Clinical Features of a Newly Described Mutation of Myelin Protein Zero in a Family.

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy. Duplication of the peripheral myelin protein-22 (PMP22) gene is the most frequent genetic abnormality in CMT disease. Although rare compared to PMP22 gene mutations, many different myelin protein zero (MPZ) gene mutations have been described in patients with CMT disease. MPZ gene mutations are known to cause hereditary neuropathies with heterogenous phenotypes ranging from early-onset severe demyelinating to adult-onset axonal forms. MPZ, the major protein component of peripheral nerve myelin, is important for myelin compaction. We report a family in which a mother and her son, both with adult-onset CMT disease, showed a newly described mutation p.Glu37Lys of the MPZ gene. The clinical features of the mother provided insight into the progression of the disease over decades, while features in the early stage of the disease could be studied in the son. Clinical, electrodiagnostic, and sonographic findings are described in the early and late stages of the disease. The MPZ gene mutation p.Glu37Lys is associated with clinical features of a progressive axonal type of adult-onset CMT disease.

Nerve Ultrasound Findings before and after Surgery in a Patient with Charcot-Marie-Tooth Disease Type 1A and Comorbid Carpal Tunnel Syndrome.

The diagnosis of comorbid carpal tunnel syndrome (CTS) in patients with Charcot-Marie-Tooth (CMT) disease is challenging due to the overlapping symptoms and inconclusive electrodiagnostic studies (EDX). This case report is aimed at illustrating the value of ultrasonography (US) in a patient with CMT1 disease and comorbid CTS. A 28-year-old woman presented with symptoms of painful paresthesia and weakness of both hands. EDX demonstrated a demyelinating sensory-motor polyneuropathy in the upper and lower extremities, consistent with CMT1 disease. US showed an increased cross-sectional area (CSA) of the median nerve at the carpal tunnel inlet (CTI) with a significant drop in the diameter within the carpal tunnel, confirming concurrent CTS. Genetic testing confirmed PMP22 duplication consistent with CMT1A. Bilateral carpal tunnel releases were performed with partial symptom resolution within 3 weeks. Postoperative EDX demonstrated improved motor conduction across the wrist, but the sensory potentials continued to be unrecordable. US showed a significant reversal of the diameter-drop of the median nerve within the carpal tunnel and decrease in CSA at the CTI. US imaging is a valuable technique for identifying comorbid CTS in patients with CMT and directing appropriate treatment.

Importance of Electrodiagnostic Testing Prior to a Tethered Cord Release in a Patient with Overlapping Symptoms of Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder causing a symmetric, slowly progressive distal neuropathy of the legs and arms. Tethered cord syndrome (TCS) encompasses a constellation of neurological, gastrointestinal, musculoskeletal, and urinary abnormalities resulting from spinal cord traction. The signs and symptoms of CMT and TCS may be very similar. Electrodiagnostic (EDX) studies are crucial in differentiating between these two conditions. We describe a 20-year-old woman with a history of low back pain, right leg tingling, and difficulty in walking. She experienced bowel and urinary incontinence 11 years earlier as well as back pain, in-toeing gait, and difficulties with balance and coordination. Urodynamic studies and cervical, thoracic, and lumbar magnetic resonance imaging (MRI) were normal, with the latter demonstrating the tip of the conus medullaris in the normal position at the L1-2 interspace and the filum terminale demonstrating no thickening or fatty infiltration. Despite the absence of radiological evidence of TCS, she underwent a tethered cord release (TCR) with improvement of the pain postoperatively. Two years later, the back pain recurred with increasing pain, paresthesia, and weakness of the lower extremities with frequent trip and fall episodes. EDX studies of the lower extremities were requested. Clinical findings included weakness of flexion and extension of the toes as well as dorsiflexors of the ankles bilaterally. The knee and ankle reflexes were absent bilaterally. EDX testing of the lower extremities were non-diagnostic due to loss of sensory and compound muscle action potentials. EDX studies of the upper extremities suggested a demyelinating polyneuropathy, most likely CMT disease. Genetic studies subsequently confirmed CMT type 1A (CMT1A) disease. Ensuing EDX studies on the patient's father and brother also suggested CMT1A disease. Physicians should be aware of the overlapping signs and symptoms of CMT disease and TCS. Performing comprehensive EDX studies prior to a TCR particularly in cases when a lumbar MRI is negative may prove valuable in identifying cases of CMT disease with subsequent confirmation by genetic testing.

Early-Onset Dropped Head Syndrome and Person-in-the-Barrel Syndrome After Radiation Therapy: Clinical, Electromyographic, and MRI Findings.

