Vascular Headache Epilepsy Immunology Movement Neuromuscular Dementia Other Topics Neurosurgery

Last Minute Review

Neuromuscular — Last Minute Review

A last-minute review of high-yield facts — dense tables and one-liners for RITE/Board prep. Not a substitute for the full notes.

Polyneuropathy Classification

Axonal vs Demyelinating NCS

Feature	Axonal	Demyelinating
Amplitudes (CMAP/SNAP)	↓↓ (primary finding)	Normal or ↓ (secondary to CB)
Conduction velocity	Normal or mildly ↓ (>70% LLN)	Markedly ↓ (<70% LLN)
Distal latencies	Normal	Prolonged (>130% ULN)
F-waves	Normal	Prolonged or absent
Conduction block	Absent	Present (acquired > hereditary)
Temporal dispersion	Absent	Present (acquired only)

GBS Subtypes

Subtype	Antibody	NCS Pattern	Key Feature	Prognosis
AIDP	None specific	Demyelinating	Most common in Western countries; sural sparing pattern	Good (80% walk at 6 mo)
AMAN	GM1, GD1a	Axonal (motor only)	Post-Campylobacter; common in Asia/Mexico	Variable; can recover fast
AMSAN	GM1, GD1a	Axonal (motor + sensory)	Severe axonal; worst prognosis	Poor
MFS	GQ1b	Often normal	Ophthalmoplegia + ataxia + areflexia	Excellent
Pharyngeal-cervical-brachial	GT1a, GQ1b	Axonal (upper limb)	Bulbar + neck + arm weakness; legs spared	Good

GBS vs CIDP

Feature	GBS	CIDP
Onset	Acute (<4 weeks to nadir)	Chronic (>8 weeks progressive)
Course	Monophasic	Relapsing or progressive
Weakness pattern	Ascending, distal > proximal	Proximal + distal, symmetric
CSF	Albuminocytologic dissociation	Elevated protein (may have mild pleocytosis)
NCS	Demyelinating (sural sparing)	Demyelinating (no sural sparing)
Steroids	NOT effective	Effective
IVIg / PLEX	Yes	Yes

💎 Board Pearl

Sural sparing pattern (absent sensory SNAPs in arms but preserved sural) is the electrodiagnostic hallmark of AIDP
GQ1b antibody → think MFS (ophthalmoplegia + ataxia + areflexia) or Bickerstaff brainstem encephalitis
If GBS relapses ≥3 times or progresses >8 weeks → reclassify as CIDP

Key Neuropathy Syndromes

CMT Comparison

Type	Gene	Inheritance	NCS	Unique Feature
CMT1A	PMP22 duplication	AD	Uniform slowing (<38 m/s)	Most common CMT; onion bulbs on biopsy
CMT1B	MPZ (P0)	AD	Very slow (<20 m/s in severe)	More severe than 1A; early onset
CMT2A	MFN2	AD	Axonal (normal CV, low amplitudes)	Optic atrophy possible; most common axonal CMT
CMTX1	GJB1 (Connexin 32)	X-linked	Intermediate CV (25–40 m/s)	Males > females; may have transient CNS symptoms
HNPP	PMP22 deletion	AD	Prolonged distal latencies; CB at entrapment sites	Recurrent pressure palsies; “tomaculous” (sausage-shaped) myelin

Clinical Pearl

Hereditary vs acquired demyelinating neuropathy: Uniform slowing + no conduction block = hereditary (CMT1). Non-uniform slowing + conduction block + temporal dispersion = acquired (CIDP).

Diabetic Neuropathy Types

Distal symmetric polyneuropathy — most common; length-dependent, small fiber → large fiber
Diabetic amyotrophy (lumbosacral radiculoplexopathy) — acute proximal thigh pain + weakness; weight loss; often self-limited
Autonomic neuropathy — orthostatic hypotension, gastroparesis, erectile dysfunction
Cranial mononeuropathy — CN III palsy with pupil sparing (vs. aneurysm = pupil involved)
Mononeuropathy/entrapment — median (CTS), ulnar
Truncal radiculopathy — band-like thoracoabdominal pain; often misdiagnosed

