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We investigated the expression of neuronal nitric oxide synthase (nNOS) and dystrophin in the regenerating skeletal muscles of rats after cardiotoxin-induced myonecrosis by immunohistochemical studies and western blot analysis. In normal muscles, nNOS was moderately immunostained on type 2B fibers, but was faintly immunostained on type 2A or type 1 fibers. In immunohistochemical studies of regenerating muscles, nNOS was first observed at the sarcolemma of type 2B fibers on day 10, when the type discrimination between types 2A and 2B was first detected by ATP reactions. Subsequently, the immunostaining of nNOS grew progressively stronger in type 2B fibers, with faint staining in type 2A and type I fibers until day 28. Meanwhile, the immunostaining of dystrophin grew stronger equally in all three fibers until day 21. In western blot analysis of regenerating muscles, nNOS regenerated more slowly than dystrophin. The present data suggest that the expression of nNOS is related to the muscle fiber type differentiation, and that the role of nNOS is related to the function of the type 2B fibers of the muscle.

Individual vulnerability to reactive intermediates and oxidative stress accompanying metabolism of endogenous toxic compounds in the brain may promote the development of PD. Phase II detoxification enzymes such as glutathione S-transferase M1 (GSTM1), NAD(P)H:quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH):quinone oxidoreductase 2 (NQO2) are important as cellular defenses against catecholamine-derived quinones and the oxidative stress that arises as a consequence of their metabolism. We conducted a study of the potential association between idiopathic Parkinson's disease and polymorphisms of GSTM1, NQO1, and NQO2. DNA samples from 111 unrelated outpatients with idiopathic PD and 100 unrelated healthy volunteers were analyzed. GSTM1 deletion polymorphism exhibited no positive association with PD (P = 0.596, odds ratio: 1.135), although GSTM1 were grouped into three genotypes (deletion/deletion, deletion/nondeletion, and nondeletion/nondeletion). In addition, polymorphism of the NQO1 gene caused by a C to T substitution in exon 3 presented no association with PD (P = 0.194, odds ratio: 1.31). However, polymorphism in the form of an insertion/deletion (I/D) of 29 base pairs (bp) nucleotides in the promoter region of the NQO2 gene, which contains four repeats of the putative core sequence (GGGCGGG) of the Sp1-binding cis-element, did associate with PD. The frequency of the D allele was significantly higher in patients with PD than in controls (P < 0.0001, odds ratio: 3.463). Our data suggested that the deletion of 29-bp nucleotides in the promoter region of the NQO2 gene associates with the development of PD., (Copyright 2001 Academic Press.)

We report a case of a 70-year-old man who developed Churg-Strauss syndrome (CSS), diagnosed by characteristic histological findings, clinical presentations of mononeuritis multiplex, and multiple small intestinal ulcers with perforations, after discontinuation of corticosteroid therapy. The patient had developed asthma at age of 45, treated with oral prednisolone (10-20 mg daily) from that time. At the age of 70 he developed pneumonia. The condition responded to antibiotics, and the corticosteroid was quickly tapered and discontinued. He was never given leukotriene receptor antagonists during the course of treatment. Approximately two weeks after discontinuation of steroid therapy, he developed severe abdominal pain and mononeuritis multiplex, confirmed by nerve conduction studies. Laboratory evaluation revealed an eosinophil count of 30,450/microliter, and P-antineutrophil cytoplasmic antibody (ANCA) was positive. An abdominal CT scan revealed free air in the abdominal cavity. Laparotomy revealed multiple small intestinal ulcers with perforations. Histologic examination of the intestine showed eosinophilic vasculitis and fibrinoid necrosis. Treatment with systemic corticosteroid (prednisolone 60 mg daily) led to a clinical improvement of neurological and gastroenterological deficits. The prednisolone dose was tapered to 20 mg daily without disease flares. Recently, there have been several reports of CSS that manifested after withdrawal of steroid therapy. CSS can be precipitated in patients with adult-onset, steroid-dependent bronchial asthma after corticosteroid withdrawal.

In the presence of a catalytic amount of ruthenium(II) complexes, [RuCl(2)(cod)](n)(), RuCl(2)(cod)(MeCN)(2), [RuCl(2)(nbd)](n)(), [RuCl(2)(CO)(3)](2), and Cp*Ru(cod)Cl, 1,6-dienes were effectively converted into the corresponding exo-methylenecyclopentanes in good to excellent yields with good isomer purity in i-PrOH at 90 degrees C. The alcoholic solvent was essential for the present catalytic cyclization, and the efficiency increased in the following order: t-BuOH << EtOH < or = i-PrOH. In contrast, a Ru(0) complex, (C(6)Me(6))Ru(cod), catalyzed the cycloisomerization only in 1,2-dichloroethane. The unusual isomer-selectivity occurred when a 1,7-octadiene was subjected to cyclization to give a similar exo-methylenecyclopentane isomer as the major product. The identical isomer selectivity was observed for the cyclization of unsymmetrical 1,6-dienes having one terminal- and one internal-alkene termini. On the basis of the results from the studies using the known ruthenium hydrides and deuterium-labeling substrates, the novel mechanism via the Ru(II) <--> Ru(IV) system involving a ruthenacyclopentane(hydrido) intermediate was proposed, which better explains the particular regiochemistry of the present cyclization than other previous mechanisms.

