Eduovisual
Nervous System & Special Senses
Encephalitis: HSV and autoimmune
— Distinguished from meningitis (meningeal signs, preserved cognition) and encephalopathy (toxic/metabolic, no inflammation).
— HSV-1 is the most common identified cause of sporadic fatal encephalitis in adults (~10% of all cases, ~2 per million/yr).
— Autoimmune encephalitis now rivals or exceeds viral causes in young adults; anti-NMDA receptor encephalitis is the leading autoimmune form, especially in women 18–35.
— Up to 50% of encephalitis cases remain etiology-undetermined despite workup.
— Any patient with fever + altered mental status + new behavioral, language, or seizure activity → empiric acyclovir within 6 hours while workup proceeds.
— Young woman with subacute psychiatric symptoms, orofacial dyskinesias, autonomic instability, and seizures → think anti-NMDA receptor; search for ovarian teratoma.
— Older adult with limbic symptoms (memory loss, temporal seizures, hyponatremia, faciobrachial dystonic seizures) → think LGI1 autoimmune encephalitis.
Step 3 management: In the CCS case of fever + confusion, do not wait for LP or MRI results — order IV acyclovir 10 mg/kg q8h empirically the moment encephalitis is on your differential. Simultaneously order blood cultures, CBC, CMP, HIV, CT head (if focal/papilledema/immunocompromised), then LP. The clock starts at triage, not at diagnosis confirmation.
— Subacute over 1–7 days: fever, headache, behavioral change, aphasia, anosmia/olfactory hallucinations, complex partial seizures localizing to temporal lobe.
— Ask about preceding URI-like prodrome, cold sores (absent in most cases — do not require labial lesions).
— Personality change, hypersexuality, Klüver-Bucy features reflect bitemporal involvement.
— Stage 1 (prodrome): viral-like illness, headache, low-grade fever (~2 weeks).
— Stage 2 (psychiatric): anxiety, paranoia, delusions, mania — often admitted to psych first.
— Stage 3 (neurologic): seizures, mutism, catatonia, orofacial dyskinesias, choreoathetosis.
— Stage 4 (autonomic/hypoventilation): BP/HR lability, hyperthermia, central hypoventilation → ICU.
— Ask about recent HSV encephalitis (10–30% develop post-HSV anti-NMDA in weeks following) and ovarian/testicular masses.
— Older adults (median 60), male predominance.
— Faciobrachial dystonic seizures (FBDS): brief unilateral arm + ipsilateral face jerks, dozens/day — pathognomonic.
— Subacute memory loss, SIADH-related hyponatremia in ~60%.
— Travel (arbovirus — WNV, EEE, Powassan, JEV), tick/mosquito exposure (summer).
— Animal bites (rabies — hydrophobia, brainstem signs).
— Immune status (HIV, transplant → CMV, JC virus, toxoplasma).
— Vaccination history (measles → SSPE; varicella).
— Medications, drugs of abuse, recent infections.
Board pearl: A young woman admitted to psychiatry for "new-onset schizophrenia" who then develops orofacial dyskinesia, mutism, or autonomic instability has anti-NMDA receptor encephalitis until proven otherwise — order CSF NMDA-R antibodies and pelvic US/MRI for teratoma.
— Fever in 90% of HSV; often absent or low-grade in autoimmune encephalitis early.
— Autonomic instability (BP swings, tachy/bradyarrhythmias, hyperthermia) is a hallmark of advanced anti-NMDA — triggers ICU transfer.
— Hypoventilation/apnea in late NMDA → intubation.
— Quantify with GCS and document orientation, attention (serial 7s, months backward), language (naming, repetition, comprehension), memory (3-word recall at 5 min).
— Aphasia (especially Wernicke-type) in HSV is highly localizing to dominant temporal lobe.
— Catatonia (waxy flexibility, mutism, posturing) in NMDA — often misattributed to primary psychiatric illness.
— Focal deficits (hemiparesis, visual field cut) suggest HSV temporal/frontal involvement or abscess.
— Brainstem signs → think rhombencephalitis (listeria, EV71, anti-Ma2).
— Cerebellar ataxia → VZV, EBV, anti-Yo, anti-GAD65.
