Search

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Its clinical features vary greatly in different generations of the same family. Regional cerebral blood flow (rCBF) and distribution volume (Vd) in the pons, cerebellum, and cerebral cortex were measured in 12 patients with MJD by autoradiography (ARG) and the table look-up (TLU) method of iodine-123 IMP (123I-IMP) single photon emission computed tomography (SPECT). Representative cases were as follows: A 46-year-old woman first experienced gait ataxia at age 38. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no atrophy in the pons or cerebellum, but rCBF measured by the 123I-IMP SPECT ARG method detected hypoperfusion in the pons, and cerebellar vermis and hemisphere. A 76-year-old woman first experienced gait ataxia at age 69. CT and MRI findings showed severe atrophy in the pons, and cerebellar vermis and hemisphere. Moreover, rCBF was decreased in the pons, whereas it was not decreased in the cerebellar vermis and hemisphere. In the pons of patients with MJD, rCBF was markedly decreased regardless of disease severity. Because this SPECT finding for the pons looked like a 'dot', we have called it the 'pontine dot sign'. In the MJD group, rCBF was significantly decreased in the pons (Student's t test, p0.01) and cerebellar vermis (p0.05). The Vd was also significantly decreased in the pons (p0.005) in comparison with that for normal subjects. Pearson's correlation analysis yielded a significant relationship between the rCBF in the pons and age at onset (r = 0.578, p0.05). There was a strong correlation between the Vd for the pons and age at onset (r = 0.59, p0.05). Pearson's correlation analysis also showed a significant relationship between the Vd in the cerebellar hemispheres and International Cooperative Ataxia Rating Scale (r = 0.644, p0.05). The pontine rCBFs in patients with early onset MJD, whose pons was not atrophic, decreased more than did those in patients with late onset MJD, whose pons was severely atrophic. This suggests that the SPECT findings are indicative of underlying neurodegenerative processes that began before the onset of clinical symptoms. Different processes seem to function in atrophy and the rCBF decrease in the pons of patients with MJD. These findings will be proved by the increase of the number of cases of MJD. Until now, there has been no report on rCBF and Vd obtained by 123I-IMP SPECT for patients with MJD identified by gene analysis. Our study shows that SPECT measurement of rCBF and Vd is useful for understanding the pathophysiology of MJD.

We reported two cases of cerebral embolism associated with atrial fibrillation. Left atrial ball thrombus without mitral stenosis was diagnosed by the transesophageal echocardiography, followed by successful removal. Left atrial ball thrombus has a risk for lethal complications, and a high incidence of systemic embolism even during anticoagulation therapy. An immediate surgical treatment is needed. The transthoracic echocardiography is not useful in diagnosis for left atrial ball thrombus. It is important to examine left atrial ball thrombus by the transesophageal echocardiography in patients with cerebral embolism associated with atrial fibrillation.

We analyzed 52 cases of advanced or recurrent cancer of the cervix treated by intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. IAIC regimen was separated into two groups: Group I consisted of 5-FU + MMC +/- ADR (30 cases) and group II of CDDP + MMC +/- 5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR + PR) was 71%, 87% in patients given radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in Group I and 38% in Group II (p = 0.00182) by chemotherapy regimen. Severe (more than grade III) hematological acute side effect was 48% for all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region requiring narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervix cancer. But we should check the blood flow distribution periodically, and control the concentration of drugs.

A 22-year-old woman had been suffering from blepharoptosis and fatigabilities of both shoulders for a year. She had been administered phenytoin since age 4 to prevent febrile convulsion. On admission, she had bilateral blepharoptosis with left one being more severely affected. Her pupils and eye movement were normal. Other cranial nerve functions were normal. Her both deltoid muscles were mildly weak. A repetitive stimulation study revealed a 35% decline of the evoked responses recorded from either the orbicularis oculi or the abductor pollicis brevi muscle. Antibody activity for acetylcholine receptor was higher than normal range. Her blepharoptosis transiently disappeared after an intravenous administration of 5mg of edrophonium. She was diagnosed as having myasthenia gravis. Her myasthenic signs had continued one month after phenytoin withdrawal, then an extended thymectomy was done. The thymus was histologically hypertrophic. Although a direct blocking at a neuromuscular junction by phenytoin has been reported in animal experiments, our case is not likely to be affected by this effect. Since a large population of young epileptic patients needs a long-term phenytoin therapy, detailed investigation is necessary to elucidate how frequently they manifest myasthenia gravis.

