CMT AND TREMOR – IS IT REALLY CMT?

1. Eddie L. Patton, M.D., M.S. Cecile L. Phan, M.D., F.R.C.P.C. Yadollah Harati, M.D., F.A.C.P. CMT AND TREMOR – IS IT REALLY CMT?

2. History • 71 year old man with a 30 year history of progressive extremity numbness, weakness and wasting and received a diagnosis of Charcot Marie Tooth disease • Several years after onset of numbness he developed balance problems to the point that by the time of his presentation he could not stand without holding on to something • He developed a tremor in his hands starting in the mid 1980’s and was referred to our movement disorders clinic by his brother, a physician, for possible DBS

3. History • PMH- Renal calculi • PSH- Lithotripsy, hernia repair • Allergies- NKDA • Med- primidone, hydrochlorothiazide • FH- He has four siblings and two children with no neurological problems • No family history of CMT

4. Examination • Tone- Decreased in his extremities • Atrophy- Severe atrophy of the intrinsic muscles of the hand, legs (anterior and posterior department), and forearms (extensor and flexor compartments) • Reflexes- Areflexic throughout • Gait- Very unsteady, wide based, with bilateral foot drop. He was unable to stand without support

5. Examination • Sensory Exam • Vibration- absent at the toes and ankles, significantly reduced at the knees • Joint position- Absent at the toes and ankles bilaterally • Pin prick- symmetrical reduction in stocking and glove pattern up to mid shins and mid forearm • Coordination- Dysmetria bilaterally to finger to nose and heel to shin

6. Motor Exam

7. Exam and further questions…

8. EMG/NCS • Motor Nerve Conductions- • right median, ulnar, peroneal , tibilal and femoral nerves were all non-conductable • Spinal accessory and axillary- severe delayed distal latencies and severe reduction in distal amplitudes • Sensory Nerve Conductions- absent median, ulnar and sural nerve conductions on the right • EMG- diffuse moderate denervation proximally and distally with moderate amount of spontaneous activity

9. EMG/NCS • Summary • Severe diffuse motor and sensory demyelinating polyneuropathy, distal greater than proximal, with moderate amount of axonal loss.

10. Work-up • Complete CMT genetic evaluation- normal • MAG IgM antibody- 191 (N) • CSF analysis • WBC-4 • Glucose- 57 • Protein- 364 • Increased IgG synthesis rate and IgG index • Decided at this point to perform a nerve biopsy

11. Median Antebrachial Nerve

12. Nerve Biopsy H&E- Moderatly severe decreased density of myelinated fibers

13. Nerve Biopsy Trichrome: Myelin digestive chamber Semi-thin: Many small thinly myelinated fibers

14. Nerve Biopsy Teased: Note variation in myelin thickness

15. Nerve Biopsy • Moderately severe depopulation of myelinated nerve fibers. 17% of teased fibers display evidence of dymelination/remyelination. Majority of fibers on semi-thin are small and thinly myelinated, without clusters. There were no onion bulbs noted. • Findings suggest a chronic, moderately severe demyelinating neuropathy

16. Imaging • MRI Brain- No acute abnormalities • MRI- cervical spine- enlargement of his cervical spine nerve roots

19. At this point we concluded this was not CMT based on • Negative family history • Absent onion bulbs on nerve biopsy • Marked elevated CSF protein • Negative genetic CMT evaluation

20. Diagnosis • Undiagnosed Untreated Chronic Inflammatory Demyelinating Polyneuropathy

21. Treatment • Initial course of IV Methylprednisolone at 1000 mg daily for 5 days • Weekly IVMP 1000 mg boosters for 4 weeks • Good response • He was then switched to IVIG • Initial 5 day course followed by weekly boosters

22. Nerve root involvement in CIDP • One of the first papers written about this was by Crino, Grossman and Rostami, “Magnetic Resonance Imaging of the Cauda Equina in Chronic Inflammatory Demyelinating Polyneuropathy” Annals of Neurology 1993 • 33 y/o man with 5 week history of progressive weakness and unsteady gait, CSF protein 305,WBC 5 • Nerve conduction studies and sural nerve biopsy consistent with demyelinating polyneuropathy

23. Crino et al • MRI of his lumbar/sacrum- Enhancement of the cauda equina • Enhancement suggests inflammation and compromise of BB barrier • Authors suggest that MRI could prove to be useful adjunctive study when suspecting CIDP

24. Nerve root hypertrophy in CIDP • Tazawa et al, “Spinal Nerve Root Hypertrophy on MRI: Clinical Significance in the Diagnosis of Chronic Inflammatory Demyelinating Polyradiculoneuropathy” Internal Medicine • 14 patients with CIDP and 10 controls (6 healthy and 4 other neurological condition) • Electrophysiological studies done in medial and tibial nerves in side most effected • Compared this with MRI findings (STIR images) of cervical and lumbar nerve roots

25. Tazawa et al Note marked hypertrophy in cervical nerve roots

26. Tazama et al • Conclusion • Patients with CIDP showed significantly enlargement of cervical and lumbar spinal roots on MRI compared to control • Cervical spine- 6.0-6.8 mm (normal < 5 mm) • Lumbar spine- 7.3-10.4 mm • Hypertrophic nerve root changes correlate with electrophysiological indices • F-wave conduction velocity of median and tibial nerves have a negative correlation to corresponding nerve roots

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