Since 1970 many kinds of neuropeptides have been described. The chemical structures of some neuropeptides have been determined. Studies on functions of these neuropeptides have been progressed. Among these neuropeptides, brain gut peptides are contained in both the brain and the digestive organs.
In this paper, classification, effects on central nervous system and clinical applications of these neuropeptides were reviewed and discussed. As for the effects on the central nervous system, hormonal secretions, behavioral effects, influences on memory and learning, actions towards mental disorders, regulatory effects for temperature, blood pressure, sleep and appetite, and immune function were described. From these functions, several clinical applications have been introduced, of which the basic and clinical effects of TRH on ataxia of spinocerebellar degeneration are summarised. TRH treatment for ataxia of spinocerebellar degeneration has been originally reported by the author.

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Rett syndrome, initially described by A. Rett in 1966, is a disorder of characteristic motor, mental and psychological symptoms. However, it was only recently that this disease has occupied the attention of pediatric neurologists. With regard to the pathogenesis, no metabolic, morphologic or neurologic abnormalities have been consistently found.
In this paper, the characteristic clinical symptoms of this disease and its pathophysiology are described.

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Electrophysiological verification of the neural communication between the deep branch of the ulnar nerve and recurrent branch of the median nerve (Riche-Cannieu anastomosis) in the hand was carried out. Two hundreds and twenty extremities of 110 healthy subjects (54 men and 56 women) including 25 Japanese, 30 American caucacian, 30 hispanic and 25 American black populations. Supramaximal nerve stimulation of the median and ulnar nerves at the wrist and elbow was used. The compound action potentials (CMAPs) were recorded from the abductor pollicis brevis (APB), first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles. Detection of the ulnar-to-median nerve communication was evaluated with the ulnar innervation ratio (UNIR) in APB which was calculated as a ratio of CMAPs amplitude between on the ulnar and median nerve stimulation. The communication was detected in 82.5% of 220 extremities tested. The mean UNIR in APB was 27.6±16.4% (mean±SD). In American blacks, this mean value was statistically smaller than in Japanese, caucacian or hispanic population (p<0.05). The mean median nerve innervation ratio (MNIR) was also calculated in FDI and ADM. These were significantly smaller than UNIR in APB (p<0.01). This high percentage of the neural communication between ulnar and median nerves in the hand should be looked upon as a normal neural communication rather than it may signify one of a common anomalous innervation in the hand. We should always keep in mind this neural communication when we clinically or electrophysiologically examine the patients with carpal tunnel syndrome or with ulnar nerve entrapment at the Guyon canal.

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Diagnostic methods of measuring urinary ranyllylmandelic acid (VMA) and homovanillic acid (HVA) for mass-screening of neuroblastoma has been changed.
1) From April 1981 through March 1984, the first step of mass-screening consisted of measurement of VMA by spot test and quantitative measurement of HVA by thin-layer chromatography. The samples showing top 1096 in VMA, or over 35μg/mg Cr in HVA were investigated again by high performance chromatography (HPLC). Cut-off values were set at 20μg/mg Cr in VMA and 40μg/mg Cr in HVA, respectively.
2) For two years since April 1984, a highly sensitive electric detector was equipped to HPLC, which resulted in full-automatic analysis. So, determination of the metabolites by HPLC became possible from the first step of the screening. The cases showing positive results again in the newly collected urine underwent clinical examination for the tumor in our hospital. From the data of 5000 normal infants the new cut-off values were set at 25μg/mg Cr in VMA and 32μg/mg Cr in HVA.
3) After April 1986, more convenient method was developed and samples were applied directly to HPLC without receiving any pre-treatment.
Up to now (Dec. 1986), 17 cases of the tumor have been found and treated, but the disease developed later in 4 more cases from the babies showing negative results in the mass-screening at 6-months of age. It must be stressed that further studies are necessary for the follow-up of the affected children and that accumulation of the data concerning them are very important.

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Ten patients with severe asphyxia were examined by using a real-time linear array machine with 5MHz transducer, and were correlated with neurological sequelae.
In early neonatal period, ultrasound demonstrated small or non-visualized ventricles in all patients, associated with increased cerebral echogenicity in 5 patients. Cerebral hyperechogenicity was observed diffusely which was described as ‘bright brain’ in 4 patients, and locally which was recognized as intracerebral hemorrhage in 1 patient. Ultrasound findings seen in late neonatal period included enlargement of the ventricles and dilatation of the longitudinal fissure and the cortical sulci which coincide with CT findings, the result of cerebral atrophy.
Six patients with marked cerebral atrophy showed retardation of motor development. Particularly, in 5 patients with cerebral hyperechogenicity, neurological prognosis was poor showing severe neurological deficits including death in 1 patient.
Alteration of cerebral echogenicity was effective in evaluation of neurological prognosis, and we thought cerebral hyperechogenicity was caused not only by cerebral edema but also by possible disturbance of cerebral circulation such as congestion or hemorrhage.