Other Key Neuropathies

Syndrome	Key Facts
Small fiber neuropathy	Burning pain, autonomic symptoms, NCS normal, diagnose with skin punch biopsy (↓ IENFD); causes: DM, Fabry, amyloid, sarcoid, Sjögren
Anti-MAG neuropathy	IgM kappa paraprotein; distal acquired demyelinating; wide-spaced myelin; slowly progressive; poor response to IVIg; rituximab preferred
POEMS syndrome	Polyneuropathy, Organomegaly, Endocrinopathy, M-protein (IgA or IgG lambda), Skin changes; sclerotic bone lesions; ↑ VEGF; demyelinating NCS
Vasculitic neuropathy	Mononeuritis multiplex; sural nerve biopsy → necrotizing vasculitis; treat with steroids + cyclophosphamide
MMN	Pure motor; asymmetric distal UE; anti-GM1 IgM; conduction block on NCS; IVIg works; steroids worsen
Amyloid neuropathy	Painful small fiber + autonomic; CTS common; TTR (hATTR) or AL; Congo red → apple-green birefringence

💎 Board Pearl

POEMS is always IgA or IgG lambda (never kappa); anti-MAG is always IgM kappa
MMN = IVIg responsive; steroids and PLEX can worsen MMN
Absent SNAPs in the hands but preserved sural SNAP → think GBS or CIDP, not axonal neuropathy

Mononeuropathies & Entrapment

Upper Extremity Mononeuropathies

Nerve	Syndrome	Site	Motor Deficit	Sensory Deficit
Median	Carpal tunnel	Wrist	APB weakness (thenar atrophy late)	Digits 1–3 + radial half of 4
	AIN (anterior interosseous)	Proximal forearm	FPL, FDP (index), PQ — can’t make OK sign	None (pure motor)
	Pronator syndrome	Proximal forearm	Similar to CTS but includes forearm pronation	Palmar cutaneous branch involved (vs. CTS)
Ulnar	Cubital tunnel	Elbow	FDI, ADM, lumbricals 4–5; claw hand (more severe distally)	Digit 5 + ulnar half of 4
Ulnar	Guyon canal	Wrist	Hypothenar + interossei (variable by zone)	Variable; may spare dorsal hand
Radial	Saturday night palsy	Spiral groove	Wrist drop + finger drop; spares triceps	Dorsal hand (first web space)
Radial	PIN (posterior interosseous)	Proximal forearm	Finger drop (no wrist drop — ECRL spared)	None (pure motor)

Lower Extremity Mononeuropathies

Nerve	Site	Motor Deficit	Sensory Deficit
Common peroneal	Fibular head	Footdrop (dorsiflexion + eversion)	Lateral leg + dorsal foot
Femoral	Pelvis/inguinal	Quad weakness; ↓ knee jerk	Anterior thigh + medial leg (saphenous)
Lateral femoral cutaneous	Inguinal ligament	None (pure sensory)	Lateral thigh — meralgia paresthetica
Sciatic (peroneal division)	Buttock/posterior thigh	Footdrop + hamstring weakness	Below knee (peroneal + tibial)
Tibial	Tarsal tunnel	Toe flexion weakness; intrinsic foot muscles	Sole of foot

Footdrop DDx

Feature	Common Peroneal	L5 Radiculopathy	Sciatic (peroneal division)
Dorsiflexion	Weak	Weak	Weak
Eversion	Weak	Weak	Weak
Inversion	Normal (tibial nerve)	Weak (tibialis posterior = L5)	Normal or weak
Hip abduction	Normal	Weak (gluteus medius = L5)	Normal
Knee flexion	Normal	Normal	Weak (hamstrings)
Sensory	Dorsal foot + lateral leg	Dorsal foot + lateral leg + medial foot	Entire below-knee
EMG clue	NCS abnormal at fibular head	Paraspinal fibs; tibialis posterior involved	Short head biceps femoris involved

💎 Board Pearl

Footdrop with weak inversion (tibialis posterior) = L5, not peroneal nerve
AIN = pure motor; can’t pinch (no OK sign); no sensory loss
Ulnar claw hand paradox: higher lesion = less clawing (FDP paralyzed so MCP not hyperextended)

Radiculopathy & Plexopathy Quick Reference

Cervical Radiculopathy

Root	Disc	Pain/Sensory	Motor	Reflex
C5	C4–C5	Lateral shoulder/arm	Deltoid, biceps	↓ Biceps
C6	C5–C6	Lateral forearm, thumb, index	Biceps, wrist extensors (brachioradialis)	↓ Brachioradialis
C7	C6–C7	Middle finger	Triceps, wrist flexors, finger extensors	↓ Triceps
C8	C7–T1	Ring + little finger, medial forearm	Finger flexors, hand intrinsics	↓ Finger flexor
T1	T1–T2	Medial arm/forearm	Hand intrinsics (interossei)	None reliable