— Orofacial dyskinesias, choreoathetosis → anti-NMDA.
— Faciobrachial dystonic seizures → LGI1.
— Myoclonus → CJD, SSPE, autoimmune.
— Vesicles (VZV, HSV), erythema migrans (Lyme), petechiae (meningococcus, RMSF), enanthem (enterovirus).
— Pelvic/testicular exam, lymphadenopathy, breast exam — paraneoplastic search.
— Hepatosplenomegaly (EBV, CMV, HIV seroconversion).
Key distinction: Encephalitis vs encephalopathy — both have altered mental status, but encephalitis has fever, focal deficits, seizures, or CSF inflammation; encephalopathy (uremic, hepatic, septic) typically has asterixis, symmetric findings, no CSF pleocytosis. Mislabeling delays acyclovir.
— CBC with diff, CMP, glucose, coags, blood cultures ×2, HIV 4th-gen Ag/Ab, RPR, urine tox, β-hCG in women of reproductive age.
— Sodium: hyponatremia (SIADH) suggests LGI1 or arboviral encephalitis.
— Procalcitonin, CRP, ESR — supportive but nonspecific.
— MRI brain with and without contrast is the imaging study of choice; CT is for triage to rule out mass effect/hemorrhage before LP.
— HSV: asymmetric T2/FLAIR hyperintensity in medial temporal lobes, insula, inferior frontal cortex; often hemorrhagic, with restricted diffusion. Bilateral but asymmetric is classic.
— Anti-NMDA: MRI is normal in 50–70%; when abnormal, nonspecific T2/FLAIR cortical or hippocampal changes.
— LGI1: unilateral or bilateral mesial temporal T2/FLAIR hyperintensity without restricted diffusion; later hippocampal atrophy.
— HSV: periodic lateralized epileptiform discharges (PLEDs/LPDs) over temporal lobe — highly suggestive.
— Anti-NMDA: "extreme delta brush" pattern in ~30% — near-pathognomonic when present; otherwise diffuse slowing.
— EEG also detects subclinical/nonconvulsive status (up to 25% of altered patients).
— Defer if focal deficit, papilledema, GCS depressed, immunocompromised, or seizure within 1 week → obtain CT first.
— Continue empiric acyclovir during any delay.
— Send: opening pressure, cell count + diff, protein, glucose (with serum glucose), Gram stain, bacterial culture, HSV-1/2 PCR, VZV PCR, enterovirus PCR, cryptococcal Ag if HIV+, save extra tube for autoimmune panel.
CCS pearl: Order "MRI brain with and without contrast, EEG, lumbar puncture" as a bundle the moment encephalitis is suspected — do not stagger. Acyclovir does not alter CSF HSV PCR sensitivity within the first week, so do not delay treatment waiting for LP.
— Viral encephalitis (including HSV): lymphocytic pleocytosis (10–500 WBC, predominantly lymphs), mildly elevated protein (50–100), normal glucose, normal-to-mildly elevated opening pressure. HSV often shows RBCs/xanthochromia from hemorrhagic necrosis.
— Autoimmune: mild lymphocytic pleocytosis (<100), normal-mild protein, normal glucose, CSF-specific oligoclonal bands or elevated IgG index in ~50%.
— Normal CSF does not rule out autoimmune encephalitis.
— CSF HSV-1 PCR: sensitivity 96%, specificity 99%. May be falsely negative in first 72 hours or after 10–14 days of treatment — repeat LP at 3–7 days if clinical suspicion remains and initial PCR negative.
— Serum HSV serology is not useful for acute diagnosis.
— Send paired serum + CSF for autoimmune encephalitis panel: NMDA-R, LGI1, CASPR2, GABA-B, AMPA, DPPX, GAD65, Hu, Ma2, CV2/CRMP5, amphiphysin.
— CSF testing is more sensitive than serum for NMDA-R (100% vs 85%) — always send both.
— Antibody-negative autoimmune encephalitis exists; diagnosis can be made on clinical/imaging/EEG criteria + exclusion + response to immunotherapy.
— Anti-NMDA: pelvic MRI or transvaginal US for ovarian teratoma (50% of adult women); testicular US in men.
— LGI1, CASPR2: thymoma — CT chest.
