MS - Etiology
- MS requires both an environmental and genetic[β¦] insult.
- Environmental triggers: EBV and HHV-6[β¦] viruses, low Vitamin D[β¦].
- Genetic factors: HLA DR-2[β¦], biological female sex.
Autoimmune
Autoimmune
Subspecialties Β· 192 cards
MS - Pathophysiology - Initial Insult
- APC (e.g., macrophage) engulfs an antigen β presents it on MHC-2 (HLA)[β¦] β presents to T-Helper cells[β¦].
- The Th cell may recognize an antigen looking like Myelin Basic Protein[β¦] β a mechanism called molecular mimicry[β¦].
- The Th cell crosses the BBB[β¦] (endothelial layer with tight junctions β basal lamina β astrocyte foot processes) and reaches CNS oligodendrocytes.
MS - Pathophysiology - Inflammatory Cascade
- Th cells interact with oligodendrocytes[β¦] β release IL-1, IL-6, TNFΞ±, and IFN-Ξ³[β¦].
- These cytokines: Recruit WBCs across the BBB; Vasodilate[β¦] BVs; Increase BBB permeability; Recruit B cells (chemotaxis) β become plasma cells[β¦] β release Ab against oligodendrocyte proteins; IFN-Ξ³ recruits macrophages[β¦] β phagocytose oligodendrocytes.
- Net result: oligodendrocytes destroyed β astrocytes[β¦] lay down scar tissue β creates plaques called "sclera" on axons.
- Meanwhile, Treg (regulatory T) cells[β¦] try to shut this down by secreting IL-10 and TGF-Ξ²[β¦].
MS - Disease Subtypes
- Most common (~90%): Relapsing-Remitting MS (RRMS)[β¦] β periodic flares with remission, worsening over time.
- Some RRMS patients secondarily progress to Secondary Progressive MS (SPMS)[β¦] β steady worsening of disability.
- Primary Progressive MS (PPMS)[β¦] β consistent disability progression from the start.
- Most severe: Progressive Relapsing MS (PRMS)[β¦] β constant demyelination + superimposed flares.
MS - Clinical Features - Vision / Eye
- Optic neuritis is characteristic of MS because CN2 is the only CN containing oligodendrocytes[β¦].
- Symptoms: decreased visual acuity, color blindness, and a Marcus-Gunn pupil (RAPD)[β¦].
- Bilateral INO is from demyelination of the MLF[β¦], which connects CN6 to CN3/CN4. In bilateral INO: CN6 abducts the ipsilateral eye fine, but the contralateral CN3 can't adduct β producing nystagmus toward the direction of gaze.
- At rest, there may be bilateral exotropia[β¦].
- Accommodation is intact (doesn't go through MLF, only through CN3 pathway) β so both eyes can converge with near vision[β¦].
MS - Clinical Features - Other CNS
- Pseudobulbar palsy from corticobulbar tract demyelination β bulbar symptoms with hyperactive jaw jerk and gag reflexes[β¦] (UMN signs).
- Higher cortical / limbic involvement: decreased memory (Papez circuit[β¦]) and depression (serotonin pathways).
- Cerebellar: ataxia with intention tremor[β¦] (worsens as finger approaches target).
- Lhermitte's sign[β¦]: pain shooting down the spine with neck flexion.
- Uhthoff's phenomenon[β¦]: worsening symptoms with higher temperature (reversible with cooling). Spinal cord pathway involvement: DCML: contralateral loss vib/prop; CST: contralateral UMN signs (weak, hypertonia, hyperreflexia, +Babinski); STT: contralateral loss pain/T; Autonomic dysfunction β urinary/bowel incontinence or retention.
- Charcot's triad[β¦]: nystagmus, dysarthria, intention tremor + "scanning" speech.
MS - Diagnosis
- MRI Brain + Spine wwo β lesions classically in 5 locations: Optic pathway[β¦] (nerve, chiasm, tract); Periventricular "Dawson's fingers"[β¦]; Infratentorial[β¦] (brainstem, cerebellar); Juxtacortical; Spinal cord.
- T1: hypointense[β¦] lesions; contrast enhances acute[β¦] lesions.
- T2: hyperintense[β¦] lesions.
- LP/CSF: pleocytosis[β¦] (increased WBCs) + increased oligoclonal bands[β¦] (IgG from plasma cells).
- Older 2nd-line test: visual evoked potentials[β¦] show decreased conduction velocity.
MS - Acute Treatment
- Acute MS relapse treatment: IVMP (high-dose steroids)[β¦] β inhibit cytokines (IL-1, IL-6, TNFΞ±, IFN-Ξ³)
- For severe attacks: add PLEX[β¦] β filters Ab from plasma
Transverse Myelitis - Etiology + Pathophysiology
- Etiologies:. Parainfectious: dengue, herpes, Mycoplasma pneumoniae, Schistosomiasis[name at least 4].
- Autoimmune: MS, NMO, MOGAD, ADEM[β¦].
- Pathophysiology: similar to MS/ADEM but localized to the spinal cord[β¦], particularly the thoracic[β¦] region.
Transverse Myelitis - Clinical, Dx, Tx
- Clinical features by affected pathway:. Preganglionic S neurons (T1-L2): urinary/fecal incontinence + retention[β¦]
- 4 other UMN pathways:
- DCML: contralateral loss vib/prop/discrim touch;
- CST: contralateral UMN signs;
- STT: contralateral crude touch + pain/T loss;
- Spinocerebellar tracts: ipsilateral ataxia[β¦]
- Sometimes anterior gray horn involvement β LMN[β¦] lesion (hypotonia, hyporeflexia, fasciculations)
- Diagnosis: MRI C/T/L spine wwo[β¦] β typically thoracic; T1 hypointense, T2 hyperintense. LP shows pleocytosis.
- Acute treatment: IVMP + PLEX[β¦].
- Prevention: MMF[β¦] (inhibits cytokine genes) or Rituximab[β¦] (depletes B cells).
MS DMT - General Principles + Monitoring
- MRI surveillance: baseline β ~6 months after starting treatment[β¦] β minimum yearly to monitor DMT response.
- Treatment target: NEDA (No Evidence of Disease Activity)[β¦] β no new/enlarging MRI lesions, no relapses, no disability progression.
- Switch or discontinue DMT for lack of efficacy or tolerability[β¦].
- Stable patients >45[β¦] years old at discontinuation are more likely to remain stable off treatment.
MS DMT
- IFN-Ξ²[β¦] (1993): the first DMT for MS. Indications: CIS, RRMS, or active SPMS.
- Available as injection[β¦].
- MOA: immunomodulatory β increases IL-10 and T-reg cells[β¦], reduces proinflammatory cytokines.
- Live vaccines NOT contraindicated; safe in pregnancy[β¦].
- SE/Monitoring (annually): CBC[β¦]: thrombocytopenia, leukopenia; LFTs: hepatotoxicity; Flu-like symptoms and injection-site reactions[β¦]; Suicide risk[β¦].
MS DMT
- Glatiramer Acetate[β¦] (1996). Indications: CIS, RRMS, or active SPMS.
- Available as injection[β¦].
- MOA: immunomodulatory β shifts T cells toward T-reg[β¦] cells and enhances them.
- Live vaccines NOT contraindicated; safe in pregnancy[β¦].
- SE: immediate postinjection reaction (flushing, chest pain/SOB); lipoatrophy at injection sites[β¦]. No regular lab monitoring needed.
MS DMT
- Sphingosine-1-Phosphate Receptor Modulators (2010-2021 - Indications: CIS, RRMS, active SPMS): Fingolimod (Gilenya)[β¦], Siponimod (Mayzent)[β¦], Ozanimod (Zeposia)[β¦], Ponesimod (Ponvory)[β¦]
- Fingolimod[β¦] can be used in kids >10 yo.
- Available as PO[β¦].
- MOA: down-regulate S1P receptors[β¦] β sequester lymphocytes in lymphoid tissues β reduce CNS trafficking.
- Live vaccines contraindicated; unsafe in pregnancy[β¦].
- General SE/Monitoring: CBC, LFTs; Macular edema[β¦] (esp DM/uveitis) β get ophtho eval; Infections (PML, Cryptococcus); Rebound after discontinuation; Increased malignancy risk (especially lymphoma); PRES from BP elevation.
- Pre-treatment: assess cardiac/stroke history β EKG[β¦]; pulm eval if asthma/COPD; ensure VZV vaccination. Drug-specific: Fingolimod: bradycardia/arrhythmias.
- Siponimod[β¦]: affects CYP2C9, contraindicated in 3/3 genotype. Zeposia: contraindicated in severe untreated sleep apnea, negative MAOi interactions. Ponvory: short half-life, retitrate after 4 missed doses.
MS DMT
- Teriflunomide[β¦] (2012). Indications: CIS, RRMS, active SPMS.
- Available as PO daily[β¦].
- MOA: inhibits dihydro-orotate dehydrogenase[β¦] β reduces pyrimidine synthesis β reduces lymphocyte proliferation.
- Live vaccines NOT contraindicated; unsafe in pregnancy[β¦] (also has male-mediated teratogenic risk).
- SE/Monitoring (monthly): LFTs for hepatotoxicity; Transient hair thinning[β¦], peripheral neuropathy, BP elevation; Pre-treatment: screen for latent TB[β¦].
MS DMT - Fumarates
- Fumarates (e.g., Dimethyl Fumarate (Tecfidera)[β¦]) (2013). Indications: CIS, RRMS, active SPMS.
- Available as PO BID[β¦].
- MOA: activates Nrf2 pathway[β¦] (cellular response to oxidative stress).
- Live vaccines NOT contraindicated; unsafe in pregnancy and breastfeeding[β¦].
- SE/Monitoring (periodically): CBC for lymphopenia[β¦]; LFTs; Infections (herpes, JCV/PML, opportunistic); Flushing[β¦] (mitigate with ASA) and GI issues β less with Diroximel Fumarate[β¦] vs Dimethyl Fumarate.
MS DMT
- Natalizumab (Tysabri)[β¦] (2004-2006). Indications: CIS, RRMS, active SPMS.
- Available as IV[β¦].
- MOA: monoclonal Ab binding Ξ±4 integrin[β¦] on leukocytes β blocks trafficking to the CNS.
- Live vaccines NOT recommended; unsafe in pregnancy[β¦].
- SE/Monitoring: LFTs for hepatotoxicity; JCV antibody[β¦] for PML rule-out β the key concern with natalizumab; Severe rebound[β¦] upon discontinuation; Infections (herpes, opportunistic).
