2017 Resarch Forum

IM: C-10

Applicant & Principal Investigator: Samiollah Gholam MD

A Case of Asymptomatic Charcot Marie Tooth Syndrome with Hypersensitivity to Vincristine Roopam Jariwal MS III, Benson Lee DO, Samiollah Gholam MD, A Scott Ragland DO

INTRODUCTION: Charcot Marie Tooth (CMT) is among one of the most common hereditary sensory and motor neuropathies. It is classified into seven types (CMT1 -7). Inheritance patterns include Autosomal Dominant, Autosomal Recessive, and X-linked Recessive. Most common form is CMT1A with an autosomal dominant pattern involving mutation in myelin protein 22 (MP22) gene. All forms of CMT involve demyelination of the peripheral nerves system. Prevalence is approximately 1 in 2,500 cases with a bimodal age distribution; either symptomatic at childhood or third and fourth decades of live. Based on the literature review, there are a subset of individuals that may have the physical findings of CMT such as pes cavus, hammertoes, calf muscle hypertrophy, painless and symmetric motor neuropathy, sensory loss involving vibration and proprioception and diminished deep tendon reflexes, however remain clinically silent. Here we report a case of CMT that was clinically quiescent and unmasked due to hypersensitivity to Vincristine. PURPOSE: Rare Case Presentation. DISCUSSION: 56-year-old Hispanic female presented with complaints of bilateral upper and lower extremities weakness and numbness s/p 10 days after 2nd cycle of R-CHOP therapy that she was receiving for large B-cell lymphoma. The symptoms started 4 days post 1st cycle of R-CHOP therapy with mild weakness and numbness in the tips of fingers and toes. The peripheral neuropathy worsened 10 days after 2nd cycle of R-CHOP containing low-dose Vincristine with patient now being unable to walk, perform daily living activities and being completely bed ridden. Physical examination showed severe motor weakness and decreased sensation to light touch and pinprick in bilateral upper and lower extremities, up to the knees and elbows, along with pes cavus and hammertoes in both feet. Upon further investigation, several family members in patient’s family including her father and three siblings had been diagnosed with Charcot Marie Tooth disease and patient herself had difficulty walking due to severe pes cavus since she was 50 years old. Nerve conduction and electromyogram studies of bilateral upper and lower extremities indicated severe diffuse sensory motor neuropathy with absent action potentials, severe active denervation in forearm, hands, lower leg muscles, and proximal leg muscles. Asymptomatic Charcot Marie Tooth disease can manifest in the 4 th or 5 th decade of life in the presence of neurotoxic drugs such as Vincristine. Review of previous literature indicates evidence of similar occurrences. The hallmark features of CMT 1-7 include pes cavus/valgus, hammertoes, bilateral foot drops, symmetric and bilateral weakness, loss of proprioception and sensation, loss of deep tendon reflexes, along with scoliosis, and other spine deformities. Patients who present with these symptoms and have a family history of neuropathy should receive thorough physical and foot examination. Nerve conduction, electromyogram, sural nerve biopsies and genetic testing to search for one of the 28 identified genes can be used as diagnostic tests to confirm diagnosis. Nerve biopsies show nerve hypertrophy with onion bulb formation caused by repeated demyelination and remyelination due to Schwann cell dysfunction. CONCLUSION: Severe neurotoxic effects of Vincristine along with subclinical Charcot Marie Tooth were attributed to patient’s presentation. It is pertinent to perform a thorough physical and neurological examination in patients with family history of hereditary neuropathies before administering neurotoxic drugs.