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Background: Valproic acid (VPA) has been widely used in Chinese patients after craniotomy. Many studies have focused on the influencing factors of VPA serum concentration, but conclusions are sometimes paradoxical. Furthermore, the concentration of VPA in the cerebrospinal fluid (CSF) has been rarely reported. In the present study, VPA CSF concentrations were measured, and the potential factors influencing serum concentration and CSF distribution of VPA were investigated. In addition, the functional relationship between serum and CSF concentration was explored., Methods: Subjects were patients who underwent craniotomy and were administrated with VPA and had a lumbar puncture. Serum and CSF VPA concentrations were measured by use of the Abbott i1000 system. CYP2C9 (430 C>T, 1075 A>C, 1076 T>C, 1080 C>G), UGT1A6 (541 A>G, 552 A>C), UGT2B7 (211 G>T, 802 C>T), and ABCB1 (1236 C>T, 2677 G>T/A, 3435 C>T) genotypes were determined by direct sequencing. Information, such as age, gender, and height, was collected, and their effect on serum and CSF VPA concentrations was investigated by univariate analysis and multiple linear regression analysis., Results: First, the concomitant use of carbapenems (β' = -0.422) and UGT1A6 (552 AA → AC) (β' = -0.249) had a significant negative correlation with the weight-adjusted VPA serum concentration (C:W ratio), whereas CYP2C9 (1075 AA → AC) (β' = 0.186) and gender (female compared with male) (β' = 0.322) showed a positive correlation with VPA serum C:W ratio. The coefficient of determination (R) was only 0.348. Second, the relationship between the serum concentration and the CSF square root of the concentration (R = 0.705) had a better linear fit. Third, serum VPA concentration (β' = 0.810), concomitant use of glycerol fructose (β' = 0.160), and age (≥65 compared with <65) (β' = 0.118) showed a positive correlation (R = 0.748) with the variability of square root of the concentration of the CSF., Conclusions: In Chinese patients, after craniotomy, female patients with 1 or more of CYP2C9 (1075 AC) and UGT1A6 (552 AA) genotypes required a lower VPA dosage compared with male patient. There was a better-fitted linear relationship between VPA serum and the square root of CSF concentrations. CSF VPA concentrations were relatively stable, with only age and the use of glycerol fructose having a small influence.

Objective: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy., Method: We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥ 1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency., Results: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%)., Conclusions: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy., Classification of Evidence: This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.

We have analyzed changes in cerebrospinal fluid (CSF) concentrations of monoamine-related substances to clarify the mechanism of the antiepileptic action of thyrotropin-releasing hormone (TRH). TRH-tartrate was administered to 14 patients with intractable epilepsy. Before and 2 weeks after TRH administration, CSF was collected and analyzed for tryptophan and tyrosine metabolites. Among monoamine-related substances, only CSF concentrations of kynurenine were increased after TRH therapy. Considering the fact that kynurenic acid acts as antagonist on the NMDA receptor complex, the results of this study may explain at least one of the mechanisms of the effectiveness of TRH therapy for intractable epilepsy.

To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.

Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and probenecid were examined in 14 children with epilepsy (ages 6 months to 17 years) and 17 controls (ages 14 months to 16 years). The concentrations of amine metabolites were significantly correlated with probenecid concentrations in both groups of children. Cerebrospinal fluid concentrations of 5-HIAA were 63.6 ng per milliliter plus or minus 8.23 S.E.M. and 117 ng per milliliter plus or minus 11.6 S.E.M. for the epilepsy and control groups respectively. HVA averaged 89.1 ng per milliliter plus or minus 15.2 S.E.M in epilepsy and 172 ng per milliliter plus or minus 19.2 S.E.M. in the control group. These findings indicate a significant difference between epilepsy and control groups. Probenecid concentrations were similar in each group. The reduced cerebrospinal fluid amine metabolite concentrations in children with epilepsy were not related to age, anticonvulsant medication, cerebrospinal fluid folate or protein concentration, or cerebrospinal fluid cell count. Our findings suggest a relationship between brain amines and epilepsy.

Gamma-Aminobutyric acid (GABA) has been implicated in the neurochemistry of epilepsy. Lumbar cerebrospinal fluid (CSF) GABA concentrations determined using an ion-exchange fluorometric assay reflect brain GABA content. The mean lumbar CSF GABA concentration among 21 medicated patients with intractable seizures was significantly lower (p less than 0.001) than that of 20 unmedicated normal volunteers. Patients with generalized tonic-clonic (grand mal) and complex partial (psychomotor) seizures had significantly lower (p less than 0.05) CSF GABA concentrations than those with simple partial (focal sensory/motor) seizures. Although lumbar CSF GABA levels in our seizure patients did not significantly correlate with serum concentrations of phenytoin, phenobarbital, or primidone, additional study of medication-free epileptic patients may be required to evaluate the possibility of anticonvulsant-drug-induced CSF GABA alterations.

A prospective study with a 3-year follow-up was made of 82 patients examined consecutively by pneumoencephalography. Several types of cerebral diseases were represented. The degree of mental impairment was rated. Qauntitative cisternography was performed in 70 of these patients, in which the exponential elimination of injected iodine 131-l human serum albumin from the basal cisterns was calculated. Mental impairment was found to be strongly correlated with a lack of air filling over the parietal convexities and with a slow isotope elimination from the basal cisterns, indicating a slow cerebrospinal fluid turnover. Hydrocephalus was not always present. Only eight had a convexity block for the passage of isotopes.

The level of free amino acids in cerebrospinal fluid from eight patients in comatose states has been determined. The variations of cerebrospinal fluid-free amino acids observed in coma have been compared with those reported by other authors in patients affected by epilepsy, multiple sclerosis, infantile amaurotic idiocy (GM2-gangliosidosis) and phenylketonuria.