Encephalitis

brain parenchyma · altered mentation + seizures · HSV vs autoimmune · empiric acyclovir NOW · Super Compact

  • Sx: altered mental status/behavioral change (the defining feature) + fever + headache + seizures + focal deficits; HSV — personality/memory change, temporal-lobe seizures, aphasia; autoimmune — subacute psychiatric sx, movement disorder, autonomic instability, seizures

  • Neg: denies meningitis-only picture (preserved mentation — meningitis vs encephalitis = brain dysfunction) · denies pure metabolic/toxic cause (no focal/seizure, organ failure) · denies thunderclap (SAH) · denies global toxidrome (intoxication)

  • SHx: exposures (mosquito/tick — arbovirus, travel), immune status, vaccination, recent viral illness; for autoimmune — young, ovarian teratoma (anti-NMDAR), other tumors/paraneoplastic

  • Etiology: HSV-1 (most common sporadic, treatable — temporal lobes) · other viral (VZV, enterovirus, arbovirus/West Nile, measles) · autoimmune (anti-NMDAR, LGI1, GABA-B; paraneoplastic) · post-infectious (ADEM)

  • RF: modifiable — exposure, vaccination gaps · non-mod — immunocompromise, age, underlying tumor (autoimmune)

  • Data: LP — lymphocytic pleocytosis, ↑protein, normal glucose, RBCs (HSV hemorrhagic), HSV PCR (may be neg first 72h — repeat) · MRI (HSV: temporal lobe edema/hemorrhage; autoimmune: mesial temporal/limbic) · EEG (temporal discharges; extreme delta brush in anti-NMDAR; NCSE) · autoimmune Ab panel (serum + CSF) · tumor search

  • DDx: meningitis (mentation preserved) · brain abscess (focal, ring lesion) · metabolic encephalopathy (no fever/CSF) · status epilepticus/postictal · primary psychiatric (autoimmune mimics) · stroke

  • Home Meds: continue essentials; priority is empiric acyclovir; immunosuppression decisions with neurology

Plan — ward (ICU if severe)

  • Consults: neurology · infectious disease · ICU if ↓LOC/status · oncology/gyn if autoimmune (tumor search)

  • Start acyclovir (Zovirax) 10 mg/kg IV q8h EMPIRICALLY now — do NOT wait for PCR. HSV is treatable and delay causes irreversible damage; treat all suspected encephalitis until HSV excluded

  • Hydrate well with acyclovir (crystalluria/nephrotoxicity); renally dose-adjust

  • If HSV PCR negative but high suspicion early — continue acyclovir and repeat LP in 3–7 days (early false negatives)

  • HSV confirmed: acyclovir IV ×14–21 days

  • Autoimmune (anti-NMDAR etc.): immunotherapy — high-dose steroids + IVIG or plasma exchange (first-line); rituximab/cyclophosphamide if refractory; find & remove tumor (ovarian teratoma)

  • Seizures: treat with levetiracetam (Keppra); continuous EEG if not waking (NCSE common)

  • Trend: mental status, seizures, repeat LP/MRI, antibody results

  • → ICU if: status epilepticus, ↓consciousness/airway, cerebral edema, or autonomic instability (anti-NMDAR — dysautonomia/hypoventilation)

Encephalitis

complete reference · HSV (treat empirically) · autoimmune/anti-NMDAR · LP/MRI/EEG · immunotherapy · Full Card

Symptoms / Associated Sx

  • Altered mental status or behavioral/personality change is the defining feature (distinguishing encephalitis — brain parenchymal inflammation — from meningitis, where mentation is typically preserved), accompanied by fever, headache, seizures, and focal neurologic deficits. HSV encephalitis: prominent personality/memory disturbance, aphasia, and temporal-lobe (often complex partial) seizures from its temporal/frontal predilection. Autoimmune (e.g. anti-NMDAR): a subacute progression of psychiatric symptoms (psychosis, agitation), then movement disorders (orofacial dyskinesias), seizures, autonomic instability, and decreased consciousness — classically a young woman.