— Anti-Hu, anti-Ma2: CT chest/abdomen/pelvis; consider whole-body PET/CT if initial imaging negative.
Board pearl: Repeat LP in 3–7 days if initial HSV PCR negative but clinical/MRI suspicion high — early sampling can miss it. Continue acyclovir during the wait.
— All suspected encephalitis → admit; most warrant ICU or step-down for airway protection, seizure monitoring, and autonomic instability.
— Indications for immediate ICU: GCS ≤8, status epilepticus, autonomic instability, hypoventilation, refractory ICP.
— Acyclovir 10 mg/kg IV q8h (renally adjusted, using ideal body weight in obesity to avoid nephrotoxicity).
— Ceftriaxone 2 g IV q12h + vancomycin for bacterial meningitis coverage until CSF excludes.
— Ampicillin 2 g IV q4h if age >50, immunocompromised, pregnant → Listeria coverage.
— Dexamethasone 0.15 mg/kg IV q6h if pneumococcal meningitis suspected (give with or before first antibiotic dose); generally not routine for encephalitis but increasingly used in HSV per some protocols.
— Add doxycycline if tick exposure (Rickettsia, Ehrlichia).
— Confirmed HSV PCR+ → continue acyclovir, stop antibacterials.
— Confirmed autoimmune → stop acyclovir, initiate immunotherapy.
— Many patients remain on dual therapy until PCRs return (24–72h).
— Load with levetiracetam 60 mg/kg IV (max 4.5g) or fosphenytoin if seizures occur; many clinicians give prophylaxis given high seizure rates in HSV.
— Continuous EEG if persistent altered mental status disproportionate to exam.
— Head of bed 30°, avoid hypotonic fluids, monitor sodium (SIADH common), DVT prophylaxis (mechanical → pharmacologic once stable), aspiration precautions.
Step 3 management: The mantra is "treat first, test second." Any febrile encephalopathic adult receives acyclovir + ceftriaxone + vancomycin (+ ampicillin if at-risk) within the first hour — even before CT/LP. De-escalation comes from PCRs and cultures, not from waiting at the bedside.
— Acyclovir 10 mg/kg IV q8h × 14–21 days (21 days standard in adults to reduce relapse).
— Confirm clearance with repeat CSF HSV PCR at end of treatment; if still positive, extend therapy until negative.
— Adequate hydration (1.5× maintenance) to prevent crystal nephropathy.
— Monitor creatinine daily; if rising, slow infusion to ≥1 hour and increase fluids before dose-reducing.
— Pediatric/neonatal: 20 mg/kg IV q8h × 21 days, then oral acyclovir suppression 300 mg/m² TID × 6 months to prevent neurologic relapse (CASG 204 trial).
— IV methylprednisolone 1 g daily × 5 days AND
— IVIG 0.4 g/kg/day × 5 days OR plasma exchange 5–7 sessions.
— Tumor removal (ovarian teratoma resection) is essential and accelerates recovery.
— Rituximab 375 mg/m² weekly × 4 AND/OR
— Cyclophosphamide 750 mg/m² monthly.
— Early second-line (within 4 weeks) improves outcomes per Graus/Dalmau cohorts.
— Highly steroid-responsive: IV methylprednisolone 1 g × 5 days, then oral prednisone taper over months.
— Add IVIG or rituximab if relapsing or inadequate response.
— FBDS resolve with immunotherapy, often poorly with antiseizure meds alone — treating with ASMs alone delays brain injury.
— Long-term oral prednisone taper + mycophenolate mofetil or azathioprine for 1–2 years to prevent relapse.
— Rituximab redosing q6 months in refractory cases.
Board pearl: In LGI1 encephalitis, immunotherapy treats the seizures, not antiseizure meds. Recognizing FBDS prompts steroids → prevents the cognitive decline that would otherwise follow.
— Nephrotoxicity (5–10%): crystal-induced AKI, typically within 24–48h. Prevention: pre-hydrate with 500 mL NS, infuse over ≥1 hour, avoid concurrent nephrotoxins, dose by ideal body weight.
— Neurotoxicity: confusion, myoclonus, hallucinations, especially in renal impairment — can mimic worsening encephalitis. Check CMMG levels (acyclovir metabolite) if suspected; treat with hemodialysis.