MS DMT - Anti-CD20 Monoclonals
- Anti-CD20 Monoclonal Antibodies (2017-2020 - Indications: CIS, RRMS, active SPMS):
- Ocrelizumab (Ocrevus)[β¦] (2017) β IV q6 months;
- Ofatumumab (Kesimpta)[β¦] (2020) β injection monthly
- MOA: lyses CD20 B cells[β¦] β reduces T-cell activation, proinflammatory cytokines, and ectopic meningeal lymphoid structures.
- Live vaccines contraindicated; unsafe in pregnancy[β¦].
- SE/Monitoring: CBC for lymphopenia; LFTs; Rare PML[β¦], herpes, upper/lower respiratory infections; Possible increased malignancy.
MS DMT
- Alemtuzumab[β¦] (2001) β for RRMS or active SPMS after inadequate response to β₯2 DMTs.
- Available as IV[β¦].
- MOA: lyses CD52[β¦] cells (B cells, T cells, NK cells) β CD4 T cells take years to recover.
- Live vaccines contraindicated; unsafe in pregnancy[β¦]. SE/Monitoring: CBC, CMP, UA monthly; TFTs q3 months. Anti-herpes PPx until CD4 >200.
- Major risks: Life-threatening infusion reaction or stroke[β¦] within days of infusion; Secondary autoimmune conditions: ITP, anti-GBM disease, thyroid disease[β¦]; Increased malignancy risk.
MS DMT
- Cladribine[β¦] (2019) β for CIS, RRMS, or active SPMS after suboptimal response to another DMT.
- Available as PO[β¦].
- MOA: impairs DNA synthesis[β¦] β cytotoxic to B and T cells.
- Live vaccines contraindicated; unsafe in pregnancy and breastfeeding[β¦].
- Pre-treatment: screen for HIV, TB, HBV/HCV[β¦] + vaccinate for VZV. If lymphocytes <200, give antiherpes PPx. Contraindicated if active malignancy.
MS DMT
- Mitoxantrone[β¦] (2000) β RARELY USED. Indications: SPMS, PRMS, or severe/worsening RRMS β consider only if other agents are failing due to risk profile.
- Available as IV q3 months[β¦].
- MOA: inhibits DNA topoisomerase II[β¦] β stops DNA intercalation.
- SE/Monitoring: LFTs; Dose-limiting cardiotoxicity[β¦] β check TTE; Secondary leukemia[β¦] β check CBC.
Autoimmune Encephalitis - Definition + Mechanisms
- Definition: subacute (<12 weeks)[β¦] onset of rapid neurologic progression due to Ab against self.
- Triggers: paraneoplastic (tumor), viral antigen (HSV1), ICI medications[β¦]. Two pathophysiologic categories:
- Intracellular[β¦] antigens (nucleus/cytoplasm): peptides presented via MHC1 after proteasomal degradation; mediated by cytotoxic CD8 T cells[β¦]; treatment is T-cell targeted (irreversible process).
- Cell-surface[β¦] antigens (plasma membrane): directly accessible; mediated by Ab[β¦]; treatment is B-cell targeted (reversible process).
- Examples of surface antibodies: NMDAr, AMPAr, GABAa receptor[β¦] (synapse receptors).
Autoimmune Encephalitis - Limbic Encephalitis - Overview
Limbic encephalitis presents with: Subacute (<12 weeks)[β¦] onset; AMS, neuropsychiatric symptoms, or seizures[β¦] (often in isolation).
Workup findings: MRIb: uni or BL T2 hyperintensities[β¦] in mesial temporal lobes; CSF: pleocytosis; EEG: temporal lobe activity[β¦] or slowing.
Autoimmune Encephalitis
- ANNA-1 (Anti-Hu)[β¦] Ab β Limbic Encephalitis
- Associated with SCLC[β¦]
- Additional features: sensory neuronopathy (ganglionic AChR Ab) + dysautonomia[β¦], characteristic pseudoathetosis[β¦] (writhing finger movements from sensory ataxia), GI pseudoobstruction
- Prognosis: poor response to immunotherapy[β¦]
Autoimmune Encephalitis
- LGI1[β¦] Ab β non-paraneoplastic with good prognosis.
- Hallmark: faciobrachial dystonic seizures[β¦] β short (<2 sec) dystonic posturing of arm/face/leg, hundreds per day.
- Other features: dense antegrade amnesia[β¦] from bilateral hippocampal involvement, distinctive heightened emotionality with tearfulness, hyponatremia[β¦], epigastric rising aura.
- Treatment: great response to steroids and immunotherapy[β¦]; ASMs do NOT help.
- Best detected in the serum[β¦] (CSF often normal).
- HLA typing: HLA-DRB1*07:01[β¦]
Autoimmune Encephalitis
- GAD65[β¦] Ab β Limbic Encephalitis + Stiff Person Syndrome + Cerebellar Ataxia + DM type 1 association
- CASPR2[β¦] Ab β two specific syndromes (good prognosis): Limbic Encephalitis[β¦] presentation; Morvan Syndrome[β¦] β insomnia, severe autonomic dysfunction (hyperhidrosis), neuromyotonia[β¦], psychosis, seizures
- Associated with thymoma[β¦]. Both syndromes may have episodic ataxia, myoclonus, or neuropathic pain unresponsive to therapy
- EMG shows fasciculations with myotonic & myokymic discharges[β¦]
- HLA-DRB1*11:01[β¦]
Autoimmune Encephalitis
- NMDAr[β¦] Encephalitis β often first admitted to psychiatry[β¦] due to early neuropsychiatric symptoms.
- Then progresses to AMS, seizures, dyskinesias/chorea[β¦], severe autonomic instability, hypoventilation leading to coma.
- MRI often normal[β¦]; CSF pleocytosis; EEG shows extreme delta brush[β¦].
- Associated tumors: ovarian teratoma[β¦] or testicular neoplasm.
- Ab target: NR1 subunit[β¦], more commonly in females > males.
- Post-infectious form classically follows herpes simplex[β¦] infection.
Autoimmune Encephalitis - GABA + DPPX
GABAa receptor[β¦] Encephalitis: AMS + seizures (diffuse limbic-like).
Associated with thymoma or SCLC[β¦].
MRI: multifocal cortical/subcortical non-enhancing[β¦] white matter lesions + mesial temporal FLAIR hyperintensities.
GABAb receptor[β¦] Encephalitis: can cause new-onset Refractory SE[β¦].
DPPX[β¦] Encephalitis: triad of AMS + GI symptoms (diarrhea, weight loss) + spasms/myoclonus[β¦] β GI symptoms because DPPX is expressed in the enteric plexus.
MRIb/spine usually normal; rarely associated with B-Cell Lymphoma[β¦].
Autoimmune Encephalitis
- Autoimmune GFAP Astrocytopathy[β¦]: presents as meningo-encephalo-myelitis[β¦]. CSF: pleocytosis.
- MRI: linear, perivascular enhancement perpendicular to the corpus callosum[β¦] (radial pattern).
- Ab best detected in CSF[β¦].
Brainstem Encephalitis (Rhombencephalitis)
Ma2[β¦] Ab: gait ataxia, oscillopsia/vertigo, cranial neuropathies (dysarthria, diplopia, ptosis), sleep disorders (RBD, narcolepsy)[β¦], AMS/seizures.
Tumors: testicular or lung[β¦]. MRIb: mesial temporal + diencephalon (hypothalamus) hyperintensities.
ANNA-2 (Anti-Ri)[β¦] Ab: opsoclonus-myoclonus syndrome[β¦], jaw-clenching dystonia episodes, laryngospasm, stridor during sleep. Tumors: SCLC or breast (adults), neuroblastoma (kids). +cerebellar ataxia.
KLHL11[β¦] Ab: associated with a cochleovestibulopathy[β¦] β deafness in M with testicular seminoma[β¦].
IgLON5[β¦] Ab: characterized by tau deposition[β¦] β can mimic neurodegenerative disorder. +sleep disorder (RBD, parasomnias), bulbar dysfunction.
Paraneoplastic - Cerebellar Ataxia
- Rapidly progressive cerebellar ataxia presents with nystagmus, dysarthria, dysmetria, broad-based gait, and oscillopsia[β¦].
- Associated Ab: anti-Yo (PCA-1), GAD65, CASPR2[β¦].
- PCA-1 (anti-Yo)[β¦] Ab: associated with OBGYN cancers[β¦] (breast, ovarian); poor prognosis[β¦]. Opsoclonus-Myoclonus Syndrome: chaotic multidirectional eye movements + polymyoclonus + ataxia + AMS + sleep issues.
- Associated with neuroblastoma in kids; breast or SCLC in adults[β¦] with ANNA-2 (anti-Ri).
Paraneoplastic - Movement Disorders + Chorea
- Autoimmune chorea:. CRMP5[β¦] Ab: chorea + retinopathy + symmetric longitudinally extensive encephalomyelitis involving the dorsal or lateral[β¦] tracts. Associated with SCLC. BG T2 hyperintensities on MRI.
- Autoimmune chorea is also associated with SLE and APLS[β¦]. Paraneoplastic Myelitis: motor/sensory issues + bowel/bladder symptoms.
- MRI: longitudinally extensive, tract-specific T2 signal[β¦]. Associated with amphiphysin, ANNA-1 Ab, or AQP4/MOGAD.
Stiff Person Syndrome Spectrum
SPS Spectrum: CNS hyperexcitability β rigidity and spasms[β¦] causing falls, often with exaggerated startle response.
Associated Ab: GAD65 and Glycine Ξ±1-subunit receptor[β¦].
EMG: continuous motor-unit activity[β¦] in lumbar paraspinal muscles + agonist-antagonist cocontraction.
GAD65 Ab phenotypes: SPS, Cerebellar Ataxia, or Limbic Encephalitis (significant only >10,000 titers[β¦]; low titers seen in T1DM).
Glycine Ξ±1-subunit receptor Ab: SPS + PERM (Progressive Encephalomyelitis with Rigidity & Myoclonus)[β¦]. Prominent auditory/tactile startle responses.
Paraneoplastic - Peripheral + Autonomic Neuropathy
- Peripheral neuropathy by antibody:. anti-CRMP5 (CV2)[β¦]: asymmetric, painful, axonal[β¦] polyradiculoneuropathy + SCLC.
- Amphiphysin[β¦] Ab: symmetric polyradiculoneuropathy + myelopathy + SPS.
- Associated with breast CA[β¦].
- ANNA-1/Anti-Hu[β¦]: Limbic Encephalitis + sensory neuronopathy[β¦] + dysautonomia + SCLC.
