Neurology & Infectiology & Emergency Medicine
Encéphalite | Clinique Omicron Québec
Encephalitis is an inflammation of the brain parenchyma - the neurons and glia - which differs from meningitis (inflammation of the meninges) in the presence of central neurological dysfunction: altered consciousness, acute behavioral or psychiatric disorders, focal deficits, epileptic seizures or memory impairment. In practice, meningitis and encephalitis frequently coexist (meningoencephalitis). Encephalitis falls into two main etiological categories: infectious encephalitis, caused directly by invasion of brain tissue by a pathogen (viruses - the most common cause - but also bacteria, parasites and fungi), and autoimmune encephalitis, caused by an immune reaction directed against neuronal or glial antigens (antibodies against synaptic receptors or cell surface proteins). Herpes simplex virus type 1 (HSV-1) encephalitis is the most common form of infectious encephalitis in industrialized countries - accounting for 10 to 20 % of all viral encephalitis - and constitutes an absolute neurological emergency: without early antiviral treatment, mortality exceeds 70 %, and severe neurological sequelae affect almost all survivors. Autoimmune encephalitis - long under-recognized - now accounts for a growing proportion of diagnosed encephalitis (up to 20-40 % of encephalitis in recent series) since the description of anti-NMDA receptor encephalitis by Dalmau in 2007. Early identification and treatment of these two forms - empirical antiviral + immunotherapy if autoimmune - directly conditions neurological prognosis.
Clinical presentation, etiologies and diagnostic approach
- Diagnostic criteria for encephalitis (International Encephalitis Consortium 2013): mandatory criterion: altered consciousness, behavior or personality ≥24 hours with no other identified cause; plus at least 2 minor criteria among: fever ≥38°C within 72h before/after admission + focal or generalized seizures not attributed to a pre-existing seizure disorder + new focal neurological deficit + CSF pleocytosis (leukocytes >5/mm³) + brain MRI abnormality suggestive of encephalitis + EEG abnormality compatible with encephalitis not attributable to another cause
- Infectious etiologies : herpes viruses (HSV-1 - most frequent cause of severe sporadic encephalitis - temporal lobe + insular; HSV-2 - infant + immunocompromised; VZV - varicella-zoster - immunocompromised + elderly; EBV + CMV); arboviroses (transmitted by arthropods) : West Nile virus (WNV - Quebec - summer + autumn - vector Culex spp - meningoencephalitis + flaccid paralysis) + Eastern encephalitis virus (EEE - rarer - very severe) + rabies virus (rare in Canada - bat - long incubation period - almost universally fatal) ; enterovirus (child - epidemic); influenza A (H1N1, H3N2 - post-infectious encephalopathy); measles (subacute sclerosing panencephalitis - SSPE - late sequelae); intracellular bacteria: Listeria monocytogenes (rhombencephalitis - brain stem + cerebellum - elderly + immunocompromised + pregnancy - Ampicillin) + Mycobacterium tuberculosis (granulomatous meningoencephalitis + tuberculomas); parasites: Naegleria fowleri (swimming in warm freshwater - fulminant) + Toxoplasma gondii (immunocompromised HIV CD4 <100)
- Autoimmune etiologies : anti-NMDAR encephalitis: the most common autoimmune encephalitis - young women (<35 years) - ovarian teratoma in 30-60 % of adult women - characteristic 4-phase progression: flu-like prodrome → acute psychiatric disorders (psychosis, agitation, hallucinations) → orofacial dyskinesias + mutism + vegetative disorders → refractory status epilepticus + coma; autoimmune limbic encephalitis (anti-LGI1, anti-CASPR2, anti-AMPAR, anti-GABA-B): predominant involvement of limbic structures (hippocampi, amygdala) → disorders of anterograde episodic memory + temporal seizures + psychiatric disorders; paraneoplastic (anti-Hu, anti-Yo, anti-Ri, anti-Ma2): underlying cancer (lung, testis, ovary, breast) - often severe sequelae despite treatment
