Late onset unprovoked seizures in DiGeorge syndrome.

Risk of seizure recurrence after the first late posttraumatic seizure

AimsIntracerebral hemorrhage (ICH) is a known risk factor for the development of acute symptomatic as well as late unprovoked seizures. The underlying pathophysiology of post-ICH seizures is incompletely understood and there are no reliable predictive biomarkers. An animal model to study post-ICH seizures is currently lacking. The aim of this study was to investigate (1) the occurrence of seizures and interictal epileptiform activity in the ICH rat collagenase model using long-term video-EEG monitoring (VEM) and (2) whether seizure occurrence was associated with interictal epileptiform activity and histological features.MethodsMale Sprague-Dawley rats were implanted with epidural electrodes. After 1 week of baseline VEM, collagenase was injected in left striatum to induce an ICH. VEM was continued for 180 days to assess the occurrence of post-ICH seizures and interictal epileptiform activity (spikes and epileptiform discharges). At the end of the experiment, animals were euthanized for histological characterization of the hemorrhagic lesion, using cresyl violet, Prussian blue and immunofluorescence staining.ResultsAcute symptomatic seizures occurred in 4/12 animals between 46 and 80 h after ICH induction. Late unprovoked seizures were present in 2/12 animals and started at 90 and 103 days post-ICH. Animals with late unprovoked seizures did not have acute symptomatic seizures. All electrographic seizures were accompanied by clear behavioral changes. Interictal spikes and epileptiform discharges were observed in all animals but occurred more frequently in rats with late seizures (p = 0.019 and p < 0.001, respectively). Animals with acute symptomatic seizures had more extended hemorrhagic lesions and hemosiderin deposits in the piriform cortex.ConclusionBoth acute symptomatic and late unprovoked seizures were observed in the rat collagenase model. Interictal epileptiform activity was more frequently seen in animals with late seizures. Rats with acute symptomatic seizures showed more extensive lesions and hemosiderin deposits in the piriform cortex. This model could be used to further explore possible biomarkers for epileptogenesis.

Predictors of unprovoked seizures in surgically treated pyogenic brain abscess: Does perioperative adjunctive use of steroids has any protective effect?

Background: The indication and optimal duration of antiepileptic drug (AED) prophylaxis after aneurysmal subarachnoid hemorrhage (SAH) remains controversial. Our institution practices routine seizure prophylaxis for variable durations at the discretion of the neurosurgeon and neuro-intensivist. Given the propensity of late onset seizures to progress to chronic epilepsy, we sought to investigate the efficacy of extended AED prophylaxis in reducing the risk of late seizures. Methods: This retrospective study analyzed 36 patients who were admitted to our neurosurgical intensive care unit (NICU) over a 2-year period (1st November 2015 to 31st October 2017). All hospital admissions records, electronic medication records as well as outpatient visits up to 1 year were reviewed. Late onset seizures were defined as seizures occurring more than 7 days post-intervention (or presentation if no intervention was performed) up to 1 year of follow-up. Results: Majority of the patients received Levetiracetam (94%) as seizure prophylaxis and late onset seizures occurred in 6 (17%) of the patients. Those patients who received a greater proportion of in-patient stay with AED prophylaxis had a statistically significant lower risk of developing late seizures (OR = 0.964, 95%, p = 0.02). Although the value tended towards benefit (OR = 0.382) for AED > 21 days in-hospital, the result was not statistically significant (p = 0.307). Conclusion: An extended duration of AED prophylaxis, in particular Levetiracetam, may confer some benefit in reducing risk of developing late seizures. However, the optimal duration of therapy is yet to be determined and further large multi-centered randomized studies are necessary.

