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Acetylcholinesterase (AChE), choline, monoamine and its metabolite, amino acid and superoxide dismutase (SOD) levels were measured in cerebrospinal fluid (CSF) in patients with cerebrovascular diseases. Patients were classified into the following four groups; controls: normal subjects without neurological disease, group A: cerebral hemorrhage, group B: cerebral infarction, group C: patients with mental impairment, including those in groups A and B, and a low score on Hasegawa's Dementia Rating Scale. CSF AChE level of groups A, B and C was decreased significantly, while choline concentration from patients showed a increase compared with that of control cases. CSF alanine concentration showed a tendency to increase, while glycine and glutamate tended to decrease. CSF epinephrine, norepinephrine or 3-methoxy-4-hydroxyphenylethylen glycol concentrations of groups A, B and C did not exhibit a significant difference from that in control cases. Some cases with cerebrovascular diseases showed low concentrations of both CSF 5-hydroxyindole acetic acid and homovanillic acid. However, dihydroxyphenyl acetic acid concentration was higher than in control cases. The CSF SOD level was not significantly from that in control cases. The changes in neurochemical substances in the CSF support their use as markers of cerebrovascular disease-related change.

A 55-year-old woman, who had two episodes of difficulty in putting a key into a keyhole probably due to optic ataxia at age 52 and 54 years old, developed speaking errors and was admitted to our hospital. She was 152.5 cm in height and 52.5 kg in weight. Neurological examination revealed right homonymous hemianopsia and sensory aphasia. A CSF examination revealed lymphocytic pleocytosis of 88/microliter. Serum lactate and pyruvate were remarkably increased after an aerobic exercise test. A few ragged-red fibers were present in the biopsied brachial biceps muscle. Brain MRI by FLAIR method showed scattered high signal lesions in the left temporal lobe, bilateral parieto-occipital lobes, left insular cortex and left thalamus. The left superficial temporal lesion was enhanced by gadolinium-DTPA. The proton MRS demonstrated the lactic acid peak as well as the decrease of NAA/choline ratio (0.38) in the left parieto-occipital region. Thus, she was diagnosed as a case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and successfully treated with ubidecarenone (150 mg/day). Six months later, she again developed seizure, right hemiparesis and deterioration of aphasia and presented again CSF lymphocytic pleocytoses of 15/microliter. Brain MRI demonstrated new lesions in the left temporoparietal lobes, left insular cortex and left corona radiata. Therefore, CSF pleocytosis appeared to be associated with stroke-like episodes in this case. Although the mechanism of CSF pleocytosis remains to be elucidated, it may involve the breakdown of blood-brain barrier caused by mitochondrial dysfunction. Otherwise, an inflammatory process similar to that in cases of Leber disease, who developed multiple sclerosis-like additional lesions in the central nervous system, may also take place in MELAS.

Cerebrospinal fluid flow dynamics of 15 patients with occlusive cerebrovascular diseases was studied using RI cisternography (RIC) and Metrizamide CT cisternography (CTC) and these methods were compared. RIC demonstrated RI retention in 9 patients, which was noticed in all chronic stage patients (over one month after apopletic episode). Five patients had subarachnoid block in affected cerebral hemisphere. Ventricular reflux, however, was present in only one patient. Metrizamide CTC (170 mgI/ml) showed ventricular reflux or stasis in 11 of 16 patients. Seven patients revaaled asymmetrical metrizamide filling of Sylvian fissures at 3 or 6 hours after intrathecal injection of Metrizamide. Asymmetrical demonstration of Sylvian fissure after 3 hours in 3 patients corresponded with the finding of subarachnoid block at the same side on RIC. The clinical values of CTC were emphasized on the basis of this investigation. Ventricular reflux or stasis, which indicated one of the important findings on cerebrospinal fluid flow disturbance, was easily and clearly detected. Asymmetrical metrizamide filling of Sylvian fissures at 3 hours after injection was compatible with subarachnoid block on RIC.