- Diagnostic workup : brain MRI with gadolinium (FLAIR + DWI + T1 + T2 + T1 Gd sequences): reference examination - HSV: medial temporal + insular + cingulate gyrus FLAIR/DWI hypersignal - characteristic but inconsistent in the first 24-48h; autoimmune limbic encephalitis: bilateral symmetrical hippocampal FLAIR hypersignal; lumbar puncture (CSF): essential unless intracranial hypertension evident on MRI (imminent involvement) - analysis: cellularity (lymphocytic pleocytosis >5/mm³ - typical - may be normal in the first 24-48 hours) + proteins (moderately elevated) + glucose (normal in viral encephalitis vs. decreased in bacterial meningitis and TB) + HSV PCR (gold standard - sensitivity 96 % - may be falsely negative if performed <72h from onset of symptoms - repeat if strong suspicion) + PCR VZV + enterovirus + WNV serology + autoimmune antibodies on CSF and serum (full panel: anti-NMDAR, anti-LGI1, anti-CASPR2, anti-AMPAR, anti-GABA-B, anti-DPPX); EEG : diffuse non-specific abnormalities + temporal focus (HSV) + extreme delta brush (anti-NMDAR) + FIRES in children; CBC + CRP + VS + ionogram + liver + kidney workup + blood/urine cultures + blood viral serologies (WNV IgM); thoraco-abdomino-pelvic CT + gynecological tumor workup (anti-NMDAR adult female)
Treatment
| Treatment | Mechanism, scheme and procedures | Duration, effectiveness and precautions |
|---|---|---|
| Aciclovir IV - herpes encephalitis Absolute emergency - start PCR immediately |
Aciclovir (Zovirax) IV: nucleoside analog - phosphorylated by viral thymidine kinase → inhibition of HSV DNA polymerase → cessation of viral replication; adult dosage: 10 mg/kg IV × 3/d (every 8h) infused over 1 hour - adapt to renal function (eGFR 25-50: 5 mg/kg/8h; eGFR 10-25: 5 mg/kg/12h; eGFR <10 or hemodialysis: 2.5 mg/kg/12h); dosage infant and child <12 years: 20 mg/kg/8h IV - infant <3 months: 20 mg/kg/8h; start IV aciclovir empirically as soon as encephalitis is clinically suspected - without waiting for HSV PCR results (24-48h delay) - the benefit of early treatment justifies the risk of treating some patients unnecessarily; adjuvant IV dexamethasone (0.15 mg/kg × 4/d): discussed - limited data - may reduce cerebral edema and local inflammation but not routinely recommended (GACHE trial - no proven benefit on neurological prognosis at 3 months) | Aciclovir has transformed the prognosis of herpetic encephalitis: mortality reduced from 70 % to <20 % with early treatment (Whitley 1986 NEJM - NAID Collaborative Antiviral Study Group); severe neurological morbidity (amnesic, behavioral sequelae, post-encephalitic epilepsy) in 30-50 % of even treated survivors - more frequent the longer the treatment delay; side effects of IV aciclovir: nephrotoxicity (crystalluria) - vigorous IV hydration mandatory: 1-1.5 L NaCl 0.9 % before each dose - monitor creatinine 2× /week) + neurotoxicity (confusion, myoclonus, coma - especially if CKD) + phlebitis at injection site; duration of treatment: 14 to 21 days - control HSV LCR PCR at D14 recommended before stopping (persistence of positive PCR → prolong until negativation); oral relay with valaciclovir (Valtrex) 2 g × 3/d × 90 days: reduction in sequelae in certain subgroups (Bradshaw 2018 - inconclusive data - practice varies between centers); if HSV PCR negative on 2 successive CSF + MRI not suggestive + favorable evolution → discontinuation of aciclovir may be considered after neurological opinion |
| Treatment of autoimmune encephalitis 1st and 2nd line immunotherapy |
1st-line immunotherapy (to be initiated promptly on clinical suspicion + compatible MRI + EEG, without waiting for serological confirmation - serology lead time 2-4 weeks): methylprednisolone IV (Solu-Médrol) 1 g/d × 3 to 5 days then oral decrease (prednisone 1 mg/kg/d) + intravenous immunoglobulins (IVIG) 2 g/kg over 2 to 5 days + plasma exchange (PE) 5 to 7 sessions over 10 to 14 days - combination steroids + IVIG in 1st line in most centers (Titulaer 2013 - anti-NMDAR encephalitis); 2nd-line immunotherapy (if no response after 2 to 4 weeks of 1st line): rituximab (Rituxan) 375 mg/m² IV × 4 weekly doses (B-cell depletion + reduced autoantibody production) + cyclophosphamide 750 mg/m² IV × 1/month × 3 to 6 months; treatment of underlying tumor (anti-NMDAR + ovarian teratoma): urgent laparoscopic oophorectomy or cystectomy - tumor excision significantly improves neurological prognosis and reduces the risk of relapse (Dalmau 2011 - Titulaer 2013 - accelerated clinical improvement after excision); systematic tumor workup in all autoimmune encephalitis in adults: TAP CT + PET-FDG + pelvic ultrasound + tumor markers (AFP, βHCG, PSA, CA125) | Prognosis of anti-NMDAR encephalitis with optimal treatment: 80 % of patients have good functional recovery at 24 months (mRS ≤2) - recovery time often long (6 to 18 months) - relapses in 12-25 % of cases (especially if tumor not resected or treatment insufficient); good prognostic factors: early immunotherapeutic treatment + tumor excision + absence of prolonged intensive care + young age; duration of maintenance immunotherapy: prednisone tapering off over 6-12 months + azathioprine or mycophenolate mofetil (MMF) as a cortisone-sparing agent over 2 years for severe or recurrent forms; serological monitoring of antibodies (serum + CSF) at 3, 6, 12 months: persistence or re-ascension of antibody titres often precedes clinical relapses - enables treatment intensification to be anticipated; hospitalization in neurological intensive care often necessary for severe forms (refractory status epilepticus + dysautonomia + need for mechanical ventilation) |
