Estimation of net muscle volume in patients with muscular dystrophy using muscle CT for prospective muscle volume analysis: an observational study.

OBJECTIVES: Muscle volume in patients with muscle disease is an index of disease progression. The aim of this study was to demonstrate a new method of muscle volumetry using CT of thigh muscles. DESIGN: Observational study. PARTICIPANTS: (1) For muscle volumetry using CT and dual-energy X-ray absorptiometry (DXA), 13 patients with muscle disease participated. (2) For prospective CT volumetry, 12 patients participated over 4 years. PRIMARY AND SECONDARY OUTCOME MEASURES: To establish the new CT volumetry, the results of which were correlated with the muscle mass calculated from DXA (primary outcome). To show the decrease in muscle volume using our method over 4 years (secondary outcome) METHODS: (1) Helical CT imaging of the thigh was performed. CT images were analysed by applying estimated functions, and the accumulation of outcomes resulted in muscle volumes. We refer to this method as 'net muscle volumetry'. Simultaneously, DXA was performed in these patients, and the muscle mass of the thigh was calculated with vendor-provided software. (2) To evaluate longitudinal changes in muscle volume, net muscle volumetry at the 14 cm section of the middle part of the thigh was performed repeatedly over a 4-year period. RESULTS: (1) Volumes of the thigh muscle on one side were calculated to be 300-3400 cm(3) using CT. Muscle mass of the thigh was calculated from DXA to be 1100-5000 g. These results correspond closely, with a Pearson correlation coefficient of 0.993. (2) Thigh net muscle volumes of seven patients with gait disturbance decreased over the 4-year study period (p<0.01). CONCLUSIONS: A method of measuring net muscle volume using CT, which was validated by muscle mass calculated from DXA, was developed. Decrements in net muscle volume over 4 years support the reliability of this method. This less arbitrary method is suitable for assessment of muscle volume in patients with muscular dystrophy.

Somatosensory evoked potential recovery in myotonic dystrophy.

OBJECTIVE: To evaluate recovery functions of the sensory cortex using somatosensory evoked potentials (SEPs) elicited by paired stimuli of the median nerve in patients with myotonic dystrophy (MD). SUBJECTS/METHODS: Twelve MD patients were enrolled in the present investigation. Five patients with facioscapulohumeral muscular dystrophy (FSH) and 12 healthy volunteers were studied as control groups. SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single pulse or paired-pulse stimuli at various interstimulus intervals (ISIs) (10, 20, 40, 60, 80, 100, 150, 200 and 300 ms) were given. Recovery functions of N9, N20onset-N20peak, N20-P25 and P25-N33 components were studied. RESULTS: Conventional SEPs to a single stimulus were normal in the latency and amplitude in all the patients. Recovery functions of both N9 and N20o-N20p components were normal in the patients. In contrast, in MD patients, disinhibited or hyperexcitable recovery pattern was observed in recovery curves of the N20-P25 or P25-N33 components, whereas those were normal in FSH patients. CONCLUSIONS: Disinhibited cortical excitability (or hyperexcitability) is present in the sensory cortex in patients with myotonic dystrophy. This may reflect cortical pathology or functional alteration of the sensory cortex in MD.

[A case of left subclavian artery occlusion with transient ischemic attacks probably in the internal carotid artery system].

The subclavian steal syndrome is known to steal blood flow from the vertebrobasilar system. However, we experienced a case of subclavian artery occlusion presenting transient ischemic attacks in left internal carotid system. A left handed 41-year-old man developed transient dysarthria and right hemiparesis including face several times when he physically used his arms. He had no symptoms of the vertebrobasilar system. A brain MRI revealed an old cerebral lacuna at the left putamen supplied by perforating arteries of the middle cerebral artery. The angiography demonstrated a complete occlusion of the proximal portion of the left subclavian artery without a reverse flow from the vertebral artery. Instead, descending cervical branches and deep cervical branches of the ipsilateral external carotid artery supplied collateral pathways to the occluded subclavian artery. On the basis of above observations, we speculated that he developed symptoms of the internal carotid system due to the steal through the collateral network of the cervical arteries directed to the subclavian artery. We should consider not only the vertebrobasilar system but also the internal carotid system, especially its cervical artery network, when exploring collateral pathways for the subclavian steal syndrome.

