Risk and risk factors for epilepsy in shunt-treated children with hydrocephalus

ObjectEpilepsy is a major comorbidity in children with hydrocephalus (HC) and has a serious impact on their developmental outcomes. There are variable influencing factors, thus the individual risk for developing epilepsy remains unclear. Our aim was to analyse risk factors for developing epilepsy in children with shunted HC.MethodsA retrospective, single-centre analysis of 361 patients with the diagnosis of HC was performed. Age at HC diagnosis, shunt treatment, development of epilepsy, epilepsy course, and the aetiology of HC were considered. The influence of shunt therapy, including its revisions and complications, on the development of epilepsy was investigated.ResultsOne-hundred forty-three patients with HC (n = 361) had a diagnosis of epilepsy (39.6%). The median age at the first manifestation of epilepsy was 300 days (range:1–6791; Q1:30, Q3: 1493). The probability of developing epilepsy after HC decreases with increasing age. The most significant influence on the development of epilepsy is that of the HC itself and its underlying aetiology (HR 5.9; 95%-CI [3–10.5]; p < 0.001). Among those, brain haemorrhage is associated with the highest risk for epilepsy (HR 7.9; 95%-CI [4.2–14.7]; p < 0.01), while shunt insertion has a lower influence (HR 1.5; 95%-CI [0.99; 2.38]; p = 0.06). The probability of epilepsy increases stepwise per shunt revision (HR 2.0; p = 0.03 after 3 or more revisions). Five hundred days after the development of HC, 20% of the children had a diagnosis of epilepsy. Shunt implantation at a younger age has no significant influence on the development of epilepsy nor does sex.ConclusionChildren with HC are at high risk for developing epilepsy. The development of epilepsy is correlated mainly with HC's underlying aetiology. The highest risk factor for the development of epilepsy seems to be brain haemorrhage. The age at shunt implantation appears to be unrelated to the development of epilepsy, while structural brain damage at a young age, shunt revisions and complications are independent risk factors. The onset of epilepsy is most likely to take place within the first 500 days after the diagnosis of HC.     

Outpatient initiation of the ketogenic diet in children with pharmacoresistant epilepsy: An effectiveness,safety and economic perspective

BackgroundChildren with pharmacoresistant epilepsy usually receive ketogenic diet (KD) as an inpatient, which makes it an expensive treatment.ObjectiveTo compare the effectiveness, safety, and costs of outpatient versus inpatient initiated KD.DesignRetrospective observational non-inferiority study.Patients/settingPatients (1–18 years of age) who started KD either inpatient or outpatient.Main outcome measuresEffectiveness was defined as ≥50% seizure reduction. Safety was measured by the numbers of emergency visits and complications. Economic impact was analyzed by calculating total costs of treatment.Statistical analysesNon-inferiority of outpatient initiation was tested using 95% confidence intervals of the differences in effectiveness and safety endpoints between groups with non-inferiority margins of 10%. Nonparametric bootstrap techniques were used to derive a 95% confidence interval for the mean difference in total costs between the groups.ResultsHundred and five patients started KD in the period 2001 to 2017: 43 inpatient and 62 outpatient. At three months, the KD was effective in 61% of outpatients versus 63% of inpatients. The KD was considered safe in 36% of the outpatients, as compared to 29% in the inpatients. Outpatient initiation was shown to be non-inferior to inpatient initiation in terms of safety. Total health care costs of outpatient initiation were € 2901, as compared to € 8195 of inpatient initiation per patient (mean difference € 5294, 95% CI; -€ 7653 to -€ 2935).ConclusionsOur study suggests that outpatient KD initiation is no worse than inpatient initiation in terms of effectiveness and safety, while carrying lower health care costs.     

