John Logothetis

The role of estrogens in catamenial exacerbation of epilepsy.

NEARLY a century ago, Cowers’ suspected a relationship between epilepsy and menstruation. Since then, several investigators have confirmed this observation and agreed that an exacerbation of epileptic seizures occurs primarily just before or at the time of menstruation.*4 During the last decade, however, some controversy has appeared in the literature on this subject. Among various investigators challenging a relationship between seizures and menstrual cycle, Almquistu was the first to support his conclusions with a statistic survey. Although demonstrating a definite rhythmicity in the occurrence of epileptic seizures, he maintained that menstrual phenomena are not involved. More recently, however, Laidlawe found unequivocal evidence of catamenial epilepsy in a twenty-five-year follow-up study of the occurrence of more than 33,000 seizures in 50 epileptic women. Most investigators in the literature maintain that fits exacerbate shortly before or during menstruation in about 50% of epileptic women. In these women, seizures often begin or preexisting attacks recur or become worse at the menarche. The menopause, as might be expected, seems to have a significant, depressant effect on incidence of seizures,3 while ovariectomy has been reported to relieve human epileptic fits3v7 and diminish epileptic discharges in animal^.^ There has been considerable difference of opinion regarding the pathogenesis of the catamenial exacerbation of epileptic seizures. The more important theories and ob-

Spontaneous epileptic seizures and electroencephalographic changes in the course of phenothiazine therapy

PIIENOTHIAZINES CONTINUE to account for a variety of neurologic side reactions with extrapyramidal manifestations still observed in the highest frequency. Epileptic seizures and electroencephalographic abnormalities in the course of phenothiazine kherapy have been the subject of discussion in a number of case studies; however, the extent of the potential convulsive hazard with these drugs is still unclear. Our experience with phenothiazine-induced seizures, presented here, derives from four and one-half years of observation of a large group of hospitalized psychiatric patients.

Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects.

FORTY-FIVE Y ARS AGO Cooley and Lee defined a specific disorder characterized by anemia with decreased r e d cell osmotic fragil i ty, hepatosplenomegaly, pigmentary skin changes, and thickening of the long bones and skull. Cenetic studies 2 ~ 3 established that Cooley’s anemia, or thalassemia, represents the homozygous state of a partially dominant autosomal gene, with the heterozygous state usually represented by a clinically mild anemia. Cooley’s anemia has been extensively reviewed in recent years. 4-6 There are two categories of thalassemias, corresponding to inherited depression in synthesis of either alpha or beta polypeptide chains of the globin molecule, with failure to produce red cells with normal adult hemoglobin (Hb) content. In alpha-thalassemia there is decreased synthesis of alpha polypeptide chains, resulting in decreased amounts of adult and fetal hemoglobin. In beta-thalassemia there is failure in production of beta chains with a resulting decrease in the synthesis of the major adult hemoglobin fraction, HbA (a,P,); the minor fraction, HbA, (a,s,), and fetal hemoglobin, HbF (a ,y , ) , which do not contain beta chains, go into a compensatory overproduction. The homozygous state of beta-thalassemia, referred to as homozygous beta-thalassemia or simply thalassemia major, corresponds to the clinical condition of Cooley’s anemia. Symptoms in homozygous beta-thalassemia

A new model of subarachnoid hemorrhage in experimental animals with the purpose to examine cerebral vasospasm

Using 20 rabbits, we tried to establish a new model of experimental subarachnoid hemorrhage (SAH) for examining both acute and chronic cerebral vasospasm. A cranial opening was drilled, and a puncture made on the posterior branch of the middle cerebral artery. A second puncture was made in the superior sagittal sinus for additional withdrawal of subarachnoid blood. The bleeding thus induced resulted in arterial spasm which was studied by using serial electrocorticograms, cerebral blood flow measurement with 133Xe, and videomicroscopy of the small pial vessels at various intervals. After death of the animals, the brains were observed to identify the extention of the bleeding. It was indeed obvious that large amounts of subarachnoid blood clots had accumulated. This investigation showed that the rabbit can be used as a new experimental model of SAH. With a two-puncture method, it is possible to simulate the clinical phenomenon of a ruptured aneurysm, that seems to produce acute and chronic cerebral vasospasm. For the latter, the accumulation of blood clots in the basal surfaces plays an important role. The three methods of observation, videomicroscopy, cerebral blood flow measurements, and electrocorticography appeared to provide useful information in the study of biphasic vasospasm in the rabbit.

Determination of the fatty acid composition of cerebrospinal fluid by gas-liquid chromatography.

SEVERAL PREVIOUS studies have employed gasliquid chromatography as a qualitative and quantitative tool for the analysis of fatty acids of cerebrospinal fluid in normal subjects14 and in those with demyelinating disease.l*5?6 In these studies, the extracted lipids were saponified under alkaline conditions to liberate the fatty acids prior to their conversion to methyl esters for analysis by gas chromatography. Such alkaline saponification methods do not liberate the longer chain fatty acids which characterize the sphingolipids, cerebrosides, and sphingomyelins. Thus, it is not surprising that such longer chain fatty acids have not been reported as constituents of cerebrospinal fluid lipids. In addition, such fatty acids may have been missed because of relatively insensitive methods of detection, inadequate sample size, or failure to allow sufficient time for such components to elute. In the present study an attempt is made to overcome these objections by using methods which have previously proved successful7 for the analysis of the fatty acid composition of sphingomyelins and cerebrosides isolated from nervous tissue. Principal improvements are acid-catalyzed mgthanolysis of the lipid extracts and the use of two different types of well-standardized gas chromatography columns for each analysis.

