Epilepsia partialis continua. Epileptogenic focus in motor cortex and its participation in transcortical reflexes.

We performed electrophysiologic and neuroradiologic studies on a patient who had epilepsia partialis continua (EPC) to elucidate the pathophysiologic mechanism of repeated myoclonic jerks confined to the right toes. A computed tomographic scan revealed a small cortical lesion in the left parasagittal rolandic area corresponding to the sensorimotor cortex of the right toes. A pretrigger EEG analysis with a jerk-locked averaging technique revealed a positive spike 32 ms before the jerks. A similar positive spike was evoked at a latency of 48 ms after an electrical stimulation of the right posterior tibial nerve; it was followed by a myoclonic jerk with a 32-ms latency. We suppose that in our patient, an epileptogenic focus in the motor cortex and transcortical long-loop reflexes played an important role in generating EPC.

Effect of physostigmine on constructional and memory tasks in Alzheimer's disease.

We performed a double-blind study of the effect of physostigmine vs saline on the performance of memory and constructional tasks in a patient with probable Alzheimer's disease. On the days of physostigmine administration, a remarkable improvement in copying figures was observed. However, physostigmine administration had only a limited effect on memory performance. The results are interpreted in the context of recent biochemical studies of the brain in Alzheimer's disease, which suggest selective loss in the central cholinergic system.

Pure memory loss with hippocampal lesions: a pneumoencephalographic study.

A case of pure memory loss occurred suddenly following inhalation anesthesia. Examination seven years after the onset of amnesia disclosed a profound and selective impairment of recent memory without concomitant deterioration of other higher functions or evidence of other neurologic abnormalities. Pneumoencephalotomography focused on the temporal horns showed severe atrophic changes confined to both hippocampi. This finding provides a radiologic counterpart of previously reported surgical and pathological observations of bilateral hippocampal lesions in cases with relatively pure loss of memory.

Postural hypotension and low R-R interval variability in parkinsonism, spino-cerebellar degeneration, and Shy-Drager syndrome.

Systolic blood pressure, mean R-R interval, and R-R interval variance were studied in patients with Parkinson's disease, spinocerebellar degeneration, and Shy-Drager syndrome. Postural hypotension correlated with anhidrosis (p less than 0.05), indicating sympathetic vasomotor dysfunction. Reduction of R-R interval variance while resting supine correlated with bladder-bowel dysfunction (p less than 0.05), indicating parasympathetic impairment. Reduction of R-R interval variance after postural changes correlated with constipation (p less than 0.005), postural hypotension (p less than 0.05), and anhidrosis (p less than 0.05), indicating both parasympathetic and sympathetic involvement. Dynamic study of the R-R interval provides objective information about autonomic function in neurologic disease.

Anal muscle electromyograms differ in amyotrophic lateral sclerosis and Shy-Drager syndrome.

Electromyography (EMG) of anal sphincter muscles was different in patients with amyotrophic lateral sclerosis (ALS) and Shy-Drager syndome. In 30 patients with ALS, EMG of the external sphincter muscle was essentially normal, with no signs of denervation. In eight cases of Shy-Drager syndrome, however, motor unit potentials of the anal sphincter had highly polyphasic forms of long duration and high amplitude. In the Shy-Drager syndrome, there seems to be specific damage of lower motor neurons that innervate the external sphincter muscle of the anus.

Amyotrophic lateral sclerosis: histologic, histochemical, and ultrastructural abnormalities of skin.

We studied the reticular dermis in patients with amyotrophic lateral sclerosis (ALS) and controls with or without neurologic diseases. By light microscopy, collagen bundles in ALS dermis were reduced in amount and more loosely woven than in controls. Electronmicroscopy revealed a significant negative correlation between duration of illness and the diameter of collagen fibrils in patients with ALS. There was also a marked increase of amorphous material positive for ruthenium red in the ground substance. These findings were not observed in controls.

Mounding phenomenon: an experimental study in vitro.

"Mounding" is a local contracture of skeletal muscle that is induced by tapping the muscle directly. We studied the mounding phenomenon in vitro on rat muscles that were percussed by a rotating hammer. In the bulged portion of muscle, there were scattered areas where the sarcomere length was shortened. After muscle was depolarized by the application of KCl-Ringer solution or relaxing solution, the mounding phenomenon was preserved. Agents that abolish the function of T-tubule or T-SR junction did not alter the phenomenon, either. However, after the function of intracellular membrane system such as the sarcoplasmic reticulum (SR) was destroyed by Brij 58, the mounding disappeared. Thus, the mounding is a local contracture that is probably induced by calcium ion liberated from the SR by percussion.

