To investigate the safety and effectiveness of the interferon β-1a intramuscular injection under clinical conditions in Japan, we conducted an all-case postmarketing surveillance with a 2-year follow-up of patients who were registered during the period between November 2006 (product launch) and December 2010. Case reports were collected from 397 institutions. The safety analysis included 1,476 patients, and the effectiveness analysis included 1,441 patients. Of the patients included in the safety analysis, 86.3% had relapsing-remitting multiple sclerosis. The most common adverse drug reaction was pyrexia (19.24%). Serious adverse events included multiple sclerosis relapse (26 cases) and abnormal hepatic function (10 cases). In the effectiveness analysis, the annualized relapse rate improved significantly from 1.07 to 0.29 (P < 0.001). There was also a significant improvement in in the expanded disability status scale from 3.08 to 2.94 (P < 0.001). The results of the safety and effectiveness profile were consistent with those in previous reports.
We screened anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies among 42 patients who had undiagnosed chronic myopathy from six national hospitals. Anti-SRP and anti-HMGCR antibodies were determined by RNA immuneprecipitation and enzyme-linked immune-sorbent assay (ELISA), respectively. We identified two patients with anti-SRP antibodies (4.7%) and, two with anti-HMGCR antibodies (4.7%). Both of anti-SRP-positive patients showed dysphagia with a high level of creatine kinase. Anti-HMGCR antibodies were associated with mild muscle weakness with a relatively late disease onset. Our study suggests the importance of autoantibody testing among undiagnosed chronic myopathy.
A 24-year-old woman visited our hospital with a complaint of walking disability. She had no family history of consanguineous marriage, and her developmental history was unremarkable, with good physical performance just before the onset. At the age of 13, she developed difficulty in walking and visited a pediatrician. Her serum CK level was 10,000 IU/l and she was diagnosed with muscular dystrophy by muscle biopsy. At the age of 16, she became wheelchair dependent and was admitted to our hospital. Physical examination revealed diffuse muscle atrophy and proximal weakness, with no calf hypertrophy or selectivity of muscle involvement. Needle EMG and MR images indicated inflammatory myopathy. Muscle biopsy revealed necrotic and regenerating fibers and lymphocyte infiltration. She was re-diagnosed with inflammatory myopathy and recovered walking capacity after immunotherapy. Subsequently, she was tested positive for anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. To distinguish treatable inflammatory myopathy from muscular dystrophy, a comprehensive assessment of patient history, family history, selectivity of muscle involvement, findings suggestive of inflammation in EMG and CT/MR imaging, and muscle pathology is necessary.
We herein report the findings of a 67-year-old woman with steroid-responsive multiple mononeuropathy associated with chronic natural killer (NK) cell lymphocytosis. The patient developed progressive, asymmetric weakness and numbness in all four extremities in the course of a three-month period. Nerve conduction studies revealed asymmetric demyelination in both the motor and sensory nerves, and a biopsy specimen of the sural nerve showed a conspicuous difference in the demyelination between the neighboring fascicles and the infiltration of NK cells in the endoneurium. We considered the multiple mononeuropathy in this patient to have been caused by NK cell infiltration in the endoneurium, and the observed asymmetry might have been due to differences in the NK cell intrusion among the fascicles. Corticosteroid administration resulted in a rapid neurological, electrophysiological and hematological improvement. The rapid clinical amelioration that was observed after corticosteroid therapy suggested that the neuropathy in this case had been mainly caused by the mechanical compression of the endoneurial NK cells or the inflammatory cytokines that had been released by them.
A 69-year-old man was admitted to our hospital because of disturbed consciousness and gait disturbance. He had herpes zoster (HZ) in his left thigh 10 days before admission, and motor paresis of four extremities developed. A dark red rash was observed in his left buttock and thigh (L2–3 region), which was also scattered in the right lower leg, chest wall, and both upper extremities. Brain MRI showed no lesions of demyelinating plaques. Spine MRI showed no abnormal signals in the lumbar region; however, high signals in the spinal cord from the bottom of the medulla oblongata to the upper (Th 2) thoracic region were observed. High signals were observed mainly in the central white matter. These lesions might correspond to longitudinally extensive transverse myelitis (LETM). Cerebrospinal fluid (CSF) showed increased protein and cell counts of lymphocytes and was positive for varicella-zoster virus (VZV)-DNA. His serum sample tested negative for anti-aquaporin (AQP)4 antibody but positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody (cell-based assay). Disseminated HZ was suspected on the basis of the widely scattered rash, and damage to the both lungs and liver. This is the first report of HZ-associated LETM with a high titer anti-MOG antibodies. Our case showed that HZ may trigger anti-MOG-IgG positive myelitis.
