To clarify the attitude toward genetic testing for neuromuscular diseases, a questionnaire was sent to 4,762 neurologists certified by the Japanese Society of Neurology. By December 21, 2011, 1,493 questionnaires (31.4%) were returned. Of these, 1,233 (82.6%) had experienced genetic testing, but only 396 (26.5%) had referred to the guideline for genetic testing of the Japanese Society of Neurology (2009). The numbers of respondents who were positive, or more positive than negative for genetic testing for myotonic dystrophy type 1 (DM1), Huntington's disease (HD), and familial amyloid polyneuropathy (FAP) were 753 (50.4%), 915 (61.3%), and 980 (65.6%), respectively. The predominant reason for a positive attitude toward genetic testing was to confirm or exclude the diagnosis. Conversely, the predominant reason for a negative attitude toward genetic testing differed between the diseases. For DM1, it was to confirm the diagnosis without genetic testing. For HD, it was that genetic testing would not result in effective prevention or therapy. In FAP, it was that post-testing psychosocial support for the patient and their family was difficult. Common to DM1, HD, and FAP, a significant number of respondents (approximately 60%) felt it difficult to explain the negative aspects that might occur after the disclosure of test results. Concerning predictive or prenatal genetic testing, most respondents referred at-risk individuals to specialized genetic counseling clinics. In general, neurologists are likely to conduct genetic testing properly in consideration not only of the characteristics of the diseases but also of the circumstances of each patient and his or her family. To support neurologists who are involved in genetic testing, the guidelines should be more easily accessible. Many respondents wanted information on the institutions that provide genetic counseling and testing; however, financial support to such institutions is indispensable for fulfilling this requirement.
We present the case of a 31-year-old woman who developed N-methyl-d-aspartate (NMDA) receptor encephalitis during the course of relapsing and remitting multiple brain lesions. The patient developed a tingling sensation in the left upper and lower extremities, and was first admitted to our hospital at age 27. She was tentatively diagnosed with multiple sclerosis on the basis of multiple lesions with Gd-enhancement in the brainstem, and 2 separate clinical relapses by age 28. At age 31, she developed a headache and pyrexia, followed by confusion and abnormal behavior. Her symptoms acutely progressed to stupor, and subsequently, she developed oral dyskinesia and athetosis-like involuntary movement of the left arm. The stupor state continued over 2 months. However, she had completely recovered by 3 months after the onset of psychiatric symptoms. Her serum and CSF samples tested positive for anti-NMDA receptor antibodies, and she was diagnosed with NMDA receptor encephalitis. Her serum was negative for anti-AQP4 antibody, but showed weak positivity for antinuclear antibody. Between ages 32 and 34, she experienced 2 clinical relapses, including right-hand clumsiness, confusion, aphasia, and dysphagia. FLAIR images showed a high-intensity area in the brain stem, thalamus, and subcortical white matter. No tumors were found throughout the course. A clinical entity of NMDA receptor encephalitis can include various neurologic disorders, such as the development of recurrent demyelinating brain lesions. Further investigation is required to clarify the pathophysiological role of anti-NMDA receptor antibody in our patient.
We report an elderly woman with sarcoidosis and rheumatoid arthritis who subsequently developed myasthenia gravis. She was given a diagnose of rheumatoid arthritis at the age of 65 years and sarcoidosis, proved by multiple lymphadenopathy with noncaseating granuloma at the age of 67. Prednisolone, methotrexate, and etanercept had been administrated for rheumatoid arthritis. She consulted our hospital because of bilateral ptosis with diurnal fluctuation at the age of 72. Myasthenia gravis was confirmed by an elevated serum anti-acetylcholine receptor antibody titer (1,100 nmol/l, normal <0.2) and a positive edrophonium test. A chest CT showed a small granular structure in the anterior mediastinum, suggesting thymic hyperplasia. This is the first reported case of myasthenia gravis complicated by sarcoidosis and rheumatoid arthritis. Administration of etanercept may be involved in the onset of myasthenia gravis.