In two patients with pulmonary alveolar proteinosis, PaO2 was normalized by massive bronchoalveolar lavage (BAL). Patient 1: A 29-year-old man presented with exertional dyspnea and a PaO2 of 57.8 mmHg. After four BALs, the PaO2 was 106.4 mmHg. For ten years thereafter he has been doing well. Patient 2: A 58-year-old women presented with extertional dyspnea and a PaO2 of 64.4 mmHg. The PaO2 increased to 110.6 mmHg after four BALs. BAL required much skill, but it is one of the most effective methods for the treatment of pulmonary alveolar proteinosis. Because this condition is related to an interstitial process, these two patients need to be followed carefully.

A 62-year-old woman visited her primary physician because of high fever and vomiting. From a chest roentgenogram miliary tuberculosis was diagnosed. Anti-tuberculosis drugs were prescribed. Mycobacterium tuberculosis was cultured from samples of sputum. Although she took drugs for 3 months, her symptoms did not resolve and back pain developed. A chest roentgenogram showed an egg-sized mass in the posterior part of the mediastinum. Examination of a chest CT scan showed that the mass was an aortic aneurysm. A graft replacement was done, and histologic examination of the resected specimen showed that it was a tuberculous aneurysm of the descending aorta. Her symptoms disappeared, and she recovered fully. Tuberculous aneurysms are rare: they account for only 0.3% of all aneurysms. This is only the 9th reported case of tuberculous aneurysm successfully treated with surgery in Japan. We must realize that aneurysms are life-threatening complication of miliary tuberculosis.

A 68-year-old right-handed woman showed "apraxia of eyelid opening" during an acute phase of hemorrhagic infarction in the right middle cerebral artery distribution. She showed paradoxical contraction of the bilateral orbicularis oculi muscles both against our order to open her eyes and even against her hand-movement to help her eyes open, although she could voluntarily open her eyes. She was diagnosed as "apraxia of eyelid opening". Her eyes kept closed in most of time. Spontaneous blepharospasm and a right conjugate gaze preference were also seen. These symptoms disappeared 2 weeks after the hemorrhagic infarction. Because most of cases in previous reports as well as this patient showed "apraxia of eyelid opening" after a right cerebral involvement, we propose that this symptom may attribute to right cerebral dysfunction.

Two weeks after a flu-like illness, a 59-year-old woman developed double vision, muscle weakness and sensory discomfort in the proximal portions of her limbs. On admission, there was complete external ophthalmoplegia with bilateral ptosis. The pupils were dilated and did not react to light. Swallowing and elevation of the soft palate were also limited. There was severe muscle weakness in all limbs. Deep tendon reflexes were absent. Superficial and deep sensations were impaired in the proximal portions of the extremities. Neuro-ophthalmological examinations revealed an acquired color disorder with no scotoma and normal discs. P100 latencies of flashed visual evoked potentials were prolonged on day 41, and returned to normal on day 87. Herpes simplex virus type 1 (HSV-1) infection was confirmed by isolation of the virus from her sputum and the detection of anti-HSV-1 antibody in the acute phase serum.

Two patients with Marinesco-Sjögren syndrome in a family were characterized by autosomal recessive inheritance, congenital cataract, cerebellar ataxia, mental retardation, short stature and variable skeletal abnormalities. Muscle biopsy specimens showed replacement of muscle fibers by fat and fibrous tissue, a marked variation of fiber size and a rimmed vacuole formation. Nerve biopsy specimens showed a reduced number of myelinated nerve fibers in the sural nerves. Muscle CT revealed atrophy of the quadriceps femoris, semitendinosus, gastrocnemius and soleus muscles. Accordingly, extensor muscles in the thighs were more preferentially involved than flexor muscles in the legs.

