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?

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.

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

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

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

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

Motor ExamRight Left

Deltoids 5- 5-

Biceps 5 5

Triceps 5 5

Wrist Extension 4+ 4+

Wrist Flexion 5- 5-

Digit Extension 1 1

Digit Flexion 2 2

Interossei 1 1

Illiopsoas 5 5

Knee flexors/extensors 5 5

Tibialis anterior 0 0

Gastrocnemius/soleus 0 0

Toe flexion 0 0

Toe extension 0 0

Exam and further questions…

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

EMG/NCS

Summary Severe diffuse motor and sensory

demyelinating polyneuropathy, distal greater than proximal, with moderate amount of axonal loss.

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

Median Antebrachial Nerve

Nerve Biopsy

H&E- Moderatly severe decreased density of myelinated fibers

Nerve Biopsy

Trichrome: Myelin digestive chamber

Semi-thin: Many small thinly myelinated fibers

Nerve Biopsy

Teased: Note variation in myelin thickness

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

Imaging

MRI Brain- No acute abnormalities MRI- cervical spine- enlargement of

his cervical spine nerve roots

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

Diagnosis

Undiagnosed Untreated Chronic Inflammatory Demyelinating Polyneuropathy

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

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

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

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

Tazawa et al

Note marked hypertrophy in cervical nerve roots

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

Please tell us how you are responding to treatment…