- Characteristic pseudoathetosis[β¦] from sensory ataxia.
- Autonomic neuropathy: classic with ANNA-1/Anti-Hu[β¦] + SCLC β dysautonomia (orthostatic hypotension, gut/urine dysfunction, mydriasis, anhidrosis).
NMJ + Neuromyotonia
- MG: AChR or MuSK Ab; fatigueable ptosis/diplopia β generalized weakness. EMG: >10[β¦]% decrement on RNS. LEMS: dysautonomia with areflexia facilitated by exercise.
- Associated with SCLC; PQ-type VGCC[β¦] Ab (or rarely ANNA-1).
- EMG: low CMAP that facilitates after exercise[β¦]. Neuromyotonia (Peripheral Nerve Hyperexcitability): muscle stiffness, cramps, twitches.
- CASPR2[β¦] Ab causes 2 syndromes: Morvan Syndrome (insomnia, severe autonomic, neuromyotonia, psychosis, seizures) + Limbic Encephalitis.
- Associated with thymoma[β¦].
Paraneoplastic Myopathy
- Dermatomyositis[β¦]: periorbital heliotrope rash + Gottron papules on fingers.
- IMNM (Immune-Mediated Necrotizing Myopathy)[β¦]: associated with SRP and HMGCR[β¦] Ab.
Autoimmune Encephalitis - Diagnostic Workup
- General: Send BOTH CSF and serum[β¦] Ab for most cases. Up to 30% of all AIE is seronegative.
- Do NOT wait for Ab results[β¦] before starting therapy. Regular workup: MRI brain + spine, EEG, LP/CSF, EMG.
- Suspected paraneoplastic: CT chest/abdomen/pelvis[β¦], testicular US in men[β¦], mammography or TVUS in women[β¦]. If negative, maybe FDG-PET.
- Repeat screening every 6 months for 2 years[β¦] if initially negative.
Autoimmune Encephalitis - Treatment Tiers
- 1st line: IVMP + PLEX vs IVIG[β¦].
- 2nd line (long-term steroid-sparing): Rituximab (B-cell suppression)[β¦], bone marrow suppressants (Azathioprine, MMF, Cyclophosphamide).
- 3rd line (many trials ongoing): IL-6 blockers (Toci, Satralizumab), CAR-T cell therapy, CD19 blockers, Bortezomib (proteasome inhibitor), FcRn blockers[β¦].
Immune Checkpoint Inhibitors (ICI)
- ICI pathways: CTLA-4[β¦] (higher irAE frequency); PD-1 / PD-L1[β¦]; Newer: LAG3[β¦] pathway.
- ICI Toxicities management: discontinue ICI β IVMP β IVIG or PLEX (sometimes avoid IVMP/IVIG) β 2Β° immunotherapies.
- Prognosis: synaptic/cell surface[β¦] antigen syndromes do BETTER; intracellular T-cell mediated[β¦] syndromes do WORSE.
NMOSD - Pathophysiology
- AQP4-NMOSD: AQP4-IgG1[β¦] subclass Ab activates complement β MAC formation[β¦] (directly cytotoxic) + recruits PMNs/eosinophils.
- Affects AQP4 water channels[β¦] on astrocytes β dysfunction β glutamate excitotoxicity[β¦] β necrotic, destructive neuronal loss.
- AQP4 channels are most expressed in optic nerves, spinal cord, and area postrema (brainstem)[β¦].
MOGAD - Pathophysiology
- MOGAD: MOG-IgG1[β¦] subclass activates complement less efficiently[β¦] than NMOSD
- Same pathophys as NMOSD but less destructive[β¦] β and targets oligodendrocytes/myelin[β¦] (not astrocytes)
- Disease course comparison: NMOSD (relapsing[β¦], severe, large lesions, often disabling); MOGAD (often preceded by fever/infection/vaccine; subacute, severe, large lesions; often monophasic[β¦] or relapsing with near-complete recovery); MS (variable course, no specific Ab)
Optic Neuritis - NMOSD vs MOGAD vs MS
- AQP4-NMOSD ON: unilateral or bilateral[β¦] at onset; involves more posterior[β¦] optic pathway (chiasm/optic tract). Severe vision loss/blindness.
- MRI: long nerve length + chiasm/optic tract enhancement β may produce bitemporal or homonymous hemianopsia[β¦]. Fundoscopy often normal (posterior).
- MOGAD ON: bilateral[β¦] at onset; involves more anterior[β¦] optic pathway. Blindness over hours-days.
- MRI: >50% nerve length + perineural enhancement extending to orbital tissue[β¦]. Fundoscopy: optic disc edema + retinal hemorrhages.
- MS ON: usually unilateral[β¦], short segment.
- MRI: short nerve length + homogeneous[β¦] segment enhancement.
Myelitis - NMOSD vs MOGAD vs MS
- AQP4-NMOSD Myelitis: longitudinally extensive[β¦] lesions in cervical/upper thoracic cord; affects entire cross-section[β¦].
- MRI: bright spotty lesions + marked swelling + ring/elongated ring[β¦] peripheral enhancement.
- Symptoms: para/tetraplegia + painful tonic spasms (respond to carbamazepine)[β¦].
- MOGAD Myelitis: also longitudinally extensive; typically affects conus medullaris[β¦] (β sexual/sphincter dysfunction); preferentially affects central gray matter[β¦] forming the "H sign[β¦]". Faint, poorly demarcated lesions; leptomeningeal or nerve root enhancement.
- MS Myelitis: short (<3 segment)[β¦] lesions in the peripheral[β¦] cord. Well-defined; nodular or ring[β¦] enhancement
NMOSD - Brainstem Signs
- NMOSD brainstem syndromes: Area postrema syndrome[β¦]: intractable nausea/vomiting or hiccups[β¦] β MRI shows dorsal medulla enhancement.
- Peri-ependymal involvement: affects descending corona radiata fibers (CST); MRI shows "pencil-thin periependymal[β¦]" enhancement. CN nuclei: ophthalmoplegia.
- Diencephalon (hypothalamus): narcolepsy, hypotension, SIADH[β¦].
MOGAD - Brain Presentations
- MOGAD brain syndromes:. ADEM-like or leukoencephalopathy[β¦] presentation: common in kids[β¦], presents with AMS/seizures.
- FLAMES[β¦]: unilateral cortical FLAIR hyperintensities + meningeal enhancement β seizures evolving to SE; fever + marked CSF pleocytosis[β¦] common.
- MRI features: unilateral or bilateral middle cerebellar peduncle[β¦] entire-thickness involvement; multiple large, poorly demarcated white matter/deep gray lesions; no central vein sign[β¦] like MS.
NMOSD/MOGAD - Diagnostics + Treatment
- Diagnostic approach: Serum[β¦] testing preferred for both NMOSD and MOGAD; CSF: NMOSD/MOGAD have marked pleocytosis + eosinophils + transient/lower OCBs[β¦] (vs persistent OCBs in MS)
- Acute treatment: IVMP 1 g Q5-7d for 6-12 weeks with oral taper + PLEX Γ 5 sessions[β¦] (or IVIG)
- AQP4-NMOSD maintenance (to prevent relapses): Rituximab[β¦] (CD20 blocker); Satralizumab or Tocilizumab[β¦] (IL-6 blocker); Inebilizumab[β¦] (CD19 blocker); Eculizumab[β¦] (C5 blocker)
- MOGAD maintenance (if rarely needed): IVIG 1 g/kg monthly[β¦] β especially in pediatric MOGAD
Autoimmune Movement - Cerebellar Ataxia
Autoimmune cerebellar ataxia: subacute[β¦] onset with fast progression, too fast for neurodegenerative disease.
Autoimmune/Idiopathic GAD65[β¦] (most common): associated with SPS, DM1, pyramidal signs, epilepsy.
Titers very high[β¦]. Treatment: IVIG.
Paraneoplastic PCA-1 (anti-Yo)[β¦]: OBGYN cancers.
Paraneoplastic ANNA-1 (anti-Hu)[β¦]: SCLC.
KLHL11[β¦]: testicular germ cell tumors in males β cerebellar ataxia or brainstem syndrome + cochleovestibulopathy[β¦].
CSF inflammatory with high OCBs (>6)[β¦]. Rare "hot cross buns" sign similar to MSA.
Autoimmune Movement - Chorea + Dyskinesias
NMDAr[β¦] Ab: often orofacial + limb dyskinesias[β¦] or other movement disorder.
Paraneoplastic CRMP-5[β¦] Ab: chorea + cognitive decline + optic retinopathy + myelitis + neuropathy. Associated with SCLC.
ANNA-1 (anti-Hu)[β¦]: hearing loss + GI pseudoobstruction.
LGI1[β¦]: chorea + hyponatremia + faciobrachial dystonic seizures.
IgLON5[β¦]: chorea + Huntington Disease mimic (slowly progressive) + sleep disorders + bulbar symptoms.
Autoimmune Movement - Dystonia
NMDAr[β¦] encephalitis: dystonia/other movement disorders β example: oculogyric crisis or tonic upgaze seizures[β¦], AMS, seizures.
ANNA-2 (anti-Ri)[β¦]: craniocervical[β¦] dystonia (especially jaw-opening/closing) + recurrent laryngospasm. Associated with breast CA in women.
IgLON5[β¦]: dystonia + HD mimic + sleep issues + bulbar symptoms.
LGI1[β¦]: faciobrachial paroxysmal dystonic seizures (<3 sec, hundreds/day, ipsilateral face/arm posturing). EEG normal; MRI BG hyperintensities. Often prodrome to limbic encephalitis with hyponatremia.
Excellent response to steroids[β¦].
Pseudodystonia seen with Painful Tonic Spasms in NMO/MOG[β¦]: triggered by touch/hyperventilation; treat with carbamazepine.
Autoimmune Movement - Myoclonus
NMDAr[β¦]: psychiatric symptoms + seizures + orofacial/limb dyskinesias + encephalitis.
GABAa receptor[β¦]: intractable epilepsy.
DPPX[β¦]: GI symptoms (diarrhea, weight loss) + autonomic signs.
CASPR2[β¦]: coarse leg myoclonus + neuromyotonia.
GAD65, Amphiphysin, or Glycine-r[β¦]: brainstem myoclonus + hyperekplexia[β¦] (auditory/tactile startle) with SPS or PERM. Opsoclonus-Myoclonus Syndrome: chaotic multidirectional saccades + generalized myoclonus + ataxia + AMS. Associated with neuroblastoma (kids) or lung/breast CA (adults). Some COVID-19 cases.