We report a 58-year-old man showing spastic paraparesis due to medulla oblongata compression by tortuous vertebral arteries. He noticed weakness of both legs and gait disturbance at the age of 58 years and his symptoms progressively worsened during the following several months. General physical findings were normal. Blood pressure was normal and there were no signs of arteriosclerosis. Neurological examination on admission revealed lower-limb-dominant spasticity in all four extremities, lower-limb weakness, hyperreflexia in all extremities with positive Wartenberg's, Babinski's and Chaddock's signs, mild hypesthesia and hypopallesthesia in both lower limbs, and spastic gait. Cranial nerves were all normal. Serum was negative for antibodies against human T-cell lymphotropic virus-1 antibody. Nerve conduction and needle electromyographic studies of all four limbs revealed normal findings. Cervical, thoracic and lumbo-sacral magnetic resonance imaging (MRI) findings were all normal. Brain MRI and magnetic resonance angiography demonstrated bilateral tortuous vertebral arteries compressing the medulla oblongata. Neurovascular decompression of the right vertebral artery was performed because compression of the right side was more severe than that of the left side. Post-operative MRI revealed outward translocation of the right vertebral artery and relieved compression of the medulla oblongata on the right side. The patient's symptoms and neurological findings improved gradually after the operation. Bilateral pyramidal tract signs without cranial nerve dysfunction due to compression of the medulla oblongata by tortuous vertebral arteries are extremely rare and clinically indistinguishable from hereditary spastic paraplegia (HSP). Although we did not perform a genetic test for HSP, we consider that the spastic paraparesis and mild lower-limb hypesthesia were caused by compression of the medulla oblongata by bilateral tortuous vertebral arteries based on the post-operative improvement in symptoms. Given the favorable effects of surgery, tortuous vertebral arteries should be considered in the differential diagnosis of patients presenting with progressive spastic paraparesis.
A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.
A 29-year-old man diagnosed as having pulmonary sarcoidosis in 2008, and hypothyroidism secondary to thyroidectomy for Basedow's disease was admitted to our hospital with pustular psoriasis in November 2010. He experienced high fever (38°C) and headache in late October 2010. Gadolinium-enhanced T1-weighted image showed multiple micronodular lesions with leptomeningeal enhancement, mainly in the brainstem. Cerebrospinal fluid (CSF) analysis revealed pleocytosis, raised protein level and hypoglycorrhachia (7 mg/dl). The patient was also found to have osteonecrosis of the left femoral head. Antituberculous treatment and steroid pulse therapy were started, but produced no improvement of either the symptoms or the laboratory data. Finally, the patient was diagnosed as having meningeal disseminated sarcoidosis by meningeal biopsy in late March 2011. He was started on treatment with 60 mg prednisolone per day, which resulted in marked clinical improvement. It should be borne in mind that marked hypoglycorrhachia in the CSF can also be seen in meningeal disseminated sarcoidosis.
We report a 60-year-old male with thymoma-associated myasthenia gravis with anti-MuSK antibodies. In October 2010, he had diplopia, ptosis, and dysphagia. He was diagnosed to have MG in February 2011. The neurological examination disclosed external ophthalmoplegia, bilateral ptosis, mild dysphagia, and fatigability. Repetitive nerve stimulation of the right facial nerve showed CMAP decrement greater than 10%. Patients showed an improvement in ptosis after administration of edrophonium. Anti-acetylcholine receptor antibody was negative, and anti-muscle specific receptor tyrosine kinase antibody was 66.8 nmol/l (cut-off value: 0.05 nmol/l). Prednisolone (50 mg every other day) were started. Contrast-enhanced chest MRI showed a mediastinal mass suggestive of thymoma. Extended thymectomy was performed in March 2011. Histological examination disclosed a type B1 thymoma. After resection of the tumor, the symptoms of MG improved with prednisolone (100 mg every other day). This is a rare case of MG with anti-MuSK antibodies and thymoma, which has been reported previously only in 2 cases.
A 27-year-old woman noticed diplopia when gazing left and paresthesia of the left face and headache of the left side for 8 months. Abduction and supraduction of the left eye were moderately restricted. Hypoesthesia of the face innervated by the ophthalmic branch of the left trigeminal nerve was detected. Visual disturbance due to optic neuropathy developed 5 months later. MRI with gadolinium revealed a mass lesion extending from the left cavernous sinus to the orbital apex. Ocular neuromyotonia and corresponding diplopia were induced by sustained right gaze. Such episodes occurred almost every day on awaking in the morning. Prednisolone (60 mg/day) was given and the headache and visual disturbance ameliorated in two days. The diplopia disappeared in 4 days. The patient remains free from these symptoms after 6 months. This is the first report of ocular neuromyotonia associated with Tolosa-Hunt syndrome.