A 50-year-old man had been well until three months earlier, when he felt general fatigue, and cutaneous rash with itching. Thereafter a general muscular weakness developed and the patient could not walk for a month. Four weeks before referral to our hospital, he had high fever and could not role over in the bed. On admission, the patient was able to walk. He had no skin rash. Neurologically, he showed mild weakness in proximal muscles. Hematologic examination showed mild eosinophilia and serum creatine kinase was mildly elevated. Needle electromyogram revealed a diffuse myogenic pattern in extremities. Eosinophilic myositis was diagnosed by a biopsy of the left calf muscle showing mild infiltration of eosinophilis which was identified using antibodies against eosinophilic granule protein.

A 35-year old Japanese male with adult Sandhoff disease was described, who was presented as a motor neuron disease phenotype with slow progression. At the age of 15, he first noticed weakness in his thigh. At the age of 28, his upper and lower motor neuron disturbances were disclosed. He was diagnosed as atypical amyotrophic lateral sclerosis. At the age of 34, a slight sensory disturbance appeared in the lower extremities. When he was admitted to our hospital, he displayed marked atrophy and weakness in his quadriceps femoris muscles, but no signs of mental deterioration and cerebellar ataxia. Because of the atypical course of motor neuron disease, hexosaminidase activity in peripheral leukocytes was determined. The assay of total hexosaminidase, hexosaminidase A and hexosaminidase B activities demonstrated low levels of these activities (7-15% of controls), leading the diagnosis of Sandoff disease. He was a member of non-consanguineous family, and the abnormal patterns of hexasaminidase activities were different between his father and mother. These data appear to show that he is a compound heterozygote in the locus of the hexosaminidase B gene. This is the first Japanese case of adult Sanhoff disease presented as a motor neuron disease phenotype.

We investigated clinical and pathological features of the sural nerves of 5 patients with the ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and compared these features with those of chronic ataxic neuropathies due to other causes. The CIDP patients presented with slowly progressive ataxia with deep sensory impairment. The durations of the symptoms from onset were relatively short in CIDP (4-8 months) and cancer (3 and 10 months), but long in chronic idiopathic ataxic neuropathy (24-260 months). Corticosteroid therapy elicited a good response in all the patients with CIDP, but a poor response in the patients with other ataxic neuropathies. Sural nerve biopsy of CIDP patients showed a slight or moderate loss of myelinated fiber. This report suggests that ataxic form of CIDP is a steroid-responsive ataxic neuropathy, and large myelinated fibers of the sural nerves in ataxic form of CIDP were better preserved than those in nerves with other chronic ataxic neuropathies., (Copyright 2001 S. Karger AG, Basel)

The expression of dystrophin and alpha1-syntrophin in rat tibialis anterior muscles were evaluated during a cycle of regeneration after myonecrosis induced by the injection of cardiotoxin. Immunohistochemical studies were performed in cryosections of muscles on days 1, 3, 5, 7, 10, 14, 21 and 28 after injection of cardiotoxin. Western blot analysis was also examined in muscle on days 1, 3, 5, 7, 10, 14, 21 and 28. In immunohistochemical studies, dystrophin was stained weakly at the sarcolemma of some regenerating muscle fibers on day 3, and by day 10 it was stained strongly on almost all regenerating muscle fibers. Alpha1-syntrophin was stained weakly at the sarcolemma of some regenerating fibers on day 5, and by day 14 it was detected on all regenerating muscle fibers. In Western blot analysis, dystrophin (DYS1) and alpha1-syntrophin (alpha1S) were completely absent on day 1. Re-expression of DYS1 and alpha1S was visible by day 5 and accelerated thereafter. The Western blots of DYS1 and alpha1S were densitometrically analyzed on each day. The protein levels on each day were converted to the percentage of the protein level on day 28, which was taken as 100%. From the sequential line based on these data, the following results were obtained on the chronological course of DYS1 and alpha1S. DYS1: 25% of the protein level on day 28 was reached by 3.5 days, 50% was reached by 5.3 days, and 90% was reached by 6.9 days. Alpha1S: 25% of the protein level on day 28 was reached by 4.6 days, 50% was reached by 6.0 days, and 90% was reached by 12.5 days. In this study, DYS1 regenerated earlier than alpha1S at the sarcolemma of regenerating muscle fibers.

Ischemia-reperfusion is known to induce generation of oxygen free radicals (OFRs), thereby resulting in tissue damage. To clarify the pathogenesis of diabetic neuropathy, we examined whether hyperglycemia exacerbates the effects of ischemia-reperfusion on peripheral nerves. Using light microscopy, characteristic pathological changes seen in myelin and axons of nerve fibers were classified into two types: "loose myelin" and "dark axon," respectively. After a 2-hour ischemia and 24-hour reperfusion of sciatic nerves of rats, the concentrations of lipid peroxide and "loose myelin" in the nerves were significantly increased in the diabetic rats, but not in the nondiabetic rats. Thereafter, "dark axon" was significantly increased in both diabetic and nondiabetic rats. "Loose myelin" may be increased as a result of the effects of OFRs produced by ischemia-reperfusion, which are exacerbated by hyperglycemia.

A 68-year-old man with sensory ataxic dominant neuropathy associated with polyarteritis nodosa (PAN) had deep sensory disturbance with unsteady gait and absence of the Achilles tendon reflex. Examination revealed weight loss, elevated CRP level, negative antineutrophil cytoplasm antibodies, decreased M-wave amplitude in the peroneal motor nerve and absence of action potentials in the sural sensory nerve. Sural nerve biopsy revealed a marked loss of myelinated fibers, myelin ovoid formation and necrotizing angiitis of large epineurial arterioles. Renal biopsy revealed global and/or segmental necrotizing angiitis in glomeruli, but not in the arcuate artery. These pathological findings were distinct from those of PAN, particularly microscopic polyangiitis (MPA). Treatment with a steroid improved the deep sensory disturbance, unsteady gait, and CRP level. This case is similar to ataxic neuropathy which can arise from various disorders. This is the first report of a case of sensory ataxic dominant neuropathy associated with MPA in PAN.

A 49-year-old man was admitted to our hospital complaining of dysarthria and involuntary movements of his neck and extremities. He had first begun to experience involuntary neck movements at the age of 40 and his symptoms gradually progressed thereafter. There was no family history of neurological disorders. On admission he showed memory disturbance, dysarthria, and choreic movements. The involuntary movements affected his face, neck, trunk, and extremities. MRI of the brain revealed atrophy of both the cerebral cortex and the head of the caudate nucleus. DNA samples for molecular analysis were obtained from the patient and both of his parents. In this pedigree, the father carried a premutated allele of 35 CAG repeats and transmitted an expanded allele of 43 CAG repeats to his son. Paternity and maternity were analyzed using a microsatellite marker located in a different chromosome. To our knowledge, this is the first report of a sporadic case of Huntington's disease in a non-caucasian population in which the disease prevalence is much lower than that in the caucasian population. A new mutation in the current Japanese population which shares the same mechanism as de novo mutation in Caucasians may have contributed to the frequency of HD in Japan at the present time.

Stiff-Man syndrome (SMS) is a rare disease of the central nervous system (CNS) characterized by chronic rigidity, spasms, and autoimmunity directed against synaptic antigens, most often the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). In a subset of cases, SMS has an autoimmune paraneoplastic origin. We report here the identification of high-titer autoantibodies directed against gephyrin in a patient with clinical features of SMS and mediastinal cancer. Gephyrin is a cytosolic protein selectively concentrated at the postsynaptic membrane of inhibitory synapses, where it is associated with GABA(A) and glycine receptors. Our findings provide new evidence for a close link between autoimmunity directed against components of inhibitory synapses and neurological conditions characterized by chronic rigidity and spasms.

Recent studies suggest that Parkinson's disease (PD) is associated with particular personality traits. Using Cloningers's Tridimensional Personality Questionnaire (TPQ), Menza and colleagues [1993: Neurology 43:505-508] reported a possible association between PD and a reduced score in the novelty seeking (NS) dimension of the TPQ. We sought to determine whether this association, which was found in a study conducted in the United States, could also be found among Japanese PD patients. We performed personality assessments of 67 Japanese PD patients, using the TPQ test. The results suggest that Japanese PD patients have significantly lower scores in the NS dimension of the TPQ, as well as significantly higher harm avoidance (HA) scores, compared with matched control subjects. Furthermore, the PD patients undergoing treatment for depression using antidepressant drugs scored significantly higher in the HA dimension than PD patients who did not receive antidepressant drug treatment. Our results suggest that the high HA score, and the low NS score in the TPQ test observed in patients with PD, is a cross-cultural phenomenon, although the influence of depression, long-term treatment, and premorbid gene/environmental interactions may also affect these personality traits. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:1-3, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Glucosuria was detected in a 7-year-old boy by a routine school mass examination in April 1991. The diagnosis of renal glucosuria was made in the affiliated hospital of the University of Tsukuba. The patient developed muscle weakness and gait disturbance in February 1993. Spinal fluid examination revealed a protein level of 62 mg/dl and a cell count of 4/3. Under the diagnosis of Guillain-Barré syndrome, he was treated with i.v. immunoglobulin and oral prednisolone. Although the therapy somewhat improved the symptoms, his muscle strength had not fully recovered at the end of the treatment. In November 1995, the muscle weakness became worse; he could not go up stairs, nor stand upright on one leg. In April 1996, proteinuria was detected in a school mass examination. He was referred to the University Hospital of Tsukuba for a full renal study in March 1997. Renal biopsy revealed global sclerosis in 16 of 19 glomeruli with extensive interstitial fibrosis and mononuclear cell infiltration. A diagnosis of membranous glomerulonephritis was established based on the findings of spikes in PASM staining, weak IgG deposition in the glomerular capillary and subepithelial deposits by electron microscopic study. Additionally, pituitary growth hormone deficiency was found by endocrinological examination. The diagnosis of CIDP was established by fibulal neuron biopsy, which revealed neuronal degeneration and profound demyelinization. The clinical course of the present case was unlike that of the few reported cases of MGN associated with CIDP described in the literature. The initial renal symptom was glucosuria, which started 5 years prior to the onset of proteinuria. Second, glomerulosclerosis was more extensive than that seen in the literature. We surmise that chronic interstitial nephritis of insidious onset was followed by MGN which developed subsequently, probably at the time of the start of proteinuria.

Spinocerebellar ataxia type 6 (SCA6) is one of the eight neurodegenerative diseases caused by a tri-nucleotide (CAG) repeat expansion coding polyglutamine (CAG repeat/polyglutamine diseases) and is characterized by late onset autosomal dominant cerebellar ataxia and predominant loss of cerebellar Purkinje cells. Although the causative, small and stable CAG repeat expansion for this disease has been identified in the [alpha]1A voltage-dependent calcium channel gene (CACNA1A), the mechanism which leads to predominant Purkinje cell degeneration is totally unknown. In this study, we show that the calcium channel mRNA/protein containing the CAG repeat/polyglutamine tract is most intensely expressed in Purkinje cells of human brains. In SCA6 brains, numerous oval or rod-shaped aggregates were seen exclusively in the cytoplasm of Purkinje cells. These cytoplasmic inclusions were not ubiquitinated, which contrasts with the neuronal intra-nuclear inclusions of other CAG repeat/polyglutamine diseases. In cultured cells, formation of perinuclear aggregates of the channel protein and apoptotic cell death were seen when transfected with full-length CACNA1A coding an expanded polyglutamine tract. The present study indicates that the mechanism of neurodegeneration in SCA6 is associated with cytoplasmic aggregations of the [alpha]1A calcium channel protein caused by a small CAG repeat/polyglutamine expansion in CACNA1A.

A 30-year-old female complained of lancinating pain in the bilateral thighs for 10 days. The patient had a 22-year history of insulin-dependent diabetes mellitus. Physical examination revealed swelling of the bilateral lower extremities. There was exquisite tenderness on palpation over the medial thighs, with marked increase in pain on hip and knee flexion. Muscle strength of quadriceps, hamstrings, and hip adductor was decreased due to muscle pain. Pedal pulses were palpable bilaterally. Roentogenograms of the left femur revealed calcification of the left femoral arterial wall. Venogram revealed no obstruction with normal drainage. Complete blood cell count showed left shift of the neutrophils, markedly accelerated erythrocyte sedimentation rate, prolonged prothorombin time of 9 sec (normal 11.7 sec), C-reactive protein of 7.3 mg/dl and serum creatine kinase level of 175 IU/L. FBS was 225 mg/dl and Hb A 1 c was 16.4%. An MR imaging of the thighs revealed high signal intensities in the bilateral adductor muscles on T 2-weighted images. The symptoms resolved spontaneously over a three week period. From the course of the illness and MR imaging, the patient was diagnosed having diabetic muscle infarction (DMI), a rare complication of diabetes mellitus. To our knowledge, this is the first reported case of DMI in Japan. Diabetic microangiopathy and hypercoagulability are thought to be responsible for inducing DMI. Because the diagnosis can be made from the characteristic clinical and the typical MR imaging findings, muscle biopsy is not always necessary to obtain the diagnosis of DMI.

We report the effects of double filtration plasma exchange and immunoadsorption therapy which were performed for a case of stiff-man syndrome even though the patient was negative for anti-glutamic acid decarboxylase (GAD) antibody. The patient underwent a course of four double filtration plasma exchanges, which resulted in marked clinical improvement. Painful muscle cramps disappeared and muscle stiffness reduced within a day after the first plasma exchange. The patient's improvement continued, but his condition declined again about ten months after plasma exchange. Immunoadsorption therapy was then performed, and this treatment was also effective.

Although autoimmune hepatitis and sensory-dominant neuropathy have been known to independently accompany primary Sjögren's syndrome, the combination of all these conditions in the same patient has not been described. We report the case of a woman who initially suffered from autoimmune hepatitis and later was diagnosed with primary Sjogren's syndrome upon the development of sensory-dominant neuropathy. In this patient, autoimmune hepatitis preceded neuropathy by one year. All of the diagnoses were confirmed by histological examinations of the liver, sural nerve, and minor salivary gland. Her autoimmune hepatitis was relieved with conservative treatment, and her sensory-dominant neuropathy was alleviated by prednisolone therapy. Our case indicated that the multiple organ involvement, especially that in the liver and peripheral nerves, should be taken into account in the course of primary Sjögren's syndrome.

To clarify alcohol drinking habits of patients with Parkinson's disease (PD) in Japanese, we compared mean values of alcohol consumption of PD patients and controls with special references to genetic polymorphism of ALDH2. Ninety-three Japanese outpatients with PD (39 males, 54 females) diagnosed by three skilled neurologists from 4 hospitals in Kanto area were analyzed for ALDH2 genotypes and alcohol consumption. A total of 297 healthy controls (156 males, 141 females) in the same area were also analyzed. PCR- SSCP (polymerase chain reaction-single strand conformational change polymorphism) analysis was used to determine ALDH2 genotypes. Mean values of alcohol consumption (ethanol g/month/person) from patients with PD were estimated by direct interview, and those from controls were obtained by questionnaire. Distributions of three genotypes and allele frequencies of ALDH2 were not different between patients and controls, however mean values of alcohol consumption of PD group were significantly lower than those of control group when compared between the same ALDH2 genotype. Our data suggested that the lower values of alcohol consumption in patients with PD for every ALDH2 genotypes may be caused by other factors such as premorbid personality rather than ALDH2 variant.

A 37-year-old female presented with progressive encephalomyelitis with rigidity for a period of about three months. Spasms began with several minutes of paroxysmal painful muscle stiffness in the left upper limb, followed by pain and muscle spasms in the upper limbs, shoulders, neck and back. The paroxysmal painful spasms were easily evoked by light touches and startling. The patient had contracture in the upper limbs and difficulty in relaxing the muscles. She also developed brain stem signs such as left sixth nerve palsy. The serum antinuclear antibody was positive (1 : 160). The cerebrospinal fluid examination revealed mild pleocytosis and protein elevation. Brainstem MRI, cervical MRI, and electroencephalography were normal. Surface electromyography in the arm and neck muscles showed continuous motor unit discharge elicited by passive movement of the right arm. Diazepam and baclofen were minimally beneficial. After treatment with intravenous injection of high-dose methylprednisolone and sequential oral prednisolone administration, the patient showed substantial improvement. This disorder may be part of a clinical spectrum that has an underlying autoimmune basis.

A case of hypertrophic cranial pachymeningitis associated with intramedullary lesion was reported. A 57-year-old male presented with the symptoms of Jacksonian seizure and weakness of right lower extremity. Neurological examination showed weakness and muscular atrophy of right lower extremity (MMT 1-2) and hyperreflexia. Superficial sensation and position sense were normal, however cortical sensory disturbance was recognized in his right lower extremity. MRI revealed diffuse dural thickening with gadolinium enhancement in the left convexity and hyperintense lesion in the bilateral (left dominant) frontal to parietal lobe on T2 weighted image. Magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) showed occlusion of the superior sagittal sinus. Histological examination revealed extensive fibrous tissue with lymphocytes infiltration around the vessels. The cause of the intramedullary lesion in this patient may have been related to the occlusion of superior sagittal sinus, due to thickening dura mater and influence of inflammation.

In this study we sought to learn about when and how amyloid beta-protein (A beta) accumulates in the cortex of normal individuals and about the difference in the A beta accumulation between normal aged and Alzheimer's disease (AD) brains. From consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal cortex T4 were sampled for A beta quantitation by the well characterized two-site enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42 accumulation between the ages of 50 and 70 years in T4 and a little later in CA1. The A beta 42 levels were consistently higher in T4 than those in CA1 in any given case. The levels of A beta 42 in AD brains were significantly higher than those in control brains, and the extent of A beta 42 amino-terminal modification was also much greater in AD brains than that in control brains. Even in cases in which no senile plaques were immunocytochemically detected, EIAs clearly showed that significant amounts of A beta 42 already had accumulated. In contrast to A beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high levels were found to be associated with AD.

We examined sural nerve biopsy specimens from 7 patients with pure autonomic failure (PAF). The mean unmyelinated nerve fiber density in these patients was 40% less than in age-matched controls. Increased numbers of clusters of collagen pockets not containing unmyelinated axons were the most prominent finding in PAF. This appears to reflect recent dropout of a group of sympathetic efferents and suggests grouping of unmyelinated fibers by modality at the level of the sural nerve trunk.

Livedo vasculitis is characterized by recurrent livedo reticularis of lower extremities and the histopathological findings of segmental hyalinizing vasculitis in the skin. We report a case of a 26-year-old female who manifested mononeuritis multiplex 7 years after the onset of livedo vasculitis. She showed sensori-motor disturbances in the right median and ulnar nerves and sensory deficits of the bilateral peroneal nerves. Sural nerve biopsy revealed a remarkable loss of large and small myelinated fibers and a few vasculitic changes. Steroids therapy was effective for these neurological symptoms. But paroxysmal numbness appeared later recurrently in the regions of affected nerves with painful ulcerations in the right leg. Laboratory tests indicated increased levels of serum thrombin-antithrombin complex (TAT), and antithrombotic drugs (argatroban) remarkably ameliorated the recurrent symptoms and skin lesions. These findings suggest that the pathogenesis of livedo vasculitis might be related to alterations of the blood coagulation system.

We investigated endocrine function in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy associated with ragged-red fibers (MERRF), and chronic progressive external ophthalmoplegia (CPEO). Hypothalamic-pituitary function was impaired in all three patients with MELAS or MERRF, but none of four with CPEO. A MELAS patient with dwarfism and impaired adolescent development had decreased growth hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A MERRF patient had emaciation and low adrenocorticotropin. A patient with mitochondrial encephalomyopathy transitional between MELAS and MERRF showed delayed, blunted LH and FSH response to LH-releasing hormone stimulation. We concluded that patients with mitochondrial encephalomyopathies, especially MELAS or MERRF, are likely to have hypothalamic-pituitary dysfunction.

This study was designed to assess self-efficacy and the factors leading to higher self-efficacy in Parkinson's disease patients, as measured by General Self-Efficacy Scale (GSES). Questionnaires were mailed to patients with Parkinson's disease in Tokyo. This study surveyed 73 male and 70 female patients. Approximately 66.5% of the patients fell into the low self-efficacy group. Data was divided into 3 groups (high, moderate and low) and evaluated statistically. Approximately 66.5% of the patients fell into the low self-efficacy group. Patients in the high self-efficacy group exhibited the following features: Males: 1) The male patients in the high self-efficacy group tended to belong to more groups and had less trouble than any other groups in coping with their daily lives; 2) they generally had people to turn to for mental support outside their families, and for their daily life inside or outside their families; 3) they also felt confident that they had sufficient understanding of better life styles and how to exercise. Females: 1) The female patients in the high self-efficacy group tended to go out more often than any other groups and had places to go where they could practice hobbies and exercise; 2) they generally had people outside their families to turn to for mental support; 3) their subjective symptoms, such as freezing and dysarthria, tend to be less acute than in the moderate or low self-efficacy patients. 4) had les trouble than any other groups in coping with their housing accommodations; 5) they also felt confident that they understood how to exercise. In order to increase self-efficacy among Parkinson's disease patients, this study suggests that support, both social and psychological, and providing health education, are important.

The combination of ataxia with peripheral neuropathy (ataxic neuropathy) is rare. Six elderly patients with peripheral neuropathy who developed ataxia were studied. Of the peripheral neuropathies, ataxic neuropathy was significantly more frequent in patients aged more than 65 years compared with younger patients. Ataxic neuropathy was associated with carcinoma (2 cases), Sjögren's syndrome (1 case), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, 1 case) and chronic idiopathic ataxic neuropathy (2 cases). The two cases of carcinomatous neuropathy initially showed ataxia, which preceded detection of the carcinomatous lesions in the lung by approximately 1 year. The study cases had many clinical features in common. In the nerve conduction study, sural nerve action potential could not be measured in five of the cases; sural nerve biopsy revealed a decreased density of myelinated fibers in all cases. In particular, the large myelinated fibers were markedly decreased. These findings were common, regardless of the underlying disease, except in the case of CIDP in which there was only a slight decrease in the number of large myelinated fibers. Differential diagnosis based on the clinicopathological features was difficult. Therefore, in cases of ataxic neuropathy, systemic evaluation is necessary to rule out the possibility of carcinoma or various systemic diseases, especially in elderly patients.

More than 20 years have passed since policies for dealing with intractable diseases have been instituted in Japan. This study was carried out to clarify which factors tend to promote a patient's subjective satisfaction with his or her quality of life. The subjects were 62 male and 51 female patients with Parkinson's disease. Their average age was 68.8 years. The results were as follows: 1. Patients placed more importance on trying to understand the pathophysiology of the disease than trying to improve their better-life with the disease. 2. Most male patients received care from a family member, whereas most female patients received care from a non-family member. 3. Multiple logistic regression analysis indicated that a) patients who understand how to improve their better-life with Parkinson's Disease are four times more satisfied(on-a subjective basis)than patients who do not understand how to improve their better-life, and b) patients who have a supportive caregiver are twice as satisfied as those who do not. These findings suggest that, in order to increase the subjective satisfaction of Parkinson's disease patients, it is important for them to have a supportive caregiver and to help them understand how to improve their better-life.

Here we report a case of a 56-year-old male with post-poliomyelitis muscular atrophy (PPMA), who presented with cranial nerve signs and widespread atrophy of the extremities. He had suffered from poliomyelitis at the age of 2 years. After recovery from the acute stage, the paralysis remained in his left arm. He noticed muscle weakness of the right upper and lower extremities at the age of 45 years and the muscle atrophy progressed to his arms, hip and thigh at the age of 55 years. Neurological examination revealed muscle atrophy of the neck and disturbance of left V, VIII, IX, X and bilateral XI cranial nerves. We diagnosed this case as PPMA from his history and electromyographic and muscle biopsy findings which suggested chronic denervation. Among the 21 PPMA cases in the past in which the acute poliomyelitis had resulted in paralysis of the only one limb, ours was the only case that had muscle atrophy of all the limbs. Cranial nerve involvement is known to occur in acute poliomyelitis; therefore, there is a possibility that the involvement of the cranial nerves in our case might be a delayed progressive symptoms.

We reported a rare case who had hypoxic-encephalopathy causing frontal apraxia of gait. The patient, a 34-year-old female, was admitted in July, 1994, complaining of difficulty in walking after anoxic brain damage caused by ventricular arrhythmia. She had difficulty in raising her feet, which appeared to be rooted to the floor. There was no evidence of motor paralysis, spasticity, rigidity or sensory loss, but she did show frontal lobe signs such as foot grasp reflex and Gegenhalten. Cranial MRI showed slight atrophy of the frontal lobe. On T2 weighted image, high-intensity areas were detected at the posterior internal capsule and corona radiata. Single photon emission CT (123I-IMP) demonstrated a low perfusion area which included the inferomedical part of the frontal lobe. After 8 months of hospitalization, her postural instability and unsteady gait slowly improved without treatment as frontal signs such as foot grasp reflex disappeared. We speculate that her apraxia of gait may result from grasp reflex and Gegenhalten.

We report a 47-year-old female patient showing clinical features of chronic progressive external ophthalmoplegia (CPEO) without stroke-like episodes. Large scale deletion of mitochondrial DNA (mtDNA) was not found in her biopsied muscle, whereas the A-->G transition at position 3243 (A3243G) was detected. The patient's mother had diabetes mellitus, suggesting maternal inheritance. This mutation is usually associated with MELAS, but wide clinical variety of the mutation has been recognized. Although several patients of CPEO with A3243G mutation (CPEO3243) have been found in the Western countries, only one case has been reported in detail in Japan. The CPEO3243 patients, including ours, show retinopathy less frequently, but diabetes mellitus and hearing loss more frequently than CPEO patients with deletions of mtDNA (CPEO delta). CPEO3243 is usually inherited maternally, but almost all CPEO delta is sporadic. With regard to COX activity of biopsied muscles, CPEO3243 resembles CPEO delta more than MELAS3243. This suggests that how the mutant mtDNA is distributed among cells or tissues may have more significant effect on clinical phenotype than what type of mtDNA mutation exists. The presence of such a CPEO3243 patient like ours could be an important suggestion toward further understanding of mitochondrial diseases.

