[A case of neuromyelitis optica associated with anti-aquaporin 4 antibody and other autoantibodies].

We report a patient with optic neuropathy and longitudinally extensive myelitis associated with anti-aquaporin 4 (AQP4) antibody and other autoantibodies. An 89-year-old woman presented with progressive numbness and weakness of the extremities which had acutely developed. She also complained of neck pain and gait disturbance. The results of a general physical examination were unremarkable. Neurologic examination disclosed right optic atrophy, an absence of touch sensation, pain, and muscular weakness in all her extremities. Her deep tendon reflexes were decreased, and the Babinski sign was bilaterally positive. Immunoserologic study yielded positive titers for anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Sjögren syndrome (SS)-A, anti-SS-B, and anti-ribonucleoprotein (RNP) antibodies. A lumbar cerebrospinal fluid examination showed a protein concentration of 54 mg/dL, a glucose concentration of 50 mg/dL (simultaneous blood concentration, 140 mg/dL), and a cell count of 2/mm(3). Chest radiography revealed interstitial pneumonia. Magnetic resonance imaging (MRI) of the cervical spine showed spondylotic cervical canal stenosis with cord impingement. T2-weighted MR images demonstrated increased signal intensity extending from C2 to C6, while contrast enhancement was noted in T1-weighted MR images upon gadolinium-DTPA administration. We suspected longitudinally extensive myelitis associated with the autoimmune disorders systemic lupus erythematosus and Sjögren syndrome. After intravenous methylprednisolone administration, her neurologic abnormalities gradually decreased, while MRI no longer showed increased signal or contrast enhancement. Anti-AQP4 antibody titers were positive. We consider that this patient had a neuromyelitis optica (NMO) spectrum disorder which was associated with systemic autoimmune disease. The possibility of NMO should be considered in similar patients with autoimmune disease, and anti-AQP4 antibody should be assessed.

[Autopsy case of dural thickening caused by widespread dural vein thrombosis associated with disseminated bone marrow carcinomatosis].

A 64-year-old woman was referred to our hospital because of disturbance of consciousness. She had undergone distal gastrectomy for gastric carcinoma 17 years previously. General physical examination was unremarkable, neurologic examination disclosed hyperactive deep tendon reflexes in the upper limbs. Laboratory abnormalities included elevations of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and findings suggesting disseminated intravascular coagulation (DIC). Lumbar cerebrospinal fluid showed a protein concentration of 408 mg/dl and a glucose concentration of 82 mg/dl (blood: 110 mg/dl), as well as a cell count of 16/mm3. Cranial computed tomography indicated brain edema. Magnetic resonance imaging (MRI) of the brain showed diffuse thickening of the dura mater, with contrast enhancement upon gadolinium-DTPA administration. These findings suggested hypertrophic pachymeningitis. Magnetic resonance venography (MRV) showed occlusion of the left transverse sinus and attenuation of the straight sinus. MRI of the spine as well as gallium scintigrams demonstrated multiple areas of increased uptake in areas near the skull and spine. We therefore suspected tumor metastasis. The patient was given heparin as well as pulse therapy with methylprednisolone, but she died 7 weeks after symptom onset. At postmortem examination, the dura was thickened. Histopathologically, numerous tumor cell emboli in the dura were confined to the lumens of veins. The tumor cells were thought to have metastasized to the dura through the vertebral venous plexus (Batson's plexus). Immunostaining demonstrated immunoreactivity of tumor cells to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The primary origin of the carcinoma was not precisely identified by these findings. Widespread dural vein tumor emboli should be taken into consideration as a cause in cases that develop rapid deterioration of consciousness associated dura mater thickening.

[Support of home care and rehabilitation].

With the aging of society in Japan, the figure of Parkinson's disease is gradually increasing and the percentage of patients with severe disease has also increased. Among intractable neurological diseases, the possibility of bed confinement is the highest for this disease. Therefore, in addition to appropriate control of the disease using anti-parkinsonism drugs, maintenance of QOL, rehabilitation, the daily life therapy and treatment at home are necessary in terms of long-term management. Treatment at home combined with persons who care for the patient and in cooperation with other welfare resources may improve the patient's QOL. In diseases that require long-term care such as Parkinson's disease, a comprehensive care management system should be established from the aspect of the patient's QOL.

