CSF and plasma adipokines after tonic-clonic seizures.

PURPOSE: Adipokines, especially leptin and adiponectin, have gained increasing importance in pathophysiology of various neurological diseases including epilepsy. There are experimental data suggesting a role for leptin in the genesis of seizures and neuroprotection related to seizures. However there are no clinical studies on the effects of epileptic seizures on adipokines. METHODS: We measured cerebrospinal fluid (CSF) and plasma levels of leptin, adiponectin and adipsin after provoked or unprovoked primary or secondarily generalized tonic-clonic seizures in 13 female patients and seven controls. The samples were taken within 24h after the seizure onset. RESULTS: Leptin plasma levels correlated negatively with the time to sample withdrawal, i.e. the longer the time interval between the seizure and the sample the lower the leptin levels in the patients. Interestingly, plasma adiponectin levels were significantly increased after the seizure episode. CONCLUSION: This study provides further evidence that there are seizure-induced acute changes in adipokine metabolism. Leptin concentrations seem to decrease during the first 24h after the seizure whereas adiponectin levels increase. The meaning of this response is far from clear, but it might be an endogenous attempt to prevent harmful effects of epileptic seizures in the central nervous system.

Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels.

BACKGROUND: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. METHODS: Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability. RESULTS: We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. CONCLUSIONS: Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.

Cerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure.

PURPOSE: Whether repeated brief seizures can cause neuronal damage is controversial. Cerebrospinal fluid (CSF) total tau (T-tau) and phosphorylated tau (P-tau) measurements have been suggested for the diagnosis of Alzheimer's disease, and T-tau may also be a marker of axonal damage and neuronal degeneration. We studied T-tau and P-tau levels and P-tau/T-tau ratio in CSF after epileptic seizures in order to determine whether they are increased after seizures. METHODS: A total of 54 patients with tonic-clonic or partial secondarily generalized seizures due to various etiologies were studied and CSF obtained within 48h after the seizure. RESULTS: There were no statistical differences in the levels of T-tau (p=0.09, ANOVA) or P-tau (p=0.60) between different etiologic groups or controls. No patients with epilepsy of unknown origin had abnormal CSF T-tau whereas 11 patients with acute or remote symptomatic seizures had abnormal T-tau levels and the P-tau/T-tau ratio showed significant differences between the groups and controls (p=0.003). CONCLUSIONS: Epileptic seizures with unknown etiology did not increase CSF tau levels. Abnormal tau levels were associated with either acute or remote symptomatic seizures with known etiology. The presence of elevated CSF tau increases the probability of symptomatic cause in a patient with a seizure.

Early-onset encephalopathy and cortical myoclonus in a boy with MECP2 gene mutation.

The authors report the unusual clinical and neurophysiologic features of a sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month-old boy was examined for severe developmental delay, seizures, microcephaly, breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs. Neurophysiologic study proved the cortical origin of myoclonus; however, it was not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy-phenylethylene glycol and valine concentrations were low in CSF.

Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures.

We have previously reported increased concentrations of interleukin (1L)-6 in CSF from patients with tonic-clonic seizures, where increased cytokine production most likely is a consequence of neuronal epileptic activity associated with seizures. The biological effects of IL-6 are mediated by other cytokines, which are studied here in addition to IL-6. The purpose of this study was to analyze levels of soluble cytokines from plasma and CSF from patients with newly developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor antagonist (IL-1RA), IL-1beta, tumor necrosis factor (TNFalpha) and nerve growth factor (NGF) were measured from plasma and CSF from 22 patients with newly developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The mean concentrations of IL-6 were significantly increased in CSF (P<0.001) and plasma (P<0.01) after tonic-clonic seizures, there was some indication of increased concentrations of IL-1RA and no significant change in NGF, IL-1beta or TNFalpha. Our study shows that cytokine network is activated in patients after recent tonic-clonic seizures. We provide evidence of intrathecal production of IL-6 associated with electrical seizure activity.

Studies on cerebrospinal fluid kynurenic acid concentrations in epileptic children.

Kynurenic acid (KYA), the only known endogenous antagonist of the excitatory amino acids, is a metabolite of kynurenine. In the present study the levels of KYA were measured in the cerebrospinal fluid (CSF) of epileptic children and age-matched controls to investigate the relationship between various forms of epilepsy and KYA levels. CSF samples from four patients with West syndrome (WS), four patients with epilepsy with grand mal seizures on awakening (EGSA), and four patients with childhood epilepsy with occipital paroxysms (CEOP) were collected by lumbar puncture before treatment. The concentration of CSF KYA was analyzed by HPLC with electrochemical detection and compared with those of age-matched controls. The levels of CSF KYA were significantly lower (P < 0.05) in patients with WS compared with controls. The levels of CSF KYA in patients with EGSA and with CEOP did not differ significantly from control levels. These results suggest that the presence of seizures in WS is associated with altered kynurenine metabolism. The possibility that seizures in WS may be related to decreased production of KYA is discussed.

Cerebrospinal fluid levels of neuropeptides, cortisol, and amino acids in patients with epilepsy.

