First seizure presentation: do multiple seizures within 24 hours predict recurrence?

We compared clinical features and prognosis of 72 adults with a first-ever seizure presentation comprising multiple discrete seizures within 24 hours to 425 patients presenting with a single seizure. Those presenting with multiple seizures were no more likely to have seizure recurrence, irrespective of etiology or treatment. Hence, a presentation with multiple seizures within 24 hours should be regarded as a single event, in keeping with the International League Against Epilepsy recommendations.     

Do partial seizures predict an increased risk of seizure recurrence after antiepilepsy drugs are withdrawn?

Most children who are seizure free on antiepilepsy drugs for 2 or more years remain seizure free when taken off antiepilepsy drugs. We studied 27 children with well-controlled epilepsy in whom seizures unexpectedly recurred after antiepilepsy drug withdrawal. Seizures were focal in 20 of 27 cases (74%). In 11 of the 20 cases (55%), there was also a late onset of seizures (after 2 years) and an abnormal electroencephalogram (EEG) at antiepilepsy drug withdrawal. Of the remaining 9 patients with focal seizures, 3 (15%) had only a late seizure onset, 3 (15%) had only an abnormal EEG, and 3 (15%) had neither a late onset of seizures nor an abnormal EEG. In the 7 patients without focal seizures, 6 of 7 (86%) had a late seizure onset and/or an abnormal EEG. Our study suggests that partial seizures can be the most important predictor of unanticipated seizure recurrence when antiepilepsy drugs are withdrawn, particularly with late onset of seizures and an abnormal EEG at antiepilepsy drug withdrawal. A large, multicenter, prospective study looking at these and other potential risk factors for seizure recurrence is needed.     

Do serum sodium levels predict febrile seizure recurrence within 24 hours?

The American Academy of Pediatrics Practice Parameter, The Neurodiagnostic Evaluation of a Child with a First Simple Febrile Seizure, does not recommend serum electrolytes be obtained routinely. Two reports from Europe, however, identified relative hyponatremia as a risk factor for febrile seizure recurrence within 24 hours. If confirmed, this would have potential impact on the approach to these patients. The charts of 175 sequential children ages 6 months to 5 years who presented to the Children's Hospital of Buffalo emergency room in 1999 with generalized seizures lasting less than 15 minutes were retrospectively reviewed. One hundred thirty-six patients were febrile and 39 (control group) were afebrile. Serum electrolytes were performed on all. The mean serum sodium for the 27 children with more than 1 febrile seizure in 24 hours (135.48 mmol/L) did not differ from those 109 febrile children whose seizures did not recur within 24 hours (135.56 mmol/L). Of interest, the mean serum sodium for the 109 children with simple febrile seizures, as well as those with recurrent "simple" febrile seizures were significantly lower than the control group of children with afebrile seizures. These findings reaffirm the recommendation of the American Academy of Pediatrics Practice Parameter to not routinely obtain electrolytes.     

Can Seizure-Alert Dogs predict seizures?

An index observation where a dog was trained to alert to, as well as respond to, human tonic-clonic seizures led to further research and refinement of training techniques. This was followed by anecdotal reports of pet dogs spontaneously anticipating human epileptic seizures. An industry has since developed training Seizure-Alert Dogs (SADs) to give humans warnings of their seizures. In some cases this has been accompanied by a reduction in seizure frequency. SADs may be trained along with the person with epilepsy, responding specifically to that person's seizures, or may be trained separately. Recent sceptical reports of non-epileptic seizures in some people with SADs have cast doubt on dogs' ability to anticipate true epileptic seizures. This may reflect selection criteria for training programmes as well as training methods used, but does not necessarily indicate that SADs might not be able to predict epileptic seizures. Whether the seizures are epileptic or non-epileptic, it is speculated that SADs probably alert to subtle pre-ictal human behaviour changes, but may also be sensitive to heart rate or olfactory cues. As yet, however, no rigorous data exist as to whether seizure prediction by SADS is better than chance, and what false positive and negative prediction rates might be.     

How do seizures stop?

Although often overshadowed by factors influencing seizure initiation, seizure termination is a critical step in the return to the interictal state. Understanding the mechanisms contributing to seizure termination could potentially identify novel targets for anticonvulsant drug development and may also highlight the pathophysiological processes contributing to seizure initiation. In this article, we review known physiological mechanisms contributing to seizure termination and discuss additional mechanisms that are likely to be relevant even though specific data are not yet available. This review is organized according to successively increasing "size scales"-from membranes to synapses to networks to circuits. We first discuss mechanisms of seizure termination acting at the shortest distances and affecting the excitable membranes of neurons in the seizure onset zone. Next we consider the contributions of ensembles of neurons and glia interacting at intermediate distances within the region of the seizure onset zone. Lastly, we consider the contribution of brain nuclei, such as the substantia nigra pars reticulata (SNR), that are capable of modulating seizures and exert their influence over the seizure onset zone (and neighboring areas) from a relatively great-in neuroanatomical terms-distance. It is our hope that the attention to the mechanisms contributing to seizure termination will stimulate novel avenues of epilepsy research and will contribute to improved patient care.     

Treating acute seizures with benzodiazepines: does seizure duration matter?