[A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma].

A 72-year-old woman with von Recklinghausen's disease was referred to our hospital because of pain and muscle weakness in her thighs. She had elevated serum values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase. Based on these results, a diagnosis of polymyositis was made. Treatment with prednisolone improved muscle strength, and laboratory values returned to normal. Computed tomography, magnetic resonance imaging of the abdomen, and 131I-metaiodobenzyl guanidine MIBG scintigraphy demonstrated a tumor 3 cm in diameter in the region of the left adrenal gland. Endocrinologic investigation disclosed elevation of serum and urine catecholamines. Since the blood pressure was normal, nonfunctioning pheochromocytoma was diagnosed clinically. The nonhypertensive course was attributed to reduced vascular response to noradrenaline. Serum lactate dehydrogenase. alkaline phosphatase. and asparate aminotransferase became elevated, and abdominal computed tomography showed a well-defined mass measuring 13 x 12 x 10 cm in the right lobe of the liver. The patient underwent right trisegmentectomy and left adrenalectomy. Histologically the adrenal tumor was a typical pheochromocytoma. The hepatic tumor was a leiomyosarcoma consisting of elongated spindle-shaped atypical cells arranged in intersecting bundles. Immunohistochemically, the cells of this tumor were reactive for alpha-smooth muscle actin and vimentin. The leiomyosarcoma recurred and metastasized to the liver. Eight months after onset of symptom, the patient developed hepatic coma and died. The mean age at presentation with pheochromocytoma in von Recklinghausen's disease patients age is 42 years. Our patient was considerably older. To the best of our knowledge this is the first report of a patient with von Recklinghausen's disease developing polymyositis. asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma and illustrates the need to remain aware of the possibility of cancer in von Recklinghausen's disease.

Decreased total nitric oxide production in patients with duchenne muscular dystrophy.

Plasma nitric oxide (NO) levels in Duchenne muscular dystrophy (DMD) patients were significantly lower than those observed in both healthy controls and in patients with other neuromuscular disorders. The correlation between NO level and ejection fraction was significant (r = -0.384, p = 0.0391) in the DMD group. Disruption of NO systems may contribute to the development of muscular dystrophy and have implications for therapeutic strategies.

[Intractable neurological diseases and neurology].

In intractable neurological diseases, there are often no appropriate treatment methods even after admission and the course is frequently chronic. Therefore treatment at home is a major choice. In particular, in Parkinson's disease and amyotrophic lateral sclerosis, care at home while symptoms are stable is appropriate in terms of extension of ADL and the QOL of the patient and family. We have performed continuous treatment at home according to our plan for the previous 9 years. This treatment was favorably accepted by the patient and family without major problems. It is important to organize network to support patient with intractable neurological diseases. By virtue of the care insurance system established in 2000, services of medical care, health and welfare are being collectively provided at present. But, there still remain many issues awaiting solution on the support to advanced intractable neurological diseases. A pending problem about suction of sputa for the ALS patients serving at home are being allowed to non-medical profession like home helper.

Diagnosis of dystrophinopathy by skin biopsy.

We studied the expression of dystrophin in skin biopsy samples from 19 patients with neuromuscular diseases. Immunohistochemical procedures for dystrophin analyses were performed using monoclonal antibodies for three different domains. Arrector pili muscles, which are smooth muscles in the skin, expressed dystrophin in the patients with limb-girdle muscular dystrophy (5), facioscapulohumeral muscular dystrophy (1), and spinal muscular atrophy (3), and in normal controls (2). The C-terminus of dystrophin was slightly expressed in the patients with Duchenne muscular dystrophy, whereas the rod domain and N-terminus were absent. In one patient with Becker muscular dystrophy, the expression of dystrophin was reduced. The mosaic of dystrophin positive and negative smooth muscle fibers was observed in a manifesting carrier of Duchenne muscular dystrophy. Our results suggest that skin biopsy is very useful for the diagnosis of Duchenne/Becker muscular dystrophy and manifesting carrier of Duchenne muscular dystrophy, and can be performed even at an advanced stage of the disease.