Preserved widespread N18 and progressive loss of P13/14 of median nerve SEPs in a patient with unilateral medial medullary syndrome.

Median nerve somatosensory evoked potentials (SEPs) in a patient with unilateral medial medullary syndrome of recent onset having an MRI-confirmed lesion at upper medulla were investigated. Cortical N20 following stimulation of the affected limb was extremely depressed and delayed, whereas widespread N18, which was best manifested by the CPi-C2S lead (CPi is centroparietal electrode ipsilateral to the stimulation), showed no significant difference regarding amplitude and duration between affected and non-affected sides. The result supported our previous opinion that the principal part of N18, the broad negativity lasting around 20 ms, originates from the cuneate nucleus at the medullary level. Less steep onset of N18 on the affected side suggested that some structures rostral to the cuneate nucleus, possibly the termination of the overall ascending volley, may contribute to the earliest part of N18. P13/14 on the affected side normally preserved at the first examination progressively declined and finally disappeared after 4 months, which suggested that the major part of P13/14 is generated within caudalmost medial lemniscus, as well as the occurrence of retrograde degeneration of lemniscal fibers.

[Dystrophin abnormality in a patient with polymyositis associated with primary biliary cirrhosis and myocardial injury].

We have reported a 58-year-old Japanese female with polymyositis, primary biliary cirrhosis (PBC) and arrhythmia. In contrast to the previously reported 13 cases of polymyositis associated with PBC, symptoms and laboratory data abnormalities responded to oral administration of predonisolone. Interestingly, immunohistochemical and immunoblot analyses of biopsied skeletal muscle revealed diminished expression of dystrophin carboxyl-terminal domain in the sarcolemma, suggesting that, in analogy to Duchenne muscular dystrophy, secondary abnormality of the link between the basal lamina and cytoskeleton via the dystrophinglycoprotein complex may have played a role in the molecular pathogenesis of muscle fiber degeneration in this patient.

[Abnormal head drooping in facioscapulohumeral muscular dystrophy].

Diagnosis of facioscapulohumeral muscular dystrophy (FSHD) is based on its characteristic pattern of muscle wasting. Initial symptom is usually shoulder girdle and upper arm muscle wasting resulting in difficulty in arm-lifting. Patients are aware of progressive change of facial appearance caused by characteristic facial muscle weakness. Affection of other muscles is usually realized much later, but, there is a considerable variation in pattern and severity between individuals even in the same family so that several clinical subtypes such as jump form or scapuloperoneal syndrome have been proposed. Here we described three patients with FSHD showing conspicuous head-drooping caused by severe wasting of posterior neck muscles. These patients realized abnormal neck posture much earlier than appearance of obvious gait disability, while they show other characteristic FSHD features. Familial occurrence is observed in two cases, other affected members from both families do not show abnormal head drooping. Therefore we regarded this sign as another example of clinical heterogeneity of this genetic disorder.

Structure-activity relationships of alkylamines that inhibit rat liver hydroxysteroid sulfotransferase activities in vitro.

Tetraalkylammonium salts having n-propyl to n-amyl side chains inhibited rat liver sulfotransferase (ST) activities toward dehydroepiandrosterone and cortisol, but not ST activity toward 2-naphthol, whereas trialkylamines having ethyl to n-amyl side chains inhibited ST activity toward dehydroepiandrosterone, but not ST activities toward cortisol and 2-naphthol. A comparison of I50 values, which represent inhibitor concentration resulting in 50% inhibition of dehydroepiandrosterone ST activity, revealed that the values for the tetraalkylammonium salts were 0.015 to 0.017 mM, whereas the values for the trialkylamines were 0.20 to 0.33 mM. Introduction of hydrophilic groups such as hydroxyl, thiol, nitrile and acetamide groups or substitution by methyl and allyl groups in the alkyl side chains markedly diminished the inhibitory effect of triethylamine. These data indicate that ethyl to n-amyl side chains are a prerequisite for the alkylamine-type inhibitor. Tertiary amine drugs such as imipramine, dimenhydrinate, cyclizine, chlorpromazine and promethazine inhibited ST activities toward dehydroepiandrosterone and cortisol similar to the tetraalkylammonium salts, although the drugs were weaker inhibitors of hydroxysteroid ST activities. These results imply that in addition to trialkylamine side chains, the other portion of the drugs may participate in the inhibition of hydroxysteroid ST activities.