— Phlebitis at infusion site; use central access for prolonged courses.
— Indicated if no clinical improvement after 5–7 days with negative repeat PCR conversion and documented thymidine kinase mutation, mostly in immunocompromised.
— Dose: 60 mg/kg IV q8h; major toxicities are nephrotoxicity, electrolyte wasting (Ca, Mg, K, PO4), and seizures.
— Aggressive electrolyte repletion and saline hydration mandatory.
— PJP prophylaxis (TMP-SMX) if prednisone ≥20 mg/day for ≥4 weeks.
— Stress-dose protocols, glycemic control, bone health (calcium/vitamin D, DEXA, bisphosphonate if prolonged), GI prophylaxis (PPI), VTE risk.
— Pre-medicate with acetaminophen/diphenhydramine; risks include aseptic meningitis, AKI, thrombosis, anaphylaxis in IgA deficiency — check IgA before first dose.
— Hydrate; infuse slowly.
— Check hepatitis B serology (HBsAg, anti-HBc) before infusion → risk of HBV reactivation; treat with entecavir if positive.
— Infusion reactions; monitor CD19/CD20 counts; PML risk (rare).
— Levetiracetam preferred — minimal drug interactions, IV/PO.
— Avoid valproate if hepatic dysfunction; avoid phenytoin/carbamazepine with immunosuppressants (enzyme induction).
Step 3 management: Rising creatinine on acyclovir → increase fluids and lengthen infusion before reducing dose; reflexive dose reduction risks subtherapeutic levels in an infection where every hour matters.
— Higher baseline mortality from HSV encephalitis (>40% even with treatment); recovery slower and less complete.
— Delirium superimposed on dementia masks encephalitis presentation — low threshold for LP in any febrile elderly patient with new confusion.
— LGI1 encephalitis peaks in 60s–70s — consider in any older adult with subacute memory loss + new seizures + hyponatremia, especially before attributing to Alzheimer disease.
— Polypharmacy interactions: review for sedatives, anticholinergics that worsen encephalopathy.
— Steroid risks amplified: hyperglycemia, fracture, delirium, infection.
— CrCl 25–50: 10 mg/kg q12h.
— CrCl 10–25: 10 mg/kg q24h.
— CrCl <10 or HD: 5 mg/kg q24h, post-dialysis on dialysis days.
— Use ideal body weight in obesity; actual weight overdoses and drives nephrotoxicity.
— Daily creatinine; hold for AKI (Cr increase ≥0.3 from baseline) → assess for crystal nephropathy via urinalysis (needle-shaped crystals).
— Acyclovir minimally hepatically metabolized — no dose adjustment.
— Caution with valproate, carbamazepine for seizures; prefer levetiracetam.
— Corticosteroids well tolerated but monitor for hepatic encephalopathy worsening with infection.
— Acyclovir is hemodialyzable — dose post-HD.
— IVIG fluid load may precipitate volume overload in ESRD — coordinate with nephrology, may need ultrafiltration.
— Severe HSV encephalitis with bilateral temporal necrosis in frail elderly → discuss prognosis early; consider palliative trajectory if no improvement at 2 weeks.
Board pearl: For acyclovir in obese patients, always dose by ideal (or adjusted) body weight — actual body weight dosing is the most common preventable cause of acyclovir AKI on inpatient services.
— Acyclovir is Category B, safe and recommended in pregnancy; do not withhold for suspected HSV encephalitis.
— Anti-NMDA encephalitis can present peripartum; teratoma search includes ovarian US (avoid CT/gadolinium when feasible — use noncontrast MRI).
— IVIG safe in pregnancy; rituximab, cyclophosphamide — avoid in first trimester, use only if benefits outweigh risks; involve MFM.
— Steroids: use lowest effective dose; monitor glucose for gestational diabetes.
— Acquired intrapartum from maternal genital HSV; presents days 5–21 of life with seizures, lethargy, sepsis-like picture, vesicles (only 50%).
— Acyclovir 20 mg/kg IV q8h × 21 days, followed by oral acyclovir suppression × 6 months (300 mg/m²/dose PO TID) — improves neurodevelopmental outcomes.
