Search

Abstract Background Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. Case presentation A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). Conclusions In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.

Background Autoimmune autonomic neuropathy with onset of acute autonomic nerve dysfunction is often misdiagnosed because its main symptoms are syncope and gastrointestinal motility disorder. This study summarized the clinical, electrophysiological and pathological changes of peripheral nerve biopsy of patients of autoimmune autonomic neuropathy with onset of acute autonomic nerve dysfunction, which could provide reference for diagnosis, differential diagnosis and treatment. Methods and Results The clinical data of 3 patients diagnosied with autoimmune autonomic neuropathy with onset of acute autonomic nerve dysfunction who were hospitalized in Department of Neurology, Peking University First Hospital from February 2016 to February 2019 were collected. All of the 3 patients were young women, presented with onset symptoms as acute orthostatic hypotension and gastrointestinal motility disorder. Two patients had dysuria and dyshidrosis, and 2 patients had pupil changes. Electrophysiology revealed decreased sensory and motor nerve conduction velocity in 2 patients. Abnormal F wave and H reflex were found in 2 patients. The conduction velocity of large myelinated fibers was normal in one patient. In the autonomic function test, 2 patients had decreased Valsalva ratio, decreased heart rate variability of deep breathing. The blood pressure changes during tilt test between lying and upright position of 2 patients in acute stage was more than 30/15 mm Hg. Two patients underwent lumbar puncture, and one patient showed albuminocytologic dissociation. Sural nerve biopsies showed moderate to marked loss of small myelinated fibers and unmyelinated fibers. Two patients in acute stage were treated with immunomodulatory therapy (glucocorticoid combined with intravenous immunoglobulin), and their symptoms improved in varying degrees. Conclusions Autoimmune autonomic neuropathy with acute autonomic nerve dysfunction has unique clinical manifestations. Early consideration of autoimmune autonomic neuropathy followed by diagnostic work⁃up and prompt immune treatment will help to improve the prognosis. DOI:10.3969/j.issn.1672⁃6731.2020.10.005

Objective To investigate the clinical and neuropathological features of N-hexane toxic peripheral neuropathy which was misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Methods and Results Two patients presented with subacute or chronic peripheral neuropathies after close exposure of N-hexane for 6 to 8 months, starting from weakness and numbness of bilateral distal lower limbs and gradually progressing to proximal lower limbs and upper limbs. The worsening of clinical symptoms was delayed after keeping out of toxic working environment. Decreased motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of all limbs as well as marked decrease of amplitude, with lower extremities predominantly, were detected in both cases. Sural nerve biopsies revealed mild to moderate loss of myelinated fibers, formation of giant axons, Wallerian degeneration and rare regenerating clusters. The giant axons were filled with neurofilaments and granular materials. The patients were required to keep away from toxic working environment and were treated with vitamin B, and the prognosis was good. Conclusions The clinical symptoms and cerebrospinal fluid (CSF) findings of N-hexane toxic peripheral neuropathy are similiar to CIDP. Peripheral nerve biopsy can play a key role in the diagnosis of the disease. DOI: 10.3969/j.issn.1672-6731.2019.06.006

Objective To investigate the clinical manifestations and auxiliary examination features of necrotizing autoimmune myopathy (NAM). Methods According to the inclusion criteria from European Neuromuscular Center (ENMC) International Workshop on idiopathic inflammatory myopathies published in 2004, 57 patients were diagnosed as NAM from 107 patients with necrotizing myopathy (NM). The risk factors, clinical symptoms, laboratory tests, electrocardiography (ECG), electromyography (EMG), skeletal muscle MRI and muscle pathology were retrospectively analyzed. Results There were more female patients than male patients (male∶female = 1.00∶1.59), with the peak onset age during 40 to 59 years old (43.86% , 25/57) in this study. Clinical types included idiopathic NAM, NAM with connective tissue disease, statin-associated NAM and NAM with cancer. Muscle weakness mainly affected proximal muscle, while it may simultaneously affect distal muscle (28.07% , 16/57). Serum creatine kinase (CK) elevated apparently (420-15 320 U/L). Serum anti-signal recognition particle (SRP) antibodies were detected in 24 out of 44 patients (54.55%). A total of 41 in 45 patients (91.11%) were detected myogenic damage on EMG, and 15 patients (33.33%, 15/45) also had spontaneous potentials. Thigh muscle MRI showed edema in 25 out of 27 patients (92.59% ) and fatty infiltration in 16 out of 27 patients (59.26% ). Other than necrotic fibers, major histocompatibility complex-1 (MHC-1) on sarcolemma were positive in 98.25% (56/57) cases, and membrane attack complex (MAC) deposition on capillary walls was detected in 92.98% (53/57) cases. Conclusions NAM can happen in all ages, mainly during 40 to 59 years old. Idiopathic NAM is the main type. Its main manifestation involves weakness of proximal muscle, sometimes with distal muscle. Extra-muscle symptoms are rare. Serum anti-SRP antibodies are common in NAM and edema is prominent change in thigh MRI. DOI: 10.3969/j.issn.1672-6731.2016.10.009