A 67-year-old woman developed weakness of the entire left side of the body and disturbance of consciousness, and was admitted to our hospital. She had atrial fibrillation (AF) on arrival at the hospital. Diffusion weighted magnetic resonance imaging showed high intensity area in the right basal ganglia, and magnetic resonance angiography showed occlusion of the right internal carotid artery (ICA). Thrombolytic therapy with intravenous tissue plasminogen activator (IV tPA) was administered 225 minutes after onset, and endovascular procedure also performed. After endovascular therapy, the patient had successful recanalization of the right ICA. Transesophageal echocardiography (TEE) showed a mass in the left atrium. Cardiac surgery for the excision of a left atrial mass and the maze procedure for atrial fibrillation were performed on the 29th hospital day. The mass was pathologically confirmed as thrombus. Follow up TEE after cardiac surgery revealed recurrence of thrombus at the both origin of pulmonary vein in the left atrium. Finally, the thrombus was disappeared at 6-month after onset with taking warfarin. She had no stroke events during the clinical course.
We report the case of a 77-year-old woman with diabetic chorea, which presented as hemiballism of the right limbs. Initial blood examination revealed that sugar and hemoglobin A1c levels were 732 mg/dl and 12.2%, respectively. Thus, a diagnosis of hyperglycemic hyperosmolar syndrome was made at a previous hospital. Ballism of the right limbs developed after 10 days and progressively worsened. After a month, the patient was admitted to our hospital. Brain MRI (axial T1-weighted imaging) revealed a high-signal-intensity area in the left striatum. Dopamine transporter SPECT demonstrated reduced 123I-ioflupane binding in the bilateral striatum with left side predominance. Although haloperidol and risperidone were ineffective for her involuntary movement, chlorpromazine had a little effect. Levodopa and gabapentin combination treatments were effective in decreasing the symptoms. It was considered that dopamine antagonist was the medical treatment for diabetic chorea and that levodopa could worsen neurological symptoms such as chorea-ballism. However, in our case, levodopa treatment was effective.
A 45-year-old male was admitted with an acute-onset visual field defect. Goldmann perimetry revealed an incongruent, incomplete right homonymous hemianopia. The left eye showed a wedge-shaped, horizontal right hemianopia, whereas the right eye showed constriction of the right visual hemifield. MRI showed acute infarction localized to the left lateral geniculate body (LGB). LGB has a dual blood supply: from the anterior choroidal artery and from the lateral posterior choroidal artery (LPChA). The LPChA territory of LGB receives projection from the retinal area around the macula and horizontal meridian. Therefore, an LPChA territory infarction of LGB can cause a wedge-shaped, horizontal visual field defect. The visual field defect in our patient would be caused by an LPChA territory infarction of LGB. Our patient showed an incongruent homonymous hemianopia. LGB has six laminae, with the ipsilateral retinal fibers terminating in layers two, three, and five and the crossed fibers terminating in layers one, four, and six. The laminar structure provides the anatomical basis for the incongruous visual field defects in a case of partial lesion of LGB. Based on the present data, we believe that an ischemic lesion localized to LGB should be considered in patients presenting with incongruous, incomplete homonymous hemianopia.
A 24-year-old man developed subacute onset of numbness and pain in the upper and lower limbs. Physical examination demonstrated decreased pinprick sensation, but was otherwise normal. Blood and cerebrospinal fluid parameters were normal except for mild hepatic dysfunction. No data were suggestive of connective tissue disease. Nerve conduction studies demonstrated sensory neuropathy. A detailed medical interview revealed that the patient had been taking self-imported 2,4-dinitrophenol (DNP) for 2 months to decrease body weight. Six months after discontinuing DNP, subjective symptoms and liver dysfunction resolved completely, and the patient was diagnosed with drug-induced peripheral neuropathy and hepatopathy. There are no case reports of health risks posed by DNP in Japan, and even worldwide, cases of peripheral neuropathy due to DNP are rare. Obtaining a detailed drug history is important, as is providing information on the dangers of self-imported medicines.