— Repeat CSF PCR at end of IV therapy; must be negative before stopping.
— Anti-NMDA in children presents with behavioral regression, mutism, movement disorders, seizures — often misdiagnosed as autism regression or psychiatric illness.
— Ovarian teratomas less common in prepubertal girls; tumor search lower yield but still indicated.
— First-line steroids + IVIG; early rituximab improves outcomes.
— Broaden differential: CMV encephalitis (ventriculitis, periventricular enhancement), JC virus/PML (subcortical white matter, no enhancement, no mass effect), toxoplasmosis (ring-enhancing lesions), cryptococcus, HHV-6.
— Send CMV, JC, HHV-6 PCR on CSF; serum cryptococcal antigen; toxo IgG.
— HSV still common — acyclovir empirically. Maintain higher index of suspicion for acyclovir-resistant HSV in HIV/transplant; ready foscarnet.
— Lower steroid threshold for autoimmune in transplant; coordinate with transplant team for immunosuppression adjustments.
Key distinction: Neonatal HSV requires 20 mg/kg q8h × 21 days IV plus 6 months oral suppression — adult regimen is 10 mg/kg q8h × 14–21 days without oral suppression. Mixing them up is a classic pediatric error.
— Status epilepticus (focal or generalized) — 20–40% of HSV cases; nonconvulsive status in altered patients without overt seizures → continuous EEG.
— Cerebral edema and herniation — hemorrhagic necrosis of temporal lobes can cause uncal herniation; manage with HOB 30°, mannitol/hypertonic saline, neurosurgery consult.
— SIADH — hyponatremia in 30%+, especially LGI1; fluid restrict, tolvaptan if severe.
— Autonomic instability in anti-NMDA — labile BP/HR, hyperthermia, hypoventilation; may require ICU, intubation, vasopressors/beta-blockers.
— Anterograde amnesia from bitemporal hippocampal damage in HSV — often permanent; profound functional impact.
— Personality change, executive dysfunction, Klüver-Bucy syndrome (hyperorality, hypersexuality, placidity) from bitemporal damage.
— Aphasia if dominant temporal lobe affected.
— Epilepsy — post-HSV symptomatic epilepsy in 25–60%; lifelong antiseizure meds.
— Cognitive impairment in 60–80% of HSV survivors; rehabilitation often needed.
— Relapse rate 12–25% (higher without tumor identification/removal).
— Post-encephalitic psychiatric symptoms (mood disorders, sleep disturbance) persist months to years.
— Sleep dysfunction prominent in late recovery.
— 10–30% of HSV encephalitis patients develop anti-NMDA receptor encephalitis 2–16 weeks after acyclovir completion — re-presents with movement disorder, behavioral change, seizures without recrudescent HSV PCR positivity.
— Critical to recognize; treat with immunotherapy, not more acyclovir.
— Acyclovir nephrotoxicity, neurotoxicity.
— Steroid-induced hyperglycemia, infection, psychosis.
— IVIG thrombosis, aseptic meningitis.
Board pearl: A patient who improved on acyclovir but returns 1 month later with new behavioral/movement symptoms has post-HSV anti-NMDA receptor encephalitis until proven otherwise — send CSF NMDA-R antibodies, start immunotherapy. HSV PCR is typically negative.
— GCS ≤8 or rapid neurologic deterioration.
— Status epilepticus (convulsive or nonconvulsive).
— Autonomic instability (BP swings, dysrhythmias, central hyperthermia/hypothermia) — characteristic of anti-NMDA.
— Hypoventilation or apnea requiring mechanical ventilation.
— Signs of elevated ICP (Cushing triad, papilledema, herniation).
— Need for continuous EEG monitoring.
— Neurology at admission for every suspected encephalitis case — lead EEG/MRI interpretation, immunotherapy planning.
— Neurosurgery if mass effect, hydrocephalus, or need for EVD.
— Infectious disease for antimicrobial stewardship and atypical pathogens, especially in immunocompromised.
— Rheumatology/Neuroimmunology for autoimmune encephalitis management.
— Gynecology/Urology for teratoma resection in anti-NMDA.
— Oncology for paraneoplastic workup and tumor management.