Lumbosacral Radiculopathy

Root	Disc	Pain/Sensory	Motor	Reflex
L2–L3	L2–3/L3–4	Anterior thigh	Hip flexion (iliopsoas), quad	↓ (none reliable / patellar)
L4	L3–L4	Medial leg (saphenous)	Knee extension (quad), tibialis anterior	↓ Patellar (knee jerk)
L5	L4–L5	Lateral leg, dorsal foot, great toe	Ankle dorsiflexion, hip abduction, toe extension, inversion	↓ Medial hamstring (inconsistent)
S1	L5–S1	Lateral foot, sole, calf	Ankle plantarflexion, eversion, hip extension	↓ Achilles (ankle jerk)

Brachial Plexopathy

Erb-Duchenne (upper trunk, C5–C6) — “waiter’s tip”; shoulder abduction + elbow flexion lost; traction/birth injury
Klumpke (lower trunk, C8–T1) — hand intrinsic weakness + claw hand; may have Horner syndrome (T1 sympathetic); Pancoast tumor
Parsonage-Turner (neuralgic amyotrophy) — acute shoulder pain → patchy UE weakness; often post-viral; long thoracic nerve (winged scapula) commonly affected

Cauda Equina vs Conus Medullaris

Feature	Conus Medullaris (S3–S5)	Cauda Equina (L2–S5 roots)
Onset	Sudden, bilateral, symmetric	Gradual, unilateral → bilateral
Pain	Less prominent	Severe, radicular
Weakness	Symmetric; mild; distal LE	Asymmetric; can be severe; multisegmental
Sensory	Perianal saddle anesthesia (symmetric)	Asymmetric; radicular distribution
Bladder/bowel	Early; prominent	Late (unless severe)
Reflexes	Bulbocavernosus absent; may have UMN signs	Absent (LMN); areflexia

Motor Neuron Disease

ALS Key Facts

Combined UMN + LMN signs in multiple regions; no sensory loss
Split hand sign: APB/FDI wasting > hypothenar (ADM) — unique to ALS
Split leg sign: tibialis anterior (dorsiflexion) weaker than tibialis posterior (inversion)
Awaji criteria: fasciculation potentials = fibrillations for diagnosis
El Escorial categories: Definite (3 regions), Probable (2 regions), Possible (1 region with UMN+LMN), Suspected (LMN only in ≥2 regions)
Riluzole: ↑ survival ~2–3 months; edaravone/AMX0035: modest benefit
Tofersen: antisense oligonucleotide for SOD1 ALS

ALS Genetics

Gene	Frequency	Key Feature
C9orf72	Most common familial + sporadic	Hexanucleotide repeat expansion (GGGGCC); ALS + FTD spectrum; TDP-43 + p62 inclusions
SOD1	20% familial	First ALS gene discovered; tofersen available; misfolded SOD1 protein; typically no FTD
TARDBP	~4% familial	Encodes TDP-43; cytoplasmic TDP-43 inclusions; ALS ± FTD
FUS	~4% familial	Young onset; aggressive; FUS inclusions (NOT TDP-43)

ALS Mimics

Cervical myelopathy — UMN in legs + LMN in arms; MRI shows cord compression
MMN — pure LMN, asymmetric, anti-GM1, conduction block; IVIg responsive
Kennedy disease (SBMA) — X-linked; CAG repeat in androgen receptor; gynecomastia, perioral fasciculations, elevated CK, slow progression
Inclusion body myositis — finger flexor + quad weakness; can mimic ALS LMN pattern
Benign fasciculation syndrome — fasciculations without weakness, atrophy, or EMG denervation
Hirayama disease — young males; asymmetric hand wasting; cervical flexion myelopathy; non-progressive

SMA Types

Type	Onset	Max Motor Milestone	SMN2 Copies	Natural History
SMA 0	Prenatal	None	1	Death in weeks
SMA 1 (Werdnig-Hoffmann)	<6 months	Never sit	2	Death <2 years without treatment
SMA 2	6–18 months	Sit, never walk	3	Survive to adulthood; wheelchair-bound
SMA 3 (Kugelberg-Welander)	>18 months	Walk independently	3–4	Normal lifespan; progressive weakness
SMA 4	Adult	Normal	4+	Mild; normal lifespan

3 FDA-approved treatments: nusinersen (intrathecal ASO), onasemnogene (gene therapy, <2 yrs), risdiplam (oral SMN2 splicing modifier)