| Antiepileptic treatment Frequent seizures - refractory malaise |
Epileptic seizures are frequent in encephalitis (50-70 % of cases) and may progress to refractory status epilepticus (REMS) - particularly feared in anti-NMDAR encephalitis and FIRES (febrile infection-related epilepsy syndrome in children); 1st-line treatment of acute seizures: lorazepam (Ativan) 0.1 mg/kg IV (max 4 mg) or diazepam (Valium) 0.15 mg/kg IV; if IV not available: midazolam IM 0.2 mg/kg or rectal diazepam 0.5 mg/kg; background antiepileptics for repeated seizures: levotetracetam (Keppra) 1,500-3,000 mg/d IV or per os (good tolerance + few drug interactions); sodium valproate (Depakene) 20-40 mg/kg/d IV: alternative - caution if liver disease; phenytoin (Dilantin) or fosphenytoin: option if levotetracetam insufficient; refractory status epilepticus: midazolam IV continuous infusion (0.1-2 mg/kg/h) + phenobarbital IV + propofol IV (intensive care) + ketamine IV (NMDA antagonist effect - useful in anti-NMDAR encephalitis with EMER - 1-5 mg/kg/h); barbiturate anesthesia (thiopental) if super-refractory EMER | Antiepileptic drugs control seizures but do not treat the cause of encephalitis - etiological treatment (antiviral or immunotherapeutic) remains the priority; seizures in autoimmune encephalitis are often pharmaco-resistant to conventional antiepileptic drugs - immunotherapy is the only truly effective treatment for seizures in this context; in FIRES (child): cannabidiol (Epidiolex) + IV ketamine + phenobarbital + ketogenic diet show the best efficacy data in this catastrophic syndrome; duration of antiepileptic treatment after encephalitis : variable - depends on persistence of EEG abnormalities and type of encephalitis - case-by-case decision with the neurologist - post-encephalitis epilepsy is common (30-50 % of HSV encephalitis); do not drive a vehicle for the duration of antiepileptic treatment and at least 12 months after the last seizure (Quebec regulations - SAAQ) |
| Specific viral encephalitis - WNV, VZV, rabies Targeted treatments and prophylaxis |
West Nile Virus (WNV) in Quebec: transmission by Culex mosquito bite in summer/fall - active INSPQ surveillance - incubation 2-14 days - invasive neurological syndrome (meningoencephalitis + acute flaccid paralysis due to involvement of the anterior horns) in 1 % of those infected (mostly >50 years, immunocompromised); treatment : no specific antiviral approved - supportive treatment (anticonvulsants + ventilation if respiratory paralysis); high-dose IVIg (containing high titers of anti-WNV): insufficient data - not routinely recommended; VZV (varicella-zoster): VZV encephalitis in the immunocompromised or elderly - treatment: aciclovir IV 10-15 mg/kg/8h × 14-21 days (same protocol as HSV); rabies (Rabies): exposure to suspect animal (bat in North America) → immediate post-exposure prophylaxis (PEP) = rabies vaccine (4 doses D0-J3-J7-J14) + rabies immunoglobulin (RIG) around wound - efficacy close to 100 % if started before symptoms; overt clinical rabies : almost uniformly fatal - Milwaukee protocol (induced coma + antivirals) - exceptional survival reported; mandatory notification (MADO) in Quebec: rabies + WNV (neuroinvasive forms) | In Quebec, WNV surveillance is carried out by the INSPQ and regional Public Health Departments (DSP) - neuroinvasive human cases are compulsorily reported - seasonal peak July to October - personal protection: DEET or icaridine repellents + covering clothing at dawn and dusk + elimination of stagnant water (larval breeding grounds); preventive rabies vaccination (pre-exposure) : recommended for veterinarians, wildlife protection officers, cavers, travelers to endemic areas with difficult medical access; any exposure to a bat (direct contact or presence in the bedroom while sleeping) in Canada → urgent medical consultation + PPE if unvaccinated or vaccination status uncertain - the Public Health Department must be contacted (1-877-644-4545 in Quebec); tick-borne encephalitis (TBE): rare in Quebec, but reported in forested areas - vaccine available (Ticovac) for travelers in European or Asian endemic zones |