We measured lumbar cerebrospinal fluid (CSF) levels of somatostatin, cholecystokinin, neurotensin, atrial natriuretic factor, vasoactive inhibitory peptide, neuropeptide Y, adrenocorticotrophic hormone, corticotropin releasing hormone, beta-endorphin, metenkephalin, cortisol, alanine, glycine, aspartate, glutamate, taurine, and gamma-aminobutyric acid in 25 inpatients with epilepsy at known interictal and postictal times and in 11 neurologically normal volunteers. There were no significant differences between interictal or postictal complex partial seizures (CPS), postictal generalized tonic-clonic seizures (GTC), and control CSF neuropeptide, cortisol, and amino acid (AA) levels. However, there were nonsignificant trends for CSF levels of several neuropeptides to be increased after CPS and GTC as compared with interictal baseline levels. There were significant correlations between levels of certain CSF neuropeptides or (AAs) and serum antiepileptic drug (AED) levels. Several correlations were noted between CSF levels of AAs, including a correlation between the excitatory neurotransmitters aspartate and glutamate identified only after CPS.

Cerebrospinal fluid and serum levels of dopa, catechols, and monoamine metabolites in patients with epilepsy.

We measured CSF and serum concentrations of monoamines and monoamine metabolites in normal control subjects and in patients with partial epilepsy between and less than 2 h after complex partial seizures (CPS) or secondarily generalized tonic-clonic seizures (SGTCs). After SGTCs, concentrations of norepinephrine in CSF were significantly higher (p less than 0.05) than interictal concentrations, concentrations after PSs, and concentrations in control subjects. Serum epinephrine levels also were significantly higher after SGTCs than interictal and control subjects' levels. CSF HVA levels were significantly higher after PSs than interictal or control subjects' levels. CSF concentrations of norepinephrine and its intraneuronal metabolite, dihydroxyphenylglycol, were highly correlated, both interictally and following SGTCs, whereas correlations between serum and CSF levels of these catechols generally were not statistically significant. The results indicate that seizures are associated with release of catecholamines in the central nervous system.

Amino acid levels in cerebrospinal fluid of rats after administration of pentylenetetrazol.

1. We studied the effect of pentylenetetrazol (PTZ)-induced myoclonic jerks and generalized clonic-tonic convulsions (GC) on the levels of neurotransmitter amino acids in the cisternal CSF of rats. 2. The levels of aspartate, glutamate, glycine, and taurine were elevated in the CSF during myoclonic jerks and more distinctly immediately after GC. 3. During the recovery period of postictal depression seen in EEG (5 min after GC), the CSF levels of transmitter amino acids were lower than in the control group. 4. PTZ-induced irritative activity in the EEG disappeared in 24 hr but the levels of amino acids remained abnormal. 5. Amino acid changes in the CSF following PTZ-induced convulsions might indicate that the release of amino acids into the extracellular space is increased before and during the propagation of PTZ-induced seizure and decreased during postictal depression.

[Changes in the cerebrospinal fluid levels of adenosine cyclic- 3',5'-monophosphate (c-AMP) in patients with generalized tonic-clonic epileptic seizures]. / Zmiany stezenia cyklicznego adenozyno 3'5' monofosforanu (c-AMP) w plynie mózgowo rdzeniowym (p.m.r.) u chorych z uogólnionymi toniczno-klonicznymi napadami padaczki.

Authors evaluated the activity of c-AMP in the CSF as the biochemical marker for evaluation of epileptic seizure activity in patients with epilepsy. The impact of monitored phenytoin treatment on c-AMP activity in CSF was investigated. It was shown that the general tonic-clonic seizures cause a significant concentration increase of c-AMP in CSF. Monitored phenytoin treatment had a stabilizing effect on c-AMP activity in CSF.

Low levels of gamma-aminobutyric acid in cerebrospinal fluid of dogs with epilepsy.

gamma-Aminobutyric acid (GABA) levels were determined in cisternal cerebrospinal fluid (CSF) of 19 epileptic dogs with generalized tonic-clonic (grand mal) seizures using a radioreceptor assay. Thirty-four healthy age-matched dogs served as controls. The average CSF GABA level in epileptic dogs (40 pmol/ml) was significantly lower than that determined in controls (66 pmol/ml). Treatment with phenobarbital or primidone seemed not to affect CSF GABA levels.

Low cerebrospinal fluid gamma-aminobutyric acid content in seizure patients.

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.

Cerebrospinal fluid GABA reductions in seizure patients evoked by cerebellar surface stimulation.

Lumbar cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) levels determined by fluorometric assay in four seizure patients were found to be significantly lower during bilateral, continuous cerebellar stimulation than those determined after a 7-day period without stimulation. The CSF GABA concentrations during chronic unilateral, alternating cerebellar stimulation were reduced in three seizure patients but unchanged in a fourth patient. The percentage decrease in CSF GABA appeared to be independent of cerebellar stimulation frequency. These findings suggest that GABA-mediated neuronal transmission is depressed during cerebellar surface stimulation and this evoked reduction in GABA activity may compromise the efficacy of cerebellar stimulation in the treatment of epilepsy. Lumbar CSF cyclic guanosine monophosphate levels determined by radioimmunoassay were not significantly altered by either mode or frequency of cerebellar stimulation.