Concussive convulsions: seizure or no seizure?

Convulsions following traumatic brain injury (TBI) represent a diagnostic and therapeutic challenge. They can be differentiated into late (> 7 days after TBI), early (1 - 7 days after TBI), immediate (within the first 24 h after TBI), and impact seizures (within seconds after TBI). Some authors suggest that most impact seizures are non-epileptic in origin and hence coined the term "concussive convulsions" for benign impact seizures. Early and late post-traumatic seizures frequently indicate structural brain damage and transition to chronic, post-traumatic epilepsy. The data for impact seizures or concussive convulsions is less clear: only a small percentage of impact seizures is associated with structural brain damage and the development of post-traumatic epilepsy, rather the majority of cases are benign and associated with an excellent prognosis. Here, we present a case report as a starting point for pathophysiological and clinical considerations regarding convulsions that start within seconds after TBI.     

What makes a simple partial seizure complex?

The assessment of ictal consciousness has been the landmark criterion for the differentiation between simple and complex partial seizures over the last three decades. After review of the historical development of the concept of “complex partial seizure,” the difficulties surrounding the simple versus complex dichotomy are addressed from theoretical, phenomenological, and neurophysiological standpoints. With respect to consciousness, careful analysis of ictal semiology shows that both the general level of vigilance and the specific contents of the conscious state can be selectively involved during partial seizures. Moreover, recent neuroimaging findings, coupled with classic electrophysiological studies, suggest that the neural substrate of ictal alterations of consciousness is twofold: focal hyperactivity in the limbic structures generates the complex psychic phenomena responsible for the altered contents of consciousness, and secondary disruption of the network involving the thalamus and the frontoparietal association cortices affects the level of awareness. These data, along with the localization information they provide, should be taken into account in the formulation of new criteria for the classification of seizures with focal onset.     

Persistent hand spasm: movement disorder or seizure?

Dystonia is a movement disorder characterized by involuntary, sustained or repetitive, patterned muscle contractions or spasms, frequently causing squeezing and twisting movements or abnormal postures. Dystonic posturing could be one of the accompanying features of epilepsy. We report an elderly lady with intractable focal seizure who presented with more than a year of persistent hand spasms. The clinical importance of differentiating epilepsy from movement disorders is discussed.     

Is seizure detection based on EKG clinically relevant?

Objective

Real-time EKG-based automated seizure detection is emerging as a complement or supplement to that based on cortical signals, but its value is unproven. This study assesses the clinically relevance of EKG-based seizure detection by comparing the information content in EKG and ECoG.

Methods

ECoGs (6935 h; 241 clinical and 4311 sub-clinical seizures) with simultaneous EKG from 81 subjects undergoing surgical evaluation were used in these analyses. Differences, if any, between clinical and sub-clinical seizures in variables such as intensity, duration and their product severity, were investigated with a multi-variate regression model.

Results

Highly statistically significant differences in severity between clinical and sub-clinical seizures were discerned with EKG and ECoG. Furthermore, EKG-based seizure severity was linearly correlated with that estimated using ECoG.

Conclusions

These findings support the notion that EKG-based seizure detection is clinically relevant in certain localization-related epilepsies, providing similar information to that yielded by neuronal electrical signals.

Significance

The information content equivalence between EKG and ECoG would enable automated seizure detection, quantification and therapy delivery, without resorting to cortical monitoring. The considerably higher S/N and ease of acquisition and processing of EKG compared to ECoG/EEG may foster widespread clinical applications of this novel detection approach.     

Do depression symptoms predict seizure frequency--or vice versa?

OBJECTIVE: The aim of this study was to test a theoretical explanatory model of the relationship between depression symptom scores and seizure frequency in people with epilepsy. METHODS: A community-based sample of adults with active epilepsy provided information on depression symptom scores and seizure frequency at two time points, 1 year apart. RESULTS: One thousand two hundred ten patients completed the initial questionnaire, and 976 of these individuals (80.7%) completed the final questionnaire. Depression scores and seizure frequency were significant predictors of each other, both within (beta = .07, P < .05 and beta = .09, P < .05) and across time (beta = .03, P < .01 and beta = .07, P < .05). CONCLUSION: The relationship between depression symptom scores and seizure frequency in those with epilepsy is bidirectional.     

Can a generalized kindling seizure induce a reward state?