Letter to the Editor Regarding “Normal Pressure Hydrocephalus and Parkinsonism: Preliminary Data on Neurosurgical and Neurological Treatment”

Objective:Several endocrine manifestations have been described in patients with 22q11 deletion syndrome, including growth retardation, hypoparathyroidism, and thyroid disorders. This study aimed to characterize these abnormalities in a Colombian retrospective cohort of children with this condition.Methods:A retrospective study comprising a cohort of children with 22q11 deletion syndrome in Medellín, Colombia followed up between 2011 and 2017 was conducted.Results:Thirty-seven patients with a confirmed diagnosis of 22q11 deletion syndrome were included. 37.8% had some endocrinopathy, the most frequent being hypoparathyroidism (21.6%), followed by hypothyroidism (13.5%), hyperthyroidism (2.7%) and growth hormone deficiency (2.7%). There was wide heterogeneity in the clinical presentation, with late onset of severe hypocalcemia associated with seizure or precipitated in postoperative cardiac surgery, which highlights the importance of continuous follow-up as indicated by the guidelines. Short stature was mainly related to nutritional factors. Growth monitoring is required with the use of syndrome-specific charts and careful monitoring of the growth rate.Conclusion:As previously reported, a significant proportion of patients with endocrine abnormalities were found in this cohort. This highlights that it is essential to carry out an adequate multidisciplinary follow-up, based on the specific clinical guidelines, in order to avoid serious complications such as convulsions due to hypocalcemia. It is important to track size with curves specific to the syndrome and analyze the growth rate.

Epileptic seizures are a common complication of several clinical conditions affecting the CNS. In these cases, the occurrence of seizures and epilepsy may increase the functional damage provoked by the underlying epileptogenic condition and affect the patient's quality of life to a significant extent. Therefore, the search of effective means for primary prevention of seizures and epilepsy is necessary in these cases. However, the use of antiepileptic drugs for the primary prevention of seizures and epilepsy can be considered only if the ratio between efficacy, safety and tolerability of treatment is favorable, in that the advantages, in terms of seizure prevention, outweigh the disadvantages in terms of adverse effects and overall costs of treatment. In this article, the efficacy, safety and tolerability of antiepileptic drugs for the primary prevention of seizures and epilepsy are reviewed. The areas covered include: the definition of early (provoked) and late (unprovoked) seizures; knowledge of the overall risk of seizures and epilepsy in CNS disorders for which primary prevention of seizures can be attempted; rationale for the use of antiepileptic drugs for the primary prevention of epilepsy; experimental data on the antiepileptogenic properties of antiepileptic drugs; available literature findings on the prevention of early and late seizures, with specific emphasis on randomized clinical trials; and the main problems with experimental trials for the primary prevention of epileptic seizures. On this basis, practice recommendations for the primary prevention of epilepsy will be offered where indicated. Suggestions for future research are also made as concluding remarks, by indicating the areas of investigation and the design of future studies.

A 43-year-old woman with medical history of hypertension, myocardial infarction, ischemic cardiomyopathy, and systolic heart failure with an ejection fraction of 20% to 25% on a recent echocardiogram developed sudden onset of left hemiparesis, left hypoesthesia, left gaze deviation, and mutism. Two hours after symptom onset her initial National Institutes of Health Stroke Scale score was 25. A computed tomography of the head was unremarkable, but a computed tomography angiogram showed a distal right middle cerebral artery occlusion. She was given intravenous tissue-type plasminogen activator, but soon after tissue-type plasminogen activator administration, the patient had a generalized tonic clonic seizure. A repeat computed tomography of the head immediately after the seizure showed no hemorrhage, and the patient received mechanical thrombectomy for a her right middle cerebral artery occlusion. She was started on levetiracetam for secondary seizure prevention. MRI showed multiple areas of diffusion restriction involving all vascular territories consistent with a cardioembolic source and her history of dilated cardiomyopathy. She was started on anticoagulation. Importantly there were both cortical and subcortical areas with diffusion positive signal. Electroencephalography showed severe diffuse encephalopathy without epileptiform discharges. She made a good recovery and her discharge National Institutes of Health Stroke Scale score was only 4. She had no more seizures and was discharged home on warfarin, statin, and levetiracetam with seizure restrictions. Two months later she had a minimal hemiparesis and returned to work. She had no further seizures. Although it was explained that the plan had only been to continue anticonvulsants for 3 months, she wanted to drive as soon as possible and elected to continue anticonvulsants indefinitely. Stroke is …