💎 Board Pearl

ALS spares: eye movements (CN III/IV/VI), sphincters (Onuf nucleus), and sensory nerves
Kennedy disease: X-linked, CAG repeat in androgen receptor → gynecomastia + perioral fasciculations + sensory neuropathy; slowly progressive — NOT ALS
SMA = homozygous SMN1 deletion; SMN2 copy number determines severity

Myasthenia Gravis & NMJ Disorders

MG Antibody Table

Antibody	Frequency	Clinical Features	Thymus
AChR	85% generalized; 50% ocular	Classic MG; any age; generalized or ocular	Thymoma (10–15%); thymic hyperplasia (60–70%)
MuSK	5–8%	Young women; bulbar-predominant; facial/tongue atrophy; poor response to AChE inhibitors	No thymoma; thymectomy NOT beneficial
LRP4	1–3%	Milder phenotype; limb-predominant	Rare thymoma
Seronegative	5–10%	Treat as AChR-MG; may have low-affinity AChR or clustered AChR antibodies	Variable

AChR vs MuSK MG

Feature	AChR MG	MuSK MG
Gender	F > M (young); M > F (late-onset)	F >> M
Distribution	Ocular → generalized	Bulbar, facial, neck > limbs
Muscle atrophy	Uncommon	Common (tongue, facial)
Pyridostigmine	Helpful	Often poorly tolerated / ineffective
Thymectomy	Beneficial	NOT beneficial
IVIg/PLEX	Effective	PLEX preferred; IVIg less effective
Best steroid-sparing agent	Azathioprine, mycophenolate	Rituximab (excellent response)
RNS	Proximal muscles	May need facial/trapezius muscles

MG vs LEMS vs Botulism

Feature	MG	LEMS	Botulism
Target	Postsynaptic (AChR)	Presynaptic (VGCC)	Presynaptic (ACh release)
Weakness pattern	Ocular → bulbar → limbs; fatigable	Proximal legs first; improves with activity	Descending: cranial → limbs → respiratory
Reflexes	Normal	Absent (facilitation after exercise)	Absent or diminished
Autonomic	No	Yes (dry mouth, constipation, erectile dysfunction)	Yes (dilated pupils, constipation, urinary retention)
Pupils	Normal	Normal	Dilated, fixed
RNS (2–3 Hz)	Decrement >10%	Decrement (low baseline CMAP)	Decrement (low baseline CMAP)
High-rate RNS (50 Hz) / post-exercise	No increment	Increment >100%	Increment (mild, 30–60%)
Association	Thymoma	SCLC (50–60%)	C. botulinum toxin

Myasthenic Crisis

20/20/20 rule for intubation: FVC <20 mL/kg, NIF <−20 cmH₂O, >20% decline from baseline
Treat with IVIg or PLEX; optimize immunosuppression
Distinguish myasthenic crisis (undertreated) from cholinergic crisis (overtreated) — both cause weakness; cholinergic adds SLUDGE (salivation, lacrimation, urination, diarrhea, GI cramps, emesis)

Medications to Avoid in MG

Category	Drugs
Antibiotics	Aminoglycosides, fluoroquinolones, macrolides, telithromycin
Cardiac	Beta-blockers, calcium channel blockers, procainamide, quinidine
Neuromuscular blockers	Succinylcholine (prolonged), non-depolarizing agents (enhanced sensitivity)
Other	D-penicillamine (can induce MG), magnesium, botulinum toxin, immune checkpoint inhibitors

💎 Board Pearl

LEMS: ↑ CMAP >100% after brief exercise (post-exercise facilitation) or high-rate RNS
Immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) can cause de novo MG or MG flares
Ice pack test: improvement of ptosis with ice = positive (cooling reduces AChE activity) — quick bedside test for MG

Inflammatory Myopathies

DM vs PM vs IBM vs IMNM

Feature	Dermatomyositis	Polymyositis	IBM	IMNM
Age	Any (bimodal); children + adults	Adults >18	>50 years	Any adult
Weakness	Proximal, symmetric	Proximal, symmetric	Quad + finger flexors (asymmetric)	Proximal, severe, symmetric
CK	↑↑ (10–50×)	↑↑ (10–50×)	Normal to mildly ↑ (1–10×)	↑↑↑ (often >50×)
Skin	Gottron papules, heliotrope rash, V-sign, shawl sign	None	None	None
Biopsy	Perifascicular atrophy; perivascular CD4+/B cells; complement C5b-9 on capillaries	Endomysial CD8+ T cells invading non-necrotic fibers	Rimmed vacuoles; endomysial CD8+ T cells; congophilic inclusions (amyloid)	Necrotic/regenerating fibers; macrophages; minimal lymphocytes
Cancer risk	HIGH (especially TIF1-γ, NXP-2)	Moderate	No	Anti-HMGCR: low; anti-SRP: low
Treatment	Steroids + steroid-sparing; IVIg	Steroids + steroid-sparing	Resistant to immunotherapy; IVIg may slow progression	Steroids + IVIg + steroid-sparing

