神經發言 Nervestalk

Ataxia Evaluation & Diagnostic Framework

1. Physical Examination & Clinical Clues

• Initial Step: Differentiate Cerebellar ataxia vs. Sensory ataxia.
• GI & Systemic:
  • Diarrhea, body weight loss: Whipple disease (Oromasticatory myorhythmia, Vertical gaze palsy), AVED, Abetalipoproteinemia.
• Eyes & Vision:
  • AOA: AOA1, AOA2 (Ki-jih bang).
  • K-F ring: Wilson disease.
  • Cataract: CTX.
  • Telangiectasia: AT, ATLD (Cancer + Ataxia: consider Paraneoplastic or AT together).
• Skin & Appendages:
  • Check Xanthoma: CTX.
  • Ichthyosis, Over-riding toes: Refsum disease.
  • Skin purpura, Skin lesions: Vasculitis, Cryoglobulinemia.
• Key Demographics:
  • Common hereditary disease: SCA.
  • $> 50\text{ y/o}$ male: Consider FXTAS.

2. Acquired Etiologies (VITAMIN Framework)

• V (Vascular):
  • Stroke: Hearing loss (AICA territory).
  • Hypoxic encephalopathy: History of hypoxia.
  • Superficial siderosis: Hearing impairments (CN8); MRI (T2WI/SWI).
• I (Infectious):
  • Cerebellitis: Meningismus; CSF study (HSV, EBV, Syphilis).
  • Whipple disease: Diarrhea, Oromasticatory myorhythmia; Small bowel biopsy; Antibiotics treatment.
  • HIV infection.
  • PML: JC virus (CSF).
  • CJD: Rapid progressive dementia, Myoclonus; CSF 14-3-3 protein, EEG (PSWC), MRI (Cortical ribbon signs, Pulvinar signs).
• T (Toxic & Medications):
  • Medications: AEDs (CBZ, PHT), Amiodarone, Metronidazole, Chemotherapy (5-FU, Methotrexate).
  • Alcohol: History of alcohol abuse; Wernicke-Korsakoff syndrome triad, CN6 palsy.
  • Heavy metals / Others: Lithium, Bismuth, Lead, n-hexane, Toluene.
• A / I (Autoimmune & Demyelinating):
  • NMOSD, MS: Demyelinating symptoms, Ab, MRI.
  • GBS (MFS, Bickerstaff): Ophthalmoplegia, Ataxia, Areflexia (OAA).
  • Gluten disease: Diarrhea (may or may not present); Anti-gliadin Ab, Anti-transglutaminase 6 (TG6, type 2 for celiac disease); Gluten-free diet.
  • Other antibody: Anti-GluR$\delta$2.
  • Neurosarcoidosis: Multiple brain regions involvement, Multiple cranial nerve deficits.
  • Stiffperson syndrome: Anti-GAD65 (DM also in family members).
  • SREAT (Hashimoto encephalopathy): Check thyroid palpation; Anti-TG, Anti-TPO.
• M (Metabolic & Nutritional):
  • Vitamin B1 deficiency: Wet or Dry beriberi; Thiamine 100 mg TID $\times$ 5 days.
  • Vitamin B12 deficiency: Check proprioception; Vit. B12, MMA, Homocysteine; B12 supplement.
  • Vitamin E deficiency: AR inheritance, Head titubation.
  • GLUT1 DS: Seizure Hx; CSF glucose / serum glucose $< 0.5$; Genetic testing; Ketogenic Diet.
• N (Neoplastic / Paraneoplastic):
  • Paraneoplastic (PCD): Body weight loss, B symptoms.
  • Antibody panels: Anti-Hu (ANNA1, SCLC), Ma2, Yo (PCA1, Gyn/BrCA), Ri (SCLC), Tr, Zic4, mGluR1 (HL), CV2/CRMP5 (SCLC), VGCC, CASPR2.
• Degenerative: MSA.

3. Hereditary Ataxia

• Autosomal Dominant (AD):
  • SCA series: Genetic testing.
• Autosomal Recessive (AR):
  • FA, AVED, Abetalipoproteinemia, Refsum disease:
    • NCS: Neuropathy, Demyelinating neuropathy.
    • AVED: TTPA gene.
    • Abetalipoproteinemia: MTP gene.
  • AT, AOA1, AOA2:
    • Chorea, Dystonia.
    • AT: AFP elevated, IgG/A decreased.
    • AOA1: Cholesterol elevated, Albumin decreased.
    • AOA2: Cholesterol and AFP elevated.
  • NPC, LOTS, CTX:
    • NPC: PSP-like disease, Splenomegaly.
    • CTX: Achilles tendon xanthoma, Cataract; CYP27A1 gene.
    • LOTS: HEXA/HEXB gene.
  • EA1 / EA2: Persistent or Episodic presentation; EA1 (KCNA1), EA2 (CACNA1A).
  • CANVAS:
    • Chronic cough, Sensory neuronopathy, HINTS (bilateral peripheral vestibulopathy).
    • Gene: RFC1 (AAGGG repeats).
    • DDx: MSA, FA, Mitochondrial ataxia.
• X-Linked (XL):
  • FXTAS:
    • Action tremor + Parkinsonism + Dementia in $> 50\text{ y/o}$ male.
    • Family history of developmental delay, autism, mental retardation.
    • Can mimic X-linked MSA.
    • Gene: FMR1 55–200 premutation (CGG repeats); MRI: MCP sign.
  • X-ALD.
• Mitochondrial (Mito):
  • MIRAS: DM, eye signs, hearing impairments.

4. SCA Subtype Characteristics

• Onset & Progression:
  • Childhood onset: SCA7, SCA13, DRPLA.
  • Young onset: SCA1, SCA2, SCA3, SCA21.
  • Late onset / Slowly progressive: SCA6.
  • Progression: SCA1, SCA2, SCA3, SCA6.
• Pure Ataxia:
  • SCA5, SCA6, SCA15, SCA16, SCA26, SCA30, SCA31.
• Movement Disorders Overlap:
  • Dystonia: SCA3, SCA14, SCA17, SCA20, DRPLA.
  • Chorea: SCA2, SCA17, SCA27, DRPLA.
  • Parkinsonism: SCA2, SCA3, SCA8, SCA10, SCA17, SCA21.
  • Myoclonus: SCA2, SCA14, (SCA17, SCA19), DRPLA.
  • Tremor: SCA12, SCA16, SCA19, SCA27.
• Pyramidal & Neuromuscular Signs:
  • Spastic ataxia: SCA1, SCA3, SCA7, SCA8, CTX, LOTS, ARSACS.
  • ALS-like features: SCA2, SCA8, SCA36.
  • Areflexia (LMN signs): SCA2, SCA3, SCA4, SCA19, SCA21.
  • UMN signs: SCA1, SCA3, SCA7, SCA8, SCA12.
  • Autonomic dysfunction: SCA12.
• Ocular & Neuropsychiatric Features:
  • Visual loss / Maculopathy: SCA7.
  • Slow saccades: SCA2, SCA7, SCA12 (SCA2 > 7 > 12).
  • Ophthalmoplegia: SCA2, SCA3, SCA28, SCA40.
  • Dementia: SCA2, SCA7, SCA10, SCA17, DRPLA.
  • Seizure: (SCA2, SCA17), SCA7, SCA10, DRPLA.
  • Psychiatric symptoms: SCA2, SCA17.