— Psychiatry for behavioral management in NMDA (avoid neuroleptics where possible — risk of NMS-like reactions, worsening movement disorders).
— PM&R early for rehabilitation planning.
— Community hospital without neurology/MRI capability → start acyclovir + empiric antibiotics → transfer to tertiary center with neuro-ICU.
— Do not delay acyclovir for transfer.
— Communicate clearly: pending studies, doses given, last seizure, current GCS, isolation status (droplet for meningococcus until excluded).
— Early family meetings; severe bitemporal HSV with persistent coma at 14 days carries poor prognosis — discuss tracheostomy, PEG, code status.
CCS pearl: "Move patient to ICU" is the right CCS action for any encephalitis with status epilepticus, GCS ≤8, or autonomic instability. Simultaneously: consult Neurology, ID, Neurosurgery if indicated; continuous EEG; ABG; intubate if airway not protected.
— Acute fever, headache, neck stiffness, AMS; CSF: neutrophilic pleocytosis (>1000), high protein, low glucose.
— Treatment: ceftriaxone + vancomycin + dexamethasone; ampicillin if Listeria risk. Distinguished from encephalitis by prominent meningismus, lack of focal cortical findings, neutrophilic CSF, low glucose.
— Ring-enhancing lesion on MRI with restricted diffusion (vs ring-enhancing toxoplasmosis/CNS lymphoma without restricted diffusion in HIV); subacute headache, focal deficit, seizure.
— Treat with drainage + prolonged antibiotics.
— VZV: vasculopathy, stroke pattern, dermatomal rash often. CSF VZV PCR; treat with acyclovir.
— Arboviruses (WNV, EEE, Powassan, JEV): summer/fall, mosquito exposure; WNV can cause flaccid paralysis (anterior horn cell); diagnose by CSF IgM, supportive care.
— Enterovirus, EV71: brainstem encephalitis in children.
— Rabies: hydrophobia, hypersalivation, autonomic storm; fatal once symptomatic.
— CMV, HHV-6, JC virus: immunocompromised.
— Subacute, basilar meningeal enhancement, cranial neuropathies, hydrocephalus; CSF: lymphocytic, high protein, low glucose; AFB stain + culture + GeneXpert MTB. RIPE × 12 months + steroids.
— HIV with CD4<100; high opening pressure; CSF cryptococcal antigen + India ink. Amphotericin B + flucytosine induction.
— ADEM — post-infectious demyelination, multifocal white matter lesions, often pediatric, monophasic; steroids.
— Neurosarcoidosis — basilar meningitis, cranial neuropathies, hypothalamic involvement.
— CNS vasculitis — multifocal strokes, headache; angiography, brain biopsy.
— Hashimoto encephalopathy (SREAT) — steroid-responsive; high TPO antibodies.
Key distinction: Low CSF glucose points away from viral/autoimmune encephalitis toward bacterial, TB, fungal, or carcinomatous meningitis — change your antimicrobial and diagnostic strategy immediately.
— Hepatic, uremic, hypercapnic, hypoglycemic, hyponatremic.
— Generalized symmetric findings, asterixis, no fever (usually), no CSF inflammation.
— Reverse the metabolic insult; LP only if cause unclear or fever present.
— Serotonin syndrome (hyperreflexia, clonus, diaphoresis), NMS (rigidity, hyperthermia, recent antipsychotic), anticholinergic toxidrome, lithium, salicylate, alcohol withdrawal/DTs.
— History and exam clinch; tox screen.
— New-onset psychosis in young adults — always exclude anti-NMDA receptor encephalitis before settling on schizophrenia, especially with movement disorder, seizure, autonomic features, or atypical neuroleptic response (catatonia, NMS-like).
— Catatonia workup: lorazepam challenge, ECT consideration if confirmed primary psych.
— Prolonged postictal confusion can mimic encephalitis; EEG distinguishes.
— Nonconvulsive status presents as unexplained altered mental status.
— Sudden onset, vascular territory, no fever; MRI/MRA distinguishes.
— Posterior reversible encephalopathy syndrome (PRES) — HTN, eclampsia, immunosuppressants; parietooccipital edema.
— Confusion, ophthalmoplegia, ataxia; alcohol use disorder or malnutrition.