Dropped head syndrome (DHS) involves severe weakness of the neck extensor muscles causing the mandible to drop to the chest wall. Isolated neck extensor weakness is a rare complication of radiotherapy. This condition may result within a few weeks or months following radiotherapy (early-onset) or several years after radiotherapy (late-onset), with the latter more commonly encountered. Person-in-the-barrel syndrome is marked by bilateral brachial diplegia, intact cranial nerves, and preserved lower extremity strength. We describe the unique clinical profile of a patient with a six-week history of significant neck and bilateral upper extremity weakness who was diagnosed three months prior to the onset of these symptoms with moderately differentiated squamous cell carcinoma within the base of the tongue (Stage III T2N1M0) and metastasis to the cervical lymph nodes. She underwent concurrent chemotherapy with three cycles of cisplatin (197 mg {100 mg/m2} x 197 m2) and hyperfractionated external beam radiation therapy (total dose cGy 7000 cGy in 35 fractions {200 cGy per fraction}). She reported the rapid onset of neck and bilateral upper extremity weakness six weeks following cisplatin termination and four weeks after radiation termination. A cervical MRI suggested myositis of the cervical paraspinal muscles, and electrodiagnostic studies indicated an inflammatory myopathic process involving the cervical paraspinal and shoulder girdle muscles. The patient attained a complete resolution of her symptoms eight months after onset. This case illustrates the rare phenomenon of early-onset DHS and person-in-the-barrel syndrome caused by radiation-induced myositis. Prompt recognition of the symptoms associated with DHS and timely treatment offer the best prognosis for recovery.

Transhemispheric cortex remodeling promotes forelimb recovery after spinal cord injury.

Understanding the reorganization of neural circuits spared after spinal cord injury in the motor cortex and spinal cord would provide insights for developing therapeutics. Using optogenetic mapping, we demonstrated a transhemispheric recruitment of neural circuits in the contralateral cortical M1/M2 area to improve the impaired forelimb function after a cervical 5 right-sided hemisection in mice, a model mimicking the human Brown-Séquard syndrome. This cortical reorganization can be elicited by a selective cortical optogenetic neuromodulation paradigm. Areas of whisker, jaw, and neck, together with the rostral forelimb area, on the motor cortex ipsilateral to the lesion were engaged to control the ipsilesional forelimb in both stimulation and nonstimulation groups 8 weeks following injury. However, significant functional benefits were only seen in the stimulation group. Using anterograde tracing, we further revealed a robust sprouting of the intact corticospinal tract in the spinal cord of those animals receiving optogenetic stimulation. The intraspinal corticospinal axonal sprouting correlated with the forelimb functional recovery. Thus, specific neuromodulation of the cortical neural circuits induced massive neural reorganization both in the motor cortex and spinal cord, constructing an alternative motor pathway in restoring impaired forelimb function.

Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion.

STUDY DESIGN: A retrospective review of patients who underwent an anterior cervical fusion using recombinant human bone morphogenetic protein (rhBMP)-2 with an absorbable collagen sponge (INFUSE; Medtronic Sofamor Danek, Minneapolis, MN). OBJECTIVE: To ascertain the complication rate after the use of high-dose INFUSE in anterior cervical fusions. SUMMARY OF BACKGROUND DATA: The rhBMP-2 has been primarily investigated in lumbar spine fusions, where it has significantly enhanced the fusion rate and decreased the length of surgery, blood loss, and hospital stay. METHODS: We present 151 patients who underwent either an anterior cervical discectomy and fusion (n = 138) or anterior cervical vertebrectomy and fusion (n = 13) augmented with high-dose INFUSE between July 2003 and March 2004. The rhBMP-2 (up to 2.1 mg/level) was used in the anterior cervical discectomy and fusions. RESULTS: A total of 35 (23.2%) patients had complications after the use of high-dose INFUSE in the cervical spine. There were 15 patients diagnosed with a hematoma, including 11 on postoperative day 4 or 5, of whom 8 were surgically evacuated. Thirteen individuals had either a prolonged hospital stay (> 48 hours) or hospital readmission because of swallowing/breathing difficulties or dramatic swelling without hematoma. CONCLUSIONS: A significant rate of complications resulted after the use of a high dose of INFUSE in anterior cervical fusions. We hypothesize that in the cervical area, the putative inflammatory effect that contributes to the effectiveness of INFUSE in inducing fusion may spread to adjacent critical structures and lead to increased postoperative morbidity. A thorough investigation is warranted to determine the optimal dose of rhBMP-2 that will promote cervical fusion and minimize complications.