Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan.

Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT.

A Computed Tomographic Assessment of Tracheostomy Tube Placement in Patients with Chronic Neurological Disorders: The Prevention of Tracheoarterial Fistula.

Objective Tracheoarterial fistula (TAF) is a rare but devastating complication of tracheostomy caused by pressure necrosis from the elbow, tip, or over-inflated cuff of the tracheostomy tube. The incidence of TAF is reportedly higher in patients with neurological disorders than in those without such disorders. To evaluate the incidence of and factors contributing to the misalignment of tracheostomy tubes in bedridden patients with chronic neurological disorders. Methods We retrospectively assessed three-dimensionally reconstructed serial computed tomography (CT) images to see if the tip of the tube made contact with the tracheal wall and if the main arteries were running adjacent to the tube's elbow, tip or cuff. Results The tip of the tube was in contact with the tracheal wall in 14 of the 30 patients assessed. Among them, the tip was adjacent to the innominate artery in eight, the aortic arch in three and an aberrant right subclavian artery in one. In one patient with the tube tip adjacent to the aortic arch and the other four patients, the cuff of the tube was adjacent to the innominate artery across the tracheal wall. Patients with the tube tip in contact with the anterior tracheal wall had a significantly greater cervical lordosis angle than those without contact (p<0.05). Conclusion More than half of tracheostomized patients with chronic neurological disorders had a latent risk of TAF. The variability in the location of the innominate artery, anomalies of the aortic arch, and skeletal deformities may therefore be contributing factors.

The characteristics of camptocormia in patients with Parkinson's disease: A large cross-sectional multicenter study in Japan.

PURPOSE: The goal of the present study was to clarify the clinical characteristics and laboratory results of parkinsonian symptoms among patients with and without camptocormia. METHODS: Seventy-eight Parkinson's disease (PD) patients with camptocormia and 78 PD patients without camptocormia underwent a neurological examination, a blood test, and spinal magnetic resonance imaging (MRI). PD with camptocormia group and PD with non-camptocormia group were matched on age, age at PD onset, and sex. PRINCIPAL RESULTS: Camptocormia group had significantly higher prevalence of compression fractures, more severe parkinsonian symptoms, and a greater incidence of dementia than those without camptocormia. Serum creatine kinase levels in camptocormia group significantly elevated compared with non-camptocormia group. There were higher prevalence of abnormal findings in spine MRI including compression fractures and paravertebral muscle changes in camptocormia group compared with non-camptocormia group. MAJOR CONCLUSIONS: Camptocormia is associated with a greater prevalence of compression fractures and associated with greater UPDRS part II, part III score, axial score, and lower MMSE in this cross-sectional study. Thus, it can be concluded that camptocormia in PD is predominantly myopathic.

Retroauricular pain preceding Bell's palsy: report of three cases and clinical analysis.

A retroauricular pain (RAP) ipsilateral to the side of facial paralysis (FP), often experienced patients with Bell's palsy, usually occurs around the onset of FP. Whether RAP is a risk factor for incomplete recovery from FP is controversial. This paper reports three patients with Bell's palsy in whom acute RAP preceded FP by several days. The intervals between the onset of RAP and FP were 6, 12, and 12 days, and the quality of RAP was dull/tight or neuralgic. All patients received prednisolone and acyclovir orally, and their facial functions recovered within 8 weeks. Based on the serological tests, FP was diagnosed as due to varicella-zoster virus in two patients and as idiopathic in the other. Among 58 consecutive patients with Bell's palsy, including the three patients described, 26 (44.8%) experienced RAP, the onset of which ranged from 12 days before to 2 days after the onset of FP. While the prognosis of FP was not different between patients with and without RAP, FP recovered well in all seven patients in whom RAP preceded the onset of FP by 4 days or more. These findings suggest that RAP preceding by several days may predict the good prognosis of FP. As RAP can be a preceding symptom of acute FP, patients with acute RAP require medical attention for at least 2 weeks.