— Give thiamine 500 mg IV TID × 3 days before glucose in any malnourished altered patient.
— Primary CNS lymphoma, gliomatosis, leptomeningeal carcinomatosis — subacute, can have CSF pleocytosis. MRI, cytology, flow cytometry.
— Rapidly progressive dementia + myoclonus + ataxia; MRI cortical ribboning/basal ganglia DWI hyperintensity, RT-QuIC CSF, elevated 14-3-3 protein.
Step 3 management: In any altered patient, check glucose, give thiamine before dextrose, screen for tox, naloxone if opioid suspected — these "ABCs of altered mental status" precede the encephalitis workup but never delay acyclovir when encephalitis is on the differential.
— Complete 21 days IV acyclovir; confirm negative CSF HSV PCR before stopping.
— No routine oral suppression in adults (unlike neonates); some experts add valacyclovir 1 g TID × 3 months in select cases but not standard.
— Antiseizure med continuation: typically ≥1 year if seizures occurred; many patients require lifelong therapy. Levetiracetam preferred for cognitive sparing.
— Screen for post-HSV autoimmune encephalitis at 2-month follow-up — new behavioral/movement symptoms warrant CSF NMDA-R antibodies.
— Oral prednisone taper over 6–12 months (start ~1 mg/kg/day, taper slowly).
— Steroid-sparing agent: mycophenolate mofetil 1 g BID or azathioprine 2 mg/kg/day for 1–2 years.
— Refractory/relapsed: rituximab redosing q6 months × 2 years.
— Tumor surveillance: if no teratoma found initially, repeat pelvic imaging q6 months × 2 years, then annually × 4 years.
— Oral prednisone taper over 6–12 months; many require longer immunotherapy given relapse rate ~30%.
— Repeat antibody titers and MRI to monitor; address SIADH if persistent.
— Hippocampal atrophy on follow-up MRI predicts cognitive sequelae.
— PJP prophylaxis with TMP-SMX if on prednisone ≥20 mg/day × 4+ weeks.
— Pneumococcal (PCV20 or PCV15+PPSV23), influenza, COVID, HBV before prolonged immunosuppression.
— Avoid live vaccines on immunosuppression.
— Bone health: calcium 1200 mg, vitamin D 800–1000 IU, DEXA at baseline, bisphosphonate if prolonged steroid use.
— Most states require seizure-free interval (often 3–6 months) before resuming driving; counsel and document.
Step 3 management: Discharge bundle = confirmed pathogen clearance + structured antiseizure plan + immunosuppression maintenance with steroid-sparing agent + opportunistic infection prophylaxis + vaccination update + driving counseling + scheduled outpatient neurology and (if applicable) gyn-onc follow-up.
— Neurology at 2 weeks (medication tolerance, seizures), then 1, 3, 6, 12 months, then annually.
— Repeat MRI at 3 months to assess hippocampal atrophy and detect autoimmune sequelae or chronic changes.
— Neuropsychological testing at 3 and 6–12 months to quantify cognitive sequelae and guide rehabilitation.
— EEG if breakthrough seizures or to consider antiseizure med taper.
— Primary care monthly during steroid taper for BP, glucose, weight, infection screen.
— MMF/azathioprine: CBC, LFTs monthly × 3, then q3 months. Check TPMT before azathioprine to avoid severe myelosuppression.
— Rituximab: CD19/CD20 q3–6 months; immunoglobulin levels (hypogammaglobulinemia risk).
— Steroids: glucose, BP, lipids, DEXA at baseline and yearly; ophthalmology yearly (cataracts, glaucoma).
— PT/OT for motor and ADL recovery.
— Speech therapy for aphasia, dysphagia, cognitive-communication.
— Cognitive rehabilitation and neuropsychology for memory, executive function — particularly important after HSV.
— Psychiatry support for mood, PTSD (especially post-ICU and post-NMDA psychiatric phase).
— Inpatient rehab vs SNF vs home with services determined by functional status.
— Realistic prognosis: many HSV survivors have permanent memory impairment; recovery from anti-NMDA can take 18–24 months, often substantial.
— Relapse warning signs: new behavioral change, seizures, movement disorder → urgent neurology evaluation.