Neg

  • Mentation is impaired (not preserved) — distinguishes encephalitis from meningitis (meningoencephalitis overlaps; the presence of brain dysfunction defines the encephalitic component)

  • Fever, CSF pleocytosis, and/or seizures present, not a pure metabolic derangement — argues against toxic-metabolic encephalopathy (which lacks fever, CSF inflammation, and usually focal signs)

  • No thunderclap onset/cisternal blood — argues against SAH; no global intoxication toxidrome — argues against drug effect.

  • In subacute psychiatric presentations, the presence of seizures, movement disorder, autonomic instability, or CSF inflammation argues against a primary psychiatric disorder and toward autoimmune encephalitis (a frequently missed, treatable mimic of "new psychosis")

Social History (SHx)

  • Exposures — mosquito/tick bites and travel (arboviruses, West Nile), animal exposure (rabies), sick contacts, season; immune status and vaccination history; recent viral illness (post-infectious ADEM).

  • For autoimmune encephalitis: age and sex (young women — anti-NMDAR), known or occult malignancy (ovarian teratoma, small-cell lung cancer, thymoma), prior tumor history.

Main Etiology

  • Viral: HSV-1 (the most common sporadic and the critical treatable cause — temporal lobe), VZV, enteroviruses, arboviruses (West Nile, others), less commonly measles/mumps, rabies, HIV. Autoimmune/paraneoplastic: anti-NMDA-receptor (most common autoimmune; ovarian teratoma association), LGI1 (limbic, hyponatremia, faciobrachial dystonic seizures), GABA-B, and paraneoplastic antibodies. Post-infectious: acute disseminated encephalomyelitis (ADEM). A specific cause is never identified in a substantial fraction.

RF

  • Modifiable: vector exposure, vaccination gaps, unprotected travel.

  • Non-modifiable: immunocompromise, age extremes, underlying or occult tumor (autoimmune/paraneoplastic).

Data

  • Lumbar puncture — typically lymphocytic pleocytosis, elevated protein, normal glucose; red cells/xanthochromia suggest hemorrhagic (HSV) involvement. HSV PCR is the key test (high sensitivity/specificity) — but can be falsely negative in the first 72 hours, so a negative early PCR with high suspicion warrants continued acyclovir and a repeat LP. Send a meningitis/encephalitis multiplex panel and autoimmune antibody panel (paired serum and CSF).

  • MRI brain (HSV: unilateral or bilateral temporal-lobe and insular/cingulate edema, often hemorrhagic; autoimmune limbic encephalitis: mesial temporal T2/FLAIR signal; ADEM: multifocal white-matter lesions)

  • EEG (temporal lobe epileptiform discharges/PLEDs in HSV; "extreme delta brush" suggestive of anti-NMDAR; detects non-convulsive seizures)

  • Tumor search if autoimmune suspected — pelvic MRI/transvaginal US (ovarian teratoma), CT chest/abdomen/pelvis, age-appropriate cancer screening.

DDx

Meningitis (mentation preserved; meningoencephalitis overlaps) · brain abscess (focal, ring-enhancing lesion) · toxic-metabolic encephalopathy (no fever/CSF inflammation, organ failure) · status epilepticus / prolonged postictal state (EEG) · primary psychiatric disorder (autoimmune encephalitis mimics new psychosis — don't miss it) · stroke / PRES (imaging pattern) · CNS vasculitis

Home Meds

  • Continue essential home medications; the immediate priority is empiric acyclovir.

  • Immunosuppression and steroid decisions (for autoimmune encephalitis) are made with neurology once HSV is being addressed.

Plan

Consults

  • Neurology — diagnosis, EEG, autoimmune workup and immunotherapy.

  • Infectious disease — antiviral therapy and duration, atypical pathogens.

  • ICU — depressed consciousness, status epilepticus, or autonomic instability.

  • Oncology / gynecology — tumor search and removal in autoimmune/paraneoplastic disease.