This is the first report on the analysis of the proteins in the single muscle fibers with rimmed vacuoles. A new method was developed to analyse single muscle fibers which had been histologically characterized in the freeze-dried sections of muscles. Muscle biopsy was performed in three patients with distal myopathy and one patient with Kearns-Sayre-like syndrome associated with rimmed vacuoles (Table 1). Ten (30 micron thick) frozen serial sections were dried according to Lowry and Passonneau, and further five consecutive sections were cut and stained with usual histochemical methods including Gomori trichrome and NADH-TR staining. Each muscle fiber in the freeze-dried sections could be identified with the corresponding one in the stained sections, and it was possible to determine whether the fiber had rimmed vacuoles or not (Fig. 2). Particular fibers were identified in the consecutive freeze-dried sections and cut out from three sections with no contamination of the interstitial tissue, and they were subjected to SDS gel electrophoresis. Resultant gel patterns showed substantial increase of 55 k dalton band, the extent of which was much more larger in that of the fiber with rimmed vacuoles than that without vacuoles (Fig. 3). This feature was common to all of the gels from four patients. A portion containing a number of muscle fibers of a freeze-dried section from each of the four patients and the two controls was subjected to two-dimensional gel electrophoresis (2-D). Of 55 k dalton proteins, three spots around the isoelectric point of alpha-actin were found to be increased (Fig. 4).(ABSTRACT TRUNCATED AT 250 WORDS)

From 1981 to 1987, 15 cases of malignant tumors of the ethmoid sinuses were treated by radiotherapy, either with or without chemotherapy. Pathologically, these cases consisted of 7 squamous cells ca., 2 transitional cells ca., 3 anaplastic ca., 1 adenoid cystic ca., 1 malignant teratoma, and 1 rhabdomyosarcoma. The three-year survival in all cases 37%. Of eight patients determined to be in stages I and II, 4 patients had a localized relapse locally within 10 months after treatment and a distant metastases developed at a later time in 4 patients, whereas in 7 patients in stage III and IV, a distant metastases developed in 5 patients immediately after radiotherapy.

In 1980, Fukuhara et al. have reported two patients with "myoclonus epilepsy associated with ragged-red fibers" (MERRF), which is at present accepted as a distinctive clinical entity among the mitochondrial encephalomyopathies. We describe here postmortem findings of the case whose clinical findings were reported in detail by Fukuhara et al. (1980) as Case 1. The neuropathological findings were summarized as follows: 1) degeneration of dentate nucleus, red nucleus, globus pallidus, subthalamic nucleus and pontine tegmentum, 2) degeneration of the Clarke's column, spinocerebellar tract, posterior column and corticospinal tract, as well as of the posterior spinal nerve root and sural nerve, and 3) degeneration of substantia nigra, locus ceruleus, cerebellar cortex and inferior olivary nucleus. The lesions were degenerative in nature, and their distribution was different from those of dentato-rubropallidoluysian atrophy, Joseph's disease or Friedreich's ataxia. It was concluded that MERRF is a single disease entity also from pathological point of view.

A 53-year-old female with sensori-motor neuropathy associated with bilateral club feet was reported. She was admitted because of numbness in the bilateral feet and gait disturbance. Her parents were not related. There was no family history of any neurological diseases. She had bilateral club feet which were present at birth to developed in early childhood. She could walk, but could not run. Since 5 years prior to the admission she noted gradually increasing disturbance of gait. Neurological examination revealed muscular weakness and wasting in the distal parts of the lower extremities and decreased deep tendon reflexes. There were hypesthesia, hypalgesia and dysesthesia in the lateral portions of the bilateral feet. Deep sensation was normal. There was no weakness or wasting in the upper extremities. Motor nerve conduction velocities were normal and sensory nerve conduction velocities were reduced in the median nerve. No action potentials could not be elicited in the bilateral tibial and peroneal nerves. A sural nerve biopsy showed a markedly hypertrophic perineurium, 28-150 micron thick, a large Renaut body measured 140 micron by 200 micron in diameters and a markedly reduced number of the myelinated fibers. Fiber size histogram showed many unmyelinated fibers larger than 1 micron, despite loss of fibers of the usual size. Therefore, a part of the unmyelinated fibers might be demyelinated. There were no axonal degeneration and onion-bulb formation. Segmental demyelination was found in approximately 30% of the myelinated fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

