Overview

• Post-infectious or post-vaccination monophasic demyelinating disorder
• Predominantly affects children (mean age 5–8 years); rare in adults
• Typically follows a viral prodrome 1–4 weeks prior (measles, mumps, varicella, influenza, EBV, URI)
• Pathophysiology: molecular mimicry → autoimmune attack on CNS myelin
• Monophasic by definition — if relapses occur, reconsider MOGAD or MS

Clinical Features

• Encephalopathy is REQUIRED (altered consciousness, behavioral change, confusion) — distinguishes ADEM from first MS episode
• Multifocal neurological deficits: optic neuritis, hemiparesis, ataxia, cranial nerve palsies, seizures
• Fever common at presentation
• May present with LETM (longitudinally extensive transverse myelitis)

Diagnosis

• MRI brain: large, fluffy, bilateral but asymmetric T2/FLAIR lesions; deep white matter, thalami, basal ganglia, brainstem; poorly demarcated
• Thalamic involvement is characteristic of ADEM (rare in MS)
• All lesions enhance simultaneously (same age) vs. MS lesions of different ages
• CSF: lymphocytic pleocytosis, elevated protein; OCBs may be present but are transient (unlike MS where persistent)
• MOG-IgG: positive in ~30–50% of pediatric ADEM; MOG+ relapsing disease → reclassify as MOGAD

ADEM vs MS

Treatment

• First-line: IV methylprednisolone — pediatric: 20–30 mg/kg/day (max 1 g) × 3–5 days; adult: 1 g/day × 3–5 days — followed by oral taper over 4–6 weeks
• Refractory: IVIg or PLEX
• Prognosis: generally good; 70–90% recover fully or near-fully

Acute Hemorrhagic Leukoencephalitis (Hurst Disease)

• Most severe form of ADEM — hyperacute, often fatal
• Follows prodromal infection; rapid progression to coma over days
• Pathology: perivascular demyelination with ring and ball hemorrhages, fibrinoid necrosis of venule walls
• MRI: hemorrhagic white matter lesions with mass effect
• Aggressive treatment with steroids, PLEX, decompressive surgery if needed

Definition & Classification

• Inflammatory myelopathy causing motor, sensory, and autonomic dysfunction at and below the lesion level
• Acute to subacute onset (nadir reached between 4 hours and 21 days from symptom onset)
• Must exclude compressive myelopathy first (urgent MRI spine)

Etiologic Pattern Recognition

Workup

• MRI spine with gadolinium (entire spine) + MRI brain
• Serum: AQP4-IgG, MOG-IgG, ANA, dsDNA, ACE, SSA/SSB, HIV, HTLV-1, B12
• CSF: cell count, protein, OCBs, cytology, cultures
• VEP: subclinical optic neuritis supports MS or NMOSD

Overview

• Inflammatory demyelination of the optic nerve; can be isolated or first manifestation of MS, NMOSD, or MOGAD
• Acute to subacute unilateral (or bilateral) painful vision loss over hours to days
• Pain worsened by eye movement; RAPD (Marcus Gunn pupil) on exam
• 20–25% of MS patients present with optic neuritis as initial manifestation

Optic Neuritis by Etiology

Optic Neuritis Treatment Trial (ONTT)

• IV methylprednisolone (1 g/day × 3 days → oral taper) hastens recovery but does NOT change final visual outcome at 6 months
• Oral prednisone alone (1 mg/kg) showed NO benefit AND increased recurrence rate — contraindicated
• ~50% develop MS within 15 years (ONTT); risk ~25% if baseline brain MRI normal, ~72% if ≥1 lesion at presentation
• Best predictor of MS after ON: presence of ≥1 demyelinating lesion on brain MRI at presentation

Differential Diagnosis of Optic Neuropathy

Overview

• Rare autoimmune disorder characterized by progressive axial rigidity and stimulus-triggered spasms
• Median onset age 40–50; slight female predominance
• Strong association with anti-GAD65 antibodies (present in ~60–80%)
• Associated with type 1 diabetes mellitus and other autoimmune diseases (thyroiditis, pernicious anemia, vitiligo)

Clinical Features

• Axial stiffness: progressive rigidity of trunk and proximal limbs; exaggerated lumbar lordosis (hyperlordosis); board-like abdominal rigidity
• Painful spasms: triggered by unexpected stimuli (noise, touch, emotional stress); can be severe enough to cause fractures
• Task-specific phobia: fear of crossing streets, walking in open spaces (due to risk of falls from spasms) — often misdiagnosed as psychiatric
• Continuous motor unit activity on EMG even at rest; disappears with diazepam or sleep
• No UMN or LMN signs on exam; strength is normal; deep tendon reflexes preserved

