Amelioration of frozen gait by tandospirone, a serotonin 1A agonist, in a patient with pure akinesia developing resistance to L-threo-3,4-dihydroxyphenylserine.

A 71-year-old woman presented with severe akinesia, frozen gait, and compromised postural reflexes, without rigidity, tremor, or vertical gaze disturbance. With a working diagnosis of pure akinesia, we administered amantadine (150 mg/d) and L-threo-3,4-dihydroxyphenylserine (DOPS) (600 mg/d), which alleviated her symptoms. When frozen gait recurred 2 months later, we increased the dose of L-threo-DOPS to 900 mg/d and added levodopa (300 mg/d) combined with carbidopa, but this failed to improve the patient's symptoms. We then combined administration of tandospirone, a serotonin (5-HT) 1A agonist with L-threo-DOPS (600 mg/d), resulting in marked clinical improvement. Tandospirone is reported to activate noradrenergic neurons via the 5-HT 1A receptor, which could account for such striking improvement in a patient previously responsive to the noradrenergic precursor L-threo-DOPS given alone.

Increased blood flow and nerve firing in the cat canine tooth in response to stimulation of the second premolar pulp.

Mustard oil or mechanical stimulation was applied to maxillary second premolar tooth pulps and pulpal blood flow and or intradental nerve activity in the ipsilateral canine tooth were recorded in the cat. Mustard oil application to the second premolar pulp significantly increased blood flow in the canine tooth pulp to 162.0+/-65.8% (n = 16) of the prestimulation flow compared to control data obtained with application of mineral oil (107.0+/-5.1%, n = 6) (Mann-Whitney U-test, p = 0.0009). Sectioning of the infraorbital nerve and its branches on the experimental side (n = 4) did not affect this increase in pulpal blood flow. The paraperiosteal injection of 2% lidocaine (1.0 ml) without vasoconstrictor significantly inhibited the increase in canine pulpal blood flow induced by mustard oil application to the second premolar pulp (109.8+/-6.8% of the prestimulation level, n = 7) (Mann-Whitney U-test, p = 0.0013). Sporadic firing or sometimes bursts of action potentials in the canine pulp nerves were recorded during and/or after the mustard oil application to the second premolar pulp in three of 16 cases. Four single pulp nerve units firing in synchrony with the mechanical stimulation of the second premolar pulp were recorded in two of eight canines, which substantiated the existence of branched afferents innervating both teeth. These findings suggest that stimulation of the second premolar pulp may induce axon reflex-related vasodilation and intradental nerve firing in the canine pulp via branched afferent fibres innervating both the second premolar and canine teeth.

[Multivariate analysis of the problems of long-term levodopa therapy in Parkinson's disease].

We investigated clinical features of adverse reactions to long-term levodopa therapy by the multivariate analysis. Dyskinesia, wearing off effect, on-off effect, mental symptoms, and frozen gait were noted in 29 (11.2%), 78 (30.0%), 17 (6.5%), 45 (17.7%), and 52 (20.0%), respectively, of 260 patients with Parkinson's disease to whom levodopa had been administered for over one year. In the statistical investigation by the multivariate analysis (quantification method type II), the age of initial levodopa therapy, the duration from the onset to the initiation of levodopa therapy, and the duration of levodopa therapy were not closely related to the development of any adverse reaction, while Hoehn & Yahr's stage and the dosage of levodopa had the most significant influence on the development of adverse reactions. Furthermore, concomitant use of amantadine hydrochloride produced an inhibitory effect on the development of dyskinesia. We conclude that early institution of levodopa therapy in Parkinson's disease may not be an important risk factor of adverse reactions.

Predictive factors for efficacy of interferon therapy in chronic hepatitis type C.

BACKGROUND/AIMS: It has recently become possible to quantify HCV-RNA in serum and to analyze the HCV-RNA genotype. In this study, we investigated the relationship among the response to interferon therapy, the HCV-RNA concentration, genotype and histological findings of the liver. PATIENTS AND METHODS: Sixty-three patients with chronic hepatitis type C received interferon alfa therapy for 24 weeks. The HCV-RNA concentration in serum was measured semiquantitatively with reverse transcript semi-nested polymerase chain reaction and classified as negative to +3. HCV-RNA genotype was analyzed using a mixture of four type specific primers. RESULTS: HCV-RNA concentration was significantly higher in patients with genotype II and CAH2B than genotype III, CPH and CAH2A (p < 0.05). At 24 weeks after the end of interferon therapy, HCV-RNA in serum disappeared in 24 of 63 patients (38%). Strong resistance to the therapy was noted in patients with both genotype II and a high concentration of HCV-RNA in serum (the efficacy was only 7%). Therapy efficacy decreased with the severity of liver histological findings, reaching only 20% in those with CAH2B. CONCLUSION: Both the concentration and genotype of HCV-RNA seem to be important factors in determining the efficacy of interferon therapy.