DM Antibody Table

Antibody	Association	Key Feature
Mi-2	Classic DM	Good prognosis; classic skin findings; responds well to treatment
MDA5 (CADM-140)	Clinically amyopathic DM	Rapidly progressive ILD (can be fatal); minimal weakness; skin ulcers, palmar papules
TIF1-γ (p155/140)	Cancer-associated DM	Highest cancer risk (~60%); screen extensively for malignancy; adults
NXP-2 (MJ)	Cancer-associated DM; juvenile DM	Calcinosis (children); cancer (adults); edema
Jo-1 (+ other antisynthetases)	Antisynthetase syndrome	ILD + arthritis + mechanic’s hands + Raynaud + fever + myositis
SAE	DM with dysphagia	Skin-predominant onset → severe dysphagia

IBM & Antisynthetase One-Liners

IBM: most common inflammatory myopathy >50 years; finger flexors + quadriceps (asymmetric); rimmed vacuoles + amyloid deposits on biopsy; resistant to immunotherapy; often misdiagnosed as PM that “doesn’t respond to steroids”
Antisynthetase syndrome: Jo-1 (most common); mechanic’s hands + ILD + non-erosive arthritis + Raynaud + fever + myositis; ILD drives prognosis
IMNM antibodies: anti-SRP (severe, refractory) and anti-HMGCR (statin-exposed but can occur without statins; very high CK)

💎 Board Pearl

Perifascicular atrophy on biopsy = DM (even without skin findings)
Rimmed vacuoles on biopsy = IBM
TIF1-γ or NXP-2 antibody in an adult = mandatory cancer screening
PM is a diagnosis of exclusion — always rule out IBM, IMNM, and muscular dystrophy first

Muscular Dystrophies

DMD vs BMD

Feature	DMD	BMD
Gene/Protein	Dystrophin absent (out-of-frame deletion)	Dystrophin reduced/abnormal (in-frame deletion)
Onset	2–5 years	5–15 years
Wheelchair	By age 12	After age 16 (variable)
Cardiac	Dilated cardiomyopathy (by teens)	Cardiomyopathy (may precede skeletal weakness)
Cognition	↓ IQ (~1 SD below mean); 30% cognitive impairment	Usually normal
Lifespan	20s–30s without intervention	40s–50s+
CK	Massively elevated (10,000–50,000+)	Elevated (5,000–20,000)

DM1 vs DM2

Feature	DM1 (Steinert)	DM2 (PROMM)
Gene	DMPK (CTG repeat, chr 19)	CNBP/ZNF9 (CCTG repeat, chr 3)
Inheritance	AD; anticipation	AD; minimal anticipation
Weakness	Distal (grip, ankle dorsiflexion); facial	Proximal (hip flexors, thighs)
Myotonia	Prominent (grip, percussion)	Milder, often subclinical
Congenital form	Yes (severe, maternal inheritance)	No
Cardiac	Conduction defects (heart block); sudden death	Arrhythmias (less severe)
Other	Cataracts, frontal balding, daytime somnolence, insulin resistance, testicular atrophy	Cataracts, myalgia (pain more prominent than weakness)

High-Yield Dystrophy Table

Dystrophy	Gene/Protein	Inheritance	Unique Feature
DMD	Dystrophin (absent)	XR	Gowers sign; calf pseudohypertrophy; wheelchair by 12
BMD	Dystrophin (reduced)	XR	Milder DMD; cardiomyopathy may precede weakness
DM1	DMPK (CTG)	AD	Distal weakness + myotonia + cardiac conduction + cataracts + anticipation
DM2	CNBP (CCTG)	AD	Proximal weakness + pain-predominant + no congenital form
FSHD	DUX4 (D4Z4 contraction, chr 4)	AD	Face → shoulder → hip; asymmetric; scapular winging; can’t whistle/drink through straw
LGMD	Multiple (sarcoglycans, calpain, dysferlin, etc.)	AR (most) or AD	Proximal limb-girdle pattern; “dystrophin-minus” on biopsy panel guides subtyping
EDMD	Emerin (XR) or Lamin A/C (AD)	XR or AD	Early contractures (elbows, Achilles, neck extensors) + cardiac conduction defects; humeroperoneal weakness
OPMD	PABPN1 (GCG repeat)	AD	Onset >40 years; ptosis + dysphagia; French-Canadian heritage; NO diplopia (vs. MG)