Stiff-Person Spectrum

Diagnosis

• Serum anti-GAD65 antibodies: typically very high titers (>10,000 IU/mL) — low titers are non-specific and seen in type 1 DM
• EMG: continuous motor unit activity in agonist and antagonist muscles simultaneously; normalizes with diazepam or general anesthesia
• If anti-GAD negative, check anti-amphiphysin (paraneoplastic) and anti-glycine receptor (PERM)
• Cancer screening: mandatory if anti-amphiphysin positive (breast cancer, SCLC); CT chest/abdomen/pelvis, mammography

Treatment

Overview

• Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT) — preferred term over “Hashimoto encephalopathy”
• Subacute encephalopathy with elevated anti-thyroid antibodies (anti-TPO, anti-thyroglobulin)
• Diagnosis of exclusion — must rule out all other causes of encephalopathy
• Thyroid function is usually normal or mildly abnormal — the encephalopathy is NOT caused by thyroid dysfunction
• Pathogenesis unclear — anti-thyroid antibodies are likely a biomarker of autoimmunity, not directly pathogenic

Clinical Features

• Two clinical patterns:
  • Relapsing-remitting (vasculitic type): stroke-like episodes, seizures, focal deficits
  • Progressive (diffuse type): gradual cognitive decline, psychiatric symptoms, dementia-like presentation
• Common features: confusion, cognitive impairment, tremor, myoclonus, seizures, psychiatric symptoms, ataxia
• Typically affects middle-aged women (F:M ratio ~4:1)
• May mimic CJD (rapidly progressive cognitive decline + myoclonus)

Diagnosis

• Anti-thyroid antibodies (anti-TPO and/or anti-thyroglobulin) elevated by definition; anti-TPO present in ~85–95%; anti-thyroglobulin also often elevated
• Thyroid function: usually euthyroid or subclinical hypothyroidism; NOT severely hypothyroid
• CSF: elevated protein in ~75%; mild pleocytosis possible; OCBs may be present
• EEG: diffuse slowing (non-specific); may show epileptiform activity
• MRI brain: often normal; may show non-specific white matter changes or transient T2 lesions
• Diagnosis requires: (1) encephalopathy, (2) elevated anti-thyroid antibodies, (3) exclusion of other causes, (4) response to steroids

Treatment

• High-dose IV methylprednisolone followed by oral prednisone taper — dramatic response is the hallmark
• Lack of objective steroid response should prompt reassessment for mimics — autoimmune encephalitis, prion disease, infection, malignancy, metabolic disease, or primary psychiatric disease. SREAT remains a diagnosis of exclusion
• Relapse is common on steroid taper — may need long-term immunosuppression (azathioprine, mycophenolate)
• IVIg or PLEX for steroid-refractory cases

Overview

• Immune checkpoint inhibitors (ICIs): anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab)
• ICIs remove T-cell inhibitory signals → enhanced anti-tumor immunity but also immune-related adverse events (irAEs)
• Neurological irAEs in ~1–5% of patients; can be severe and life-threatening
• Combination therapy (anti-PD-1 + anti-CTLA-4) carries highest risk
• Onset typically weeks to months after starting therapy

Neurological irAEs

Management Principles

• Grade 1 (mild): consider continuing ICI with close monitoring
• Grade 2 (moderate): hold ICI; oral prednisone 0.5–1 mg/kg
• Grade 3–4 (severe/life-threatening): permanently discontinue ICI; IV methylprednisolone 1–2 mg/kg; IVIg or PLEX for refractory; ICU for MG crisis/myocarditis
• Do NOT rechallenge ICI after grade 3–4 neurological irAEs (especially MG, encephalitis, GBS)
• Involve neurology early; some syndromes (MG + myocarditis) carry high mortality without rapid treatment

PML (Progressive Multifocal Leukoencephalopathy)

• JC virus reactivation in immunosuppressed patients (natalizumab, rituximab, HIV CD4 <200)
• MRI: asymmetric white matter lesions involving subcortical U-fibers; NO enhancement, NO mass effect
• Diagnosis: CSF JC virus PCR (sensitivity ~80%); brain biopsy if PCR negative
• Treatment: immune reconstitution (stop causative drug; PLEX for natalizumab; cART for HIV)
• PML-IRIS: new enhancement appears after immune reconstitution; paradoxical worsening; treat with steroids if severe/symptomatic — balance against need for ongoing immune reconstitution