Modafinil exerts a dose-dependent antiepileptic effect mediated by adrenergic alpha1 and histaminergic H1 receptors in mice

Epilepsy is characterized by neuronal hyperexcitability and hypersynchronization. Disruption of electroencephalographically (EEG) synchronized epileptiform discharges may be a possible therapy for epilepsy. In the present study, to clarify the role of EEG desynchronization on epilepsy, we investigated the effect of modafinil, a potent wake-promoting substance with EEG desynchronization activity, on epilepsy in mice and clarified the receptors involved in the suppression of seizure caused by maximal electroshock (MES) and pentylenetetrazol (PTZ) kindling models. Modafinil given at 22.5, 45, and 90 mg/kg, i.p. significantly decreased the incidence of tonic hindleg extension in MES seizure models, and protected against PTZ-induced convulsive behaviors in a dose-dependent manner. In addition, modafinil at 180 mg/kg exerted an antiepileptic effect in the MES model; however, at the same dosage it increased the seizure stage in the PTZ-kindling model. The antiepileptic effect in both MES and PTZ models was antagonized by the adrenergic alpha(1) receptor antagonist terazosin, but not by the adrenergic alpha(2) receptor antagonist yohimbine or by dopaminergic receptor antagonists, SCH-23390 (for D(1) receptors) and haloperidol (for D(2) ones). Pyrilamine, a histaminergic H(1) receptor antagonist, counteracted the antiepileptic action of modafinil in the PTZ induced-kindling model, but not in the MES seizure model. Taken together, the present findings indicate that modafinil exerted its antiepileptic effect via adrenergic alpha(1) and histaminergic H(1) receptors, and might be of potential use in the treatment of epilepsy.     

新生大鼠反复惊厥对脑内γ-氨基丁酸A受体α1和β2亚单位表达的短期影响

目的：γ-氨基丁酸A受体（GABAAR）作为脑内最重要的抑制性受体在脑功能中起重要作用。该实验通过研究新生期反复惊厥对大鼠脑内GABAAR α1和β2亚单位表达的短期影响，探讨其与发育中脑损伤的关系。方法：生后7 d的Sprague-Dawley大鼠随机分成两组，每组32只，惊厥组每日吸入三氟乙醚诱导惊厥发作1 次，每次持续30 min，连续6 d；对照组同样操作但不吸入三氟乙醚。分别于反复惊厥后1 d和7 d每组各处死16只大鼠，每个时间点分别采用免疫组化方法和Western blot方法观察大鼠大脑皮层及海马GABAAR α1和β2亚单位表达的变化。结果：反复惊厥后1 d时，在惊厥组大鼠顶叶及海马齿状核、CA3和CA4区GABAAR α1亚单位免疫化学累积光密度（AOD）较对照组明显增高（P＜0.05），反复惊厥后7 d时，在惊厥组大鼠顶叶及海马齿状核、CA1至CA4区GABAAR α1亚单位免疫化学AOD较对照组明显增高（P＜0.05），反复惊厥后1 d和7 d时，在惊厥组大鼠大脑皮层和海马区GABAAR α1亚单位蛋白表达均明显高于对照组（P＜0.01）。反复惊厥后7 d时，在惊厥组大鼠海马CA1、CA2区GABAAR β2亚单位免疫化学AOD明显高于对照组（P<0.05），在丘脑区明显低于对照组（P<0.05），惊厥组大鼠海马区GABAAR β2亚单位蛋白表达明显高于对照组（P<0.05）。结论:新生大鼠反复惊厥造成脑内GABAAR α1和β2亚单位表达的短期改变，这种改变可能参与发育期惊厥性脑损伤。     

Seizure heralding functional recovery in a patient with apallic syndrome: A case report with retrospective-prospective observation

BACKGROUND: It has been suggested that there exists a close relationship between seizure discharges and functional recovery from brain injury, and that paroxysmal bombardment in late seizures may herald functional recovery or may "kick-start" recovery. CASE REPORT: We report the case of a 52-year-old patient who, following a subarachnoid hemorrhage and multiple surgeries, experienced discernible apallic syndrome of long duration. His hospitalization is well documented. The patient underwent protracted, intense rehabilitation, but he remained in this prolonged state of loss of consciousness and behavioral passivity until he experienced a series of periodic seizures. Widespread improvement in his cognitive and functional abilities coincided closely with the seizure activity. The literature on this topic is reviewed. CONCLUSION: This case confirms the close relationship between seizure discharges and functional recovery reported in preclinical literature.     

