[Complete response in a case of advanced gastric cancer with liver and intra-abdominal lymph node metastases treated by combined chemotherapy of TS-1 and CDDP].

A 67-year-old male patient with gastric cancer of Borrmann type 2 and liver and intra-abdominal lymph node metastases was treated by combined chemotherapy of TS-1 and CDDP TS-1 (100 mg/day) was administered for 14 days followed by 14 days rest as one course. CDDP (70 mg/m2) was administered in 24-hour continuous intravenous infusion at 8 days after the start of TS-1. After 3 courses of treatment, X-ray and endoscopic examinations revealed complete disappearance of the primary tumor and no cancer cells were detected by endoscopic biopsy. A CT-scan also showed complete disappearance of metastatic sites. This combined chemotherapy was finished after 5 courses, and no high grade toxicities (WHO grade 3 or 4), specifically nausea, diarrhea, or leucocytopenia, were seen. This TS-1/CDDP chemotherapy seemed to be effective for advanced gastric cancer in view of toxicities, antitumor effect and QOL of the patient.

Sisters homozygous for the spinocerebellar ataxia type 6 (SCA6)/CACNA1A gene associated with different clinical phenotypes.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by a CAG repeat expansion in the CACNA1A gene. The neurodegeneration that occurs in CAG repeat diseases is considered to share a common mechanism that may result in the gain of a toxic function related to the expanded polyglutamine tracts. However, the phenotypic expression in homozygotes for CAG repeat diseases has been controversial, and is not clearly related to a gain of functional mechanism. We identified a Japanese family with two sisters who were homozygous for the SCA6 with identical CAG repeat expansion (25/25). They showed an earlier age of onset (27 years in both) than their father (44 years), a heterozygote with an expanded allele showing the same CAG repeat length as the homozygotes (25/14). Interestingly, the two sisters showed differences in disease progression and severity, although the age of onset and CAG repeat length were identical. These findings strongly suggest that the gene dosage influences the age of onset, but other unknown factors are also important in the phenotypic expression of homozygous SCA6.

[Therapeutic case of general paresis manifested by bradykinesia and recent memory loss].

We reported a 32-year-old man with general paresis. He showed slowly progressive bradykinesia and recent memory loss. Argyll Robertson pupils were not present. Muscle strength and sensations were normal except for slight vibratory disturbance. Tendon reflexes were slightly exaggerated. MMSE, HDS-R and WAIS-R scores showed the intellectual impairment. His laboratory investigations revealed elevated both TPHA and FTA-ABS titers in the serum and the CSF. The CSF contained leukocytosis (25/mm3) and protein 80 mg/dl. Cranial CT and MRI demonstrated diffuse cortical atrophy. SPECT revealed marked reduction of the blood flow in bilateral cerebral hemisphere. Cerebral angiography revealed moderate stenosis of the major vessels. The diagnosis of neurosyphilis (general paresis) was made and the treatment of intravenous benzyl penicillin potassium 24 million units per day was started. After 6 weeks of the treatment, the clinical signs (includes MMSE, HDS-R and WAIS-R scores) and the findings of SPECT and cerebral angiography showed improvement. Although the cell count and protein in the CSF became decreased, the titers of TPHA and FTA-ABS in the serum and the CSF were not decreased. Neurosyphilis should always be considered in a etiologically unknown case with bradykinesia and dementia.

[Clinicopathological characteristics of Creutzfeldt-Jakob disease with a PrP V180I mutation and M129V polymorphism on different alleles].