SSPE (Subacute Sclerosing Panencephalitis)

• Fatal late complication of measles; onset 6–15 years after infection
• Progressive cognitive decline → periodic myoclonus → rigidity → vegetative state → death
• EEG: Radermecker complexes (periodic high-amplitude slow-wave bursts every 4–15 seconds)
• CSF: markedly elevated measles antibody titers; elevated IgG
• No effective treatment; prevention = measles vaccination (MMR)

IRIS (Immune Reconstitution Inflammatory Syndrome)

• Paradoxical worsening after immune recovery (HIV starting cART; natalizumab withdrawal)
• MRI shows new enhancement in previously non-enhancing lesions
• Treatment: steroids if severe; continue immune reconstitution
• Delay cART 4–6 weeks after starting antifungals in cryptococcal meningitis to prevent IRIS

Neuromyelitis Optica Spectrum Disorder (NMOSD) — Quick Reminder

• See dedicated NMOSD & MOGAD topic for full coverage
• Key distinction from MS: MS DMTs (interferon, fingolimod, natalizumab) can WORSEN NMOSD — always test AQP4-IgG and MOG-IgG before starting MS therapy in atypical cases

Overview

• Large demyelinating lesions (≥2 cm) with surrounding edema and mass effect that mimic CNS tumors (glioma, lymphoma, metastasis) or abscess
• Can be the initial presentation of MS (clinically isolated syndrome) or occur during the course of established RRMS as an atypical/severe relapse
• More common in younger adults; female predominance
• Often follows immune-modulating drug changes (e.g., fingolimod withdrawal)

Imaging Features

• Size: ≥2 cm with surrounding vasogenic edema and mass effect
• Enhancement pattern: incomplete / open-ring enhancement, with the open segment facing the cortex/gray matter (vs. the deep white matter side, which enhances) — highly suggestive of tumefactive demyelination
• T2 hypointense rim at the lesion margin (vs. tumor, which typically lacks this)
• Less mass effect than expected for size (“mass effect mismatch”)
• MR spectroscopy: elevated choline and lactate (can mimic tumor); MR perfusion typically NOT elevated (unlike high-grade glioma)

Diagnosis & Management

• Often diagnosed only after brain biopsy when imaging suggests tumor; pathology shows demyelination with relative axonal preservation, foamy macrophages, reactive astrocytes
• Always send CSF for OCBs, MOG-IgG, AQP4-IgG; check for prior MS history
• Treatment: high-dose IV methylprednisolone (1 g/day × 5 days); PLEX for steroid-refractory cases; consider long-term MS DMT after recovery
• Prognosis: generally good with treatment; many patients eventually meet MS criteria

Overview

• Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids
• Rare CNS inflammatory disorder centered on the brainstem (especially pons)
• Mean age ~50; no clear sex predominance
• Dramatically steroid-responsive — relapses on taper are characteristic

Clinical Features

• Subacute brainstem syndrome: ataxia, dysarthria, diplopia, facial paresthesias, cranial neuropathies
• May extend to cerebellum, spinal cord, supratentorial regions
• Cognitive symptoms uncommon early

Imaging & Pathology

• MRI: punctate and curvilinear (“salt-and-pepper”) gadolinium enhancement peppering the pons, with extension into cerebellum, midbrain, and (variably) supratentorial white matter and cord
• Lesions are typically <3 mm; little to no mass effect
• Pathology: dense lymphocytic perivascular infiltrate (predominantly T cells), no granulomas, no demyelination, no vasculitis
• CSF: mild lymphocytic pleocytosis ± elevated protein; OCBs usually negative

Treatment & Differential

• High-dose IV methylprednisolone with slow oral taper; chronic immunosuppression (methotrexate, azathioprine, mycophenolate) to prevent relapse
• Relapses common if steroids withdrawn rapidly
• Critical mimics to rule out: CNS lymphoma (most important — can present identically and worsen with steroids before declaring), neurosarcoidosis, Behçet, vasculitis, infections (TB, fungal), gliomatosis cerebri
• Biopsy often needed if atypical features, poor steroid response, or large/coalescent lesions

Overview

• Rare post-infectious autoimmune brainstem encephalitis on the anti-GQ1b antibody spectrum (along with Miller Fisher syndrome and GBS)
• Typically follows GI or respiratory infection (Campylobacter jejuni, Haemophilus influenzae)
• Usually monophasic with good recovery

