一、Neurological Examination
- Scapular winging: Pompe, LGMD (1B, 2A).
- Calf hypertrophy: DM2, DMD, BMD, Amyloidosis, Hypothyroidism, SMA.
- Fluctuation?:
- Consider NMJ (MG, LEMS), Periodic Paralysis.
- Exercise-related weakness (Metabolic myopathy, Mitochondria).
- “Feeling Tight / Spasm" (“會緊緊的"):
- Demyelinating disease (NMO, MS painful tonic spasm).
- Spasticity, Rigidity, Dystonia.
- Myotonia / Paramyotonia, Cramping (check periodic PP or PKD / PNKD / PED), Contracture.
- Root lesion or plexopathy: Test Long thoracic nerve and Dorsal scapular nerve.
- Infection: Consider Poliovirus.
二、鑑別診斷
1. Distal Weakness
A. Motor Neuron
- ALS / PMA.
- MMN.
- Monomelic: Hirayama / Wasting leg syndrome.
B. Neuropathy
- AIDP.
- AMAN, AMSAN.
- CIDP.
- MADSAM.
- Mononeuritis multiplex: Vasculitis, Ischemic lesion.
- Infection: HIV, Lyme.
- Toxin: Lead (Pb) poisoning (Drop wrist, Drop foot).
- Metabolic: DM, Uremia, Thyroid dysfunction.
- Inflammation: FAP.
- POEMS syndrome.
C. NMJ
- Pre-synaptic: LEMS, Botulism.
- Post-synaptic: MG.
- Others: Congenital myasthenic syndrome.
D. Muscle
- IBM: Upper distal, lower proximal (上遠下近).
- Distal myopathy: Nonaka (AT), Miyoshi (PC), Udd / Welander / Markesbery-Griggs.
- DM1: Percussion myotonia.
- LGMD series: 1A (Myofibrillar), 1B, 2B, EDMD.
2. Proximal Weakness
A. Myopathy (Examine: Scapular winging, Percussion myotonia, Muscle tenderness)
- Inflammatory myopathy: DM / PM (Skin rash, Palmar papules), Sarcoidosis.
- Anti-synthetase syndrome: Anti-Jo-1, PL-12, PL-7 (with severe ILD).
- Immune-mediated necrotizing myopathy (IMNM): Anti-SRP, Anti-HMGCR.
- Metabolic: Hyperthyroidism, Hypothyroidism, Cushing syndrome, Hyperkalemia, Hypokalemia.
- Infection: HIV, Lyme…
- Drugs: Medication-related (Statins, Colchicine, Amiodarone, Steroids).
- Toxins: Alcohol.
- Storage disease:
- Pompe disease (axial weakness, hepatosplenomegaly).
- Gaucher disease.
- Glycogen storage disease: McArdle (second-wind phenomenon), Tarui (out-of-wind).
- Lipid metabolism disorders.
- Mitochondrial myopathy: MERRF, MELAS (screen for myoclonic epilepsy).
- Neuropathy mimicking proximal weakness: Porphyria (Proximal muscle and distal radial nerve).
- Hereditary:
- AD: LGMD1, FSHD (Asymmetric), OPMD (Oral-facial), DM2, Emery-Dreifuss.
- AR: LGMD2.
- X-linked: Duchenne MD, Becker MD, McLeod syndrome.
- Channelopathies: CLCN1 (Myotonia congenita), SCN4A (Paramyotonia congenita, HyperKPP triggers).
- Others: Critical Illness Myopathy (CIM).
B. Other Localization Overlaps
- NMJ: MG, LEMS.
- MND: ALS, PMA, SMA, MMN, Flail arm, Flail leg, SBMA.
- Radiculopathy: CIDP, AIDP, Diabetic amyotrophy.
- Plexopathy: Erb’s palsy.
- Central / Vascular: Watershed infarction.
3. Fluctuation & Trigger Profiles
- NMJ: MG, LEMS.
- Periodic paralysis: HyperKPP, HypoKPP.
- Dyskinesia: PKD, PNKD, PED.
- Ataxia: EA1, EA2.
- Parkinsonism: YOPD, DRD, DLB.
- Trigger by cold: Paramyotonia congenita, SCN4A myotonia.
- Trigger by heat: NMOSD / MS / MOGAD (Uhthoff phenomenon, demyelinating diseases).
- Trigger by sleep: Neuromyotonia, ADCY5 mutation.
- Trigger by exercise:
- Short exertion: Glycogen storage diseases.
- Prolonged exertion: Lipid storage diseases.
- Fatigue / After event: Mitochondrial disorders.
- Episodic diseases: Migraine, Seizure, TIA.
- Others (Frequently Overlooked): HNPP, Porphyria.
4. Combined UMN + LMN Signs
- ALS (bvFTD [C9orf72]).
- Metabolic & Nutritional Deficiencies:
- Vitamin B12 deficiency.
- Copper deficiency.
- Zinc excess / toxicity.
- Infections:
- Tabes dorsalis (Syphilis).
- HIV myeloneuropathy.
- Structural & Vascular: Ischemic cord + Anterior horn involvement.
- Demyelinating: Demyelinating disease (MS / NMOSD) + Anterior horn involvement.
- Paraneoplastic / Autoimmune: Anti-Hu, Anti-CV2/CRMP5, Anti-CASPR2 (Morvan syndrome).
- Endocrine: Thyroid dysfunction (Hyper- / Hypothyroidism).
- Lysosomal & Storage Diseases: GM1, GM2 gangliosidoses, Tay-Sachs, Sandhoff, Gaucher, MLD, Krabbe disease.
- Peroxisomal: X-ALD / AMN.
- Systemic Autoimmune Diseases: SLE, RA, Sjögren syndrome.
- Spinocerebellar Ataxias: SCA3, SCA1, SCA2.
- Hereditary Ataxias: FRDA, AVED.
- Hereditary Spastic Paraplegia (HSP).
- Charcot-Marie-Tooth: CMT2A.