— Support resources: Autoimmune Encephalitis Alliance, Encephalitis Society.
— Employment, school accommodations (504/IEP for children, ADA for adults).
Board pearl: Recovery from anti-NMDA encephalitis follows a reverse trajectory through stages: autonomic/movement → seizures → psychiatric → cognitive — full recovery may take 1–2 years. Counsel families to expect prolonged but often substantial improvement.
— Encephalitis patients frequently lack decision-making capacity during acute illness — engage surrogates (POA, next of kin per state hierarchy) early for consent to LP, intubation, central lines, immunotherapy.
— Document capacity assessment (understanding, appreciation, reasoning, choice).
— Anti-NMDA patients with psychiatric symptoms may refuse care due to delusions — consider emergency hold (psychiatric hold) under involuntary treatment statutes if needed for life-saving therapy; document medical decision-making.
— Young woman with new psychiatric symptoms admitted to psych and started on antipsychotics → catatonia, NMS-like reaction, or worsening movement disorder should prompt re-evaluation for autoimmune encephalitis, not dose escalation.
— Document differential and trigger for workup.
— Some encephalitis etiologies are reportable to public health (arboviruses, rabies exposure, measles, meningococcus). Know your state's list.
— Rabies exposure → notify public health, initiate post-exposure prophylaxis for exposed contacts.
— Patients with seizures must not drive until state-mandated seizure-free period elapses; some states require physician reporting (e.g., California). Document counseling.
— Occupational restrictions for pilots, commercial drivers, heavy machinery operators.
— Highest-risk handoff is psych ward → medical floor when autoimmune encephalitis is finally recognized; ensure full medication reconciliation, especially neuroleptics (taper, may worsen NMDA presentation).
— Discharge to rehab/SNF with active immunosuppression: ensure written taper schedule, follow-up appointments, PJP prophylaxis instructions, and explicit warning signs.
— Discharge antibiotic/antiviral OPAT requires home health, PICC line care, weekly labs, ID follow-up.
— Anti-NMDA in young women: counsel that future pregnancies are possible, but relapse risk exists peripartum; coordinate with MFM.
Step 3 management: In a confused encephalitis patient, identify the surrogate within 24 hours, document capacity, and obtain consent for ongoing invasive procedures and immunotherapy — do not rely on "implied consent" for elective elements of the workup beyond the initial emergency stabilization.
— Temporal lobe predilection (medial > inferior frontal > insula).
— PLEDs on EEG = classic.
— Hemorrhagic necrosis on MRI; RBCs in CSF.
— Empiric acyclovir before LP; 21 days IV; repeat CSF PCR before stopping.
— Untreated mortality ~70%; treated ~20–30%.
— Young women; ovarian teratoma in 50%.
— Stages: prodrome → psychiatric → neurologic → autonomic.
— Extreme delta brush on EEG.
— CSF antibody > serum antibody for diagnosis.
— Treatment: steroids + IVIG/PLEX + tumor removal; second-line rituximab/cyclophosphamide.
— Post-HSV NMDA encephalitis in 10–30% — relapse 2–16 weeks after HSV treatment.
— Older men; faciobrachial dystonic seizures + memory loss + hyponatremia (SIADH).
— Mesial temporal T2/FLAIR hyperintensity.
— Steroid-responsive; ASMs alone inadequate.
Board pearl: Match the antibody to the tumor — NMDA→ovarian teratoma, LGI1→thymoma, GABA-B→SCLC, Ma2→testicular GCT, Yo→ovarian/breast, Hu→SCLC — these pairings are exam gold.
Key distinction: When the stem mentions young woman + new psychosis + movement disorder + autonomic instability → autoimmune encephalitis. When it mentions fever + temporal lobe focal signs + aphasia or olfactory hallucination → HSV. Both get acyclovir empirically until clarified.
Encephalitis is fever + altered mental status + focal/inflammatory CNS findings — start empiric IV acyclovir within one hour for any suspected case, pursue HSV PCR and autoimmune antibody panels (paired serum and CSF) with MRI and EEG, and remember that anti-NMDA receptor encephalitis can follow HSV by weeks and that LGI1 limbic encephalitis demands immunotherapy not just antiseizure medication.