The postictal behavioral depression (PBD), characterized by behavioral immobility and unresponsiveness to environmental stimuli, observed after a stage 5 kindling seizure is opioid dependent. Morphine injection prolongs while naloxone and naltrexone (opioid antagonists) reduce or eliminate PBD. Opioids have clear rewarding actions that can be easily detected by place preference conditioning (PPC). In the present study, we evaluated if the opioid release after a stage 5 kindling seizure that produces PBD could induce PPC. Male rats were kindled in the medial preoptic area (MPOA), the amygdala (AMG) or insular cortex (IC). After kindling was established their initial preference in a three-compartment chamber was determined. During conditioning, subjects received a standard kindling stimuli that evoked a stage 5 seizure. At the end of the after discharge and during the PBD the animals were placed in the non-preferred chamber for 30 min. On alternate days they were placed without stimulation in the preferred chamber. At the end of conditioning the kindled groups showed a clear change of preference. This change of preference was completely blocked by injection of naloxone. These results suggest that opioid release after a stage 5 kindling seizure can induce a positive affect of sufficient intensity and duration to induce conditioning.     

Oral baclofen in cerebral palsy: possible seizure potentiation?

Baclofen, a gamma-aminobutyric acid agonist, is widely used to treat spasticity of cerebral and spinal origin. Patients with both acute baclofen overdose and withdrawal have developed seizures. After several reports of new-onset seizures in children treated with oral baclofen at our institution, we reviewed our experience regarding possible effects of baclofen on seizure induction in a childhood movement disorders program over a 2-year period. Of 54 children (ages 1-10) treated with oral baclofen, 19 (35%) had a prior history of seizures. Five children (14%) developed new-onset seizures after starting baclofen. Although epilepsy is very common in children with cerebral palsy, these findings raise the possibility that baclofen may potentiate seizures in certain young children with cerebral palsy. Further study of the effects of baclofen on seizures is warranted.     

β-Hydroxybutyrate increases the pilocarpine-induced seizure threshold in young mice

This study was designed to investigate the effects of β-hydroxybutyrate (BHB) on pilocarpine-induced seizures in young mice. Eighty-five male, postnatal day 21, ICR mice were used. All mice were pretreated with scopolamine methylbromide (1 mg/kg) 30 min prior to pilocarpine administration. Experimental mice (n=46) were injected intraperitoneally with BHB (20 mmol/kg), 15 min prior to pilocarpine administration; control animals (n=39) were administered normal saline. Pilocarpine (300 mg/kg) was then administered intraperitoneally to induce seizures. Mice were monitored for 2 h after pilocarpine injection, and seizure behavior grades were evaluated according to Racine's scale. All mice developed typical seizure behaviors of grade 3 or higher. Although the severity in terms of seizure behavior grade was not significantly different between groups, the mean (±SD) latency to the onset of seizure was significantly prolonged in BHB-treated mice (5.15±2.19 min) compared with controls (2.95±1.06 min; p<0.001). This study demonstrates that treatment with BHB significantly prolongs the latency to the onset of seizures induced by pilocarpine in mice and suggests that BHB, one of the ketone bodies, may be direct anticonvulsant.     

Which factors determine febrile seizure recurrence? A prospective study

PURPOSE: Many factors have been studied as potential predictors of recurrent febrile seizures (FS), however the available data in literature are inconsistent. The aim of the present paper is to determine which factors are responsible for the first and for multiple recurrences of FS, in a large sample of children with a long-term follow up. METHODS: Two hundred and sixty children were followed after their first FS. The inclusion criteria were: a history of a first febrile seizure; no personal history of afebrile seizures; no previous anticonvulsant medication and age between three months and six years. The median time of follow up was 4.3 years. We had a contact with the families of the children every 4-6 months and also in every recurrence. RESULTS: Very significant prognostic markers for the first FS recurrence were low age at onset, recurrence within the same illness, frequent febrile episodes and maternal preponderance. Powerful prognostic factors that may predispose children who already have one recurrence to a second or more are low age at onset and especially positive family history of FS. Additionally, low temperature prior to the initial seizure is a powerful predictor for three or more recurrences. CONCLUSIONS: Prognostic factors for FS recurrence are a useful tool for the clinician. It is obvious that as many powerful predictors a child has, the greater will be the risk for FS recurrence.     

Premonitory features and seizure self-prediction: artifact or real?

Seizure prediction is currently largely investigated by means of EEG analyses. We here report on evidence available on the ability of epilepsy patients themselves to predict seizures either by means of subjective experiences ("prodromes"), apparent awareness of precipitants, or a feeling of impending seizure (self-prediction). These data have been collected prospectively by paper or electronic diaries. Whereas evidence for a predictive value of prodromes is missing, some patients nevertheless can forsee impending seizures above chance level. Relevant cues and practical implications are discussed.     

Pregnant serum induces neuroinflammation and seizure activity via TNFα

Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective role of the BBB that prevents exposure of the brain to hyperexcitable factors.