A report is given of an association of dyssynergia cerebellaris myoclonica associated with Friedreich's ataxia and mitochondrial myopathy in 2 patients. They had suffered from gradually increasing bursts of myoclonus since the wage of 14 and childhood, respectively. The other striking clinical features included generalized convulsions, mental deterioration, intention tremor, ataxia, muscular atrophy and deformity of feet. Muscle biopsies revealed ragged-red fibres in both cases. On electron microscopy these fibres contained subsarcolemnal aggregations of abundant abnormal mitochondria with proliferation of inner membranes or paracrystalline inclusions. One of these patients showed elevated blood lactate and pyruvate with an increased lactate/pyruvate ration, apparently of primary origin. These 2 cases resemble those reported briefly by Tsairis et al. (1974). An association of dyssynergia cerebellaris myoclonica associated with Friedreich's ataxia and mitochondrial myopathy in these 2 patients is unlikely to be coincidental but may represent one nosological entity. This myoclonus epilepsy syndrome associated with ragged-red fibres is compared with other possibly related mitochondrial encephalomyopathies.

We used histologic evidence of degenerative changes in both the gray and white matter of the brain to diagnose a patient as having the panencephalopathic type of Creutzfeldt-Jakob disease (CJD). This type of CJD is relatively common in Japan, but not in North America or Europe. We recovered a transmissible pathogen (Echigo-1 strain) from an autopsy specimen of the patient9s brain and passed it serially in Hartley guinea pigs. After a long latent period, it caused degenerative changes, mainly in the thalamic area of the guinea pig brain. On the 4th passage, a substrain emerged with a short latent period. When cross-transmitted to Golden Syrian hamsters, this substrain induced severe degeneration in both the thalamus and cerebral cortex. We compare our results with those for other experimental CJDs produced by other types of this disease.

As a preparative procedure for bone marrow transplantation, intermittent total body irradiation (TBI) has been used in our hospital. The biological significance of this method, in which the instantaneous dose rate is high but the average dose rate is low, has not been evaluated to date. The hematopoietic responses caused by both intermittent and continuous TBI were compared. In the intermittent irradiation, mice in a moving irradiation chamber were exposed under a small field (2 X 35 cm2), and the instantaneous and average dose rates were 1 Gy/min and 0.25-0.12 Gy/min, respectively. The average dose rate was adjusted to the same level in both irradiation methods. LD50/30 and survival of colony-forming units (CFU) in culture and survival of endogenous CFU in the spleen from female BDF1 mice were the same with the two methods. These results show that the response of hematopoietic stem cells depends on the average dose rate, not on the instantaneous dose rate. Our findings suggest that intermittent irradiation, as well as the continuous method, would be useful for preparing patients before bone marrow transplantation.

The characteristic features observed in the muscle fibers of nemaline myopathy are the presence of rods mainly in type I fibers, and the predominance and atrophy of type I fibers. In order to detect the abnormal proteins in the rods and clarify whether type I or II fibers have abnormal structural protein, we examined proteins in the muscles of patients with nemaline myopathy by one and two-dimensional gel electrophoresis (2-D). These freshly frozen muscles were cut to 20 microns thick and freeze-dried. Pieces were chosen and teased under a dissecting microscope with reference to the stained specimens of the same part, and electrophoresed. At first, we examined the proteins of the type I and II fibers in normal and type grouping fibers of patients with motor neuron disease by SDS gel electrophoresis and found no abnormality of the protein pattern in this disease. Then we examined each of the following fibers of the nemaline muscle; type I fibers with many rods and type II fibers with no rods. Each of the electrophoresed gel patterns of the nemaline muscle was compared with those of grouping type I and II fibers. The SDS gel electrophoresis showed and increase of the intensity of 55 K band in nemaline myopathy, especially in type I fibers with rods, which was thought as desmin. In 2-D, the pattern of type I fibers with rods were identical to that of the grouping type I fibers except the 55 K spot which showed a slow form of tropomyosin alpha-subunit (TM-alpha), troponin-C (TN-C) and myosin light chains (LC) although both contained small amounts of fast form LC2 and LC3.(ABSTRACT TRUNCATED AT 250 WORDS)

We documented the presence of a point mutation in the tRNALys gene of mitochondrial DNA (mtDNA) in various postmortem tissues from two patients with myoclonus epilepsy associated with ragged-red fibers (MERRF). The percentages of the mutant mtDNA were similar (93 to 99%) in both clinically affected and unaffected tissues, suggesting that preferential clinical involvement of certain tissues in MERRF is based not only on the variation of distribution of the mutant mtDNA, but also on other factors such as differences in the threshold in various CNS regions and organs.