We report an 80-year-old Japanese man with histologically-diagnosed Creutzfeldt-Jakob disease (CJD). The patient was admitted to our neurological unit because of sudden onset motor aphasia-like symptoms and right hemiparesis. His medical and family histories were unremarkable, and he had taken no medications. Urine, blood counts and blood chemistry were all within normal limits. Cerebrospinal fluid was normal except for elevation of neuron specific enolase (29.9 ng/ml). High-signal intensity was demonstrated in the cortex of the left temporal lobe on T2-weighted MRI images, and the lesion swelled during the initial stage of the disease. There was no enhancement with Gd-DTPA. Serial MRI showed that the high-signal lesion had spread into the bilateral cerebral cortex. The patient developed myoclonus followed by akinetic mutism within 6 months of onset. Consecutive EEGs revealed no periodic synchronous discharge (PSD). He died of pneumonia 21 months after of admission. Autopsy revealed spongiform changes in the cerebral cortex with Kuru plaques, confirming the diagnosis of CJD. The Cerebellar cortex was well preserved. The high-signal lesions corresponded to the spongiform changes in the cerebral cortex. Immunohistochemical analysis showed weak synaptic prion staining. Prion protein (PrP) gene analysis of genomic DNA isolated from the autopsied brain by polymerase chain reaction, the restriction fragment length polymorphisms, and direct sequencing revealed a point mutation (Val-->Ile) at codon 180 and a polymorphism (Met/Val) at codon 129 on different alleles. A few CJD patients with point mutations in codon 180 of the PrP gene have been reported. Combination of the codon 180 point mutation and codon 129 polymorphism may yield an atypical clinicopathological form of CJD that includes late onset, negative PSD, and atypical MRI findings, with preservation of the cerebellar cortex.

[The effects of dopamine on regional cerebral blood flow in patients with Parkinson's disease before and after L-dopa--measurement by Xe-enhanced CT].

Regional cerebral blood flow (rCBF) was measured using the stable xenon enhanced CT method in previously untreated 13 patients with Parkinson's disease to evaluate CBF abnormality related to dysfunction of the nigrostriatal dopaminergic neurons. The patients comprised 5 men, 8 women with Hoehn-Yahr stage II-III. Age at onset ranged from 51 to 73 years (mean +/- SD, 61.8 +/- 8.9) and the duration of illness ranged from 1 to 96 months (15.1 +/- 24.1 months). In this series, there was no clinical evidence of hypertension, diabetes mellitus and cognitive impairment. rCBF was measured during 4-5-minutes inhalation of 33% stable xenon gas-67% oxygen. The first measurement of rCBF was performed in all of the patients before L-dopa treatment. After initiation of L-dopa treatment (333.3 +/- 47.1 mg/day), the second measurement was carried out in 6 patients (1 man and 5 women) who had shown symptomatic improvement. The interval between both measurements was 57.7 +/- 16.9 days. The following results were obtained. 1) No significant CBF asymmetry was noted in any of the striatum, pallidum, thalamus, cerebrum, cerebellum and frontal lobe in untreated patients with Parkinson's disease. 2) After L-dopa treatment, rCBF was significantly increased only in the striatum as compared with the pretreatment level (51.9 +/- 9.3-->63.1 +/- 9.9 ml/100 g/min, p < 0.01). 3) This increase was significantly greater on the more severely affected side (contralateral to the predominantly symptomatic limb) (p < 0.05). These results suggest that the increase of rCBF in the striatum is closely related to functional improvement of the nigrostriatal dopaminergic neurons.

[Crossed cerebellar diaschisis after brainstem infarction].

Metabolic depression in the cerebellar hemisphere contralateral to supratentorial stroke termed "Crossed Cerebellar Diaschisis" (CCD) was first described by Baron and coworkers and now interpreted as a transneuronal deactivation resulted from loss of excitatory afferent inputs. Among the cerebrocerebellar pathways possibly involved, the corticopontocerebellar pathway is considered to be the most important to induce CCD. According to the hypothesis that CCD results from the destruction of the corticopontocerebellar pathway, any lesion wherever located in the corticopontocerebellar pathway may induce CCD. Little is known, however, about CCD after the brainstem lesion. Our case presented here showed that a brainstem lesion actually induced CCD and that CCD resulted from transneuronal deactivation. An 80-year-old female was admitted to the neurological department of Kasugai City Hospital because of left-sided hemiparesis of sudden onset on March 19, 1989. On admission and 5 days after admission CT scan of the brain was performed, but no stroke lesion was found. Magnetic resonance imaging of the brain disclosed a localized lesion in the right peduncle and tegmentum of the midbrain. Single photon emission computerized tomography of the brain using N-isopropyl-P-(123I) iodoamphetamine (IMP) performed about a month after admission disclosed decreased blood flow in the left hemisphere of the cerebellum compared with the right one and the findings of CCD were observed.