[An autopsy case of ataxic form of Creutzfeldt-Jakob disease].

An autopsy case of ataxic form of Creutzfeldt-Jakob disease (Brownell and Oppenheimer, 1965) was reported. The patient, a 71-year-old male, noticed ataxic gait at the beginning of June in 1988, and was admitted to the Hiroshima City Hospital for the neurological examination at the end of June. He showed ataxia of the left arm and legs and diplopia. Gradually he became delirious at night. On July 16, tremor-like involuntary movement of the left hand was noticed. On July 20, he became somnolent and doubly incontinent. Myoclonus and paratonic rigidity were also observed. The EEG showed periodic synchronous discharge on July 25. The brain CT and MRI were normal. He became apallic gradually and died on October 28. The duration of illness was 5 months. At autopsy, brain weighed 1000gr. Cerebral atrophy and slight enlargement of the ventricles were observed. The cerebellum was also slightly atrophic. Histologically, the destruction of the cerebral cortical layer, slight sieve-like spongy state of the neuropil, slight neuronal loss of the thalamus and sieve-like spongy state of the striatum were observed. The cerebellar lesion was the most severe, where granular cell loss and gliosis of the cortex were observed.

[A case of Binswanger disease with numerous diffuse plaques in the neocortex].

A case of Binswanger disease with numerous diffuse plaques in the neocortex was reported. This male patient had a previous history of hypertension and myocardial infarction. From the age of 60, he developed dysarthria, bradykinesia, marche à petit pas and falling down. Neurological examination at his first admission disclosed muscular rigidity and increased jaw and deep tendon reflexes, but dementia was not found. Brain CT showed moderate brain atrophy and EEG consisted of slow wave dysrhythmia. He was diagnosed of Parkinsonism and treatment started without effects. During his second admission for the treatment of myocardial infarction, at the age of 64, delirium developed. Progressive dementia began and finally he was confined to bed. From the age of 69, spontaneous speech became almost lost. Contracture of the extremities, increased deep tendon reflexes and force grasping were noted. Brain CT showed symmetrical low attenuation in the frontal and parietal white matter with moderate dilatation of the lateral ventricles. At the age of 70, he died of general prostration about ten years after the initial symptoms. Neuropathological findings: Macroscopic findings: The brain weighed 1300 g. Atherosclerotic changes of the large arteries at the base of the brain were moderate. Coronal sections of the brain showed moderate enlargement of the lateral ventricles with multiple small lacunes in the basal ganglia. Microscopic findings: Bilateral diffuse demyelination of the white matter with sparing of the U-fibers was noted. Holzer stain revealed fibrillary gliosis in the left parietal and occipital white matter. Marked adventitial fibrosis of the deep white matter arteries and terminal stages of hyalinosis of the perforating arteries were found. Basal ganglia showed status lacunaris. Bilateral pyramidal tracts were atrophic secondly.(ABSTRACT TRUNCATED AT 250 WORDS)

[A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers].

A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti-dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution.

[A case of bilateral necrosis of the basal ganglia after hypotensive shocks].

We reported a case with bilateral necrosis of the basal ganglia after hypotensive shocks. The patient was a 69-year-old woman, who fell into a hypotensive shock (B.P. below 40 mmHg) of unknown origin during examination of her bladder cancer and was admitted into CCU. After admission, hypotensive shocks were repeated four times (B.P. below 50 mmHg each time). Neurological examination revealed a left spastic hemiplegia. Brain CT on 10th day showed bilaterally low density areas around the basal ganglia and a diagnosis of brain infarction was made. She gradually presented quadriplegia and symptomatic changes from pyramidal to extrapyramidal signs. Brain CT on 24th day showed bilateral hemorrhagic infarction of the basal ganglia with enhanced effect. On 79th day, she again fell into shock and died. Neuropathological examination of the brain was as follows. 1) laminar necrosis of the deep layers of the cerebral cortex, 2) bilateral necrosis of the hippocampal Sommer sector, 3) bilateral necrosis of the caudate nucleus, putamen and pallidum with neuronal loss and infiltration of fat granule cells, 4) sparing of the internal capsules, 5) bilateral necrosis of the reticular zone of the substantia nigra, 6) foci of fresh necrosis and loss of Purkinje cells in the cerebellum. These lesions are consistent with those of selective vulnerability in hypoxia as described by Scholz et al. An extensive distribution of cerebral as well as basal ganglia necrosis in this case was caused by repeated shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acetylcholinesterase activity in CSF in senile dementia of Alzheimer type, vascular dementia, and Parkinson's disease].