Several clinical trials have shown improved seizure control and outcome by early initiation of treatment with benzodiazepines, before arrival in the emergency department and before intravenous access can be established. Here, evidence is provided and reviewed for rapid treatment of acute seizures in order to avoid the development of benzodiazepine pharmacoresistance and the emergence of self‐sustaining status epilepticus. Alterations in the physiology, pharmacology, and postsynaptic level of GABA‐A receptors can develop within minutes to an hour and hinder the ability of synaptic inhibition to stop seizures while also impairing the efficacy of GABAergic agents, such as benzodiazepines, to boost impaired inhibition. In addition, heightened excitatory transmission further exacerbates the inhibitory/excitatory balance and makes seizure control even more resistant to treatment. The acute increase in the surface expression of NMDA receptors during prolonged seizures also may cause excitotoxic injury, cell death, and other pathological expressions and re‐arrangements of receptor subunits that all contribute to long‐term sequelae such as cognitive impairment and chronic epilepsy. In conclusion, a short window of opportunity exists when seizures are maximally controlled by first‐line benzodiazepine treatment. After that, multiple pathological mechanisms quickly become engaged that make seizures increasingly more difficult to control with high risk for long‐term harm.     

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.     

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.     

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.     

Atonic seizures in children with surgically remediable epilepsy: a motor system seizure phenotype?

Aim. Atonic seizures are common in some epileptic syndromes beginning in infancy or early childhood but they are rarely described in epilepsy with focal seizures of structural aetiology. We aimed to characterize the electroclinical features of atonic seizures in surgically remediable paediatric patients and to study the spatiotemporal organization of the underlying epileptogenic networks. Methods. We retrospectively analysed two consecutive, longitudinally evaluated and surgically treated paediatric patients presenting with atonic seizures as a manifestation of pharmacoresistant epilepsy of structural aetiology, evidenced by scalp‐ and stereotactic intracerebral video‐EEG‐recordings. A quantitative analysis of the epileptogenic zone organization was performed using the “epileptogenicity index”. Results. Long‐lasting generalized ictal atonia, occurring in infancy, was a predominant clinical feature in both patients, with some hints of focal origin present in one case. The seizure phenotype evolved at later age into subtle segmental atonia, associated with prominent positive motor signs. The epileptogenic zone was localized within the dorsolateral or mesiolateral premotor region. Its spatial organization was focal, matching the lesional cortex in one and distributed involving several lesional and non‐lesional structures in the other case. The emergence of atonic semiology temporally correlated with involvement of both lateral and mesial premotor, as well as primary motor areas. Conclusion. We hypothesize that atonic seizures may be considered as a motor system seizure phenotype in the setting of structural epilepsy. Complete removal of the epileptogenic area provided excellent seizure control.     

Temporal lobe epilepsy: where do the seizures really begin?

Defining precisely the site of seizure onset has important implications for our understanding of the pathophysiology of temporal lobe epilepsy, as well as for the surgical treatment of the disorder. Removal of the limbic areas of the medial temporal lobe has led to a high rate of seizure control, but the relatively large number of patients for whom seizure control is incomplete, as well as the low rate of surgical cure, suggests that the focus extends beyond the usual limits of surgical resection. Reevaluation of the extent of the pathology, as well as new data from animal models, suggests that the seizure focus extends, at least in some cases, beyond the hippocampus and amygdala, which are usually removed at the time of surgery. In this review, we examine current information about the pathology and physiology of mesial temporal lobe epilepsy syndrome, with special emphasis on the distribution of the changes and patterns of seizure onset. We then propose a hypothesis for the nature of the seizure focus in this disorder and discuss its clinical implications, with the ultimate goal of improving surgical outcomes and developing nonsurgical therapies that may improve seizure control.     

What happens now? Ongoing outcome after post-temporal lobectomy seizure recurrence

We studied outcome subsequent to the initial post-temporal lobectomy seizure recurrence (n = 202) or remission. Two years after recurrence, there was 74% (95% CI 67% to 79%) probability of further seizures. Two years after a 2-year seizure remission, there was 68% (95% CI 52% to 79%) probability of remaining seizure-free (n = 50). Remission after seizures had a significantly poorer outcome than an equivalent period of complete seizure freedom after surgery. Implications for outcome classification are discussed.     

Can we predict early recurrence in acute stroke?

BACKGROUND: The prevention of early recurrent stroke, which worsens outcomes after a cerebral infarction, is a major objective for acute stroke therapy. The ability to predict which patients are at risk for early recurrence would be useful for both the management and design of clinical trials. METHODS: Using the prospective database with the 1,266 stroke patients admitted in the TOAST study, we analyzed all the patients who had suffered either a transient ischemic attack (TIA) or a recurrent stroke within 3 months after stroke, and their possible association with 20 selected clinical variables. Both univariate and stepwise regression analyses were performed. RESULTS: Sixty-two patients (4.9%) had a second stroke, and 47 patients (3.7%) had at least one TIA. No particular high-risk period was observed. Early recurrent stroke was associated with the large artery atherosclerosis subtype. A prior history of TIA increased the odds for recurrent stroke (OR = 2.52; 1.16-5.46) or poststroke TIA (OR = 3.46; 1.59-7.48). In addition, patients who had a TIA after the stroke had a 17% chance of having an early recurrent stroke, as compared with 4.4% among those that did not (p = 0.001). CONCLUSION: Our present ability to identify patients at risk for early recurrence based on baseline clinical features remains limited. While the presence of TIA before or after the stroke denotes a subgroup of acute stroke patients at higher risk for early recurrence in the first 3 months, no other factors reliably identify high-risk patients.