Swimmer's migraine.

Three cases of sudden, severe headache occurring during swimming are described. A 51-year-old female had been engaging in a swimming exercise for about 20 minutes when she suddenly experienced a pulsating headache in the parietotemporal region, accompanied by nausea. A few days later, she experienced a similar episode, again during swimming practice. A 45-year-old male developed a pulsating headache with nausea immediately after diving into a swimming pool, and had a similar attack during diving practice 1 week later. A 32-year-old male developed a pulsating headache accompanied by nausea while swimming in the sea. In all three cases, blood pressure, pulse rate, neurological findings, cervical spinal x-rays, brain CT scans, and hematological findings were normal and the outcome was good. Although these patients' headaches were diagnosed as benign exertional headache, pathophysiologically they appeared to resemble the headache associated with sexual activity.

[Swimming induced vascular headache].

We experienced 3 cases of characteristic headache induced by swimming. The first case was a 51-year-old woman who suffered from a sudden attack of throbbing headache in the parieto-temporal region, accompanied by nausea, after 20 minutes of swimming practice in a pool. The headache disappeared after about 3 hours of bed rest. However, soon after she began to practice swimming in the pool a few days later, throbbing headache in the same region recurred. Though the headache improved upon bed rest, dull pain was persistent till bed time that evening. Two days later, as she squatted down with alacrity at her home, she felt intense pain in the whole head as if struck with a hammer. She was seen at our neurological clinic the following day but was found to be neurologically normal with a blood pressure of 130/70 and a pulse rate of 78/min. Blood chemistry tests, hematology, head digital subtraction angiography, cerebral CT and X-ray films of the cervical spine were all normal. After swimming was prohibited, the prognosis was good and the patient experienced no episode of headache at all during the intervening period of 2 years and 5 months after the first visit. The second case was a 45-year-old man who felt throbbing headache affecting the whole head immediately after diving in a swimming pool. The headache improved after about 3 hours of bed rest. One week later, an attack of similar headache occurred immediately after a dive in the swimming pool.(ABSTRACT TRUNCATED AT 250 WORDS)

[An autopsied case of type II citrullinemia--transient effectiveness with either citrate or benzoate to the consciousness disturbance].

A 44-year-old man suffered from repeated impairment of consciousness associated with flapping tremor, myoclonus and generalized convulsions, and died in coma 6 months after admission. He had had a psychosomatically underdeveloped childhood, with a propensity for legumes without a family history of the same or a record of consanguinity. On admission, he had disturbed consciousness and emaciation without other physical abnormalities. The EEG revealed diffuse slow waves with occasional appearance of triphasic waves. A high level of serum citrulline (534.7 nmol/ml) was recognized and the assay of urea cycle enzymes in the liver demonstrated decreased argininosuccinate synthetase (ASS) activity (0.062 U/g liver, 7.4% of that in normal liver), although no kinetic abnormality was found. Accordingly he was diagnosed as having type II citrullinemia. In addition, this case could be classified as cluster type of localization of the ASS in the liver by immunohistochemical study. There were characteristic findings concerning his clinical picture and laboratory data, such as a significant correlation between the grade of disturbed consciousness and arterial blood gas pH (r = 0.61, p less than 0.01). However, the blood ammonia level did not always correlate with the severity of disturbed consciousness. Oral treatment with sodium citrate and sodium benzoate was very effective, though transiently, for disturbed consciousness in this case. Pathological findings of the autopsied liver were fatty change and fibrosis. Neuropathologically, characteristic findings were brain edema with cerebellar tonsilar herniation, laminar necrosis with spongy formation in cerebral cortex, and Alzheimer type II glia. The relationship between citrullinemia and other hepatic encephalopathy was also discussed.