Acetylcholinesterase (AChE) activity was measured in cerebrospinal fluid (CSF) from 25 patients with senile dementia of Alzheimer type (SDAT), 11 patients with vascular dementia (VD), 26 patients with Parkinson's disease (PD), and 30 normal controls. AChE activity also was measured in 46 normal subjects whose ages ranged from 15 to 85 to evaluate the effect of age on AChE activity. CSF AChE activity for the SDAT, VD and PD groups showed no significant difference compared with the value for the control group. However, there were significant decreases in CSF AChE activity in the VD and PD groups with the development of ventricular enlargement. There was no significant correlation between CSF AChE activity decrease and ventricular enlargement in the SDAT group. AChE activity increased significantly over the age range of 15 to 85. These results suggest that, although CSF AChE activity is not a useful parameter in the diagnosis of dementia, it may be a marker indicating abnormalities of the intracerebral cholinergic system during the process of cerebral atrophy.

A case of progressive supranuclear palsy with fibrillary gliosis of the midbrain and pontine reticular formation.

An autopsy case of progressive supranuclear palsy with onset at age 53 and a clinical course of 7 years is reported. The clinico-pathological characteristics of the case were as follows: Fibrillary gliosis of the midbrain and pontine reticular formation corresponded clinically to personality changes: The patient had formerly been irascible and became extremely mild-mannered. He showed lack of spontaneity and initiative and slowing of thought processes, taking him longer than normal to find words and ideas. Gliosis of the nucleus ventralis lateralis of the thalamus was secondary to the degeneration of the cerebellar dentate nucleus and the globus pallidus from which they receive fibers. Neurofibrillary tangles were found in the cerebral cortex.

[A study on mental symptoms developing during the treatment of Parkinson's disease (author's transl)].

UNLABELLED: We studied on mental symptoms which developed during the treatment of Parkinson's disease. Hallucination, delusion, and/or delirious state were observed in 23 (22.8%) of 101 cases. The cases with mental symptoms were studied for the incidence, detail of the symptoms, and the factors involved in their development. RESULT: 1) Mental symptoms were observed in 23 patients and the incidence tended to be highest in the patients in their sixties. 2) In classification of the cases with mental symptoms, 12 cases showed the change of visual experience as main symptom and 3 cases had delusion. In these two cases, disturbance of consciousness was minimum, if any. Eight cases showed delirious state. 3) As for mental symptoms, visual hallucination was most frequently observed. 4) Complication of hypertension and history of depressive state were more frequently observed in the cases with mental symptoms than in those without. 5) Mean daily dose of L-dopa upon the onset of mental symptoms was less than mean daily maximum dose in the cases without mental symptoms. 6) The cases with cerebral atrophy in CT had a tendency to develop mental symptoms. 7) The cases with abnormal EEG were liable to develop mental symptoms. 8) The cases with mental symptoms were more often complicated by dyskinesia than those without. CONCLUSION: The incidence of mental symptoms during the treatment of Parkinson's disease tended to be high in the aged patients who had all or some of these findings as previous history of psychiatric illness, hypertension, cerebral atrophy and abnormal EEG.

[Left atrial myxoma with repeated multiple cerebral emboli].

A case of left atrial myxoma with repeated multiple cerebral emboli is reported. A-44-year-old man first developed a sudden right hemiparesis in October 1969. After intensive physical theraphy, strength improved and he was able to return to his work. In March 1970, he suddenly lost consciousness and remained comatose for a day. Upon waking, he had a profound right hemiparesis, motor aphasia and Gerstmann's syndrome. He was admitted to Hiroshima City Hospital on August 1, 1970. The cardiac examination, including an electrocardiogram, was entirely normal. Laboratory studies revealed a normal blood count and urinalysis; erythrocyte sedimentation rate was elevated (32mm/hour). On a left cerebral angiographic study, performed on September 6, 1971, multiple aneurysmal dilatations of the branches of the left middle cerebral artery were demonstrated. No specific diagnosis was made. In January 1973, he developed dysarthria, dysphagia and quadriplegia because of the recurrent cerebral attacks. He had a high temperature continuously for three days and died on May 30, 1974. At autopsy a myxoma with the peduncle was attached to the septal wall of left atrium, and there were old infarcts in the brain, the myocardium and the kidneys.