Corticofugal projections to the motor nuclei of the brainstem and spinal cord in humans.

We studied corticofugal projections to the motoneurons with Nauta-Gygax's technique in a patient with cerebral infarction of both hemispheres. Motoneurons in the brainstem motor nuclei and spinal anterior horns seem to receive direct cortical projections, except for the oculomotor and abducens nuclei and Onuf's nucleus in the sacral cord.

The Crow-Fukase syndrome: a study of 102 cases in Japan.

Clinical manifestations of 102 cases with the Crow- Fukase syndrome (the syndrome of polyneuropathy, anasarca, skin changes, endocrinopathy, dysglobulinemia, and organomegaly), with or without myeloma, were reviewed. Fifty-six cases with myeloma consisted of 31 with osteosclerotic, 17 with mixed osteosclerotic and osteolytic, and 8 with osteolytic. Forty-six cases without myeloma consisted of 2 with extramedullary plasmacytoma, 33 with M protein alone, and 11 with polyclonal protein alone. There was no significant difference in incidence of the major clinical manifestations between the two groups with and without myeloma. They had a common characteristic histologic finding of the lymph node resembling that of Castleman's disease.

Tridimensional distribution of markers of neurotransmitters within the "accumbens area" of normal human brains.

The distribution of glutamate decarboxylase and choline acetyltransferase in the accumbens area of five neurologically normal human brains was investigated. (1) For rostrocaudal distribution, frozen samples were taken by the punching method from several transverse sections (150 micron) of the accumbens area and the caudate-putamen were assayed. The glutamate decarboxylase activity was highest in the middle of the accumbens area. The choline acetyltransferase activity in the accumbens area was the same as that in the caudate-putamen at the rostral half and gradually decreased caudally, while the caudate-putaminal choline acetyltransferase remained unchanged throughout. (2) For a mapping of the distribution of both enzymes, a pair of transverse sections of the accumbens area was cut into 1 mm X 1 mm square blocks by the grid microdissection method. The glutamate decarboxylase activity was highest at the ventromedial part; the glutamate decarboxylase-rich area could be reconstructed as a confined ellipsoid zone deep in the accumbens area. The choline acetyltransferase activity was patchily distributed in the rostral half of the accumbens area. Although the demarcation of the human nucleus accumbens inferred from choline acetyltransferase and glutamate decarboxylase distribution is not precise, it is clear that the accumbens area which corresponds to the animal nucleus accumbens is separated from the remainder of the striatum.

Lifetime data analysis of disease and aging by the Weibull probability distribution.

We applied the Weibull distribution to the life-table and age-patterns of diseases in Japan. The life-table follows a composite Weibull distribution composed of initial failure and two stage wear-out failure periods. The extension of lifespan during the past century is manifested as increases in the scale parameters in all three periods and the shape parameters in the wear-out periods with female predominancy. The shape parameters of diseases show time-independent sex-dependent specific values. When consistent changes are observed, such as increases in the shape parameters of tuberculosis and pneumonia, legitimate causes such as prevention and repair at the societal and medical level are present. Cancer and arteriosclerosis share a common range of shape parameters suggesting analogous underlying biological processes. An analysis of the epidemiology of human aging and disease by the Weibull distribution discloses intrinsic properties of man as a biological organization as well as a societal presence.

A dose-response study with dihydroergotoxine mesylate in cerebrovascular disturbances.

Basic pharmacologic evidences have suggested the effects of dihydroergotoxine mesylate (DEM) on neurotransmitters. In its clinical use, however, various therapeutic effects and side effects are observed when the dose is changed, because of the complexity of this compound and the delicate mechanism of neurotransmitters in the brain, especially when modified by aging and vascular lesions. In order to investigate the optimal dose, a double-blind study in 550 patients with cerebrovascular disorders was carried out at 68 centers under observation by experienced specialists. Dihydroergotoxine mesylate in sublingual tablets, 3 mg daily, and in oral tablets, 6 mg daily, respectively, was given for 12 weeks, and therapeutic effects at those doses were compared by a double-blind method. In utility ratings for subjective and psychiatric symptoms, the effects in the oral tablet group at a daily dose of 6 mg were significantly superior to those in sublingual tablet group at a daily dose of 3 mg. There was no significant difference between those two groups in the comparison of side effects. These results show that the daily oral administration of 6 mg of DEM is more suitable for the improvement of subjective and psychiatric symptoms due to cerebrovascular disorders than is the daily sublingual administration of 3 mg. These results suggest that, despite much complexity in the neurohumoral transmitter mechanism in the brain, relatively simple dose-dependent efficacy of the drug in the range of the therapeutic doses was confirmed for many subjective and psychiatric symptoms of patients with cerebrovascular disorders.

