/kg IV Q8H with 250cc IVF bolus for pre-hydration
  1. Treat seizure if present
  1. For cases in which subsequent work-up suggests an auto-immune etiology, consider immunomodulatory therapy in consultation with neurology
  1. Solumedrol 1g IV QD While steroids are associated with worse outcomes in COVID-19 patients, it is currently unclear how to weigh risk/benefits with concurrent CNS process; decisions will need to be made on a case-by-case basis
  2. IVIG Caution with IVIG in COVID-19 patients given risk of thrombotic complications
  3. PLEX
  4. In cases of ANE: consider tocilizumab given IL-6 is typically elevated and one pediatric case series (n=3) (Koh, Ped Neurol, 2019) showed favorable clinical outcomes (however, study was not controlled/randomized, and all patients also received high dose steroids)
  5. Of note, immune-modulating treatments have shown no clear benefit in acute flaccid myelitis (Hopkins, Curr Treat Options Neurol, 2020)