The peptide, 7B2, originally isolated from pituitary, has been shown to be present in endocrine tumors of high concentrations in pancreatic islet tumors. Plasma from most of these patients showed very high 7B2 immunoreactivity (IR-7B2) though there is a lack of knowledge concerning physiological and pathological changes in plasma IR-7B2 levels in other conditions. To assess whether or not there is any alteration in circulating IR-7B2 levels due to age, sex or any specific condition, plasma levels of IR-7B2 were measured in the fasting state in 106 healthy subjects aged 3 months to 91 years, 101 diabetics, 28 patients with hyperthyroidism. 7 patients with primary hypothyroidism, 13 patients with liver cirrhosis, 43 patients with chronic renal failure, 35 patients with cerebral vascular accident, and 26 pregnant subjects. Twenty-four cord bloods were also included. The responses of circulating IR-7B2 to oral glucose, intravenous arginine infusion, volus thyrotropin (TRH) or volus luteinizing hormone-releasing hormone (LH-RH) injection were also evaluated. Particularly high IR-7B2 levels were found to exist in cord blood. Postnatally the concentrations decreased gradually with age to adult values (15.6 +/- 2.9pmol/liter (mean +/- SE) in 20's-60's), though plasma IR-7B2 levels again increased significantly in over 70's (37.1 +/- 3.2pmol/liter; P less than 0.01). There was no significant difference in plasma 7B2 levels in either sex. Among the pathological conditions studied, significantly high IR-7B2 levels were observed in patients with chronic renal failure (175.1 +/- 35.9pmol/liter). Some of the pregnant patients in their third trimester also showed high plasma IR-7B2 levels. A small but significant rise in plasma IR-7B2 was observed after a glucose load in control subjects and diabetics. Intravenous LH-RH exerted a rise in plasma 7B2 concentrations though arginine and TRH showed no significant effect on plasma IR-7B2 concentrations. Compared with the plasma concentrations, ten to fifty-fold high levels of IR-7B2 were observed in cerebrospinal fluid (CSF) from patients with cerebrovascular accidents or multiple sclerosis. These results suggested that the kidney plays a major role in 7B2 degradation and that LH-RH simulates IR-7B2 release from the pituitary gland. Whether reduced clearance or increased production was responsible for the IR-7B2 elevation in subjects under 10 years or over 70 years requires investigation. Furthermore, high levels of IR-7B2 in CSF might indicate its specific role for the central nervous system.

A prospective high performance liquid chromatography (HPLC) study was performed in eighteen patients with head injury and stroke and four control volunteers to evaluate creatinine and purine metabolites concentration (adenosine, inosine, hypoxanthine, uric acid) in cerebrospinal fluid (CSF). The present HPLC method is rapid, accurate and sensitive in the same isocratic run and no specimen pretreatment of 0.02 ml CSF is necessary. The creatinine level in CSF was increased from 122 to 169 mumol/l in some patients, and was found unrelated to that of serum. The uric acid levels varied between 5.8 and 121 mumol/l and were associated with decrease in Glasgow Coma Scale score and had a critical point of 30 mumol/l. We present initial results in application of HPLC method to measure the creatinine and purine metabolites in CSF. This preliminary report presents that these high levels in CSF of head injury and stroke patients probably reflect tissue damage and an increased tissue catabolism.

Two grams of cefotaxime (CTX) were administrated by drip infusion to 10 patients (11 material) with acute or chronic stage of intracranial diseases. Concentrations of CTX in the serum and the cerebrospinal fluid (CSF) were determined at 15, 30, 60, 120, 240 and 300 minutes after injection. The results obtained were summarized as follows: Serum levels: Peak levels of CTX in sera were 66.2 +/- 10.23 (S.E.) micrograms/ml in the acute stage group (ASG), and 75.7 +/- 31.39 (S.E.) micrograms/ml at 15 minutes after injection in the chronic stage group (CSG). There were no significant difference between the 2 groups. CSF levels: Peak levels of the drug in CSF were 1.35-4.32 micrograms/ml in ASG and 0.18-0.7 microgram/ml in CSG. Average concentration at 60 minutes after injection was 1.11 +/- 0.09 (S.E.) micrograms/ml in ASG and 0.30 +/- 0.08 (S.E.) micrograms/ml in CSG. The value in ASG was significantly higher than the value in CSG by t-test. The ratio between CSF and serum levels: The levels increased as time passed in both groups and the values in ASG were higher than those in CSG at all time points. Average ratios at 60 minutes after injection were 3.85 +/- 0.29 (S.E.)% in ASG and 1.12 +/- 0.50 (S.E.)% in CSG. The value in ASG was significantly higher than that in CSG by t-test. From the above results, it is considered that CTX is useful for the prophylaxis of postoperative infections in intracranial diseases.

Elucidation of the alterations of intracerebral neurotransmitters in cerebrovascular dementia is of prime importance not only in revealing patho-physiological mechanism but also in developing the therapy for the disease. We measured monoamine metabolites and norepinephrine (NE) in cerebrospinal fluid of patients with cerebrovascular dementia, to study the effects of administration of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-metyl-1,4-benzoquinone (idebenone, CV-2619). Six patients with cerebral infarction and 1 with cerebral hemorrhage, at the mean age of 65.4 years, were enrolled as subjects. All patients had mental and intelligent impairment, and the Hasegawa's Dementia Rating (DR) Scale was performed. The patients were medicated with 90 mg daily dose of CV-2619 for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG), NE in cerebrospinal fluid were determined by high-performance liquid chromatography before and also after the medication. Before the medication, HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly low (p less than 0.01), compared with controls at a similar age: 5-HIAA was 18.5 +/- 2.7 ng/ml, and MHPG, 9.5 +/- 0.7 ng/ml, both of which were not significantly low, but tended to be low, compared with the controls. NE was similar to the control value. With the administration of CV-2619, HVA measured 27.1 +/- 3.2 ng/ml, showing a tendency to increase; 5-HIAA was 26.7 +/- 2.3 ng/ml, and MHPG, 10.7 +/- 0.6 ng/ml, both of which increased significantly (p less than 0.05), compared with the respective premedication values.(ABSTRACT TRUNCATED AT 250 WORDS)