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Acute arterial occlusion, particularly of the internal carotid and middle cerebral arteries, may on occasion produce an acute brain swelling and cause death within a few days especially in younger patients (younger than 65 years). The brain swelling is so rapid that the patients complain headache, nausea, and vomiting with deterioration of consciousness. In older patients however, the brain is more atrophic and contains dilated ventricles that might accomodate localized edema and decrease the degree of midline shift.
Conventional treatments to prevent brain edema consist of the administration of adrenocorticosteroids and hyperosmolar solutions but they may be ineffective in some cases. Some neurosurgeons have treated intracranial vascular obstructions using EC/IC bypass operation, but this must be done within 12 hours after the onset of the disease.
For these reasons, decompressive craniectomy seems to be effective and lifesaving against brain edema in patients with impending tentorial herniation.
The following factors should be taken into consideration in deciding the operation:
1) the age of patient-younger than 65 years; 2) dominance of hemisphere-nondominant hemisphere; 3) associated diseases such as severe heart or lung disease, uncontrolled diabetes mellitus, dementia might adversely influence prognosis ; and 4) the attitude of the family towards preservation of the patient's life.

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Muscle atrophy in the affected extremities is frequently seen among stroke patients. Whether this is caused by disuse or not is still controversial. We attempted to make this clear by measuring the circumferences of the forearms, the thighs and the lower legs in 67 patients with stroke. Compared with those of the non-affected side, the circumferences of the affected side were smaller. Computerized tomograph (CT) of the extremities of the affected side showed muscle atrophy. Of these 67 patients, 12 patients demonstrated severe atrophy and they were carefully analyzed. Brain CT findings revealed putaminal lesion in six of these 12 patients. The difference of the circumferences was increased by physical exercises. The compensatory effect of the non-affected side was important. Therefore, after the physical exercises, the discrepancy became greater. We conclude that the brain lesion and the physical exercises are important factors to determine the difference of the circumferences of the forearms, the thighs and the lower legs.

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Motor impairment in Parkinson's disease, clinically defined as “bradycinesia or akinesia” has been considered as resulting only from motor system involvement. Combined analysis of the afferent sensory and efferent motor systems was studied in 20 patients with Parkinson's disease with a simple aiming task on a visuomotor performance system. Dynamic characteristics in patients with Parkinson's disease were assessed by two main parameters decreased amplitude of the voluntary movement (=low gain constant) and delayed initiation of the voluntary movement (=prolonged reaction time). The visual-event-related potentials (P300) elicited in a target detection paradigm was recorded in 12 patients. P300 latency was significantly prolonged in the patient group than in the normal subjects (p<0.02). P300 has been shown to be intimately related to the cognitive process in the human brain and might serve as a tool to monitor and evaluate the cognitive state in a clinical situation. The main cause of cognitive impairment in Parkinson's disease may include coexisting dementia and defective motivation. This type of cognitive dysfunction may also serve partly as a cause of motor performance involvement, bradycinesia.

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In order to study the possible correlation between the so-called “on-off” phenomena and levodopa metabolites, we have examined diurnal fluctuations of performance and the plasma 3-0-methyl dopy (3-OMD) and dopa levels in 34 patients with idiopathic Parkinson's disease.
The patients were given levodopa alone or in combination with peripheral dopa decarboxylase inhibitor (DCI: carbidopa or benserazide) orally twice a day every four hours after breakfast. The venous blood sample (5ml) was obtained every 30 minutes or every hour, in total, 10 times during 8 hours. 3-OMD and dopa were isolated, using Dowex 50W column, and their levels were measured by the high performance liquid chromatography electrochemical detector (Yanako). Akinesia and dyskinesia of the patients were investigated by two neurologists. The results were summarized as follows:
1) The plasma 3-OMD levels before drug administration in 15 patients who showed the “on-off” phenomena were, on the average, 3477±291 (SEM)ng/ml. In 12 patients who had no “on-off” phenomena, the 3-OMD level was 906±126ng/ml. The clinical background of the two groups was similar, but the daily doses of levodopa or levodopa plus DCI given were much higher in the former group.
2) The plasma dopa level (20±4ng/ml) of the “on-off” positive group before drug administration was not significantly different from that of “on-off” negative group (14±3ng/ml).
3) The plasma 3-OMD and dopa levels in 7 virgin (the first treatment with L-dopa) cases before drug administration were 12.3±3ng/ml and 8±2ng/ml, respectively.
4) In both the groups of patients with and without the “on-off” phenomena, the plasma 3-OMD level increased slowly 30 minutes to 8 hours after the levodopa administration. These changes were however very small, compared with those in the dopa level which showed two peaks, revealing several hundred fold fluctuations.
5) The correlation between the performance fluctuation and the plasma dopa level observed after the initial administration of L-dopa was more dominant than that after the second administration in the “on-off” phenomena group.
From these results, it is suggested that the dopa uptake into the central nervous system may be impeded by the high plasma level of 3-OMD, thereby resulting in the “on-off” phenomena.