💎 Board Pearl

Frame-shift rule: out-of-frame dystrophin deletion → DMD; in-frame → BMD
DM1 “Christmas tree cataracts” (multicolored iridescent posterior subcapsular) are pathognomonic
FSHD: retinal telangiectasias (Coats disease) + high-frequency hearing loss are associated features
EDMD: always screen for cardiac conduction defects — pacemaker/ICD may be needed before significant weakness develops

Channelopathies & Metabolic Myopathies

Periodic Paralysis

Feature	HypoKPP	HyperKPP	Andersen-Tawil
Gene	CACNA1S (70%), SCN4A (10%)	SCN4A	KCNJ2 (Kir2.1)
K+ during attack	Low (<3.5)	High (>5.0) or normal	Low, high, or normal
Triggers	Carbs, rest after exercise, insulin, stress	Fasting, rest after exercise, cold, K+ load	Variable
Attack duration	Hours to days	Minutes to hours (shorter)	Hours to days
Myotonia	No	Yes (lid lag, grip myotonia)	No
Unique features	Most common PP; severe attacks; vacuolar myopathy long-term	Earlier onset; milder attacks; may have paradoxical myotonia	Cardiac arrhythmias (prolonged QT, bidirectional VT) + dysmorphic features (low-set ears, hypertelorism, clinodactyly)
Prevention	Acetazolamide; avoid carbs	Acetazolamide or dichlorphenamide; avoid fasting/cold	Acetazolamide; cardiac monitoring

Metabolic Myopathies

Disease	Enzyme/Defect	Key Feature	Diagnostic Clue
McArdle (GSD V)	Myophosphorylase	Exercise intolerance + contractures + “second wind” phenomenon; rhabdomyolysis risk	No lactate rise on forearm exercise test; ↑ CK; ↑ ammonia
CPT II deficiency	CPT II (fatty acid transport)	Recurrent rhabdomyolysis triggered by prolonged exercise, fasting, illness, cold	Most common cause of recurrent rhabdomyolysis in young adults; acylcarnitine profile abnormal
Pompe (GSD II)	Acid maltase (GAA)	Infantile: cardiomegaly + hypotonia + macroglossia; Late-onset: proximal + respiratory weakness (diaphragm early)	Dried blood spot GAA enzyme; ERT available (alglucosidase alfa)
Acid maltase (late-onset)	GAA (partial deficiency)	Adult limb-girdle weakness + early respiratory failure; mimics LGMD or PM	Diaphragm weakness out of proportion to limb weakness; ↑ CK (mild); vacuolar myopathy

Mitochondrial Myopathy Syndromes

Syndrome	Mutation	Key Features	Board Clue
MELAS	m.3243A>G (tRNA^Leu)	Stroke-like episodes (not vascular territory); seizures; lactic acidosis; short stature; DM	Young patient + “stroke” not following vascular territory + ↑ lactate
MERRF	m.8344A>G (tRNA^Lys)	Myoclonus epilepsy; ataxia; ragged red fibers; lipomas	Myoclonus + ataxia + ragged red fibers
CPEO/KSS	Large mtDNA deletions	CPEO: progressive ptosis + ophthalmoplegia; KSS adds: cardiac conduction block + retinitis pigmentosa + onset <20	Bilateral ptosis + ophthalmoplegia WITHOUT diplopia; if onset <20 with heart block → KSS
NARP	m.8993T>G (ATP6)	Neuropathy, ataxia, retinitis pigmentosa	Higher mutation load → Leigh syndrome (infantile)

Malignant hyperthermia: RYR1 mutation (AD); triggered by inhaled anesthetics (halothane, sevoflurane) + succinylcholine; treat with dantrolene; associated with central core disease

💎 Board Pearl

McArdle: “second wind” = exercise tolerance improves after 10 minutes (switch to fatty acid metabolism)
CPT II: rhabdomyolysis triggered by prolonged exercise (not brief); contrast with McArdle (triggered by brief intense exercise)
KSS = CPEO + cardiac block + retinitis pigmentosa + onset <20 — mandatory cardiac monitoring
Ragged red fibers (Gomori trichrome) = mitochondrial myopathy hallmark