Coexistence of fast and slow types of myosin light chains in a single fiber of rat soleus muscle.

Single muscle fibers were isolated from soleus and extensor digitorum longus muscle of adult rats. The muscle fiber type of single fibers was determined physiologically by the skinned fiber method according to the sensitivity to strontium (Sr) ions. The fiber type of single fibers was contrasted to the pattern of myosin light chains analyzed by one and two dimensional gel-electrophoreses. All the type 2 fibers isolated from soleus muscle contained both fast and slow types of myosin light chains.

Topographical study of the distribution of gamma-aminobutyric acid (GABA) in the human substantia nigra. A case study.

The topographical distribution of gamma-aminobutyric acid (GABA) in the substantia nigra of a 28-year-old male 4 h after death was investigated. In a preliminary study the entire substantia nigra was dissected from transverse sections. The results showed that there was no correlation between the GABA concentration and the number of melanin-rich nigral cell bodies. This was especially so in the rostral third of the substantia nigra. Using the method of Miyata and Otsuka, transverse sections (150 mum) of the rostral, middle and caudal substantia nigra were cut into 500 mum X 500 mum square blocks which were assayed for GABA by an enzymatic method. In the rostral substantia nigra the GABA distribution was markedly uneven. The highest concentration of GABA was found in the pars reticulata. Within the pars reticulata the highest levels of GABA clearly occurred in two separate regions, a medial and a lateral. In the middle and caudal substantia nigra the GABA distribution was again uneven; however, the highest GABA levels were divided between the pars reticulata and the pars compacta. The results support the view that in the substantia nigra the greatest part of the GABA content is due to the presence of striato-nigral nerve terminals which are known to synapse with the dendrites of the substantia nigra dopamine neurons. In the rostral substantia nigra the concentration of GABA within the pars reticulata is in keeping with the presence of dendrites of such neurons in this region. Presumably on this basis it can be assumed that in the middle and caudal substantia nigra the dendrites are oriented in a more rostro-caudal direction.

An electro-oculographic study of ocular bobbing and intermittent vertical oscillations occuring in the same patient.

A surviving patient with two rare types of abnormal eye movements, typical ocular bobbing and subsequently developed intermittent vertical oscillations of the eyes, is described, and a follow-up series of electro-oculographic recordings of these eye movements is analyzed. It is suggested that these two types of vertical eye movements might have a common pathophysiological background and the activity of remaining functional oculomotor pathways may play an important role in their occurrence.

Anticoagulant therapy in recurrent cerebral embolism: a retrospective study in non-valvular atrial fibrillation.

For the prevention of recurrent embolic stroke, 23 elderly patients with non-valvular atrial fibrillation (NVAF) were treated with oral anticoagulants (warfarin) during a mean period of 3.8 years. Only one patient suffered recurrent embolism, and another had acute myocardial infarction. There was no cerebral haemorrhage during the treatment. In an untreated control group (from an autopsy series), recurrent embolic strokes occurred in 18 of 70 NVAF patients (26%) during a mean period of 1.3 years. Long-term anticoagulant therapy appears to be effective in the prevention of recurrent embolic stroke in elderly patients with NVAF.

Rimmed vacuolar distal myopathy: a clinical, electrophysiological, histopathological and computed tomographic study of seven cases.

The following report describes the clinical, laboratory, electrophysiological, histopathological and computed tomographic studies of seven cases of distal myopathy with rimmed vacuoles in the muscle fibers. Each displayed several characteristic features. First, the onset was in early adulthood. Second, there was a unique distribution of muscle involvement: tibialis anterior and extensor digitorum and hallucis muscles were initially and most severely affected. The hamstrings and adductors of the thigh were also markedly involved. The gluteus medius and minimus muscles and the neck flexors were mildly affected in the relatively early stages. In contrast, the gastrocnemius, soleus, quadriceps femoris, and gluteus maximus muscles were well preserved until an advanced stage. Third, serum creatine kinase activity was normal or only mildly elevated; fourth, EMG were mainly myopathic, with certain neuropathic features; and fifth, histopathologically rimmed vacuoles in muscle fibers were found associated with certain "neuropathic" features, such as angular fibers, clustering of atrophic fibers, pyknotic nuclear clumps, and fiber-type predominance. The characteristic distribution of skeletal muscle involvement was particularly noticeable, together with certain "neuropathic" features of the EMG and muscle biopsy in rimmed vacuolar distal myopathy.