Clinical Features

• Triad: ophthalmoplegia + ataxia + encephalopathy (impaired consciousness)
• Often with hyperreflexia and/or pyramidal signs (distinguishes from Miller Fisher, which has areflexia)
• Significant overlap with Miller Fisher syndrome (ophthalmoplegia + ataxia + areflexia) and GBS
• May progress to coma and respiratory failure

Diagnosis

• Anti-GQ1b IgG antibody positive in ~66–68% of cases (also positive in Miller Fisher syndrome ~90%)
• MRI brain: often normal; may show brainstem T2 hyperintensities
• CSF: albuminocytologic dissociation (elevated protein with normal cell count), like GBS
• EEG: diffuse slowing

Treatment

• IVIg (first-line); PLEX as alternative
• Supportive care including airway protection if obtunded
• Prognosis generally favorable with treatment

Overview

• Neurologic involvement occurs in ~5–15% of systemic sarcoidosis; isolated CNS sarcoid is rare
• Non-caseating granulomatous inflammation affecting any part of the nervous system
• Most common in adults aged 20–50; higher incidence in Black patients

Clinical Features

• Cranial neuropathies: most common manifestation; CN VII palsy (often bilateral) is the most characteristic; CN II also common
• Basilar meningitis: multiple cranial neuropathies, hypothalamic-pituitary dysfunction (diabetes insipidus, panhypopituitarism), communicating hydrocephalus
• Parenchymal disease: granulomatous mass lesions, encephalopathy, seizures
• Spinal cord: myelopathy with dorsal subpial “trident sign” enhancement on MRI
• Peripheral: small fiber neuropathy, mononeuritis multiplex, muscle involvement

Diagnosis

• CSF: lymphocytic pleocytosis, elevated protein, low glucose (helpful clue); CSF ACE has limited sensitivity and variable specificity — supportive in context but cannot be used to rule in or rule out neurosarcoidosis. Tissue confirmation of systemic or nervous-system sarcoidosis remains central when feasible
• Serum ACE: non-specific (sensitivity ~50%); not reliable alone
• MRI brain/spine with gadolinium: leptomeningeal and/or pachymeningeal enhancement, especially basal meninges; parenchymal granulomas; dorsal subpial cord enhancement
• Gallium-67 scan: “panda sign” (lacrimal/parotid uptake) + “lambda sign” (mediastinal/hilar nodes) = highly suggestive of systemic sarcoidosis
• FDG-PET: identifies extraneural biopsy targets (lymph nodes, lung)
• Tissue biopsy showing non-caseating granulomas = definitive (lymph node, salivary gland, lung; CNS biopsy if no accessible systemic site)
• Must exclude TB and fungal infection before steroids (stain, culture, PCR)

Treatment

• First-line: high-dose corticosteroids (prednisone 1 mg/kg/day; IV methylprednisolone for severe disease)
• Steroid-sparing agents: methotrexate, azathioprine, mycophenolate mofetil
• Refractory disease: anti-TNF biologics (infliximab) — growing evidence for refractory neurosarcoid
• Treat hydrocephalus with VP shunt if symptomatic; hormone replacement for hypopituitarism
• Long-term immunosuppression often required; relapse common with rapid taper

Overview

• Sjögren syndrome = autoimmune exocrinopathy (dry eyes, dry mouth) with neurologic involvement in up to 20% of patients
• Neurologic involvement may precede sicca symptoms in many patients — check for Sjögren in any unexplained sensory ganglionopathy or atypical demyelinating disease
• Strong female predominance (9:1)

Neurologic Manifestations

• Sensory ganglionopathy / ataxic neuropathy (MOST CHARACTERISTIC): non–length-dependent sensory loss, prominent proprioceptive loss with sensory ataxia, pseudoathetosis; areflexia; preserved strength
• Small fiber neuropathy: burning pain, autonomic dysfunction; epidermal nerve fiber density on skin biopsy
• Mononeuritis multiplex: vasculitic; abrupt asymmetric mononeuropathies
• Trigeminal sensory neuropathy: classically unilateral facial numbness
• Myelopathy: may present as LETM and overlap with NMOSD (check AQP4-IgG)
• Cranial neuropathies, optic neuropathy, brainstem encephalitis
• CNS: cognitive dysfunction, psychiatric symptoms; can mimic MS