Autoimmune Movement - Parkinsonism
CRMP-5[β¦] Ab: involves BG[β¦] on MRI.
Ma2[β¦] Ab: mimic of PSP[β¦] β rigid parkinsonism + gait instability + supranuclear vertical gaze palsy + eyelid opening apraxia + hypothalamic-pituitary dysfunction (narcolepsy, weight gain, RBD). MRI: thalamic + hypothalamic T2 hyperintensities.
Associated with testicular[β¦] tumors.
IgLON5[β¦]: can mimic HD, MSA (if RBD/ataxia/dysautonomia), PSP (if vertical supranuclear gaze palsy), CBD (if asymmetric parkinsonism + apraxia). +breathing issues (may require trach), sleep disorder, bulbar symptoms.
Autoimmune Movement - Tremor
GFAP Astrocytopathy[β¦] (with tremor): meningo-encephalo-myelitis.
MRI: radial linear periventricular or cerebellar enhancement[β¦]. May also have optic retinopathy/neuritis, headache from meningitis.
SPS - Pathophysiology + GAD-Spectrum Phenotypes
Pathophys: Ab against GAD[β¦] (synthesizes GABA) β inhibits these pathways β hyperexcitability[β¦] β stiffness/rigidity/spasms.
Associated with DM1[β¦] and reduced seizure threshold.
GAD65+ phenotypes (treatment response varies): SPS[β¦] (good response); Cerebellar Ataxia, Autoimmune Epilepsy, Limbic Encephalitis[β¦] (poor response).
SPS - Clinical Features
SPS symptoms:. Stiffness in proximal & axial muscles[β¦] (especially abdominal & thoracolumbar paraspinals) β hyperlordosis with S-shape thoracolumbar curvature[β¦], uncontrolled falls, difficulty turning/bending, slow gait with "freezing-like" appearance ("walking statue").
Episodic painful spasms[β¦] in trunk/extremities triggered by strong emotions, startle, or task-specific phobias (crossing a street).
Status spasticus[β¦]: continuous spasms/stiffness in pharyngeal muscles β breathing/speaking issues β treat with emergency IV diazepam[β¦].
Disease course: progressive without treatment[β¦].
Serum: very high GAD titers (>10,000)[β¦]; <2000 is insignificant.
EMG: continuous motor-unit firing at rest[β¦] + concurrent agonist-antagonist firing.
SPS - Associated Conditions
PERM (Progressive Encephalomyelitis with Rigidity & Myoclonus): associated with Glycine-r[β¦] Ab; increased spinal cord/brainstem FLAIR hyperintensities.
Can also be seen with DPPX[β¦] Ab (which also has GI symptoms).
GAD+ Nystagmus: typically downbeat or horizontal[β¦] nystagmus.
Other autoimmune diseases associated with GAD+: DM Type 1, pernicious anemia, vitiligo, thyroid disease[β¦].
SPS - Treatment
General supportive: PT, yoga, meditation, muscle relaxants (Tizanidine, Cyclobenzaprine, Methocarbamol, Botox). 1st-line antispasmodics (increase GABA): Benzos (diazepam, clonazepam)[β¦]; Baclofen or Gabapentin/Pregabalin[β¦].
2nd-line (immunotherapy) if not fully functioning after 2-3 months: IVIG 2 g/kg/month based on IBW[β¦] (not total body weight); Rituximab[β¦] if IVIG ineffective. Severe acute exacerbations: PLEX (limited data). Steroids, AZA, MTX, Cyclophosphamide, MMF, Tacro all have poor data.
Last option for refractory progressive disease: autologous HSCT[β¦].
Autoimmune Epilepsy & Limbic Encephalitis: start with IVMP 1 g Q24h Γ 3-5 days[β¦] β then IVIG/Rituximab as needed.
GBS + Variants
GBS: acute, monophasic[β¦], often infectious[β¦] trigger. Variants by Ab:
AMAN (Acute Motor Axonal Neuropathy)[β¦]: GD1a or GM1 Ab; Miller-Fisher Syndrome[β¦]: triad of ataxia, areflexia, ophthalmoplegia[β¦]; GQ1b Ab; GBS with ophthalmoplegia: GQ1b Ab; Bickerstaff Brainstem Encephalitis (BBE)[β¦]: GQ1b Ab; Pharyngeal-Cervical-Brachial[β¦] Variant: GT1a Ab; Acute Sensory Ataxic Neuropathy: GD1b Ab.
Autoimmune Nodopathies
Autoimmune nodopathies target nodal/paranodal proteins[β¦].
Poor response to IVIG[β¦] (unlike AIDP/CIDP) but good response to Rituximab[β¦]. Pathology shows no onion bulbs, no macrophage-mediated demyelination + axonal degeneration.
Neurofascin 155 IgG4 (most common): distal weakness + sensory symptoms β ataxia + tremors[β¦]; may have CN neuropathies + optic disc edema.
Neurofascin 186 IgG: severe subacute polyradiculoneuropathy + FSGS[β¦] (nephrotic syndrome).
Pan Neurofascin Ab: "explosive GBS"[β¦] β fulminant/monophasic with sensorimotor tetraplegia + CN neuropathies + autonomic dysfunction requiring intubation. Often + nephrotic syndrome.
Contactin-1 (CNTN1) IgG: acute-subacute + CN neuropathies (facial) + sensory polyradiculopathy + nephrotic syndrome[β¦]. CASPR1: acute-subacute weakness + sensory ataxia + neuropathic pain + CN neuropathies + respiratory failure.
Treatment: steroids + PLEX or Rituximab[β¦].
Other Autoimmune Demyelinating Neuropathies
Distal Acquired Demyelinating Symmetric (DADS) Neuropathy: length-dependent symmetric sensory or sensorimotor neuropathy; starts in lower extremities[β¦] then spreads upward. May have tremors.
Associated with anti-MAG IgM Ab[β¦] >10,000 titers.
EMG: prolonged distal latencies + low terminal latency index[β¦].
Treatment: usually refractory to IVIG[β¦].
Multifocal Motor Neuropathy (MMN): slow stepwise progression of focal, asymmetric motor weakness[β¦] without sensory symptoms, often starting in upper extremities[β¦].
Associated with GM1 IgM Ab[β¦].
EMG: focal conduction block[β¦] without significant temporal dispersion; no sensory involvement.
Paraneoplastic Axonal Polyradiculoneuropathy + Ganglionopathy
Paraneoplastic Axonal Polyradiculoneuropathy:. CRMP-5[β¦]: asymmetric, painful + SCLC β steroids β Cyclophosphamide.
Amphiphysin[β¦]: asymmetric, severe neuropathic pain + myelopathy.
ANNA-1/anti-Hu[β¦]: myeloneuropathy.
Ganglionopathy (Sensory Neuronopathy): sensory ataxia + asymmetric sensory loss + pain + dysautonomia β localizes to the DRG or dorsal columns[β¦].
EMG: asymmetric, absent SNAPs[β¦]. LP/CSF: lymphocytic pleocytosis + high protein.
Associated with ANNA-1/anti-Hu or CRMP-5[β¦] Ab.
Motor Neuronopathy: bulbar-onset, may mimic ALS[β¦].
Associated with IgLON5[β¦] (chorea, RBD, vocal cord paresis). Treat with IVMP.
Autonomic Neuropathy + Neuromyotonia
Autonomic Neuropathy:. LGI1[β¦]: subacute nociceptive pain with good response to immunotherapy.
ANNA-1/anti-Hu and CRMP-5[β¦]: GI pseudoobstruction. Neuromyotonia (Peripheral Hyperexcitability): stiffness, cramps, twitching, fasciculations, myokymia, dysautonomia.
EMG: myotonic or myokymic discharges + widespread fasciculations[β¦].
Isaac Syndrome[β¦]: cramps, fasciculations, stiff/neuropathic pain, myokymia, dysautonomia. Associated with thymoma.
Morvan Syndrome[β¦] = Isaac + insomnia + limbic encephalitis.
Associated with CASPR2 and LGI1[β¦] Ab. Rippling Muscle Disease: myalgias + visible wavelike muscle contractions induced by stretch/percussion. EMG: silent during episodes. Biopsy: mosaic CAV3 loss.
Associated with CAVIN4[β¦] Ab and thymoma.
MG vs LEMS
- MG (Myasthenia Gravis): Ptosis, binocular diplopia, dysarthria/dysphagia/hypophonia[β¦], fatigueable oculo-bulbar-extremity weakness (proximal>distal); Ab: AChR, MuSK, LRP4, or seronegative; EMG: >10% CMAP decrement on RNS[β¦]; Associated with thymoma[β¦] or ICI use; "Triple M syndrome" = myositis + myocarditis + MG.
- LEMS (Lambert-Eaton Myasthenic Syndrome): BLE weakness, hyporeflexia, dysautonomia[β¦]; EMG: facilitation >100% CMAP amplitude increase[β¦] with RNS or 10-12s exercise; PQ-type VGCC[β¦] Ab; Associated with SCLC; ICI rarer than MG.
IMNM (Immune-Mediated Necrotizing Myopathy)
IMNM: subacute, progressive, proximal weakness; rhabdomyolysis; respiratory failure as emergency. CK > 1000[β¦]. EMG: myotonic discharges + fibrillation spontaneous activity + myopathic motor unit potentials. Muscle MRI: inflammation or atrophy/fatty replacement.
Pathology: no lymphocytic infiltrate[β¦].
Associated with: Statin use[β¦] (anti-HMGCR Ab); SRP Ab[β¦]: more severe, refractory, with worse weakness/dysphagia/respiratory/cardiac involvement and muscle atrophy.
Treatment: SRP cases may benefit from Rituximab[β¦].
Pediatric Autoimmune - Aicardi-Goutières + HLH
Aicardi-GoutiΓ¨res Syndrome[β¦]: Pathophys: gene variations β upregulation of Type 1 IFNs[β¦] ("interferonopathy"); MRI: intracerebral calcifications in BG and deep white matter[β¦] mimicking demyelinating syndromes + progressive atrophy; Treatment: JAK1 inhibitors[β¦].
Hematophagocytic Lymphohistiocytosis (HLH)[β¦]: Pathophys: defects in T-lymphocyte and NK cell cytotoxicity β cytokine storm[β¦] β multiorgan failure; Can be primary (genetic) or secondary (infection, autoimmune, cancer); Criteria: >5/8 of fever, splenomegaly, pancytopenia, hyperTG/fibrinogen/ferritin, high IL-2R, low NK cell activity, hemophagocytosis; Test kids with CLIPPERS[β¦] for HLH even without systemic features; Treatment: autologous HSCT[β¦].