Epilepsy: A Clinical Overview

The diagnosis and treatment of seizures and epilepsy is a common task of the physician. Approximately 1 in 10 people will have a seizure during their lifetime. Epilepsy is the tendency to have unprovoked seizures. Epilepsy is the fourth most common neurological disorder and affects 1 in 26 people in the United States and 65 million people worldwide. Evaluation of a patient presenting with a seizure involves excluding an underlying neurologic or medical condition, classifying the seizure type and determining if the patient has epilepsy. Proper treatment requires accurate diagnosis of the epilepsy type and syndrome and use of a medication that is effective and without adverse effects. Most patients can achieve complete seizure control with medication, but if medication is unsuccessful, surgical treatment can be an option. Special situations in the care of people with epilepsy include status epilepticus, women with epilepsy, the older adult, and safety issues.     

Modulation in time of the interictal spiking pattern related to epileptic seizures

ObjectiveTo test the hypothesis that significant changes in the occurrence of interictal epileptiform electroencephalography (EEG) discharges (EDs) are associated with seizures: while some EDs are pro-convulsive, increasing at seizure-occurrence, others are protective, showing decrease related to seizures.MethodsWe analyzed 102 consecutive, long-term video-EEG monitoring sessions, from 98 patients. Using a semi-automated spike-detection method, we quantified the occurrence of EDs, grouped according to their location and morphology (clusters) and we constructed graphical representation of data, showing changes in time of the spiking patterns (spike-histograms). We compared the spike-histograms with the time-points of the seizures (pre-, peri- and postictal changes).ResultsTotally 179 ED-clusters were identified. Modulation of the spiking pattern, associated with seizures, was observed in 66 clusters (37%), from 47 patients (48%). Most of these changes (40 clusters; 61%) were related to increase in the spiking-pattern.ConclusionsChanges in spiking-pattern were associated with more than one third of the EDs. Both increasing and decreasing patterns were observed.SignificanceEDs are more often pro-convulsive, with increasing spiking patterns associated with seizures. However, in more than one third of the ED clusters modulated by seizures, the spiking pattern decreased, raising the possibility of an anticonvulsive function of these discharges.     

Delta oscillation underlies the interictal spike changes after repeated transcranial direct current stimulation in a rat model of chronic seizures

BackgroundTranscranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation.ObjectiveTo determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures.MethodsRats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats.ResultsInterictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham.ConclusionsThe inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.     

Cyclooxygenase‐2 in epilepsy

Epilepsy is one of the more prevalent neurologic disorders in the world, affecting approximately 50 million people of different ages and backgrounds. Epileptic seizures propagating through both lobes of the forebrain can have permanent debilitating effects on a patient's cognitive and somatosensory brain functions. Epilepsy, defined by the sporadic occurrence of spontaneous recurrent seizures (SRS), is often accompanied by inflammation of the brain. Pronounced increases in the expression of key inflammatory mediators (e.g., interleukin ‐1β [IL‐1β], tumor necrosis factor alpha [TNFα], cyclooxygenase‐2 [COX‐2], and C‐X‐C motif chemokine 10 [CXCL10]) after seizures may cause secondary damage in the brain and increase the likelihood of repetitive seizures. The COX‐2 enzyme is induced rapidly during seizures. The increased level of COX‐2 in specific areas of the epileptic brain can help to identify regions of seizure‐induced brain inflammation. A good deal of effort has been expended to determine whether COX‐2 inhibition might be neuroprotective and represent an adjunct therapeutic strategy along with antiepileptic drugs used to treat epilepsy. However, the effectiveness of COX‐2 inhibitors on epilepsy animal models appears to depend on the timing of administration. With all of the effort placed on making use of COX‐2 inhibitors as therapeutic agents for the treatment of epilepsy, inflammation, and neurodegenerative diseases there has yet to be a selective and potent COX‐2 inhibitor that has shown a clear therapeutic outcome with acceptable side effects.