It is well known that the permeability of the blood brain barrier and blood cerebrospinal fluid barrier changes more or less in various diseases of the central nervous system. At present, thee is no clinically available index which reflects the alteration of the permeability of the blood brain barrier and blood cerebrospinal fluid barrier. The brain scintiraphy is an examination which detects a breakdown in the blood brain barrier, its clinical usefullness is limited only in a localized and extremely pathological proces of the brain. In this report, a cerebrospinala fluid isotope measurement comined with the brain scintigraphy was presented as a clinical examination for blood brain barrier function. Thirty minutes prior to brain scintigraphy, potassium perchlorate (4 mg/kg) was given orally to reduce the accumulation of 99mTc04-in the choroid plexus and to minimize iradiation for tr other organs. Spinal tap was performed two hours after injection of 99mTc04- according to Haines's method...

It is recognized that absorption of C.S.F. occurs mainly at the superior sagittal sinus through arachnoid villi after study of the Retzius (1875) and Weed (1914). We are interested in C.S.F. circulation and pathway on the obstructed superior sagittal sinus. At the border of middle one third and posterior one third of the superior sagittal sinus was obstructed experimentally. 1. When evans blue 0.5 to 1.0 ml was injected into lateral ventricle or cisterna magna, the evans blue was recognized on basal surface in either normal and obstructed dog of the superior sagittal sinus. Evans blue stained the convexity of normal dog, however, did not stain the convexity in the dog of obstructed superior sagittal sinus contrally. This was caused by the disturbance of C.S.F. circulation toward superior sagittal sinus. On the intraventricular injection of evans blue, it infiltrated into parenchym from ventripcle due to C.S.F. circulatory disturbance. 2. Study of radioactivity in the peripheral blood after intracisternal or intraventricular injection of RISA 100 muCi revealed that the radioactivity in the blood lowered with day after obstruction of superior sagittal sinus comparing with normal dogs. 3. Macroautoradiography after intracisternal or intraventricular injection of P 2mCi showed lower RI activity at the convexity, but increased activity at the basal brain in the obstructed dogs of superior sagittal sinus. These results showed that C.S.F. in normal dog was absorbed through the brain surface, expecially the basal surface of brain, other than through the superior sagittal sinus. Absorption of C.S.F. through the convexity of brain was disturbed significantly in the obstructed dogs of superior sagittal sinus. C.S.F. absorption into peripheral blood decreased in chronic stage after occlusion of surperior sagittal sinus and it suggested that the absorptive function of C.S.F. through the basal surface of brain was restricted.

Experimental evidence has shown that the amount of 5-HIAA in the CSF reflects the metabolism of serotonin in the brain if this metabolite is eliminated from the brain and flows into the CSF at a constant rate. We studied the concentration of 5-HIAA in the lumbar CSF in several neurological diseases to elucidate the alteration in abnormalities of serotonin metabolism. The concentration of 5-HIAA in the CSF was measured in 94 patients with cerebral infarction, 30 with vascular dementia, 25 with dementia of the Alzheimer type, 28 with Parkinson's disease and 6 with hypoxic encephalopathy. Patients with cerebral infarction were classified into 24 with a solitary cerebral infarct and 70 with multiple cerebral infarcts. Patients with Parkinson's disease were subdivided into 12 with various psychiatric symptoms including depressive state, hallucination and/or intellectual impairment and 16 without psychiatric symptoms. Patients with hypoxic encephalopathy consisted of 5 with apallic syndrome and one patient with Lance-Adams syndrome. The concentration of 5-HIAA in solitary cerebral infarct, multiple cerebral infarcts and vascular dementia did not exhibit a significant difference from that in control cases (54.6 +/- 23.1 ng/ml). But patients with dementia of the Alzheimer type (34.5 +/- 10.9, p less than 0.001) showed a significantly lower concentration. This fact seems to reflect the pathological finding that the number of large neurons is decreased and neurofibrillary tangles are increased in the nucleus raphe dorsalis of patients with Alzheimer type dementia.(ABSTRACT TRUNCATED AT 250 WORDS)