Neuromuscular Emergencies

GBS Intubation Criteria

20/30/40 rule: FVC <20 mL/kg, NIF <−30 cmH₂O, >30% decline from baseline — prepare for intubation
FVC <15 mL/kg or NIF <−20 cmH₂O → intubate
Other red flags: rapid progression, bilateral facial weakness, autonomic instability, inability to count to 20 in one breath
Do NOT rely on SpO₂ alone — desaturation is a late finding in neuromuscular respiratory failure

CIP vs CIM

Feature	CIP (Critical Illness Polyneuropathy)	CIM (Critical Illness Myopathy)
Pathology	Axonal sensorimotor polyneuropathy	Thick filament (myosin) loss myopathy
NCS	↓ CMAP + ↓ SNAP amplitudes	↓ CMAP amplitudes; SNAPs normal
EMG	Fibrillations; neurogenic MUAPs	Fibrillations; myopathic MUAPs (or inexcitable muscle on direct stimulation)
CK	Normal or mildly elevated	Elevated (may be very high)
Sensory	Impaired	Normal
Risk factors	Sepsis, SIRS, multiorgan failure	Steroids + neuromuscular blocking agents; sepsis
Prognosis	Slower recovery; may be incomplete	Generally better prognosis; faster recovery

Acute Flaccid Paralysis DDx

Diagnosis	Pattern	Reflexes	Sensory	CSF	Key Distinguisher
GBS	Ascending, symmetric	Absent	± (paresthesias)	High protein, normal cells	Post-infectious; NCS demyelinating
Transverse myelitis	Level; bilateral LE > UE	Initially absent → UMN later	Sensory level	Pleocytosis	Bladder involvement early; MRI cord lesion
Poliomyelitis/AFM	Asymmetric; LMN only	Absent	Normal	Pleocytosis	Anterior horn cell destruction; MRI anterior horn signal
Botulism	Descending; cranial → limbs	Absent	Normal	Normal	Dilated pupils; autonomic; contaminated food/wound
Tick paralysis	Ascending; mimics GBS	Absent	Normal	Normal	Find and remove tick → rapid recovery
Hypokalemia	Proximal > distal	Decreased	Normal	Normal	K+ low; ECG changes; rapid resolution with K+ replacement
West Nile virus	Asymmetric LMN (like polio)	Absent	Normal	Pleocytosis	Older adults; encephalitis + AFP; IgM in CSF

Toxin Comparison

Feature	Botulism	Organophosphate	Tick Paralysis
Mechanism	Blocks ACh release (presynaptic)	AChE inhibitor (excess ACh)	Blocks ACh release (presynaptic)
Pattern	Descending paralysis	Cholinergic crisis (SLUDGE + weakness)	Ascending paralysis (mimics GBS)
Pupils	Dilated, fixed	Miotic (pinpoint)	Normal
NCS/EMG	Low CMAPs; incremental response	Repetitive CMAPs after single stimulus	Low CMAPs; may have decremental response
Treatment	Antitoxin + supportive	Atropine + pralidoxime (2-PAM)	Remove tick → rapid recovery

💎 Board Pearl

CIM: SNAPs are normal (pure myopathy); CIP: SNAPs are reduced (neuropathy with sensory involvement)
Tick paralysis mimics GBS perfectly — always do a thorough scalp/skin exam in any ascending paralysis
Organophosphate: pinpoint pupils + SLUDGE + fasciculations (excess ACh at all receptors)

EMG/NCS Patterns

Neurogenic vs Myopathic MUAPs

Parameter	Neurogenic	Myopathic
Duration	↑ (long)	↓ (short)
Amplitude	↑ (large)	↓ (small)
Phases	Polyphasic (reinnervation)	Polyphasic (fiber variability)
Recruitment	Reduced (fewer MUAPs firing fast)	Early (many small MUAPs at low force)
Fibrillations/PSWs	Present (active denervation)	Present in inflammatory/necrotic myopathies
Fasciculations	May be present (ALS, radiculopathy)	Absent

RNS Patterns

Condition	Baseline CMAP	2–3 Hz RNS	High-rate RNS / Post-exercise
MG	Normal	Decrement >10%	No significant increment; post-exercise repair (transient normalization then fatigue)
LEMS	Low	Decrement	Increment >100% (pathognomonic)
Botulism	Low	Decrement	Mild increment (30–60%)