| Rehabilitation and after-effects Prolonged recovery - multidisciplinary follow-up |
Neurological sequelae are common after severe encephalitis - their nature and severity depend on etiology, time to treatment and extent of brain damage; sequelae of herpetic encephalitis: Korsakoff-like amnesic syndrome (bilateral hippocampal lesions - impaired anterograde and retrograde episodic memory) + behavioral disorders (frontal syndrome, disinhibition) + post-encephalitic epilepsy (30-50 % - long-term antiepileptics) + agnosia + aphasia depending on location + late psychiatric disorders (sometimes similar to autoimmune encephalitis - post-HSV autoimmune mechanism - anti-NMDAR or anti-GABA-A antibodies discovered secondarily) ; neuropsychological rehabilitation : full neuropsychological assessment at 3 months post-encephalitis + cognitive rehabilitation program (memory, attention, executive functions) + speech therapy if aphasia + physiotherapy if motor deficit + occupational therapy; psychiatric follow-up: depression + PTSD + anxiety disorders frequent after severe encephalitis - psychotherapy + pharmacotherapy if indicated | Recovery time after autoimmune encephalitis is often long and may surprise families and clinicians - progressive improvement over 12 to 24 months is the rule, even after a very severe form requiring several months in intensive care; keep expectations realistic while actively encouraging rehabilitation ; post-encephalitis epilepsy may appear late (months to years after the acute episode) - educate patients and their families about the warning signs; the risk of autoimmune encephalitis recurrence justifies lifelong neurological follow-up with monitoring of antibody titres and rapid resumption of immunotherapy in the event of relapse; patient associations (e.g. : Autoimmune Encephalitis Alliance): educational resources + psychosocial support + contact with specialized neurologists - relevant for patients and their families in the prolonged recovery phase |
ℹ️
Anti-NMDAR encephalitis - not to be confused with psychosis: Anti-NMDA receptor encephalitis typically begins with acute psychiatric symptoms - agitation, hallucinations, paranoid delusions, insomnia - which often lead to psychiatric hospitalization before a neurological diagnosis is made. The average diagnostic delay is 4 to 6 weeks. Elements that should point to encephalitis rather than primary psychosis are: a rapid and severe course, atypical for a first psychosis; the onset in a young woman with no psychiatric history; the secondary appearance of dyskinesias (involuntary orofacial movements), mutism, vegetative disorders (tachycardia, hypertension, hyperthermia) or convulsions. In the event of an acute psychiatric presentation in a woman under 45, autoimmune encephalitis should be suspected, and a neurological work-up (MRI + EEG + CSF + anti-NMDAR antibodies) initiated without delay.
Emergency - Encephalitis = immediate hospitalization
Dial 911 or go immediately to the emergency room if : fever + altered consciousness + confusion + convulsions → encephalitis until proven otherwise - aciclovir IV should be started within hours of admission.
Acute psychiatric disorders + abnormal movements + vegetative instability in a young woman → anti-NMDAR encephalitis - urgent neurological assessment + immunotherapy without delay.
Sudden thunderclap headache + stiff neck + fever + photophobia → bacterial meningoencephalitis - ceftriaxone IV + dexamethasone IV as an absolute emergency even before lumbar puncture if bacterial meningitis with signs of severity is suspected.
Consult at Clinique Omicron
Encephalitis is a neurological emergency requiring immediate hospitalization. Clinique Omicron's physicians immediately refer any patient presenting signs of encephalitis to the emergency department, participate in post-hospital follow-up (anti-epileptic monitoring, rehabilitation coordination, long-term immunotherapy follow-up) and ensure the prevention of avoidable infectious encephalitis (vaccinations - VZV, WNV, rabies). Consultations are available at our points of service in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for information purposes only and does not replace the advice of a qualified healthcare professional. Encephalitis is a medical emergency requiring hospitalization and immediate specialized neurological care.
Omicron Clinic
Need to consult a doctor?
Treatment within 24-48 hours. In-clinic or telemedicine, anywhere in Quebec.
Insurance receipts. 7j/7. No family doctor required.