Should levodopa therapy for Parkinson's disease be started early or late? Clinical course of the major tetrad in 122 parkinsonian patients treated with levodopa over 14 years.

The study was carried out to clarify whether levodopa should be started early or late in the course of Parkinson's disease. In this study, 122 patients treated with levodopa over 14 years were included. The time course of each of the four major signs (rigidity, static tremor, akinesia and postural instability) and Yahr stage was investigated in three groups, Yahr stage I/II group, Yahr stage III group and Yahr stage IV/V group, taking into consideration the time period preceding the initiation of levodopa therapy. When the time periods in years since onset of symptoms were matched, no significant differences were recognized among the three groups. There seemed to be no benefit in delaying levodopa therapy but, rather, levodopa therapy should be started as early as possible. The declining efficacy often recognized during levodopa therapy was thought probably due to progression of Parkinson's disease itself rather than to levodopa.

[A case of left hand agraphia without callosal apraxia].

A 65-year-old male who had agraphia confined to the left hand was reported. The patient was admitted to the neurological department of Kasugai city Hospital because of suddenly-developed mild right-sided hemiparesis with central facial palsy. Computerized tomography of the brain was performed 2 and 14 days after admission. As a result, low-density regions were found in the left cingulate and medial frontal gyri and the trunk of the corpus callosum. Magnetic resonance imaging of the saggital plane more clearly visualized a localized infarction affecting both the trunk of the corpus callosum and its leftward outflow. Neuropsychological findings of the patient were summarized as follows. 1) He had no difficulty in any of the actual use of object, copying the manipulation of objects, and proper use of objects according to verbal commands. 2) With the eyes closed, he could correctly name the objects handed over to the right hand, while he could do only 15 out of 20 objects handed over to the left hand. However, whichever hand an object was handed to, he could explain how to use the object. 3) He could write Hiragana, Katakana, and Kanji correctly with his right hand in accordance with verbal commands, whereas with his left hand he could do only for 20% of Hiragana, 20% of Katakana, and 90% of Kanji. 4) He could copy Kanji, Hiragana, and figures with either right or left hand. 5) He could point out verbally-presented letters using letter cards whether with the right hand or with the left hand, and could also select the letter card corresponding to the letter visually-presented.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of thallium-201 single-photon emission computed tomography and electrocardiography in Duchenne and other types of muscular dystrophy.

Single-photon emission computed tomography (SPECT) using thallium-201 was compared with 12-lead electrocardiography (ECG) in patients with Duchenne (29), facioscapulohumeral (7), limb-girdle (6) and myotonic (5) dystrophies, by dividing the left ventricular (LV) wall into 5 segments. SPECT showed thallium defects (37 patients, mostly in the posteroapical wall), malrotation (23), apical aneurysm (5) and dilatation (7). ECG showed abnormal QRS (36 patients), particularly as a posterolateral pattern (13). Both methods of assessment were normal in only 7 patients. The Duchenne type frequently showed both a thallium defect (particularly in the posteroapical wall) and an abnormal QRS (predominantly in the posterolateral wall); the 3 other types showed abnormalities over the 5 LV wall segments in both tests. The percent of agreement between the 2 tests was 64, 66, 70, 72 and 72 for the lateral, apical, anteroseptal, posterior and inferior walls, respectively. The 2 tests were discordant in 31% of the LV wall, with SPECT (+) but ECG (-) in 21% (mostly in the apicoinferior wall) and SPECT (-) but ECG (+) in 10% (mostly in the lateral wall). Some patients showed large SPECT hypoperfusion despite minimal electrocardiographic changes. ECG thus appeared to underestimate LV fibrosis and to reflect posteroapical rather than posterolateral dystrophy in its posterolateral QRS pattern. In this disease, extensive SPECT hypoperfusion was also shown, irrespective of clinical subtype and skeletal involvement.