Pediatric Autoimmune - Differences from Adults
Major differences from adult syndromes β generally lower disability levels[β¦] due to better neuroplasticity.
NMDAr Encephalitis: prepubertal kids β florid movement disorder[β¦] presentation; postpubertal β neuropsychiatric[β¦] presentation.
Many centers use Rituximab first-line[β¦].
Limbic Encephalitis: kids typically seronegative[β¦]; Ab less associated with tumors.
Opsoclonus-Myoclonus Syndrome: mostly neuroblastoma[β¦] in kids.
MOGAD: <10 yo β ADEM phenotype[β¦]; >10 yo β ON phenotype.
Use Tocilizumab[β¦] for fulminant MOGAD if unresponsive to steroids/PLEX.
MS: higher relapse rate, worse cognitive/disability outcomes; almost exclusively RRMS[β¦]; higher inflammatory activity; DMTs often off-label. NMOSD: more inflammatory; shorter time to first relapse.
Rheumatoid Arthritis - Neuro Manifestations
RA neuro manifestations:. CNS: meningitis or vasculitis[β¦] commonly.
PNS: CTS or cervical myelopathy[β¦] due to atlantoaxial (C1/2) joint instability[β¦] with pannus around the odontoid[β¦] process.
Serology: RF and anti-CCP[β¦] Ab. Meningitis: frontoparietal much more common than posterior fossa with lepto/pachymeningeal enhancement.
Vasculitis: affects both small and medium-sized[β¦] vessels.
SjΓΆgren Syndrome - Neuro Manifestations
SjΓΆgren: glandular inflammation β sicca symptoms (dry eyes/mouth)[β¦].
PNS: trigeminal neuropathy with isolated sensory deficits[β¦] (unlike trigeminal neuralgia). CNS: similar to demyelinating disorders.
Serology: SSA (Ro) / SSB (La)[β¦] Ab. Cerebellar ataxia is non-vasculitic, non-demyelinating with prominent gait dysfunction or dysarthria. Cognitive dysfunction is possible.
Neuropsychiatric SLE
Neuropsychiatric SLE diagnostic criteria include delirium, psychosis, and seizures[β¦] (CNS > PNS).
Acute psychosis: often younger male patients with monophasic disease course[β¦]; MRIb and CSF often normal; good prognosis.
Demyelinating disease: often longitudinally extensive[β¦].
Meningitis: complement inhibitors like eculizumab[β¦] increase meningococcal infection risk.
Chorea: highly associated with antiphospholipid[β¦] Ab.
APLS: >1 thrombotic or obstetric event + lupus anticoagulant, anticardiolipin, or Ξ²2-glycoprotein[β¦] Ab. Thrombosis: can commonly affect cerebral arteries β strokes (especially if triple positive for Ab).
Behcet Disease
Behcet presents with oral/genital ulcers + skin lesions + ocular involvement[β¦].
Associated with HLA-B51[β¦].
Parenchymal disease: most commonly hits the brainstem[β¦] β headache + localized signs.
LP/CSF: PMN then lymphocytic predominance[β¦].
Spinal cord MRI: "Bagel sign[β¦]" β thick hyperintense rim + hypointense core.
Nonparenchymal disease: most commonly CVST[β¦] (subacute headache, high ICP). Get MRI/MRV to demonstrate thrombosis; CSF for OP.
IgG4-Related Disease
IgG4-RD: autoimmune fibrosing disorder affecting multiple organs (autoimmune pancreatitis, cholangitis, sialadenitis), commonly affecting the orbit[β¦].
Diagnosis: elevated serum IgG4 is nonspecific[β¦]; diagnosis requires biopsy showing storiform fibrosis + IgG4-positive plasma cells/lymphocytes[β¦]. CNS IgG4-RD:
Meningeal disease: idiopathic hypertrophic pachymeningitis[β¦]; MRI: hypertrophic/nodular dura.
Spinal cord: progressive myelopathy with ventral + dorsal involvement[β¦].
Neurosarcoidosis - Presentation
Neurosarcoidosis: multisystem granulomatous[β¦] inflammation commonly hits ocular, salivary, and thoracic involvement.
Meningitis: lepto > pachymeninges[β¦] typically at the base of the skull[β¦] β headache, cranial neuropathies, communicating hydrocephalus, myelopathy. MRI: leptomeningeal enhancement.
Cranial neuropathies: commonly optic, facial, and vestibulocochlear (VIII)[β¦].
Parenchymal disease: discrete lesions affecting hypothalamus, pituitary, and infundibulum[β¦].
Spinal cord (Myelopathy): subacute-chronic, longitudinally extensive >2 vertebral segments + dorsal subpial enhancement[β¦].
May see "braid pattern[β¦]" (dorsal subpial) or "trident sign[β¦]" (dorsal subpial + central canal on axial).
Neurosarcoidosis - Diagnostics + Treatment
Diagnostic workup:. Serum & CSF ACE[β¦] is nonspecific[β¦] (elevated in neuro-TB, CNS lymphoma); not recommended for diagnosis.
IL-2R[β¦] is nonspecific. CSF B-Cell Activating Factor is under investigation.
Imaging first step: PET-CT[β¦] for systemic sarcoidosis (may show mediastinal/hilar lymph node prominence) + biopsy target identification. PET > CT.
Diagnosis: biopsy[β¦] for tissue diagnosis is traditionally required.
Treatment: infliximab + MTX[β¦] + steroids with weeks-long taper.
Hypertrophic Pachymeningitis + DDX
Hypertrophic Pachymeningitis: inflammation β focal/diffuse dural thickening[β¦]. Wide DDX: SIH, lymphomatous meningitis, lymphoma, RA, SjΓΆgren, SLE, IgG4-RD, ANCA-associated vasculitis.
ANCA-associated vasculitides: GPA (Granulomatosis with Polyangiitis)[β¦] is most associated with pachymeningitis; also Microscopic Polyangiitis and Eosinophilic GPA (Churg-Strauss).
Polyarteritis Nodosa (PAN)[β¦] can affect small-medium arteries β pachymeningitis.
Cryoglobulinemia[β¦]: Ig precipitate at certain temperatures β meningitis. Large vessel vasculitides: Giant Cell Arteritis (GCA) and Takayasu Arteritis.
CAA-ri[β¦]: milder perivascular inflammation with vasogenic edema + leptomeningeal enhancement.
If more severe vessel wall inflammation β ABRA (Amyloid-Ξ² Related Angiitis)[β¦].
Primary Angiitis of CNS (PACNS) + Susac
PACNS[β¦] (diagnosis of exclusion after ruling out systemic disease): Presentation: subacute headache, FND, seizures, cognitive changes[β¦]; MRI: multifocal infarcts + hemorrhages + meningeal enhancement + beading on MRA[β¦]; VWI[β¦] shows vessel wall enhancement; Biopsy[β¦] often necessary; DDX: RCVS (Reversible Cerebral Vasoconstriction Syndrome)[β¦] β thunderclap HA, multifocal narrowing, reversible, associated with serotonergic medications.
Susac Syndrome[β¦]: microvascular endotheliopathy β triad of AMS + BRAO + sensorineural hearing loss[β¦] (many have incomplete triad).
MRI: "snowball lesion[β¦]" in corpus callosum + leptomeningeal enhancement + enhancing cortical lesions.
Treatment: Steroids[β¦] mainstay β steroid-sparing agents next.
Autoimmune Tx - IVMP (Acute)
Steroids reduce inflammation & restore BBB integrity. Adults: IVMP 1 g QD Γ 5 days[β¦] β PO taper 60 mg/day.
Kids: IV dose is ~Β½[β¦] of adults (2 mg/kg/day up to 60 mg/day).
SE: Psychiatric: insomnia, psychosis, irritability[β¦]; Metabolic: hyperglycemia, HTN, weight gain; Systemic: fluid retention, avascular necrosis of hip, osteoporosis, adrenal insufficiency, GI bleed, myopathy[β¦].
Mitigation: Ca/Vit D supplementation, GI PPx, and PJP pneumonitis PPx with SMX-TMP[β¦].
Autoimmune Tx - PLEX + IVIG (Acute)
PLEX: 5-7 sessions[β¦] to remove circulating Ab/cytokines/immune complexes.
Requires central line[β¦].
Don't use PLEX after IVIG[β¦] (blunts beneficial effects by removing Ig). SE: hematologic (hypofibrinogenemia, thrombocytopenia), electrolytes (hypoCaΒ²βΊ/MgΒ²βΊ), hemodynamic (large fluid shifts).
Avoid ACEi[β¦] Γ 24h afterward due to bradykinin-mediated hypotension risk with albumin replacement. IVIG: multiple mechanisms β neutralizes Ab, decreases Ab recycling, inhibits complement/cytokines.
Adults: 0.4 g/kg/day Γ 5 days[β¦].
Kids: 1 g/kg/day Γ 2 days[β¦]. Use IVIG when PLEX is unavailable, contraindicated, or failed.
SE: infusion reaction (esp IgA deficiency β anaphylaxis)[β¦]; hyponatremia; prothrombotic risk.
Autoimmune Tx - B-Cell Targeting (Maintenance)
B-cell targeting therapies block Ab secretion β reduces T-cell + cytokine activation. Anti-CD20[β¦] (hits pre-B cell[β¦], narrower range): Rituximab, Ocrelizumab (Ocrevus), Ofatumumab (Kesimpta), Ublituximab (Briumvi)[β¦]; Very effective in Autoimmune Encephalitis, NMOSD, Pediatric CNS inflammatory disorders[β¦]; SE: rare PML infection risk.
Anti-CD19[β¦] (hits pro-B cell[β¦], broader range β inhibits plasmablast formation): Inebilizumab (Uplizna)[β¦] approved 2026 for MG & NMOSD; ongoing in NMDAr Encephalitis (ExTINGUISH).
Anti-BTK[β¦] (crosses BBB; regulates B-cell function, microglia, myelin repair): Drugs with "-tinib" suffix; SE: drug-induced liver injury.
Autoimmune Tx - Complement Inhibitors
Complement inhibitors: Effective in IgG1[β¦] mediated disease (NMOSD, MOGAD, AChR+ MG); Ineffective in IgG4[β¦] mediated diseases (MuSK+ MG).
Anti-C5[β¦] (blocks C5 cleavage to C5a/C5b β prevents MAC): Eculizumab[β¦] (AChR MG, NMOSD; historically for aHUS, PNH); Ravulizumab[β¦] (MG, NMOSD); Zilucoplan[β¦] (AChR MG).