[Autosomal recessive oculopharyngeal "muscular dystrophy"--clinical features and association with reduced activity of myophosphorylase].

We reported two cases of brothers demonstrating oculopharyngeal muscular dystrophy (OPMD). The cases had consanguineous parents and five healthy siblings, which suggested the autosomal recessive inheritance. The initial symptom was slowly progressive blepharoptosis with onset in the third decade. On examination, total external ophthalmoplegia was observed in both patients. Additionally, the elder, a 57-year-old man, exhibited dysarthria, dysphagia and muscular weakness with atrophy of the face, bilateral proximal upper limbs and diffuse lower limbs. The younger brother, a 55-year-old man, displayed muscular weakness and atrophy distributed in the face and four limbs. Muscle biopsy of both cases revealed rimmed vacuoles and spheroid bodies in the atrophic and normal-sized fibers. Biochemical study of the biopsy specimens of the elder brother disclosed the myophosphorylase activity reduced to about 40% of the normal value, although in the younger brother, that activity was normal. OPMD is usually inherited in the autosomal dominant mode, and autosomal recessive OPMD is rare. The onset age of our cases was younger than that of the autosomal dominant OPMD. There were some differences in the clinical manifestation between the presented cases, which could be interpreted as phenotypic variation. The elder brother was thought to be associated with McArdle's disease.

[A case of chronic inflammatory demyelinating polyradiculoneuropathy with orthostatic hypotension].

A 27-year-old man was admitted to our hospital for his legs' numbness of subacute onset and discomfort while standing. No specific previous history was found and his family history was non-contributory. On admission, his general status was unremarkable except for arterial hypertension and mild tachycardia. Moderate impairment of superficial sensations and dysesthesia were noted in the distal extremities, tongue, oral cavity, and lips. Deep sensation was moderately impaired in the lower legs. Romberg sign was positive. He had mild weakness in the proximal muscles of the lower extremities. Hyporeflexia was noted in all extremities, but Achilles reflexes were absent. Pathologic reflexes were not noted. He fainted after two minute standing. On laboratory examination, serum IgM, C3, and C4 were mildly elevated. CSF protein level was prominently high without CSF pleocytosis. MCV was mildly decreased, and F wave conduction velocity was prominently decreased in the posterior tibial nerve, SCV was also mildly decreased in the right sural nerve. Needle electromyography showed mild neuropathic changes. Left sural nerve biopsy showed no abnormal finding in the myelinated and unmyelinated fibers. A 60 degree head-up tilting test caused a hypotensive attack, and Valsalva ratio was decreased. However, hand grip test and cold pressor test were normal. The response to noradrenaline infusion test and CVR-R were also normal. Muscle sympathetic activity (MSA) was recorded from the tibial nerve using a tungsten microelectrode (Iwase, et al.). His basic activity was higher and responsiveness was lower than age-matched normal controls. The regression line existed above the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

[MRI pathology of the globus pallidus in a patient with oculogyric crisis and tremor].

A 24-year-old woman developed occasional attacks of oculogyric crisis at the age of 18. She also suffered from postural tremor, dystonic gait, pyramidal tract signs, and peripheral nerve damages. No history of encephalitis was elicited. Nerve conduction velocity revealed decreased velocity and amplitude. Needle electromyography showed a neurogenic pattern. Sural nerve biopsy showed marked Wallerian degenerations. Muscle biopsy revealed small grouped atrophies. It was unlikely that she suffered from juvenile Parkinsonism, and we failed to obtain an evidence of neuronal intranuclear inclusion disease. Recently, Furumoto et al. reported a similar case who developed oculogyric crisis at the age of 12. So far, some authors have reported about changes of MRI image in the putamen and the substantia nigra in extrapyramidal movement disorders. However, few have paid attention to the changes of the pallidum. The most characteristic finding in the present case was the restoration of signal intensity of the globus pallidus on T2 weighted high-field MRI. It is known that pallidal damages produce dystonic disorders. However, the exact role which the pallidum played in pathogenesis of our patient's signs and symptoms is unknown at now.