Fatty acids in spinal fluid and serum of patients with demyelinating disorders

THE CEREBROSPINAL FLUID is being continuously investigated in order to develop better laboratory criteria for the diagnosis of multiple sclerosis and the determination of its degree of activity. However, good correlation is lacking today between spinal fluid changes and clinical manifestations of this disease. Although first zone colloidal gold reactions and elevation of gamma globulins may provide considerable diagnostic help, such changes are not always demonstrated, and when present usually do not correlate well with the degree of activity of the demyelinating process. A correlation has been reported recently between the free cholesterol of the spinal fluid and the activity of multiple sclerosis.1 However, further studies are needed to substantiate this observation. The present investigation was carried out in order to study the possible relationship between demyelinating disorders and the spinal fluid fatty acids. Previous reports have shown a decrease of some polyunsaturated fatty acids, phospholipids, and an increase of cholesterol esters in demyelinating plaques.2~3 With the exception of a single patient with multiple sclerosis studied by Bl~mstrand,~ no other investigation has been reported regarding the spinal fluid fatty acids in this disease.

Free amino acid content of cerebrospinal fluid in humans and dogs

IN A PREVIOUS COMMUNICATION^ we have presented a chromatographic method and a survey analysis of free amino acids in the cerebrospinal fluid of normal human subjects and those with neurologic diseases. The present report includes a more detailed study of normal human subjects based upon a larger number of cases, as well as observations regarding the free amino acid content of cerebrospinal fluid in dogs.

A Study of Free Amino Acids In the Human Cerebrospinal Fluid

THE FIRST chemical investigations of the cerebrospinal fluid, as well as the first recorded spinal puncture, were credited to Quinke in 1891. Subsequent studies on the significance of cell count and quantitation of sugar and protein by this investigator clearly demonstrated the clinical value of the determination of the cerebrospinal fluid contents. Since that time little progress has been made in the analysis of other spinal fluid constituents capable of providing aids to the diagnosis of nervous system disease. Many of these constituents may be altered in the presence of nervous system pathology. Among these substances are the free amino acids which, like the blood free amino acids, arise from absorption, synthesis, and tissue breakdown. They thus contribute to the free amino acid pool from which amino acids are continually withdrawn for the synthesis of tissue proteins and other nitrogenous compounds, as well as for energy-yielding oxidation. Alterations in the metabolism of amino acids, particularly the essential amino acids, will lead to a disturbance in tissue synthesis. Furthermore, abnormal tissue breakdown may change the normal amino acid turnover. It can be assumed, therefore, that such disturbances may be reflected in the free amino acid pool of blood and cerebral spinal fluid. Amino acid changes in blood have been demonstrated under various pathologic and experimental conditions. However, alterations in the amino acid content of the spinal fluid have never been clearly elucidated. The assumption that cerebral metabolic changes may manifest themselves by changes in the free amino acid content of the cerebrospinal fluid is an attractive hypothesis, since gross protein changes may occur in the spinal fluid in cases of central nervous system disease without demonstrable changes in plasma proteins. Amino acid alterations could then be employed as a diagnostic aid as well as in the study of the metabolism of the disease in question. The tedious and frequently inaccurate laboratory procedures necessary to the separation and quantitation of amino acids resulted in the neglect of these studies in body fluids for many years.

The fatty acids of the human cerebrospinal fluid: their relation to the serum fatty acids: A study using gas‐liquid chromatography

STUDIES of lipids in cerebrospinal fluid have been relatively difficult because of the lack of adequate technics. This subject was recently reviewed by Tourtellotte,1,2 who investigated the major lipids of the cerebrospinal fluid. Except for Blomstrand’s report on the fatty acids of the cerebrospinal fluid in 4 patients with active neurologic disorders, this aspect of cerebrospinal fluid lipids has remained unexplored. Although several studies have been published regarding the serum fatty acids in normal persons,“-G similar studies regarding the fatty acids of the cerebrospinal fluid are not available. The present work was undertaken in an attempt to determine, in “normal” subjects, the fatty acids of the cerebrospinal fluid and to correlate the findings with the values of fatty acids in the serum.

Free amino acid concentrations in cerebral cortex of guinea pigs with epileptogenic lesions

Abstract A study is presented of thirteen guinea pigs with experimentally produced focal epileptogenic lesions. In six animals the epileptogenic discharge was slight, while seven showed strong paroxysmal potentials in the electroencephalogram. Free amino acid analysis by quantitative paper chromatography revealed the most consistent change to be a low glutamic acid concentration at the sites of strong epileptogenic discharge. Active mirror foci exhibited no amino acid change.