Sensory Neuropathy and neuronopathy : Case scenario and Approach
- 1. Sensory Neuropathy and neuronopathy: Case scenario & Approache Ahmad Shahir Mawardi Neurologist Hospital Kuala Lumpur
- 3. History • 25 years old lady who was first presented in Nov 2014 to private medical centre with bilateral ULs abd LLs weakness and difficulty in swallowing for 2/52 • treated as GBS and later complicated with autonomic dysfunction ( hypotension, vomiting and diarrhea)
- 4. Examination • muscle power 3/5 • generalized areflexia • loss of sensation from face downward • loss of propioception until large joint
- 5. Investigations • CSF: prot 1719 mg/dL, glucose 2.9 mmol/l • CSF cytology : negative • CT brain:Normal • MRI brain: Normal • ANA, C3/C4, dsDNA, ENA : normal • Tumor markers: negative • Hep B/C/HIV : negative • Viral serology: Chlamydia, mycoplasma, legionella, leptospira : negative
- 6. Investigations • OGDS: pangastritis • Colonoscopy: normal. HPE normal • NCS: axonal neuropathy. Sensory>motor
- 7. • pt was given IVIg and fludrocortisone (for autonomic dysfunction. • Sx improved after 1 month • Readmitted in Jan 2015 for worsening weakness and new onset of seizure • treated as Bickerstaff encephalitis
- 8. Investigations • CT TAP: Normal • MRI brain(27 Jan 2015): Hyperintense signal in the both temporal lobes • MRI brain (21 Sept 2015) : normal • PET scan: – Absent of physiological metabolic activity in the extraocular muscle bilaterally, cauda equina – hyper-reactivity/contraction of central abdominal muscle – hypermetabolic marrow – right ovarian cyst
- 9. Investigations • Sural nerve biopsy: no evidence of amyloidosis or malignancy
- 10. NCS 2/12/2014
- 11. NCS 2/12/2014
- 12. NCS 21/9/2015
- 13. NCS 21/9/2015 Sural nerves were absent bilaterally
- 14. • Serum B12: normal • VDRL: normal • Serum EP: Normal • Urine EP: Normal • LDH: Normal • Tumour marker: Normal • T4/TSH : Normal • ESR: 20 • ENA: Boderline Investigations • Neuronal antibodies: sent to IMR
- 15. Summary • 25 y.o lady with progressive sensory axonal polyneuropathy with autonomic dysfunctions • No positive history for drug/ family history
- 19. • Immune Paraneoplastic with anti-Hu antibodies Sjögren's syndrome Acute sensory neuronopathy IgG vs FGFR3 • Idiopathic Pan-sensory Small fiber CANVAS Sensory Neuronopathies • Drugs Pyridoxine intoxication Acute High dose (100 - 200 g) Neuronopathy Chronic Moderate dose(0.2-10g/day) Distal axonopathy, Reversible cis-platinum Doxorubicin (Animals only) • Hereditary
- 20. • DRG involvement also occurs in a variety of hereditary and degenerative diseases – hereditary sensory autonomic neuropathy (HSAN); – Charcot–Marie– Tooth disease type 2B (CMT2B); – sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) – facial-onset sensory motor neuronopathy (FOSMN); – cerebellar ataxia, neuropathy vestibular areflexia syndrome (CANVAS). • approximately 50% of patients, an underlying cause is not identified (idiopathic)
- 23. Proposed strategy for evaluation of patients with acquired sensory neuronopathies
- 25. Sjögren's Syndrome • Inflammatory exocrinopathy • Affects salivary & lachrymal glands • Classification – Primary: No associated disorders – Secondary: Associated rheumatoid arthritis, lupus or progressive systemic sclerosis • Clinical features, Systemic – Xerostomia – Dry eyes • Course: Chronic, slowly progressive • Pathogenesis: Autoimmune disease • Epidemiology – Female > Male (9:1) – Incidence: 2 in 10,000, Prevalence: (0.5 to 1.0%) • Onset – Peak ~ 50 years – Range = Childhood to Late adult
- 26. Sjögren's Syndrome • Polyneuropathy: Sensory present in: 8% to 30% of 1° Sjögren's patients Clinical • Sensory loss – Distribution: Symmetric; Distal – Modalities Small fiber loss Vibration relatively preserved – Severity: Mild • Paresthesias: Frequency 59% – Painful – Distal or Non-length dependent – Legs > Arms • Other clinical features – Sweating: Abnormal in 40% – Motor: Usually normal – Tendon reflexes: Not affected – ± Carpal tunnel syndrome
- 27. Sjögren's Syndrome • Autonomic neuropathy – Adie's pupil – Blood pressure changes – Anhidrosis: Associated with small fiber neuropathy – Constipation – Bladder dysfunction – May contribute to Sjögren's features: Dry eyes & mouth – ? Associated with IgG binding to M3-muscarinic AChRs
- 28. Sjögren's Syndrome • CNS (8%) – Younger patients: < 50 years – Encephalopathy: Fatigue; Memory loss; Depression; Psychosis – Transverse myelitis – ± Focal or multifocal CNS signs: Ataxia; Hemiparesis – MRI: Hyperlucent lesions, especially in white matter, on T2 • Myopathy – Usually subclinical – Not related to muscle pain – Weakness (10%): Proximal; Arms > Legs – Serum CK: Usually normal
- 29. Sensory Neuropathy/Neuronopathy with serum IgG vs FGFR-3 • Target antigen: Fibroblast Growth Factor-3, Intracellular domain • Antibody type: IgG • Epidemiology Female:Male = 5:3 • Clinical syndrome Onset Age: 18 to 73 years Course: Progressive or Acute Sensory Loss (95%) Modalities: Large & Small fiber Limbs ± Face Pain (45%) Ataxia (60%) Associated disorders Immune (59%): Sjögren, Lupus • Laboratory NCV: Neuropathy (90%), Often non- length dependent Nerve pathology: Axon loss without regeneration
- 30. Bickerstaff brainstem encephalitis • Epidemiology: Most reports from Japan • Antecedent illness (92%): Most commonly upper respiratory infection • Age: 3 to 91 years • Onset: Diplopia or gait disorder most common • Clinical: Brainstem signs Reduced consciousness (74%): Drowsy, stupor or coma Ataxia: Often trunk & limb Eyes Ophthalmoplegia, external (100%): Relatively symmetric Pupil disorders (34%) Ptosis (29%) Nystagmus (27%) Other cranial nerves Facial diplegia (45%) Bulbar weakness (34%) Weakness: Flaccid tetraparesis (60%);Respiratory failure Pyramidal signs Tendon reflexes: Variable; Hyperreflexia to Absent Plantar responses (40%): Extensor Sensory loss Small fiber (31%) Large fiber (16%) Hemisensory loss • Course Monophasic Often good prognosis: Complete remission in 51%; Death 4%
- 31. Bickerstaff brainstem encephalitis Laboratory Serum IgG binding to GQ1b ganglioside (66%) Electrophysiology Motor axon degeneration Central involvement MRI: CNS abnormalities High intensity T2 signal Locations: Brainstem, Thalamus, Cerebellum CSF Cells: Usually normal; Occasionally high WBCs (37%) Protein: High in 59%; Higher in 2nd week than 1st Pathology Perivascular lymphocytic infitration Edema Glial nodules
Editor's Notes
- #18: Fabry's ds : is a rare genetic lysosomal storage disease Tangier ds: is a rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein