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We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.

Background: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP- N -acetylglucosamine 2-epimerase/ N -acetylmannosamine kinase ( GNE ). Objective: To determine whether DMRV and HIBM are allelic. Methods: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. Results: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. Conclusions: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with Parkinson's disease using statistical parametric mapping (SPM).Noninvasive rCBF measurements using 99mTc-ethyl cysteinate dimer (ECD) SPECT were performed on 28 patients with Parkinson's disease and 48 age-matched healthy volunteers. The Parkinson's disease patients were divided into two groups, 16 patients with Hoehn and Yahr stage I or II and 12 patients with Hoehn and Yahr stage III or IV. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images in relative flow distribution (normalization of global CBF for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM.In patients with stage I or II Parkinson's disease, we found a diffuse decrease in absolute rCBF in the whole brain with sparing of the central gray matter, hippocampus and right lower temporal lobe compared with healthy volunteers. Adjusted rCBF increased in both putamina and the right hippocampus. In patients with stage III or IV disease, rCBF decreased throughout the whole brain. Adjusted rCBF increased bilaterally in the putamina, globi pallidi, hippocampi and cerebellar hemispheres (dentate nuclei) and in the left ventrolateral thalamus, right insula and right inferior temporal gyrus.SPM analysis showed that significant rCBF changes in Parkinson's disease accompanied disease progression and related to disease pathophysiology in the functional architecture of thalamocortex-basal ganglia circuits and related systems.

Objective – The purpose of the present study was to assess the relationship between clinical characteristics of spinocerebellar ataxia type 6 (SCA6) and CAG repeat length. Materials and methods – We examined clinical symptoms of 54 patients with SCA6. CAG repeat length was compared among subgroups divided by clinical manifestations. Results – The major symptom was progressive cerebellar ataxia. Truncal or limb ataxia, dysarthria, and nystagmus were observed in more than 80% of the patients. In analysis of CAG repeat length in patients with different types of nystagmus, CAG repeat length was the longest when both upbeat and downbeat nystagmus existed (P

We report 2 familial patients with limb-girdle muscular dystrophy (LGD). The parents of patient 1 showed a consanguineous marriage and patient 2 was a paternal cousin of patient 1. Slowly progressive muscular weakness/wasting and dystrophic changes in the biopsied muscles were observed in both patients. However, a quantitative assay revealed a severely reduced myophosphorylase activity in patient 1 with normal activity in patient 2. A semi-ischemic exercise test disclosed no elevation of venous lactate in patient 1 with a normal increase in patient 2. A leukocytes DNA analysis in patient 1 did not show the gene deficits previously recognized in patients with McArdle's disease (McD). Patient 1 may only have abnormal myophosphorylase activity with dystrophic changes secondary to the myophosphorylase deficiency or coincidentally two genomic abnormalities for McD and LGD. LGD still has heterogenous etiologies and the responsible genes for these two disorders may be closely mapped.

A 48-year-old man, who had spastic tetraplegia and a marked atrophy of the medulla oblongata and upper cervical cord, was reported. He began to walk in spastic fashion at the age of 12 years, and was diagnosed as spastic paraplegia. His father, whose onset of the disorder was 35 years old and died of pneumonia at the age of 69 years, manifested symptoms and a course, both resembling those of the present patient. Generalized weakness progressed gradually, and the patient was confined to bed in his forties. On admission, he showed markedly increased tendon reflexes and pathological reflexes in all the extremities. Muscular weakness was severe in the neck, trunk and extremities, and mild in the facial muscles. There were neither bulbar sign, significant respiratory failure nor fasciculation of muscles. A needle EMG examination revealed no apparent neuropathic findings. MR imaging showed a marked atrophy of the medulla oblongata and upper cervical cord, which was not considered to be secondary to vascular or infectious diseases. Though sensory evoked potentials showed no response at the latencies of central nervous components, visual evoked potentials, brainstem auditory evoked response and blink reflex were normal. This case might represent an unknown hereditary degenerative disease with autosomal dominant inheritance.

We report a 75-year old Japanese man with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). His family had no consanguinous marriage and his grandfather had migraine attacks. His father showed uncontrollable emotion at the age of 59 followed by gait disturbance, disorientation, pseudobulbar palsy and died at the age of 63. The patient had migraine attacks with aura since 10 year-old and showed uncontrolableness of his emotion and gait disturbance at the age of 63 followed by disorientation, urinary incontinence and pseudobulbar palsy, and died from aspiration pneumonia at the age of 75. The postmortem examination revealed an arteriopathy in the cerebral white matter and meningeal vessels and multiple infarctions in the cerebral white matter corpus callosum, basal ganglia, middle cerebellar peduncle and pontine tegmentum. The affected arterial walls showed eosinophilic and periodic acid Schiff (PAS)-positive granules in the media, which were composed of numerous electron dense small granules in varying sizes on electron microscopic examinations. These granules showed complements (Clq, C3, C4)-like immunoreactivity but did not have IgG-, IgM-, IgA-, kappa and lambda chain-, or beta-amyloid-like immunoreactivities. The clinicopathological features in this patient were compatible with those reported as CADASIL in the European countries and this is the first case report of CADASIL in Japanese race.

To evaluate the clinical characteristics of Machado-Joseph disease (MJD) with reference to CAG repeat length and disease duration, we analyzed neurologic findings in 108 patients from 84 families. The majority of MJD patients presented with an ataxic gait as the initial symptom. Dysarthria and nystagmus were observed from an early stage. Bulging eyes, muscle atrophy and bradykinesia developed later. Patients with a shorter CAG repeat length or later onset had more frequent involvement of proprioceptive sensory deficit. Incidence of abnormal reflexes, tones, and proprioceptive sensation was not associated with disease duration, but with CAG repeat length. Based on these results, we propose a new clinical classification: type A (juvenile type), with hyperreflexia and dystonia, but without a proprioceptive sensory deficit; type C (adult type), with hyporeflexia and a proprioceptive sensory deficit, but without dystonia; and type B (intermediate type), the remaining patients with a mixed presentation.

We report 2 autopsy-proven cases of motor neuron disease/amyotrophic lateral sclerosis (MND/ALS), who developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) prior to the respiratory failure. With respect to the underlying mechanisms of SIADH in the cases, we considered two factors; 1) dysfunction of the feedback system in ADH secretion via intrathoracic volume receptors caused by changes in intrathoracic circulation, and 2) primarily functional abnormalities in the limbic system which could influence hypothalamic osmoreceptors. It appears that SIADH can be followed by an exacerbation of respiratory dysfunction in MND/ALS.

We describe a kindred with autosomal dominant myopathy with preferential proximal limb muscle involvement. This disorder is characterized clinically by early adult onset, slow progression, normal life expectancy, weakness and atrophy of proximal limb muscles, especially in the lower limbs. Laboratory examinations showed myopathic changes mixed with neuropathic components on needle electromyography, slight elevation of serum creatine kinase, and absent cardiac involvement. In biopsied muscle findings of two patients, the presence of rimmed vacuoles was the most striking finding to explain muscle degeneration, though a few necrotic fibers were present. The pathologic and clinical findings in the present family are almost similar to those seen in "adult-onset autosomal dominant limb-girdle muscular dystrophy" reported by Chutkow et al.

Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as the cause of the disease. We have analyzed 90 MJD individuals from 62 independent MJD families and found that the MJD1 repeat length is inversely correlated with the age of onset (r = -0.87). The MJD chromosomes contained 61-84 repeat units, whereas normal chromosomes displayed 14-34 repeats. In the normal chromosomes, 14 repeat units were the most common and the shortest. In association with the clinical anticipation of the disease, a parent--child analysis showed the unidirectional expansion of CAG repeats and no case of diminution in the affected family. The differences in CAG repeat length between parent and child and between siblings are greater in paternal transmission than in maternal transmission. Detailed analysis revealed that a large degree of expansion was associated with a shorter length of MJD1 gene in paternal transmission. On the other hand, the increments of increase were similar for shorter and longer expansion in maternal transmission. Among the three clinical subtypes, type I of MJD, with dystonia, showed a larger degree of expansion in CAG repeats of the gene and younger ages of onset than the other types.

We describe two brothers with early onset cerebellar ataxia associated with hypoalbuminemia (EOCAH). Choreo-athetoid movements preceded the cerebellar ataxia, and serum pseudocholinesterase elevation preceded the hypoalbuminemia. The parents are first cousins. Patient 1, the 22-year-old elder brother, developed choreoathetoid movements of the neck and extremities at the age of eighteen months. He later developed slowly progressive cerebellar ataxia with decreased tendon reflexes. The choreoathetoid movements ceased at about 16 years of age. A recent examination revealed cerebellar ataxia, action myoclonus of the neck and upper limbs, diminished tendon reflexes, mild sensory disturbance in the lower extremities, and very slight amyotrophy of the feet. Patient 2, the 18-year-old younger brother, developed choreo-athetoid movements at the age of 6 years, followed by slowly progressive cerebellar ataxia with disminished tendon reflexes. No scoliosis, ECG abnormalities, or edema was detected. Serum biochemistry studies revealed elevated pseudocholinesterase (6,226 to 2,390 IU) in the patient's early teens. Serum albumin levels tended to be low (3.7 to 4.1 g/dl). Serum triglyceride and beta-lipoprotein levels were elevated in the patients' late teens. Genetic studies showed slight linkage of D9S15. The maximum lod score was 0.289 (recombination fraction rate was 0.14).

Magnetic resonance images in some cases of amyotrophic lateral sclerosis (ALS) revealed abnormal signals in both the paraventricular white matter and in the posterior limbs of the internal capsule. We examined T2- and diffusion-weighted MR images of these lesions in 18 cases of ALS. There were symmetrical high-signal areas in the posterior limbs of the internal capsule in all of the cases. The high-signal areas in the internal capsule corresponded to the pyramidal tracts in the anatomical atlas by Talairach. In 5 of the cases of ALS, T2- weighted MR images showed discrete paraventricular white matter lesions as well. The mean age of the ALS patients with paraventricular white matter lesions was higher than that of the ALS patients without such lesions. Proton densities calculated from the conventional MR images were higher in both the capsular and paraventricular lesions. The diffusion coefficients perpendicular to the pyramidal tract in the internal capsula lesions were within the normal range, where as the diffusion coefficients in the paraventricular lesions were increased in all directions. Thus, diffusion anisotropy was lost in the paraventricular lesions. These findings are similar to those observed in the white matter lesions of cerebro-vascular origin. As a result, the pathology of the paraventricular lesions in ALS was confirmed to be different from that of the internal capsular lesions.

Diffusion MRI studies were performed on 14 patients with diffuse high-signal lesions of the cerebral white matter on T2-weighted MR images. There were two patients with adrenoleukodystrophy, four with dentato-rubro-pallido-luysian atrophy, three with familial spastic paraplegia, two with myotonic dystrophy and three with dementia of unknown origin. In addition, a patient with of Sanfilippo disease and one of the three patients who exhibited dementia of unknown origin were also found to be low-signal in the cerebral cortex T2-weighted MR images. In every case except the last two, diffusion-weighted MR images yielded significantly higher apparent diffusion coefficients perpendicular to nerve fibers in the frontal white matter and the corpus callosum than in the normal controls. The lesions displayed increased diffusion anisotropy, calculated as the ratio of the diffusion coefficient perpendicular to the nerve fibers to the diffusion coefficient parallel to the nerve fibers, i.e., diffusion anisotropy was lost in the white matter, suggesting a demyelinating process in the lesion. In the last two cases, on the other hand, the diffusion coefficient and diffusion anisotropy were within normal range. The white matter lesions in these cases were thought to represent degeneration secondary to the cortical involvement. Thus, it was confirmed that diffusion-weighted MR images, unlike T2-weighted MR images, were confirmed to allow differentiation between at least two types of white matter lesions.

FLAIR (fluid-attenuated inversion recovery) images are MR images obtained with an inversion recovery sequence having a long inversion time (TI) and a long echo time (TE). Twenty healthy adults and twenty patients with multiple cerebral infarction, multiple sclerosis, temporal epilepsy, or brain trauma were examined with FLAIR sequences of several types having repetitive times (TR) of 4000-8000 msec, inversion times of 1200-2400 msec and echo times (TE) of 140-200 msec, and the results were compared with spin-echo sequences (TE = 20 msec and TE = 90 msec). With a long repetitive time of 6000 msec and a long inversion time of 1400-1600 msec, the cerebrospinal fluid signals in the lateral ventricles and the cerebral sulci were low-intensity with brain tissue appearing as high signal intensity areas with good T2 contrast. The FLAIR image signal intensities correlated well with T2 relaxation times under 100 msec. Cystic lesions with long T2 relaxation times over 100 msec in multiple sclerosis and cerebral infarction appeared as low-signal areas, and the lesions surrounding the cystic lesions as high-signal areas. In patients with temporal lobe epilepsy, the hippocampus was visualized as a high-signal area. Hippocampal lesions were demonstrated better with FLAIR images than with conventional T2-weighted images or proton-density images. In a cerebral contusion patient, the FLAIR images revealed a lobulated structure with the residual cortex appearing as high-signal areas. The lesions surrounding the cystic change were imaged as high-signal areas. These structural changes were demonstrated better with FLAIR images than with conventional T2-weighted sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, radiological, and histological examinations were performed on eight patients with autosomal-dominant dentato-rubro-pallido-luysian atrophy (DRPLA) including an autopsy case, to investigate the abnormal findings of the cerebral white matter in DRPLA. Three of the eight patients were found to have diffuse low density on CT or diffuse high-signal areas on T2-MRI in the white matter of the brain. There were no correlations between abnormal findings in the white matter and the following factors; age of onset, duration of the disease, clinical manifestations, disease severity, Hachinski score, or EEG abnormality. Single-photon emission tomography failed to reveal any relative decrease in cerebral blood flow in the white matter, even in the three patients with abnormal findings in the white matter. MRI perfusion studies did not suggest any decrease in cerebral blood volume in any of the patients examined, but in the DRPLA patients the latency, i.e., the interval from the time of injection to the time of the minimum signal intensity, was significantly prolonged in comparison with the results in normal controls. On histopathological investigation, there was diffuse decreased staining in the centrum semiovale and deep white matter of the temporal lobes bilaterally, but no gliosis, or arteriolar thickening or hyalinization were detected. These findings confirmed that the lesions in the white matter in DRPLA are not attributable to cerebral ischemia. The abnormal findings are presumably the result of the degeneration which occurs in DRPLA itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, neurophysiological and neuropathological investigations were performed on five patients from two families with autosomal dominant distal amyotrophy followed by spastic paraplegia and with a positive history in two generations of these two families. All cases in the two families had a benign clinical course, although two mothers could not walk without support at around 60 years old. Neurophysiological studies revealed normal maximum conduction velocities of peripheral sensory and motor nerves, and the central spinal sensory pathway. Distribution of motor nerve conduction velocities in the ulnar nerve had a normal pattern except for one patient who had severe deformities of the cervical vertebrae. The biopsied sural nerve disclosed no distinct abnormalities in any cases. From these results, we confirmed preservation of the myelinated nerve fibers of motor and sensory peripheral nerves.

We analyzed diffusion weighted magnetic resonance images (diffusion MRI) of the basal ganglia, which were obtained from four patients with Wilson's disease, and compared them with the images from ten age-matched normal individuals. In all patients, T2-MRI of the basal ganglia disclosed low or iso-signals, but diffusion MRI revealed abnormal high signals in some areas of the basal ganglia in each case. Pathological changes except for copper and/or iron deposits are difficult to estimate by T2-MRI because the low signal on T2-MRI emphatically reflects the deposits, while the abnormal high signal on diffusion MRI is thought to reflect parenchymal lesions such as cell loss, demyelination and/or increase of the extracellular fluid. From our results, we confirmed that diffusion MRI was very useful for estimating parenchymal lesions with metal deposits.

We report a case of 33-year-old man with multiple sclerosis, showing piano playing movement in both hands. His course of multiple sclerosis was remittent/progressive during 2 years and the clinical manifestation suggested the spinal cord involvement. On July 15, 1991, he was admitted with numbness of the right limbs, and then developed piano playing movement in both hands, more marked in the right side. Neurological examination revealed mild weakness in the right upper extremity, and rough touch, pain, and temperature sensation were slightly decreased. However, there was no deep sensory abnormalities, such as vibration, fine touch, and position senses. Vibration sense was lost below ilium. CSF examination showed elevation of IgG index (1.6), three oligoclonal bands and myelin basic protein content of 2.4 ng/ml. There was no HTLV-I antibody in CSF. SSEP, elicited by median nerve stimulation at the right wrist, showed no N13 and low amplitude of N20. T2-weighted images of cervical MRI revealed area of high signal intensity at the C3-C4 level. The piano playing movement gradually improved and disappeared by the initiation of steroid hormone therapy. It was considered that involuntary movement in this patient was due to the spinal cord lesion caused by multiple sclerosis. These findings suggested that the involuntary movement like pseudoathetosis could present without deep sensory abnormalities.

Serial examination of magnetic resonance images (MRI) for two months were carried out on two cases of multiple cerebral infarction during the acute stage. The T2-weighted MR images at the onset of the infarction showed both acute (new) and chronic (old) lesions appearing as high signal area. While on the diffusion weighted images only an acute lesion was detected as a high signal area with good contrast. The diffusion coefficient of the acute lesion was lower than that of normal white matter. Diffusion coefficient of the chronic lesions were higher than that of normal white matter. Therefore, on the apparent diffusion coefficient mapping images (ADC images) only an acute lesion appeared as a low signal area. The examination of diffusion images was very useful for distinguishing an acute lesion from a chronic lesion during the acute stage of multiple infarction. The diffusion weighted images after 4 weeks from the onset showed the diffusion coefficient of the "acute" lesion to be the same level of normal white matter. And after 8 weeks from the onset, increased to a level higher than that of normal white matter to the same level of the "chronic" lesion.

We reported a 29-year-old woman with autoimmune polyglandular deficiency (APGD) type 1 accompanied by progressive myopathy. She had chronic mucocutaneous candidiasis at the age of 3, primary hypothyroidism at 12, insulin dependent diabetes mellitus at 27, and adrenal insufficiency at 29 years. Laboratory findings indicated an underlying defect in cell mediated immunity. Meanwhile, she had progressive muscular weakness and wasting at the age of 22 years which brought her to our hospital at 29 years. On admission, she could not walk without support and raise her arms up to the level of shoulders. Moderate to severe muscle wasting as well as weakness was observed in the limb girdle muscles. Serum CK levels were mildly elevated. A needle EMG examination disclosed short-duration and low-amplitude polyphasic motor units at voluntary contraction with few fibrillations and positive sharp waves at rest. On muscle CT examination, decreased density was detected in the neck extensor, paravertebral, rectus femoris, vastus intermedius, biceps femoris and soleus muscles. Muscle biopsy was performed on the biceps brachii and rectus femoris muscles. The former showed chronic dystrophic changes including marked variation in fiber size with necrotic and degenerating process, interstitial fibrosis, and lobulated and right fibers. In the latter, in addition to variation in fiber size with some necrotic fibers and occasional multi-core structures, nemaline bodies were seen in approximately 30% of muscle fibers. The progressive muscle involvement in our patient might be induced from 1) endocrine abnormality, 2) autoimmune disorder, and/or 3) coincidental complication of nemaline myopathy or limb girdle muscular dystrophy. The clinical and laboratory examinations, however, failed to support any of them.(ABSTRACT TRUNCATED AT 250 WORDS)

X-linked dystrophinopathy is the most common cause of isolated cases of myopathy in males. To investigate dystrophin abnormalities as a cause of myopathy in girls and women, we used dystrophin immunocytochemistry to study muscle biopsies from 505 girls and women with neuromuscular disease. Forty-six muscle biopsies showed a combination of fibers containing or lacking dystrophin; this mosaic immunostaining pattern denoted a carrier status. Twenty-one of 46 (45.6%) had a family history of Duchenne muscular dystrophy in males. Twenty-five of 46 (54.3%) were isolated cases, with no previous family history of neuromuscular disorder. The laboratory findings of the isolated cases were consistent with the familial cases; all showed myopathic histopathology and abnormal elevations of serum CK. The clinical presentations of the isolated cases varied but were consistent with the familial cases: 40% (10/25) of isolated cases showed proximal limb weakness before age 10, 24% (6/25) presented with myalgias or cramps, 24% (6/25) presented with incidental findings of grossly elevated CK levels, 8% (2/25) noted easy fatigue, and 4% (1/25) had slowly progressive proximal limb weakness beginning at age 45. From our data, the clinical criteria for consideration of an underlying dystrophinopathy in isolated female cases of myopathy are CK levels greater than 1,000 IU/l and myopathic histopathology. About 10% of the isolated cases of hyperCKemic myopathy (25/210) were proven by dystrophin analysis to have a dystrophinopathy as the cause of their disease (manifesting carriers of Duchenne dystrophy). However, we feel that this may be an underestimate. The correct diagnosis in these patients is imperative for appropriate genetic counseling to the patients and their families.

Follow-up magnetic resonance imaging (MRI) and computed tomography (CT) examinations were performed on five patients with Wilson's disease at intervals from 6 to 29 months. We studied the clinical correlation with MRI and CT, and whether the examination of MRI and CT could be useful for evaluation of the therapeutic effect. Positron emission tomography (PET) was also carried out on 4 cases except for an asymptomatic case (patient 2, sister of patient 1). Close relationship has been observed by MRI between dystonia and the lesion of the lenticular nuclei, abnormality of smooth pursuit eye movements and the brain stem lesion, and severe dysarthria/dysphagia and the lesion of the caudate and lenticular nuclei, respectively. In patient 4, repeated MRI of an interval of 18 months demonstrated decrease of the abnormal high signal in the lateral part of the putamen on T2-weighted image in accordance with marked improvement of clinical manifestations. In patient 3, who had severe dystonia of the extremities and trunk, T2-weighted image showed high signals in the lenticular nuclei. Marked decrease of the high signal in the lenticular nuclei was observed by MRI in this patient after 29 months, when her neurological manifestations were markedly improved. Patient 5 with severe cerebellar signs disclosed abnormal signals in the middle cerebellar peduncles, brain stem and dentate nuclei in addition to low signals in the caudate and lenticular nuclei, and high signals in the lateral part of the putamen on T2-sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Was reported a 23-year-old man with Becker muscular dystrophy (BMD), manifesting heart failure as an initial symptom. He had admitted to a hospital because of his sudden exertional dyspnea due to dilated cardiomyopathy. Because of elevated serum CK level, he had admitted to our hospital for further clinical evaluation. His uncle and male cousin were affected by a mild progressive muscle weakness since second decades. Physically, his intelligence was slightly below the average (WAIS total IQ 71). There was a slight weakness in his pelvic and shoulder girdle muscles. Pseudohypertrophy was observed in calves and tongue. Serum CK level was markedly elevated to ten times of the upper normal limits. Both EMG and muscle biopsy examinations revealed mild myopathic changes. Electrocardiogram showed tall R waves in leads V1 and V2, abnormal Q waves in I, aVL, V5 and V6 and flattened T waves in V5 and V6. On immunostaining of the biopsied skeletal muscle, patchy appearance of dystrophin on the surface membrane of the fiber was detected, which is consistent with BMD. Myocardiac damages in BMD are not always related either to the duration or the severity of the skeletal muscle weakness, as shown in our present case. The possibility that subclinical BMD is one of causes for dilated cardiomyopathy always must be considered.

A case of a unique combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) with acanthocytosis is reported. Neuropathological examination revealed pellagra-like change in Betz cells, brain-stem neurons and anterior horn cells as well as findings compatible with mitochondrial encephalomyopathies. Abnormal function of nicotinic acid-related enzymes could be the cause of the complicated clinicopathologic findings in this case. This is the first report of MELAS with acanthocytosis.

Four patients with mitochondrial abnormality had multiple muscle biopsies at several year intervals during which respiratory chain enzyme activities were shown to be quite variable. In three patients, progression of the disease paralleled the decrease in respiratory chain enzyme activity. In one patient, the clinical and pathological findings improved with age as is seen in the benign infantile form of cytochrome c oxidase (CCO) deficiency. The variability in these mitochondrial disorders may result from the varied proportions of normal and abnormal mitochondria in the muscle cells in which the mitochondria are said to be randomly replicated from numerous mitochondrial DNA copies.

A case of neoplastic angioendotheliosis demonstrating unusual manifestations is reported. A 56-year-old male showed recurrent attacks of neurological symptoms including paraplegia, brain-stem symptoms, tonic seizures, aphasia, apraxia and cortical blindness over 2 years. The EEG disclosed transient, periodic, lateralized, epileptiform discharges. Brain CT scan revealed low-density areas mainly in the white matter. Other laboratory examinations were negative except for CSF protein fractions. Post-mortem examination disclosed remarkable intravascular proliferation of atypical cells in the CNS with prominent proliferation of blood vessels and softening. Other organs were not affected, which suggested that the atypical cells had a high affinity to CNS blood vessels.

Two patients (a 50-year-old and a 35-year-old men) with focal cytochrome c oxidase deficiency, manifesting ptosis and external ophthalmoplegia of 13 and 6 years' duration, respectively, were reported. Patient 1 (a 50-year-old male) had also slight muscular weakness of the proximal limb and neck flexor muscles. Diagnosis of myasthenia gravis had been made on the clinical findings including ptosis and external ophthalmoplegia, diurnal fluctuation of symptoms, and equivocal positive Tensilon test. However, waning phenomenon on repetitive nerve stimulation or elevation of titer of the anti-acetylcholine receptor antibody was not detected on both patients. Needle EMG showed mild myopathic changes. Finally, pathological and biochemical analyses of the biopsied muscles confirmed the diagnosis of mitochondrial myopathy (focal cytochrome c oxidase deficiency).

Tubular aggregates (TA) are unusual intramuscular structures stained basophilic on hematoxilin and eosin (HE) staining and red on modified Gomori trichrome (GT) staining. The structures are said to be originated from sarcoplasmic reticulum and are collections of tubules with double membranes on electron microscopic studies. The TA are usually seen in biopsy muscles from patients with muscle pain and cramps but without muscle weakness, periodic paralysis or alcoholic myopathy. In addition, there are five reports on families with progressive myopathy and tubular aggregates in the literature. We presented here a 48-year-old postman without any family history, who had had progressive muscle weakness for 17 years. He had never noticed pain or cramps in his muscles, not taken any particular medicine, and not had regular alcoholic beverages. There was no ptosis, facial weakness, masticatory muscle weakness or dysphagia. Muscle wasting, started from the proximal part of four extremities had progressed to the distal part of them. He could not walk on heels or toes and walked with waddling gait. He stood up with Gowers' maneuver. Serum GOT, GPT and CK were elevated. EMG showed myogenic pattern and MCV was normal. The muscle biopsies were performed; the first one taken from quadriceps femoris muscle at 42 years old showed myopathic changes including marked variation in fiber sizes, with scattered necrotic fiber splitting and TA in type 2B fibers. The second biopsy from biceps brachii muscle at the age of 48 years, showed densely proliferated fibrous tissues, marked variation fiber sizes and scattered split fibers. The TA were rarely seen and type 2B fibers were decreased in number.(ABSTRACT TRUNCATED AT 250 WORDS)

We encountered two cases of typical transient global amnesia (a 53-year-old woman and a 50-year-old man). Both cases showed no evidence of abnormal findings which caused the attack on examinations of CSF, EEG, brain CT, brain MRI and cerebral angiography. Examinations of positron emission tomography, using 15O labeled CO2 and O2, were performed on 14 and 8 days after the attack in the female and male cases, respectively, and those disclosed decreased regional blood flow (CBF), increased oxygen extraction ratio (OER), and decreased oxygen metabolic ratio (CMRO2) in the bilateral medial temporal and occipital lobes, which were supplied by the bilateral posterior cerebral arteries. PET, performed on about one month after the attack, revealed normalized values of CBF, OER, CMRO2 in both cases. These findings strongly suggested that transient global amnesia in our cases may be related to ischemia of the bilateral posterior cerebral arteries.

A case of symptomatic adrenoleukodystrophy (ALD) heterozygote, manifested by spastic paraparesis, was reported. The patient's 9 year-old grandson had ALD, and her 34 year-old daughter, who was the mother of the case of ALD, was asymptomatic but accompanied by elevation of serum very long chain fatty acid (VLCFA). The patient's gait disturbance appeared at age 62 and that gradually worsened. On admission, she showed spasticity on the lower limbs with bilateral Babinski's reflexes, muscle weakness of the lower limbs and interossei muscles of the hand, and mild sensory disturbance on the distal part of all limbs. Serum VLCFA was markedly elevated. There was no abnormal adrenal function. Sensory and motor nerve conduction velocities were within normal limits. A needle EMG examination disclosed long-duration and high-amplitude potentials. Auditory brainstem response (ABR) revealed elongation of III-V wave intervals bilaterally, and somatosensory evoked potential (SEP) showed delayed N20. Brain CT scan revealed no abnormality but MRI (T2 weighted image) showed mild high intensity areas in the capsula interna and cerebral peduncles. The abnormality of MRI suspected that spastic paraparesis may result from involvement of the corticospinal tract of the cerebrum or brainstem though the symptom has been considered due to the lesion of the spinal cord. Examinations of ABR, SEP and MRI were useful methods to make a diagnosis of symptomatic ALD heterozygote.

A case of triiodothyronine (T3) toxicosis associated with hypokalemic periodic paralysis is reported. Thyrotoxic manifestation was minimal except for mild struma. Serum T3 levels were moderately elevated, though other thyroid function tests were within the normal range. The patient was treated with methimazole, and paralytic attacks ceased. This is the first report of this combination and the necessity of careful thyroid function tests in sporadic periodic paralysis is emphasized.