Empiric antiviral (do this immediately)

  • Start IV acyclovir (Zovirax) 10 mg/kg q8h empirically as soon as encephalitis is suspected — do NOT wait for the HSV PCR. HSV encephalitis is treatable and every hour of delay worsens outcome; treat all suspected viral encephalitis until HSV is excluded.

  • Hydrate generously alongside acyclovir to prevent crystalline nephropathy; adjust the dose for renal function and monitor creatinine.

  • If the initial HSV PCR is negative but suspicion is high (especially within 72h of onset), continue acyclovir and repeat the LP in 3–7 days. Confirmed HSV: complete 14–21 days of IV acyclovir.

Autoimmune encephalitis

  • First-line immunotherapy: high-dose corticosteroids (e.g. methylprednisolone 1 g IV daily ×5) plus IVIG or plasma exchange. Refractory: rituximab and/or cyclophosphamide (second-line). Find and remove the associated tumor (e.g. ovarian teratoma in anti-NMDAR) — resection is central to recovery.

Seizures / supportive

  • Treat seizures with levetiracetam (Keppra) and obtain continuous EEG if the patient is not returning to baseline (non-convulsive status is common). Supportive care for agitation/dyskinesias; manage autonomic instability closely in anti-NMDAR disease.

Always

  • PT / OT / SLP eval and treat — encephalitis often leaves cognitive and functional deficits requiring intensive rehabilitation; neuropsychiatric support.

  • Trend: mental status, seizure control/EEG, renal function on acyclovir; repeat MRI/LP and antibody results to refine the diagnosis.

  • Escalation triggers: status epilepticus → ICU · depressed consciousness/airway compromise → intubate, ICU · cerebral edema/raised ICP → ICU, neurosurgery · autonomic instability or central hypoventilation (anti-NMDAR) → ICU.

  • Discharge checklist: complete the antiviral course (HSV) via OPAT · ongoing immunotherapy plan and tumor surveillance/treatment (autoimmune) · AED if seizures occurred · intensive cognitive/physical rehabilitation referral · neurology and (as relevant) oncology follow-up · family counseling on the often prolonged recovery and possible relapse (autoimmune) · return precautions.

Red Flags — ICU / Urgent

• Any suspected encephalitis → empiric acyclovir within the hour; do not wait for confirmation.
• Status epilepticus / not waking → continuous EEG, ICU (non-convulsive status common).
• Cerebral edema / raised ICP (HSV temporal swelling) → ICU, neurosurgery.
• Autonomic instability or central hypoventilation (anti-NMDAR) → ICU monitoring.
• Rapidly declining consciousness → airway protection, ICU.
• New "psychosis" with seizures/dyskinesia/dysautonomia → think autoimmune encephalitis, not primary psychiatric.

Senior IM Resident Pearls

• Acyclovir first, questions later. The defining management decision is starting empiric IV acyclovir the moment you suspect encephalitis — before the PCR, before the MRI is read. Treated HSV has far better outcomes; untreated it is devastating.
• A negative early HSV PCR does not exclude it. Within the first 72 hours the PCR can be falsely negative — if suspicion is high, keep treating and repeat the LP in a few days.
• Encephalitis vs meningitis = brain dysfunction. Altered mentation, seizures, and focal deficits define encephalitis; preserved mentation points to meningitis. (They overlap as meningoencephalitis.)
• Hydrate with acyclovir. It crystallizes in the tubules — generous fluids and renal dosing prevent a iatrogenic AKI.
• Think temporal lobe for HSV: personality change, memory loss, aphasia, temporal seizures, and unilateral temporal edema/hemorrhage on MRI.
• "New psychosis" in a young woman with seizures and dyskinesias is anti-NMDAR until proven otherwise — send paired serum/CSF antibodies and hunt for an ovarian teratoma; immunotherapy and tumor removal are curative.
• Get continuous EEG if they don't wake up — non-convulsive status is common in encephalitis.
• Common mistake: stopping acyclovir on a single negative PCR drawn very early, or admitting an autoimmune encephalitis to psychiatry and missing the treatable tumor-associated cause.