SE: increased risk of serious meningococcal infections[β¦].
Autoimmune Tx - Cytokine Inhibitors + FcRn Blockers
Proinflammatory cytokine inhibitors: Anti-IL-6[β¦]: Tocilizumab, Satralizumab[β¦]; Anti-IL-1: Anakinra[β¦] (used in neuro for NORSE); Anti-TNF[β¦]: Infliximab[β¦] (neurosarcoid, often co-administered with MTX), Adalimumab[β¦].
Neonatal Fc Receptor (FcRn)[β¦] Blockers: block IgG recycling/transcytosis β decreases circulating IgG (functionally like PLEX).
Agents: Efgartigimod (Vyvgart), Rozanolixizumab, Nipocalimab[β¦] (used in MG; ongoing for MOGAD).
Autoimmune Tx - DNA Synthesis Inhibitors + Others
DNA Synthesis Inhibitors: Cyclophosphamide[β¦]: cytotoxic alkylating agent (2nd line).
SE: bladder toxicity, myelosuppression[β¦].
Azathioprine[β¦]: purine antagonist.
MMF[β¦]: reversible inhibitor of AMP dehydrogenase. Proteasome Inhibitors: target long-lived plasma cells.
Bortezomib[β¦] is emerging for neuro-onc/AIE.
Calcineurin Inhibitors: Tacrolimus[β¦] blocks T-cell activation; used in transplants + sometimes AIE.
JAK Inhibitors: Tofacitinib, Upadacitinib[β¦] β downregulate immune responses.
Ξ±4 Integrin Blocker: Natalizumab[β¦] β prevents lymphocytes from crossing BBB; used in MS.
SE: PML[β¦].
Autoimmune Tx - Symptomatic Management
Autonomic dysfunction: hydrate, salt tabs, abdominal binders, compression stockings, avoid heat, elevate HOB. Meds: midodrine, fludrocortisone, droxidopa[β¦]. SPS: benzos (diazepam, clonazepam) + baclofen/tizanidine/cyclobenzaprine.
Avoid SNRIs[β¦] β may exacerbate symptoms.
Tonic spasms (NMOSD): carbamazepine[β¦].
MG: Pyridostigmine (Mestinon)[β¦].
LEMS: Amifampridine (3,4-DAP)[β¦].
ASM caution: Be careful with Keppra in AIE[β¦] (severe behavioral changes); be careful with NaβΊ channel blockers in LGI1 encephalitis[β¦] (hyponatremia risk).
Autoimmune Tx - Pregnancy + Pediatric + ICI
Pregnancy considerations:. Acute: PLEX and IVIG are safe[β¦]; high-dose steroids run risks if gestational DM/HTN/preeclampsia.
Maintenance: Cyclophosphamide, MMF, BTK & Proteasome inhibitors[β¦] are all considered unsafe/teratogenic. Pediatric considerations:
AIE presents with seizures and movement[β¦] symptoms (unlike adults = psychiatric).
MOGAD presents with ADEM[β¦] commonly. Steroids/IVIG/PLEX fair game but watch long-term effects of steroids on growth/HPA axis.
Cyclophosphamide[β¦] used more frequently in peds onc + AIE than adults.
Early Rituximab[β¦] often used for NMDAr Encephalitis.
ICI toxicity grading: Grade 1 (mild): hold ICI, monitor; Grade 2-3 (moderate): hold + steroids + IVIG[β¦]; Grade 4 (severe): hold + PLEX or IVIG[β¦].
Practice Q - Ozanimod + Macular Edema
Visual distortion without pain in a patient with MS on ozanimod is concerning for macular edema[β¦] β refer to ophthalmology[β¦].
Practice Q - Sarcoid FDG-PET Targets
The three organs most often involved in sarcoidosis on FDG-PET are lymph nodes, lungs, and the heart[β¦].
FDG-PET "lights up" inflamed tissue to help guide biopsy[β¦] target.
Practice Q - CANVAS Syndrome Triad + Cough
Progressive ataxia + sensory neuronopathy + bilateral vestibular areflexia[β¦] (catch-up saccades, oscillopsia) + chronic dry cough[β¦] over years = CANVAS syndrome[β¦].
Caused by RFC1 repeat expansions[β¦].
Practice Q - Intractable Hiccups β NMOSD
Intractable hiccups[β¦] (area postrema syndrome) point strongly to NMOSD[β¦] β rarely MS.
Area postrema syndrome involves the dorsal medulla[β¦].
Practice Q - MS Urgency + Tolterodine
For neurogenic urgency/frequency in MS with low postvoid residual, tolterodine[β¦] (antimuscarinic) is preferred β relaxes the detrusor[β¦] without increasing retention risk.
Practice Q - ADEM vs MS Lesion Margins
- Lesions with poorly defined margins[β¦] on MRI suggest ADEM > MS.
- In MS, lesions are well-circumscribed, juxtaposed to ventricles, perpendicular to corpus callosum[β¦] ("Dawson's fingers").
- ADEM classically involves deep gray matter and thalamus[β¦] (rarely in early MS).
Practice Q - MS DMT Side Effect Profiles
MS DMT side effect quick reference: Flushing: Dimethyl fumarate[β¦]; Bradycardia + infection risk: Ozanimod[β¦]; Injection-site reactions: Glatiramer acetate[β¦]; Infusion-site reactions: Natalizumab[β¦]; Alopecia + GI symptoms: Teriflunomide[β¦].
Practice Q - Anti-Hu Paraneoplastic Syndrome
Severe sensory ataxia + preserved strength + dorsal cord lesion + absent sensory responses in a patient with lung cancer β anti-Hu[β¦] paraneoplastic syndrome.
Practice Q - Natalizumab in NMOSD
NMOSD should NOT be treated with natalizumab[β¦] β worsens relapse[β¦] risk. Inebilizumab, eculizumab, satralizumab, and rituximab are effective.
Practice Q - MOGAD Diagnostic Core
- A core feature for MOGAD diagnosis is longitudinally extensive myelitis[β¦] (cord lesion >3 vertebral segments).
Practice Q - Teriflunomide Male Teratogenicity
Teriflunomide has male-mediated teratogenic risk[β¦] and should prompt contraceptive counseling in men.
Practice Q - Natalizumab Discontinuation
Natalizumab[β¦] discontinuation most commonly causes severe MS rebound[β¦].
Practice Q - VEP for Optic Neuritis
Unilateral prolonged P100 latency[β¦] on VEP is diagnostic for optic neuritis.
Main pathophysiology: demyelination[β¦].
Most common cause in young adults: MS[β¦].
Practice Q - Siponimod + Arrhythmia
Siponimod[β¦] is contraindicated in MS patients with cardiac dysrhythmia history β risk of bradyarrhythmia and AV block[β¦].
Practice Q - LGI1 Subacute Presentation
The antibody most likely positive in a patient with subacute confusion, drowsiness, and frequent episodic dystonic arm movements is LGI1[β¦].
Practice Q - AQP4-IgG Testing
Serum aquaporin-4 IgG (AQP4-IgG)[β¦] testing is highly specific for NMOSD[β¦] and provides definitive diagnosis in ON + brain lesions.
Practice Q - AMAN vs AMSAN
The feature more typical of AMAN than AMSAN is intact muscle stretch reflexes[β¦].
Practice Q - Miller Fisher Ab
Miller Fisher syndrome is most commonly associated with antibodies to GQ1b[β¦] ganglioside.
Practice Q - GBS CSF WBC Cutoff
CSF WBC exceeding 50[β¦] cells/mmΒ³ in suspected GBS should prompt consideration of alternative diagnoses.
Values consistent with GBS: <20[β¦] cells/mmΒ³.
Practice Q - Infliximab + Demyelinating Neuropathy
The medication that can cause demyelinating neuropathy presenting like CIDP is infliximab[β¦] (TNF-Ξ± antagonist).
Most other drug-induced neuropathies are axonal[β¦].
Practice Q - EGPA Recognition
Mononeuropathy multiplex[β¦] + adult-onset asthma[β¦] + positive perinuclear ANCA[β¦] = eosinophilic granulomatosis with polyangiitis (EGPA)[β¦].
Practice Q - GPA Remission Induction
In severe/organ-threatening GPA[β¦] with mononeuritis multiplex, remission induction = rituximab + corticosteroids[β¦].
Practice Q - NEDA Definition + Prognosis
Achieving NEDA[β¦] (No Evidence of Disease Activity = no new MRI activity, no relapses, no disability progression) is favorable. Losing NEDA later doesn't necessarily predict poor long-term prognosis.
Practice Q - MS DMT Stopping Age
Stopping DMT[β¦] before age 45[β¦] is associated with higher relapse risk than stopping after β deferring discontinuation may reduce risk.
Practice Q - MS Cancer Screening
For MS patients on immunosuppressive DMTs: stay up to date with all age-appropriate cancer[β¦] screening.
Practice Q - IFN-Ξ² in Pregnancy
IFN-Ξ² is NOT associated with teratogenic[β¦] effects and is considered compatible with breastfeeding (only low levels in breast milk).
Practice Q - Siponimod CYP2C9 Dosing
Siponimod[β¦] dosing must be adjusted based on CYP2C9[β¦] genotype β reduced for 1/3 and 2/3, avoided in 3/3.
Practice Q - CRMP-5 + SCLC
47F smoker with bilateral papillitis + CSF/serum CRMP-5[β¦] IgG + PET-CT lung nodule β most likely tumor is SCLC[β¦].
Practice Q - LGI1 Steroid-Responsive Sz
67M with frequent faciobrachial dystonic seizures[β¦], normal MRI/EEG, poor ASM response = autoimmune seizures due to LGI1[β¦] encephalitis, steroid responsive[β¦].
Practice Q - AD vs AIE in Elderly
Elderly woman with gradual cognitive decline, hippocampal atrophy, CSF AD profile (low AΞ², high tau) + incidental thyroid peroxidase Ab β diagnosis is Alzheimer disease[β¦], not autoimmune encephalitis.
Practice Q - LGI1 Sz + Early Immunotherapy
Elderly man with arm + ipsilateral facial jerks + thermal sensations, normal MRI/CSF/EEG, poor ASM response β faciobrachial dystonic seizures[β¦]; evaluate for LGI1[β¦] antibodies; early immunotherapy prevents cognitive decline.
Practice Q - NMDAr Young Woman Psychosis
Young woman with acute psychosis, disorientation, lymphocytic CSF pleocytosis, normal MRI, positive CSF/serum antibodies β AIE due to NMDA receptor[β¦] antibodies.