The authors reported a case of potassium-sensitive periodic paralysis with cardiac dysrhythmia. The patient was a 21-year-old male and had periodic paralysis and asymptomatic cardiac dysrhythmia since the age of 12. His attacks worsened in frequency and intensity which brought him to our hospital at the age of 21. Physical examination on admission revealed slight dysmorphic features such as hypoplastic mandible and high-arched palate. He had slight proximal muscle atrophy with no myotonia. Electrocardiogram showed multifocal ventricular arrhythmia. The serum potassium levels during his paralytic attacks were normal or slightly decreased (3.6-4.2 mEq/l). Both potassium and glucose tolerance tests provoked paralytic attacks. Glucose tolerance test also aggravated his cardiac dysrhythmia. Acetazoramide administration improved his paralytic attack. Potassium-sensitive periodic paralysis with cardiac dysrhythmia can not be defined by the classification of periodic paralysis based on the serum potassium concentration. Provocative tests should be done to make a definite diagnosis and treatment should be done taking into consideration both paralytic attack and cardiac dysrhythmia.

123I-MIBG myocardial scintigrams obtained in 2 cases with pure progressive autonomic failure are presented. In the less advanced case, 123I-MIBG myocardial SPECT disclosed uptake defects of radioisotopes in both the apical region and the inferior wall and a marked decrease in uptake in the lateral wall. However, residual radioactivity was demonstrated in the anterior wall. In the terminal stage, radioactivity over the whole heart was undetectable in planar images, so as to be of no use to obtain SPECT images. These scintigrams might suggest where the sympathetic denervation began and subsequently extended to the whole myocardium in the course of the disease. In addition, 123I-MIBG scintigraphy was recommended in a case with the disease, since an unequal impairment of myocardial sympathetic nervous system has been described to probably induce fatal arrhythmias which were the cause of sudden death in this case.

Here we report two cases of pseudoradicular sensory impairment (PRSI) caused by cerebral infarctions. Case on was a 49-year-old male who presented with dysesthesia in the left ulnar nerve distribution, and case 2 was a 57-year-old male who developed dysesthesia and weakness in the left radial nerve distribution. In both cases, the symptoms began with dysesthesia, followed by disturbance of cortical sensation, and distal motor weakness of the left upper extremity. Although the temperature, superficial pain, tactile, and vibratory sensations were well preserved, position sense, and cortical sensations such as two-point discrimination, material discrimination and stereognostic sensations were severely disturbed. No abnormalities were found in nerve conduction studies or cervical magnetic resonance imaging (MRI). Findings of somatosensory evoked potential (SEP) indicated that cortical components (N20, P24, N35 and P55) were missing in the left ulnar nerve in case 1, and in the median nerve in case 2. MRI of the brain revealed cerebral infarctions in the right parietal lobe including the postcentral gyrus. From the above results sensory disturbances of these two cases are caused by infarctions of the right parietal lobe. The characteristics of sensory disturbances caused by parietal lesions in our cases are similar to the previous reports. In addition, we found that the impaired cortical and subcortical areas were larger than the predicted areas indicated by Penfield's somatosensory homunculus. From the thermography, we found that the dermal regions with sensory impairment were more or less hypothermal. This suggests that cortical and subcortical infarctions may lead to localized sympathetic dysfunctions of the skin.

We report a patient who developed keratitis and corneal edema during treatment with carbidopa-levodopa. The patient was a 34-year-old woman who complained of apraxic gait after anoxic brain damage caused by ventricular arrhythmia. She had difficulty in walking. While doses of droxidopa, flecainide acetate and amantadine HCl were kept at the same levels as before several weeks, administration of carbidopa-levodopa was gradually increased from an initial dose of 100 mg per day to 300 mg per day over a period of 10 days in an attempt to relieve her apraxic gait. Ten days after initiation of treatment with carbidopa-levodopa, her postural instability and unsteady gait slightly improved. However, after 8 days of treatment with carbidopa-levodopa, she complained of blurred vision. Ophthalmologic examination showed keratitis (corneal endothelitis) and corneal edema. After stopping carbidopa-levodopa, the keratitis dramatically improved. Cessation of the drug therapy resulted in a return of vision to normal levels by the 7th day. Although there had been no previous reports of corneal lesion caused by levodopa, we suspected that keratitis and corneal edema were associated with carbidopa-levodopa use, especially in combination treatment with flecainide acetate, and amantadine HCl. The process was reversible and presumably could have been prevented by a shorter term of medication.

We performed histologic and morphometric analyses of the sural nerve in 13 patients with vasculitic neuropathies. The ratio of vessels with vasculitis, the caliber of involved vessels, and pathologic changes of myelinated fibers were evaluated. In patients with polyarteritis nodosa (PN), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), marked vasculitis with inflammatory cell infiltration and occlusion were observed in epineurial arteries greater than 100 microns in diameter, and mild vasculitic changes were noted in arterioles 40 to 100 microns in diameter. In vessels less than 40 microns, mild vasculitis with perivascular cuffing was noted in patients with RA and SLE, but not in PN. In a patient with microscopic PN, mild inflammatory cell infiltration was encountered around small vessels at diameters less than 40 microns as well as those greater than 100 microns. In a patient with nonsystemic vasculitic neuropathy, vasculitic changes were identified only in vessels less than 40 microns. In patients with Churg-Strauss syndrome (CSS), there were no distinct findings of vasculitis in any biopsy material. In conclusion, morphometric analyses of the caliber of involved vessels may be useful in the differential diagnosis and classification of underlying vasculitic neuropathies.

Immunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and Cu/Zn-SOD) in biopsied muscles from 7 patients with mitochondrial encephalomyopathies that included mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), and chronic progressive external ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region, but it also was found in a coarsely granular, reticular, or diffuse pattern of staining within the muscle fibers. These Mn-SOD-positive fibers corresponded almost completely to the ragged-red fibers. The immunoreaction for Cu/Zn-SOD was weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD-positive fibers predominantly showed decreased cytochrome c oxidase (COX) activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX although a few were COX-negative. These findings suggest that Mn-SOD-positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the ragged-red fibers may protect against oxidative stress.

We report a case of mononeuropathy multiplex due to interferon alpha (IFN alpha) therapy for chronic hepatitis C. A 61-year-old man received IFN alpha (natural type 6 x 10(6) IU), every day for two weeks and three times a week for 22 weeks by intramuscular injection. Seventeen weeks after the initiation of IFN alpha therapy, he noticed painful dysesthesia, muscle weakness and muscular atrophy of the left lower extremity. Neurological examination revealed weakness of the left iliopsoas, quadriceps femoris and femoral adductor muscles, hypesthesia and dysesthesia. Electromyogram showed neuropathic change in the left vastus lateralis muscle. Muscle computed tomography showed muscular atrophy of the left lower extremity. Two months after discontinuation of the IFN alpha therapy, dysesthesia and muscle weakness of the left lower extremity improved spontaneously. He was diagnosed as mononeuropathy multiplex of the left femoral nerve and obturator nerve caused by IFN alpha therapy. Attention must be paid to dysesthesia, muscle weakness and muscular atrophy when IFN alpha therapy is initiated.

We present a 55-year-old man who suddenly became afflicted with a bilateral auditory disturbance. Auditory acuity was preserved relatively well. Brainstem auditory evoked potentials (BAEPs) were normal. Middle latency auditory evoked potentials (MLAEPs) revealed the total absence of all waves. Brain computed tomography (CT) showed infarctions of the temporal lobes bilaterally, involving the superior temporal and transverse temporal gyri. The recognition of verbal and nonverbal sounds was also impaired. Brain CT, MLAEPs and auditory recognition tests were useful in diagnosing the cortical auditory disorder.

We described a 56-year-old man with stiff-man syndrome, who was markedly improved after plasmapheresis therapy. He had a 12-year history of progressive painful stiffness of his back and limbs, muscle cramps and difficulty in walking. He had been taking oral diazepam and prednisolone. On examination the abdominal and paraspinal muscles and limbs were continuously contracting, confirmed by surface and needle electromyography. Antibodies against glutamic acid decarboxylase (GAD) and pancreatic islet cells in the serum were negative, but antinuclear antibody and anti-smooth-muscle antibody were present. The patient underwent a course of 4 double filtration plasma exchanges of 3,000 ml each in an 8-day period. Plasmapheresis resulted in marked clinical improvement. The disappearance of muscular cramps and a reduction of stiffness occurred within 24 hours after the first plasmapheresis, and he was able to walk unassisted. The patient's subjective improvement continued over 4 months after the plasma exchange. This case provides additional evidence of the autoimmune mechanism of stiff-man syndrome. Plasmapheresis is one choice in the management for stiff-man syndrome.

A 67-year-old woman with a one-year history of tinnitus and headache had multiple cranial nerve palsies of V, VII, VIII, IX, X, XI and spastic paraparesis. She also had a secretory otitis media. Gd-DTPA-enhanced magnetic resonance imaging (MRI) revealed hypertrophy of the dura of the posterior fossa and spinal epidural mass which extended from C7 to T10. A biopsy of the epidural mass showed chronic granulomatous change. These lesions were completely cured with administration of antibiotics. We believe this case of double-lesion of hypertrophic cranial pachymeningitis and spinal epidural granulomatous lesion originated from a bacterial infection secondary to the secretory otitis media.

We investigated the clinical usefulness of N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) for diagnosis of spinocerebellar degeneration. The uptake in the cerebellar hemispheres and vermis was decreased in sporadic cerebelloolivary atrophy (Holmes, n = 9) and sporadic olivopontocerebellar atrophy (OPCA, n = 6). The uptake in the pons was decreased in OPCA. The decrease of the uptake in the cerebellum and the pons was associated with clinical severity in OPCA. Our results show that semiquantitative SPECT analysis differentiates between the Holmes type and OPCA.

A 55-year-old woman presented with a one-year history of painful muscle cramps and progressive flexion contractures of the arms, pelvic girdles and knees. Laboratory evaluation was summarized as follows: low plasma cortisol and ACTH levels, delayed response of plasma cortisol to ACTH administration, no response of plasma ACTH level to insulin administration, and normal plasma LH, FSH, GH, TSH and PRL levels. She was diagnosed as isolated ACTH deficiency. EMG was silent in contractured muscles at rest. Biopsy of the biceps femoris muscle revealed a marked reduction in fiber size, type 2 fiber atrophy and type 1 fiber predominance. The nerve conduction velocities of the peripheral nerves were found to be decreased. The biopsied specimen of the sural nerve revealed a loss of large myelinated fibers and segmental demyelination. Both flexion contractures and nerve conduction velocities were gradually improved with the replacement of hydrocortisone.