EMG Pattern Recognition by Disease

Disease	NCS	Needle EMG	Special Finding
ALS	Normal SNAPs; low CMAPs	Widespread fibrillations + fasciculations + neurogenic MUAPs	Split hand (APB > ADM); ongoing denervation + reinnervation
GBS (AIDP)	Prolonged DL, slow CV, CB, sural sparing	Fibrillations if axonal loss (late)	Sural sparing pattern
CIDP	Demyelinating (slow CV, prolonged DL, CB, temporal dispersion)	Variable denervation	Non-uniform slowing; acquired pattern
CMT1A	Uniform slowing (<38 m/s); no CB	Chronic neurogenic changes	Uniform slowing WITHOUT conduction block = hereditary
MMN	Motor CB without sensory involvement	Neurogenic in CB distribution	Conduction block in non-entrapment sites; SNAPs normal
MG	Normal; RNS decrement	Variability in MUAP morphology (moment-to-moment)	Jitter on single-fiber EMG (most sensitive test)
Myotonic dystrophy	May be normal or mild neuropathy	Myotonic discharges (“dive bomber”)	Waxing-waning myotonic runs
IBM	Normal or mild neuropathy	Mixed neurogenic + myopathic (long + short MUAPs)	Mixed pattern in quad + finger flexors is classic
DM/PM/IMNM	Normal	Fibrillations + myopathic MUAPs	Irritable myopathy (fibs + PSWs in inflammatory/necrotic)

Top EMG Pitfalls

Normal NCS does not exclude myopathy — NCS tests nerve, not muscle; CMAPs may be low in severe myopathy
Fibrillations are not specific to neuropathy — also seen in inflammatory myopathies, muscular dystrophies, and NMJ disorders
Single-fiber EMG is the most sensitive test for MG but is not specific (abnormal in any NMJ or neurogenic disorder)
Myotonic discharges without clinical myotonia can occur in: acid maltase deficiency (Pompe), hypothyroid myopathy, statin myopathy, channelopathies
IBM has “mixed” EMG pattern (neurogenic + myopathic MUAPs) — can be misread as neurogenic alone
Temperature matters: cold limb → falsely slow CV + falsely high amplitude; warm limb before testing

💎 Board Pearl

LEMS increment >100% on post-exercise facilitation or 50 Hz RNS is pathognomonic
“Dive bomber” sound on EMG = myotonic discharge = waxing-waning frequency and amplitude
Single-fiber EMG: most sensitive for MG (95%+); increased jitter + blocking

High-Yield One-Liners

💎 Board Pearl

GBS: treat with IVIg or PLEX — steroids are NOT effective; do NOT combine IVIg + PLEX (no added benefit)
CIDP: unlike GBS, steroids DO work — along with IVIg and PLEX
MFS antibody: anti-GQ1b = ophthalmoplegia + ataxia + areflexia (triad)
Sural sparing pattern on NCS (absent median/ulnar SNAPs but preserved sural) = AIDP until proven otherwise
POEMS: always lambda light chain; ↑ VEGF; look for sclerotic bone lesions on skeletal survey
Anti-MAG neuropathy: IgM kappa; wide-spaced myelin; distal acquired demyelinating; poor IVIg response; use rituximab
MMN: anti-GM1 + conduction block; responds to IVIg; steroids WORSEN it
ALS split hand: APB/FDI wasting out of proportion to hypothenar — distinguishes ALS from cervical myelopathy
Kennedy disease: X-linked, CAG repeat (androgen receptor); gynecomastia + perioral fasciculations + sensory neuropathy — slow course
MuSK MG: bulbar > ocular; tongue atrophy; rituximab is best steroid-sparing agent; pyridostigmine often worsens
IBM: most common inflammatory myopathy after age 50; quad + finger flexors; resistant to steroids; rimmed vacuoles on biopsy
TIF1-γ antibody in DM: highest cancer risk — screen for occult malignancy
MDA5 antibody DM: rapidly progressive ILD with minimal/no weakness (amyopathic DM); high mortality
McArdle disease: “second wind” phenomenon; no rise in lactate on forearm exercise test
Malignant hyperthermia: RYR1 mutation; inhaled anesthetics + succinylcholine trigger; treat with dantrolene
DM1 anticipation: CTG repeat expands each generation; congenital DM1 inherited from MOTHER
DMD frame rule: out-of-frame dystrophin deletion = DMD (severe); in-frame = BMD (milder)
Footdrop with weak inversion = L5 radiculopathy (tibialis posterior), NOT peroneal neuropathy
CIM vs CIP: SNAPs normal in CIM (myopathy spares sensory nerves); SNAPs reduced in CIP
Tick paralysis: ascending paralysis mimicking GBS; CSF is normal; remove tick → rapid resolution