A 15-day-old girl has abnormally shaped low-set ears, left facial microsomia, and micrognathia suggestive of Goldenhar syndrome. Magnetic resonance imaging (MRI) of the brain reveals colpocephaly, membranous cleft palate, and fluid in the left middle ear cavity. Echocardiography documents normal heart anatomy and function. The infant is feeding well and has appropriate weight gain, but she has occasional decreases in oxygen saturation during feedings. Upper gastrointestinal radiographic study shows massive reflux, prompting the administration of ranitidine and positioning with her head elevated. Despite the reflux precautions, the baby continues to have episodes of low oxygen saturation while feeding, which now occur even at rest. The episodes last for less than 1 minute and are relieved by bag-and-mask ventilation. Twenty days after birth, she has a generalized clonic seizure. At this time, her glucose concentration is 67 mg/dL (3.7 mmol/L) and ionized calcium concentration is 2.48 mg/dL (0.62 mmol/L) on a capillary specimen, which is confirmed by a similarly low venous blood determination of total calcium of 4.3 mg/dL (1.08 mmol/L). She also develops a staphylococcal abscess in the left leg and left femoral vein thrombosis. Calcium gluconate infusion resulted in resolution of the seizure. However, calcium concentrations …

Stroke is one of the commonest causes of seizures and epilepsy, mainly among the elderly and adults. This seminar paper aims to provide an updated overview of post-stroke seizures and post-stroke epilepsy (PSE) and offers clinical guidance to anyone involved in the treatment of patients with seizures and stroke. The distinction between acute symptomatic seizures occurring within seven days from stroke (early seizures) and unprovoked seizures occurring afterwards (late seizures) is crucial regarding their different risks of recurrence. A single late post-stroke seizure carries a risk of recurrence as high as 71.5% (95% confidence interval: 59.7-81.9) at ten years and is diagnostic of PSE. Several clinical and stroke characteristics are associated with increased risk of post-stroke seizures and PSE. So far, there is no evidence supporting the administration of antiepileptic drugs as primary prevention, and evidence regarding their use in PSE is scarce.

Background: Seizures following a stroke often indicate a more severe incident, typically resulting in extended hospital stays and a heightened risk of long-term disability. Management strategies generally include the use of anti-epileptic drugs to mitigate the frequency and severity of seizures. Objectives: this study aims to evaluate the incidence and risk factors assosciated for seizures after stroke, differentiating between acute symptomatic seizures and late seizures. Additionally, it assess dependency levels of patients after stroke and management of seizures after stroke. Methodology: We conducted prospective observational study for 6 months which includes patients who were diagnosed with cerebrovascular accident, past history of cerebrovascular accident, experienced single or recurrent seizures of different types. Results: Out of 150 patients observed, 67 experienced seizures following stroke. Majority of these patients were male (99) predominantly aged between 50-75. Hypertension was found to be the major risk factor affecting 106(75.2%) individuals.Ischemic stroke were common. In terms of seizure occurrence, 27 patients experienced acute symptomatic seizure and 40 late onset seizure. Activity of daily living was assessed using Barthel Index Scale in which total dependency showed statistically significant relevance (P =0.01). Conclusion: In summary, the leading cause of seizure in adults is stroke. While both ischemic and hemorrhagic stroke may increase the risk of seizure, our study reveals that occurrence of seizure is greater following ischemic compared to hemorrhagic. A clinical pharmacist plays a vital role in determining prophylactic AED treatment for stroke patients and monitor to improve patient’s quality of life.