Diagnosis

• Anti-SSA/Ro antibodies: positive in ~70%; carries the classification weight in the 2016 ACR/EULAR criteria
• Anti-SSB/La antibodies: positive in ~40%; can coexist with SSA, but isolated anti-SSB is no longer a serologic criterion (2016 ACR/EULAR) due to limited specificity
• ANA often positive; rheumatoid factor may be elevated
• Minor salivary gland (lip) biopsy = focus score ≥1 (focal lymphocytic sialadenitis) = histopathologic gold standard
• Schirmer test, ocular staining score; unstimulated salivary flow
• Always test AQP4-IgG in any Sjögren-associated myelopathy (NMOSD overlap)

Treatment

• Symptomatic: artificial tears/saliva, gabapentinoids for neuropathic pain
• IVIg for sensory ganglionopathy and mononeuritis multiplex
• Corticosteroids + steroid-sparing agents (azathioprine, mycophenolate, rituximab) for severe CNS or vasculitic disease
• Treat NMOSD overlap per NMOSD protocol

Overview

• Rare autoimmune endotheliopathy/microangiopathy affecting brain, retina, and inner ear
• Predominantly affects young women (F:M ~3:1), aged 20–40
• Often monophasic but can relapse; long-term immunosuppression usually required

Clinical Triad

• 1. Encephalopathy — confusion, behavioral change, headache, cognitive decline, seizures
• 2. Branch retinal artery occlusion (BRAO) — sudden visual loss, scotomas; multiple branch occlusions; Gass plaques (yellow-white retinal arterial wall plaques) on fundoscopy; fluorescein angiography is the most sensitive test
• 3. Sensorineural hearing loss — often low-frequency, bilateral; may be accompanied by tinnitus and vertigo
• Complete triad at onset in only ~15% of patients — high index of suspicion needed; partial presentations are common

Imaging & Workup

• MRI brain (pathognomonic): “snowball” lesions in the central corpus callosum sparing the periphery (vs. MS, which involves callosal-septal interface); “string of pearls” in internal capsule; leptomeningeal enhancement possible
• CSF: often markedly elevated protein (>100 mg/dL); mild lymphocytic pleocytosis; OCBs usually negative
• Fluorescein angiography: branch retinal artery occlusions with arterial wall hyperfluorescence
• Audiogram: low-frequency sensorineural hearing loss

Treatment

• Aggressive combined immunotherapy: high-dose IV methylprednisolone + IVIg
• Rituximab or cyclophosphamide for severe or refractory disease
• Long-term immunosuppression (mycophenolate, methotrexate) to prevent relapse
• Hearing aids/cochlear implants for irreversible hearing loss

Overview

• Distinct autoimmune disease characterized by sleep disturbance + bulbar dysfunction + movement/gait disorder + autonomic features
• Unique among autoimmune neurologic conditions: combines antibody-mediated and neurodegenerative (tauopathy) features
• Adult onset; slowly progressive course over months to years

Clinical Features

• Sleep disorders (hallmark): non-REM and REM parasomnia (abnormal sleep behaviors), obstructive sleep apnea, stridor, REM sleep behavior disorder, insomnia
• Bulbar dysfunction: dysphagia, dysarthria, stridor (can cause sudden death)
• Gait and movement disorder: parkinsonism, ataxia, chorea, dystonia
• Autonomic dysfunction: orthostatic hypotension, urinary symptoms, hyperhidrosis
• Cognitive decline may emerge over time

Pathology & Immunology

• Pathology: tauopathy with 3R + 4R tau deposition, predominantly in hypothalamus and brainstem tegmentum (distinct distribution from PSP, CBD, Alzheimer)
• HLA association: strong link with HLA-DRB1*10:01 and DQB1*05:01
• Antibody: anti-IgLON5 IgG, IgG4-predominant subclass (similar to MuSK MG and anti-LGI1)
• IgLON5 is a neuronal cell adhesion molecule

Diagnosis & Treatment

• Serum and CSF anti-IgLON5 antibody testing
• Polysomnography (PSG) reveals characteristic sleep architecture abnormalities
• Limited response to immunotherapy (reflecting underlying tauopathy); some patients improve with IVIg, steroids, or rituximab if started early
• Supportive: CPAP/tracheostomy for OSA/stridor; treat parkinsonism/movement symptoms
• Prognosis guarded; sudden death from upper airway obstruction or central hypoventilation is a major concern

Overview

• Rare autoimmune encephalitis with a distinctive syndrome of CNS hyperexcitability + prominent GI symptoms
• DPPX = dipeptidyl-peptidase-like protein 6, an auxiliary subunit of Kv4.2 potassium channels — loss of function leads to neuronal hyperexcitability
• Adult onset; subacute to chronic course