Practice Q - CASPR2 Older Man
Older man with subacute behavioral change + memory issues + gait ataxia + neuropathic leg pain + abdominal rising episodes, normal MRI/CSF, positive serum/CSF antibodies β AIE due to CASPR2[β¦] antibodies.
Practice Q - Anti-Hu Smoker Multifocal
Middle-aged smoker with subacute multifocal paraneoplastic syndrome (cerebellar + sensory ataxia + neuropathy + encephalopathy + UMN signs) β anti-Hu (ANNA-1)[β¦] antibodies.
Practice Q - Paraneoplastic LEMS
Smoker with proximal leg-predominant weakness + autonomic symptoms + reduced reflexes with postactivation facilitation[β¦] + EMG presynaptic NMJ defect β paraneoplastic LEMS from SCLC[β¦].
Practice Q - Tenascin R Lymphoma
Older man with rapidly progressive treatment-refractory tremor + weight loss + inflammatory CSF + underlying lymphoma β paraneoplastic syndrome with tenascin R (TNR)[β¦] antibodies.
Practice Q - KLHL11 Testicular GCT
Middle-aged man with subacute hearing loss + cerebellar ataxia + CSF-restricted OCBs + testicular germ cell tumor β paraneoplastic cerebellar syndrome with KLHL11[β¦] antibodies.
Practice Q - MOGAD with Steroid Dependence
Young woman with severe steroid-dependent demyelinating attacks (bilateral ON + LETM + brainstem lesions) + prior "MS" without OCBs β likely MOGAD[β¦].
Practice Q - AQP4+ NMOSD Initial Pattern
Middle-aged woman with acute myelitis (short cervical/thoracic lesions) + periventricular lesion without OCBs β likely AQP4+ NMOSD[β¦] (can later evolve to LETM).
Practice Q - GAD Cerebellar Ataxia
Young woman with subacute cerebellar ataxia + vitiligo + new T1DM + no malignancy β autoimmune cerebellar ataxia from GAD[β¦] antibodies.
Practice Q - SPS + High-Titer GAD
Older woman with progressive truncal/limb stiffness + hyperlordosis + startle-induced falls + autoimmune thyroiditis + very high GAD[β¦] antibody titers β stiff person syndrome[β¦].
Practice Q - Neurofascin 155 Nodopathy
Middle-aged man with rapidly progressive ataxic neuropathy + elevated CSF protein + nerve root enlargement + no IVIG response + serum neurofascin 155 IgG4[β¦] β autoimmune nodopathy[β¦] (not classic CIDP).
Practice Q - CRMP-5 SCLC Axonal
Older heavy smoker with asymmetric painful ascending sensory loss/weakness + axonal polyradiculoneuropathy + inflammatory CSF + mediastinal SCLC β paraneoplastic CRMP-5[β¦] axonal polyradiculoneuropathy.
Practice Q - IgLON5 ALS Mimic
Older woman with MND-like presentation (fasciculations, mixed UMN/LMN) + prior bilateral vocal cord paralysis + RBD β best explained by IgLON5[β¦] paraneoplastic syndrome, NOT ALS.
Practice Q - IMNM with SRP54
Middle-aged man with subacute head drop + proximal myalgic weakness + markedly elevated CK + myopathic EMG + necrotizing biopsy + high-titer SRP54 IgG β immune-mediated necrotizing myopathy from SRP[β¦] antibodies.
Practice Q - Pediatric NMDAr Recognition
Young child with subacute encephalopathy + mutism + orofacial dyskinesias + normal MRI + encephalopathic EEG β AIE due to NMDA receptor[β¦] antibodies.
Practice Q - NMDAr + Ovarian Teratoma
Teen girl with acute psychosis + encephalopathy + movement disorder + dysautonomia + normal MRI + positive antibodies + ovarian teratoma β NMDA receptor encephalitis[β¦].
Practice Q - Seronegative Pediatric AIE
Toddler with subacute encephalopathy + seizures + abnormal movements + abnormal MRI + negative antibody panel + good response to steroids/Rituximab β seronegative autoimmune encephalitis[β¦].
Practice Q - Pediatric Opsoclonus-Myoclonus
Toddler with acute ataxia + opsoclonus + irritability + normal MRI + neuroblastoma β paraneoplastic opsoclonus-myoclonus[β¦] syndrome.
Practice Q - Neuropsychiatric Lupus
Young woman with new multiorgan SLE (lupus nephritis, low complement, rash, cytopenias) developing encephalopathy + thalamic MRI lesions + seizures + psychosis β neuropsychiatric lupus[β¦].
Practice Q - Idiopathic Pachymeningitis
Middle-aged woman with focal enhancing dural thickening + biopsy showing chronic inflammatory fibrotic dura (without infection/IgG4/systemic autoimmune cause) β idiopathic hypertrophic pachymeningitis[β¦].
Practice Q - Neurosarcoid Recognition
Previously healthy middle-aged man with acute encephalopathy + multifocal diffusion-restricting brain lesions + mediastinal/hilar hypermetabolic LAD + biopsy granulomatous disease β neurosarcoidosis[β¦].
Practice Q - AMPA Receptor Encephalitis
Limbic encephalitis with good response to immunotherapy is most classically associated with AMPA receptor[β¦] antibodies.
Practice Q - Post-HSV NMDAr
Postinfectious NMDA receptor encephalitis is most classically associated with prior herpes simplex[β¦] virus.
Practice Q - Serum vs CSF AIE Testing
The main factor guiding whether autoimmune Ab testing is done on CSF vs serum is the specific target IgG antibody[β¦] suspected.
Practice Q - Anti-Hu Cancer Re-Screening
For anti-Hu (ANNA-1)βassociated limbic encephalitis with initially negative malignancy workup, repeat cancer screening every 6 months[β¦] for 2 years.
Practice Q - LGI1 + Frequent Seizures
AIE most characteristically associated with extremely frequent seizures (often faciobrachial dystonic) is LGI1[β¦] encephalitis.
Practice Q - Morvan Syndrome Recognition
AIE with psychiatric features + dysautonomia + insomnia + peripheral nerve hyperexcitability (Morvan syndrome) = CASPR2[β¦] antibodies.
Practice Q - Ovarian Teratoma β NMDA
Ovarian teratomas are most characteristically associated with AIE due to NMDA receptor[β¦] antibodies.
Practice Q - DPPX GI Symptoms
AIE with DPPX antibodies characteristically includes prominent gastrointestinal[β¦] symptoms β especially diarrhea[β¦].
Practice Q - IgLON5 Tau Deposition
IgLON5[β¦]-antibody encephalitis is linked to abnormal, irreversible deposition of tau[β¦] protein in the brain.
Practice Q - LUZP4 + Germ Cell Tumors
Paraneoplastic encephalomyelitis with germ cell tumors is most strongly linked to LUZP4[β¦] IgG antibodies.
Practice Q - Paraneoplastic Pseudoobstruction
Paraneoplastic process that can present solely as a systemic disorder is chronic intestinal pseudoobstruction[β¦].
Practice Q - ANNA-1 Limbic Encephalitis Pathology
ANNA-1 (anti-Hu) limbic encephalitis: brain biopsy shows inflammatory infiltrates predominantly of cytotoxic T cells and macrophages[β¦].
Practice Q - Area Postrema β AQP4 NMOSD
Intractable nausea, vomiting, and hiccups from an area postrema lesion in the dorsal medulla β most characteristic of AQP4+ NMOSD[β¦].
Practice Q - Central Vein Sign for MS
The brain MRI abnormality most specific for multiple sclerosis is the central vein sign[β¦].
Practice Q - MS Cord Lesions
- Spinal cord MRI showing multiple short[β¦] T2 lesions is more suggestive of MS myelitis than AQP4-NMOSD or MOGAD.
Practice Q - MOGAD ON Pattern
Optic neuritis with anterior segment involvement and optic nerve sheath enhancement[β¦] is most suggestive of MOGAD.
Practice Q - KLHL11 OCBs
Anti-KLHL11 cerebellar syndrome typically shows inflammatory CSF with increased CSF-restricted oligoclonal bands[β¦].
Practice Q - NMDAr Younger Movement Disorder
In NMDA receptor encephalitis, a movement disorder-predominant presentation is most strongly associated with younger[β¦] age.
Practice Q - LGI1 FBDS Ipsilateral
Faciobrachial dystonic seizures in LGI1 limbic encephalitis classically involve the ipsilateral[β¦] face and arm β can switch sides, may also involve ipsilateral[β¦] leg.
Practice Q - SPS IVIG First-Line
Initial immunotherapy of choice for SPS (once symptomatic antispasmodics are insufficient) is IVIG[β¦].
Practice Q - SPS Amphiphysin Paraneoplastic
In SPS, antibodies to amphiphysin[β¦] suggest a paraneoplastic mechanism (often breast cancer[β¦]).
Practice Q - SPS GABA Mechanism
Muscle stiffness and spasms in SPS result from impaired inhibitory neurotransmission of GABA[β¦].
Practice Q - Low-Titer GAD
Low-titer GAD antibodies are most commonly detected in type 1 diabetes[β¦].
Practice Q - PERM Glycine Receptor
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is classically associated with antibodies against the glycine receptor Ξ±1[β¦] subunit.
Practice Q - PCB GBS Variant Ab
Pharyngeal-cervical-brachial GBS variant is associated with GT1a IgG[β¦].
Practice Q - Contactin-1 + Nephrotic
In contactin-1 autoimmune nodopathy[β¦], a commonly associated systemic finding is urine protein >3.5[β¦] (nephrotic-range proteinuria).
Practice Q - Ganglionic nAChR Severity
Greater disease severity correlates with higher titer[β¦] values of ganglionic nAChR IgG in autoimmune autonomic ganglionopathy[β¦].
Practice Q - CASPR2 Tumor Search
In CASPR2-positive neuromyotonia/Isaac syndrome, the most appropriate tumor search is high-resolution CT chest[β¦] for thymoma[β¦].
Practice Q - ADEM + MOG
The antibody detected in more than 50% of children with ADEM[β¦] is MOG[β¦].
Practice Q - Aicardi-Goutières Interferonopathy
The condition characterized by inappropriate activation of innate immunity with upregulation of type I interferons is Aicardi-GoutiΓ¨res syndrome[β¦].
Practice Q - Pediatric Opsoclonus + Neuroblastoma
The paraneoplastic form of opsoclonus-myoclonus syndrome in children is most commonly associated with neuroblastoma[β¦].
Practice Q - Extreme Delta Brush
Autoimmune disorder most associated with extreme delta brush[β¦] EEG pattern is NMDA receptor encephalitis.