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Continuous intravenous infusion of levodopa was tried on the 65-year-old male patient with Parkinson's disease with severe fluctuation of the clinical symptoms.
The patient had been taking 100mg of levodopa (plus 10mg of carbidopa) orally seven times a day. The fluctuation of the clinical symptoms was related to the dose of the levodopa and the deterioration was accompanied with the decrease in the plasma levodopa level.
The intravenous infusion of 250mg of levodopa was added to the oral administration of levodopa. The infusion lasted 12 hours a day. The infusion rate was changed with the fluctuation of the symptoms. After the infusion the patient showed remarkable improvement of the fluctuation.
This method should be developed as well as the subcutaneous infusion pump in diabetes mellitus.

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Treatment of twenty patients with juvenile parkinsonism is described. Juvenile parkinsonism is a specific form of parkinsonism, differing from idiopathic parkinsonism not only by their onset of age but also by their clinical manifestations. In the treatment of juvenile parkinsonism, levodopa was usually much more effective, and wearing-off phenomenon and dyskinesia appeared more easily and more severely than idiopathic parkinsonism.
To control juvenile parkinsonism we tried different methods. We administered levodopa in small doses, many times a day and when the patient was hungry. We tried administration of bromocriptine and pimozide, and we tried drug holiday therapy.
As for the result of administering levodopa in small doses, it was effective in suppressing the occurrence of dyskinesia. Administration of the drug many times a day was effetive in suppressing the weaing-off phenomenon. Administration of the drug when the patient being hungry was effective in obtaining constant efficacy of levodopa. Levodopa combined with decarboxylase inhibitor was also effective. Bromocriptine was beneficial in controlling wearing-off phenomenon, dyskinesia and reduction of the number of levodopa doses. Pimozide was effective only in controlling severe dyskinesia for a short time, but parkinsonism increased at the same time. Drug holiday was not so effective in controlling wearing-off phenomenon and dyskinesia compared to idiopathic parkinsonism. We experienced smoking efficacy in five cases of juvenile parkinsonism, and its efficacy did not last for a long time, but it was enough to control the disabilities of parkinsonism.
In the treatment of juvenile parkinsonism, it was important to choose optimal treatment case by case.

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It has been well known that patients with SMON often complain of cold sensations in distal parts of four extremities, and most of the patients complain of severe cold sensations and/or paresthesias (shibire sensation) only in lower limbs.
However, it is not obvious whether the cold sensations are caused by autonomic or sensory nervous disturbances because of a lack of objective measurement. In order to elucidate these questions, we examined skin temperature recovery rate (STRR) to cold water in upper and lower extremities of SMON patients by using thermography. The results were as follows;
(1) In the upper limbs, STRRs were significantly lower (p<0.01) in SMON patients than age-matched controls.
(2) In the lower limbs, STRRs showed no significant difference between the controls and the patients with SMON, in spite of complaining of severe cold sensation.
(3) It is suggested that the cold sensations of lower limbs in patients with SMON seem to be caused by sensory rather than autonomic nervous disturbances due to myeloneuropathy of the disease.

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The treatment with a precursor of natural noradrenaline, L-threo-3, 4-dihydroxyphenylserine (L-DOPS) was tried on orthostatic hypotension in a patient with Shy-Drager syndrome. The patient was a 61-year-old man who had had impotence, orthostatic hypotension, dysuria, anhidrosis below the neck and mild ataxia. L-DOPS was orally administered starting with 300mg/day. Maintenance dose of the drug was 600mg/day and the symptoms were carefully observed up to the 90th week after the beginning of the treatment. Immediately after the drug was administered, blood pressure in supine and standing position wasslightly elevated. The symptoms associated with orthostatic hypotension such as dizziness and syncope were significantly improved in degree and in frequency. Impotence and disturbances of urination were also improved. The effect of the treatment persisted during the period observed. No side effects were seen clinically or no abnormal laboratory findings were noted. It is suggested that the long-term oral administration of L-DOPS is useful in the treatment of orthostatic hypotension in various degenerative disorders such as Shy-Drager syndrome.

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A 43-year-old female developed Raynaud phenomenon in 1934, shortly followed by swollen hands, arthralgia, myalgia, peripheral neuropathy and gait disturbance. She was diagnosed as having MCTD. Several reports have been published that steroids were usually ineffective in the management of peripheral neuropathy of MCTD. However, various symptoms including peripheral neuropathy were adequately improved in this case with 30mg/day of prednisolone. Therefore, this case was very interesting in considering the treatment and pathogenesis of peripheral neuropathy in MCTD.

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