[Multicystic encephalomalacia in an adult--a case report].

A case of multicystic encephalomalacia found in adult life was described. A 35-year-old man was admitted to our hospital with a chief complaint of unsteadiness. He had developed normally until he fell into the shock state induced by mismatch blood transfusion at the age of 15 months. Since then he has been mentally retarded moderately and had clumsiness of the skillful movement in the right hand. The other neurological abnormality was hyperreflexia only. Laboratory examination failed to disclose metabolic defect. Both CT scan and MRI demonstrated numerous cystic lesions of various size spreading over bilateral cerebral white matter partially involving the inner layer of the cortex. On the contrary basal ganglia, cerebellum and brainstem were completely spared. The diagnosis of MCE was made from (1) anoxic-ischemic episode in infancy, (2) static clinical picture and (3) characteristic distribution of cystic lesions. It is well known that MCE results from perinatal hypoxia, but it is a polyetiologic condition caused by various damages to immature brain of early infancy and usually results in severe psychomotor retardation. Nonetheless, it is intriguing in our case that marked discrepancy was found between morphological change and neurological deficit. It is probable that at the age of 15 months the myelination of major projecting fibers was almost completed, but sufficient plasticity was preserved in immature brain. As a result, the patient had the neurological deficit in the minimum degree in spite of severe morphological change.

The measurement of gastric mucus using a computer image processing system.

The measurement of gastric mucus, and the effects of aspirin and some antiulcer drugs on the content or components of gastric mucus were investigated in normal rats by using a newly devised computer image processing system. The present method enabled us to separate mucus components into PAS positive mucus (PAS+), and AB positive mucus (AB+), and to measure the amount of each mucus. Aspirin induced significant decreases in both PAS+ and AB+, teprenone increased the total amount of gastric mucus (PAS+ plus AB+), secretin tended to increase AB+, and cimetidine and omeprazole caused no remarkable changes on mucus secretion. These changes in gastric mucus could be observed on both microscopic observation and with the computer image processing system. The results indicate that the computer image processing system is very useful for the measurement of gastric mucus.

Absorption, distribution, metabolism and excretion of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)- 1,4-dihydropyridine (PP-1466) in rats.

In this experiment, the absorption, excretion, distribution and metabolism of 2,6-dimethyl-3,5-dimethoxycarbonyl-4-(o-difluoromethoxyphenyl)-1, 4-dihydropyridine (PP-1466) were investigated following oral or intravenous administration, single dose or repeated dose administration using male SLC-Wistar rats and the results of this investigation were summarized as follows: After oral administration of 14C-PP-1466 to rats, the blood level reached the maximum at 1 h and decreased with the biological half-life of about 5 h. The unchanged drug concentration in plasma was 30% of total concentration in plasma and disappeared at 6 h. The high radioactivities in the liver, kidney, fat, lung and adrenal gland were observed after oral and intravenous administration. After oral and intravenous administrations, the excretion in feces and urine during 48 h was 63.0 and 32.4, 58.6 and 41.6%, respectively. Biliary excretion amounted to 57.6 and 46.2% during 48 h, respectively. Six metabolites were found in the urine of rats. Three of them were identified as 2,6-dimethyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid pyridine, 2-methyl-3-carbomethoxy-4-(2-difluoromethoxyphenyl)-5-carboxylic acid-6-hydroxymethyl pyridine and its lactonizing analogue. These three metabolites covered 54% of total urinary metabolites. After oral repeated administration for three weeks, the excretion ratio of radioactivity in urine and feces was constant during the administration and no accumulation was observed in rat tissues.