Practice Q - IgG4-RD Meningitis
The rheumatologic disease most likely to cause CNS meningitis (specifically hypertrophic pachymeningitis[β¦]) is IgG4[β¦]-related disease.
Practice Q - SjΓΆgren Trigeminal Neuropathy
Trigeminal neuropathy in SjΓΆgren syndrome[β¦] presents with sensory deficits only[β¦] (no motor involvement).
Practice Q - Behcet CVST
Nonparenchymal neurologic Behcet[β¦] disease most commonly presents as cerebral venous sinus thrombosis[β¦].
Practice Q - Neurosarcoid Treatment Combo
For pathology-confirmed neurosarcoidosis with disabling symptoms + multifocal CNS lesions + leptomeningeal enhancement β initial regimen is MTX + Infliximab[β¦] + steroids with weeks-long taper.
Practice Q - TB Screening Pre-Immunosuppression
Treatment planning for long-term immunosuppressant therapy should include screening for tuberculosis[β¦].
Practice Q - LGI1 Steroid Taper
After initial high-dose steroid pulse, the recommended first-line approach in LGI1[β¦] encephalitis is a prolonged corticosteroid taper (over several months), without automatically adding a steroid-sparing agent.
Practice Q - Eculizumab Mechanism
Eculizumab[β¦] acts as a complement system inhibitor β binds complement C5[β¦] and prevents its cleavage into C5a and C5b.
Practice Q - Rituximab WHO Essential
The only B-cell depleting immunotherapy on the WHO Model Lists of Essential Medicines is rituximab[β¦].
Practice Q - Paraneoplastic Mechanism 1 - Intracellular
- Mechanism 1: Intracellular Ag (irreversible cell death). Tumor makes proteins called onconeuronal Ag[β¦] that resemble neuron Ag.
- APCs grab these and present them on MHC molecules to naive T cells[β¦] in lymph nodes.
- This activates CD8+ cytotoxic T cells[β¦] β cross the BBB β kill neurons displaying these same Ag on their own MHC molecules.
- Process is irreversible[β¦] because the cell dies.
- Ab produced by plasma cells are benign bystander markers[β¦] in serum/CSF β useful for diagnosis, not pathogenic.
- Treatments target T cells[β¦] (tumor removal, MMF/Tacro, Cyclophosphamide)
Practice Q - Paraneoplastic Mechanism 2 - Surface Receptor
- Mechanism 2: Surface receptor Ab (reversible). Tumor (or idiopathic source) makes proteins resembling receptors on CNS neurons[β¦].
- APCs present them on MHC to CD4+ T cells[β¦] β activate B cells β plasma cells β IgG Ab[β¦].
- Ab flood CNS and latch onto surface receptors causing damage by: Blocking, overactivating, or internalizing[β¦] the receptor (anti-NMDAr); Activating complement β MAC formation[β¦] (anti-AQP4); Flagging Fc tail for NK cell killing (ADCC)[β¦]; Breaking apart protein complexes (LGI1-ADAM22/23 bridge).
- Process is reversible[β¦] β cell survives
Practice Q - ICI Mechanism - CTLA-4
- CTLA-4 inhibitor mechanism:. T cells upregulate surface CTLA-4[β¦] which outcompetes CD28[β¦] on T cells β preventing B7 (CD80/86) from binding and co-stimulating T cells.
- Anti-CTLA-4 ICI therapy[β¦] removes these surface "brakes" β allows more B7/CD28 binding β activates B/plasma cells β produces Ab.
Practice Q - ICI Mechanism - PD-1 / PD-L1
- PD-1 / PD-L1 inhibitor mechanism:. Tumor cells evade immunity by expressing PD-L1[β¦] which binds PD-1[β¦] on T cells to shut them down.
- Anti-PD1 or anti-PD-L1[β¦] inhibitors block this β prevents tumor escape mechanism.
- Consequence: revved-up immunity can unintentionally generate autoantibodies[β¦] against self Ag or overactivate complement.
Practice Q - LGI1 Imaging Panel
LGI1 encephalitis imaging: these pictures show faciobrachial dystonic seizures[β¦].
Practice Q - AIE Imaging Panel
A (SCLC + ANNA-1 Limbic Enceph): MRIb coronal T2W: hyperintensities in mesial temporal lobes[β¦].
B (GFAP Astrocytopathy): MRIb axial T1W postcontrast: linear radial perivascular[β¦] enhancement.
C (KLHL11 Brainstem Enceph): MRIb axial T2 FLAIR: signal change in the pons[β¦].
D (PCA-1 + GAD65 Cerebellar Atrophy): MRIb sagittal T2W: cerebellar atrophy[β¦].
E (chorea-dystonia from ICI for RCC): MRIb axial T2 FLAIR: hyperintensities in the basal ganglia[β¦].
F (anti-CRMP5): MRI spinal cord axial T1W postcontrast: enhancement of the lateral tracts[β¦].
Practice Q - Paraneoplastic Brain Imaging Panel
- A (CRMP5/CV2 + SCLC): MRI spinal cord T1W postcontrast: lateral columns[β¦] enhancement (myelitis).
- B (limbic enceph from ICI for melanoma): MRIb axial T2 FLAIR: bilateral mesial temporal[β¦] hyperintensities.
- C (ANNA1/AntiHu + ANNA2/AntiRi + lung CA + limbic enceph): R mesial temporal[β¦] hyperintensity.
- D (Ma2 + narcolepsy + testicular CA): midline hypothalamic and mesencephalic[β¦] hyperintensities.
- E (ovarian CA + ataxia + PCA1/antiYo): MRIb sagittal T1W: cerebellar atrophy[β¦]. F (anti-GABAr): MRIb coronal T2 FLAIR: multiple hyperintensities.
Practice Q - ON Imaging Panel
- A (NMOSD): ON affecting the posterior[β¦] optic pathway with chiasm T2 hyperintensity
- B (MOGAD): ON affecting bilateral[β¦] optic nerves extending >50[β¦]% of nerve length + prominent optic nerve sheath[β¦] enhancement extending to perineural tissue
- C (MS): typically unilateral[β¦] optic nerve with short[β¦] lesions and homogeneous[β¦] enhancement
Practice Q - NMOSD/MOGAD/MS Myelitis Comparison 1
- NMOSD Myelitis: single longitudinally extensive[β¦] T2 lesion in cervical/upper thoracic cord, affects entire[β¦] cross-section, postcontrast peripheral ring[β¦] pattern on sagittal.
- MOGAD Myelitis: fainter lesions affecting central gray matter[β¦] forming the "H sign[β¦]"; longitudinally extensive but shorter lesions coexist; frequent conus medullaris[β¦] involvement.
- MS Myelitis: single or multiple short[β¦] lesions in the peripheral[β¦] cord; nodular or ring[β¦]-like enhancement.
Practice Q - MS Brain Lesion Pattern
- MS brain T2 lesions: typically smaller and ovoid[β¦]-shaped on brainstem surface, cerebellar hemispheres, or around ventricles oriented perpendicular[β¦].
- Can see juxtacortical lesions with S or C shape[β¦].
- Enhancement: nodular, ring-like, or open-ring[β¦] shaped.
Practice Q - NMOSD/MOGAD/MS Disease Courses
Disease courses: NMOSD: flares with worsening baseline over time[β¦].
MOGAD: flares with return to baseline + minimal worsening[β¦].
MS: RRMS can progress to secondary progressive (SPMS)[β¦]. PPMS: flares with constant worsening baseline.
Practice Q - NMOSD Imaging Panel Brain
NMOSD brain imaging: lesions often around the 4th ventricle in dorsal medulla (area postrema)[β¦].
Extensive white matter lesions can involve the splenium of corpus callosum[β¦] β the "arch bridge sign[β¦]".
Can also see focal hyperintensity along lateral ventricle surface with linear[β¦] enhancement.
Practice Q - SPS Pathophysiology Targets
SPS pathophysiology β antibody targets:. Presynaptic: GAD enzyme[β¦] synthesizes GABA; Amphiphysin[β¦] endocytoses plasma membranes following GABA release.
Postsynaptic: Gephyrin[β¦] clusters GABAa receptors and Glycine Ξ±1 receptors (passage of Clβ»); DPPX[β¦] regulates KβΊ channels.
Practice Q - NMDAr Encephalitis Imaging Panel
- A: swelling/hyperintensity of the L hippocampus[β¦]
- B: hyperintensity in the claustra (adjacent to external capsules)[β¦] and juxtacortical white matter of temporal lobe[β¦]
- C/D: signal change of the R superior frontal gyrus[β¦]
- E: hyperintense lesion in the splenium of corpus callosum[β¦]
- F: swelling of the R temporal lobe and insular region[β¦]
- G: EEG with delta brush[β¦] pattern
Practice Q - Rheum/Vasculitis Imaging Panel
- A (RA meningitis): leptomeningeal and pachymeningeal[β¦] enhancement.
- B (GPA pachymeningitis): bifrontal dural[β¦] enhancement.
- C (IgG4-RD): bilateral mass lesions adjacent to temporal lobes[β¦] + sinusitis.
- D (Behcet): L midbrain[β¦] hyperintensity.
- E/F (APLS, SLE): diffusion restriction in multifocal vascular territories[β¦].
- G/H (amyloid-Ξ² angiitis + ARIA): leptomeningeal enhancement + ARIA-H[β¦].
Practice Q - Thalamic Imaging Panel
- A: MRIb axial FLAIR: hyperintensities in bilateral thalami[β¦] and posterior limbs of internal capsule[β¦]
- B: MRIb SWI: hypointense signal in the thalami[β¦] (hemorrhage vs iron deposition)
Practice Q - Neurosarcoid Imaging Panel
A (basilar meningitis): leptomeningeal[β¦] enhancement along cerebellar folia of vermis[β¦] + surrounding brainstem[β¦].
B: discrete enhancing dural masses[β¦].
C (BL hearing loss): bilateral CN8[β¦] enhancement.
D: L fusiform optic nerve[β¦] enhancement.
E: MRI C-spine: longitudinally extensive[β¦] spinal hyperintensity.
F: dorsal subpial[β¦] enhancement + central canal[β¦] enhancement.
G: "trident sign[β¦]" β named after a 3-pronged appearance.
H: enhancing nodules along the cauda equina[β¦]
Practice Q - MOGAD ON Image
MRIb axial T1W postcontrast: enhancement extending >1/2[β¦] length of the optic nerve[β¦] primarily in the anterior[β¦] portion, sparing the optic chiasm[β¦] β c/f MOGAD[β¦]-associated ON.