Clinical Features

• CNS hyperexcitability: agitation, anxiety, myoclonus, tremor, hyperekplexia-like exaggerated startle, seizures, PERM-like rigidity, brainstem/cerebellar signs
• GI symptoms (characteristic): severe diarrhea and significant weight loss — often precedes neurologic onset by months
• Cognitive dysfunction, psychiatric symptoms, sleep disturbance
• Autonomic dysfunction
• Occasional association with B-cell lymphoma (paraneoplastic in a minority)

Diagnosis & Treatment

• Serum and CSF anti-DPPX IgG (cell-based assay)
• MRI brain often normal or non-specific; EEG may show diffuse slowing or epileptiform activity
• Screen for underlying B-cell lymphoma (CT chest/abdomen/pelvis, lymph node evaluation)
• Treatment: first-line immunotherapy (IV methylprednisolone, IVIg, PLEX); rituximab or cyclophosphamide for refractory or relapsing disease; treat underlying lymphoma if identified
• Many patients respond to immunotherapy but relapse is common; long-term immunosuppression often needed

Overview

• Acute or subacute cerebellar ataxia driven by autoimmune/paraneoplastic mechanisms, often presenting with rapidly progressive pancerebellar syndrome
• Workup should include neuronal surface and intracellular antibody panels plus malignancy screening

Key Antibodies and Associations

Diagnosis & Treatment

• MRI brain: cerebellar atrophy late; often normal early
• CSF: lymphocytic pleocytosis, OCBs possible
• Comprehensive paraneoplastic antibody panel (serum + CSF); whole-body FDG-PET-CT and tumor-directed screening
• Treat underlying tumor when identified
• Immunotherapy: IV methylprednisolone, IVIg, PLEX; rituximab/cyclophosphamide for refractory cases
• Outcomes depend on antibody type and clinical context: most surface-antibody syndromes recover better than intracellular-antibody syndromes (Yo, Hu) where neuronal loss is established. Anti-Tr/DNER is an important exception: DNER is a surface target but the clinical phenotype behaves like a high-risk paraneoplastic cerebellar syndrome — do NOT apply the "surface antibody = reversible" rule here

Overview

• ICANS = neurologic toxicity following CAR-T cell therapy (and other immune effector cell therapies) for B-cell malignancies (DLBCL, ALL, multiple myeloma)
• Pathophysiology: systemic cytokine release → blood-brain barrier disruption, endothelial activation, and CNS inflammation; not direct CAR-T infiltration
• Distinct from but often co-occurs with Cytokine Release Syndrome (CRS); typically follows CRS by hours to days
• Onset: usually within the first 1–3 weeks after CAR-T infusion

Clinical Features

• Encephalopathy ranging from inattention/mild confusion to coma
• Expressive aphasia is an early and characteristic feature
• Tremor, dysgraphia, apraxia
• Seizures (including non-convulsive status epilepticus) — many centers use levetiracetam prophylaxis
• Severe cases: cerebral edema, intracranial hypertension, herniation, death

Grading (ASTCT consensus)

• ICE score (Immune effector Cell-associated Encephalopathy) scored 0–10 across orientation, naming, command following, writing, attention
• Grade 1: ICE 7–9; awake
• Grade 2: ICE 3–6; awake
• Grade 3: ICE 0–2; awakens to voice; non-convulsive/focal seizure that resolves; focal CNS edema on imaging
• Grade 4: unarousable, life-threatening seizures (>5 min) or status epilepticus, deep focal weakness, diffuse cerebral edema, decerebrate/decorticate posturing

Management

• Corticosteroids are FIRST-LINE for ICANS: dexamethasone (10 mg IV q6h escalating with grade) or methylprednisolone for severe disease
• Tocilizumab (anti-IL-6R) is first-line for CRS but does NOT cross the blood-brain barrier well — use tocilizumab only if concurrent CRS, not for isolated ICANS
• Levetiracetam seizure prophylaxis commonly initiated peri-infusion at many centers
• Continuous EEG for any unexplained encephalopathy (rule out NCSE)
• Neuroimaging (MRI > CT) for grade ≥3 to assess cerebral edema
• ICU-level care for grade 3–4; hyperosmolar therapy for cerebral edema; intubation for airway protection or status epilepticus
• Anakinra (IL-1 receptor antagonist) and high-dose methylprednisolone (1 g/day) for steroid-refractory ICANS