Rimmed vacuolar distal myopathy. An ultrastructural study.

An ultrastructural study of biopsied muscles was performed in seven patients with rimmed vacuolar distal myopathy, which was characterized by prominent rimmed vacuoles in the muscle fibers. The earliest changes noted were focal proliferation of the Golgi's apparatus and mitochondrial degeneration with myofibrillar loss. A proliferation of the T-system appeared later. Secondary lysosomes (autophagosomes) could be noted much later and gradually increased in number. Autophagosomes tended to coalesce and became larger autophagic vacuoles, which were surrounded in part by relatively preserved myofibrils and partly by a single membrane. Gently curved laminated structures (tubulomembranous structures) were seen in the degenerating muscle fibers and also in relatively intact fibers, satellite cells, and interstitial cells in all cases. They were closely associated with lipofuscin-like material. These findings suggest that an abnormality of the lysosomal system might be essential in the pathogenesis of rimmed vacuolar distal myopathy.

Subacute leucoencephalopathy induced by carmofur, a 5-fluorouracil derivative.

Three cases of leucoencephalopathy induced by carmofur (1-hexylcarbamoyl-5-fluorouracil), an antineoplastic derivative of 5-fluorouracil are reported and the literature is reviewed. Initial symptoms were unsteady gait and dementia developing several weeks or months after carmofur had been started. Symptoms increased gradually even after stopping the drug. Severe encephalopathy with confusion, delirium or coma appeared frequently. Symptoms were usually reversible but death occasionally occurred. The EEG showed marked slowing. Computed tomography of the brains of severely intoxicated patients showed marked hypodensity of the entire cerebral white matter. Carmofur must be discontinued immediately if any psychomotor symptoms develop.

Dementia in cerebral amyloid angiopathy: a clinicopathological study.

Dementia is in addition to cerebral haemorrhage major symptom of cerebral amyloid angiopathy (CAa). In order to explore the pathological basis for dementia in CAa-related conditions, we made a clinicopathological analysis of CAa, with special attention to dementia. Among 150 patients (mean age 78.6 years) with autopsy-proven intracranial haemorrhage in Tokyo Metropolitan Geriatric Medical Center, CAa with cerebral haemorrhage accounted for 8.0% (12 cases), associated with hypertension and metastatic brain tumour. Among 38 patients with lobar haemorrhage, CAa represented the second most common cause (21.1%) of intracranial haemorrhage after hypertension. A total of 20 patients with CAa (mean age 82.5 years) were studies clinically and pathologically. Hypertension was present in 50%. Thirteen had a history of stroke and others had either ill-defined or no strokes. The average number of strokes 2.9. Fifteen patients (75%) had dementia. Based on the clinicopathological grounds for dementia, CAa-related conditions could be divided into three subtypes: "haemorrhagic", "dementia-haemorrhagic" and "dementia" type. Haemorrhagic type (30%, 6 cases) showed multiple recurrent lobar haemorrhages caused by CAa. Hypertension was present in only 1 patient. The incidence of senile plaques and neurofibrillary tangles was generally correlated with age. Only 1 patient had dementia. The dementia-haemorrhagic type (40%, 8 patients) had recurrent strokes with cerebral haemorrhage after preceding dementia. There were two different neuropathological subsets: CAa with atypical senile dementia of Alzheimer type (SDAT) and CAa with diffuse leucoencephalopathy. Patients with CAa with atypical SDAT had multiple cerebral haemorrhages caused by CAa combined with atypical Alzheimer-type pathology. Patients with CAa with diffuse leucoencephalopathy had cerebral haemorrhages in combination with diffuse white matter damage like Binswanger's subcortical vascular encephalopathy (BSVE). The incidence of senile changes correlated with age. Patients with the dementia type (30%, 6 patients) showed progressive dementia with or without haemorrhage. All had hypertension. They had a combined condition of Alzheimer-type pathology with conspicuous CAa with BSVE. Dementia in CAa-related conditions may be responsible for multiple factors including not Alzheimer-type degeneration, but also diffuse leucoencephalopathy like Binswanger's disease. We also found an asymptomatic type, an ischaemic type, a vasculitis type and an hereditary type in this condition.