Cerebrovascular events are an important and well-known cause of seizures in adults. In an elderly population the incidence ranges from 2 to 43% in various studies, depending on seizure type, duration of follow-up and study design. The incidence rates for epilepsies have two peaks regarding age: one in the first decade of life, a second at higher age with a steep increase between age 70 and 80. Cerebral ischaemia is the single most common cause of first seizures and epilepsy in later life above the age of 60 years. The leading type of stroke-related seizures is focal with a high rate of secondary generalisation. In general, early onset seizures are differentiated from late onset seizures after stroke. However, this is only of clinical relevance if both groups are associated with different prognosis which is discussed controversially in the literature. Also, a variety of definitions for early seizures have been used regarding the time span following stroke. Large cortical infarctions in the anterior circulation have a high risk of developing seizures. Results of recent studies revealed early seizures as independent risk factor for late seizures and development of epilepsy. Despite the importance of the problem there are few data on the natural history of stroke-related seizures and no good guideposts to suggest when to initiate anticonvulsant therapy after stroke. The exact statistical risk of further seizures after a first poststroke seizure is not known, therefore, it has to be a case-by-case decision when to start medication. After a single early seizure long-term anticonvulsant therapy is usually not recommended even though recent studies could not reproduce the previously thought good prognosis of early seizures. There is also still debate about treatment after a first late seizure. After a second seizure the diagnosis of symptomatic epilepsy can be made and long-term anticonvulsant therapy is usually recommended. Poststroke seizures are in most patients well controlled with a single anticonvulsant drug. The choice of drug is given by the general recommendations of anticonvulsant medication in patients with focal seizures. In these mainly elderly patients interactions with other medications and cognitive side effects have to be considered especially. Whether the new anticonvulsants have advantages as compared to the standard medication with carbamazepine, oxcarbazepine or valproic acid is still open and under investigation.

Tissue plasminogen activator (t-PA), a proven therapy for acute ischemic stroke, is an endogenous serine protease associated with neuronal activity and synaptic plasticity in the brain. Its expression is enhanced after seizures, and is involved in seizure propagation throughout the brain. Therefore, the increased use of t-PA to treat stroke may have important implications for the development of poststroke epilepsy. Using experimental and clinical approaches, we investigated the role of t-PA in the development of epilepsy. Mice deficient in t-PA (t-PA(-/-) ) or mice transgenically modified to overexpress neuronal t-PA (T4) underwent amygdala kindling, and seizure threshold and rates of kindling were compared to those in wild-type mice. For the clinical study, we recruited acute ischemic stroke patients who either received intravenous t-PA treatment on admission to hospital (n = 177; cases) or did not (n = 158; controls). We then assessed the incidence of early and late onset seizures and epilepsy in these patients. T4 mice were more seizure-prone than wild-type mice, exhibiting lower seizure thresholds (p = 0.002), but there were no significant differences observed in the rate of kindling development when comparing either T4 mice, or t-PA(-/-) mice, to their wild-type controls. Furthermore, we found no significant differences between the proportion of poststroke patients experiencing early or late seizures, or developing epilepsy, between those who received t-PA and those who did not. Overexpression of endogenous t-PA lowers seizure threshold but does not influence kindling epileptogenesis. Moreover, the therapeutic administration of t-PA in humans does not influence the development of acquired poststroke epilepsy.

This study aimed to evaluate the outcomes and feasibility of different techniques of reconstruction of the right ventricular outflow tract (RVOT) in surgical repair of truncus arteriosus. We retrospectively reviewed all consecutive patients with truncus arteriosus who underwent successful surgical repair in our centre between 1994 and 2017. We analysed late results according to the type of RVOT repair. We collected data from 29 survivors after truncus arteriosus repair. Six (20%) of them were affected by DiGeorge syndrome. The RVOT reconstruction was achieved using a valved conduit in 58.6%, while a direct right ventricle-pulmonary artery (RV-PA) anastomosis, with or without the interposition of the left atrial appendage, was performed in the remaining. At a median follow-up time of 7.9 years (interquartile range 1.8-13.1), 6 patients (3 affected by DiGeorge syndrome) died. Between the 2 groups, there were no differences in terms of the late mortality and onset of adverse events. However, the use of a conduit seemed more prone to reintervention and onset of adverse events. Different RVOT reconstruction techniques are safe and have similar late outcomes. However, use of a direct RV-PA anastomosis and left atrial appendage interposition may reduce the need for reoperation in the long term.

Objectives: This study aimed to compare seizure types, clinical and demographic features, treatment response and prognosis among patients with early and late onset post-stroke seizures. Methods: A retrospective evaluation was made of the data of 46 patients admitted to our clinic between January 2000 and April 2006 diagnosed with cerebrovascular disease, and who had post-stroke epileptic seizures. Two types of post-stroke seizures were defined; ‘early onset’ (occurring within 14 days post-stroke) and ‘late onset’ (occurring after the 14th day). Results: Among the 46 patients, 15 (32.6%) had early onset and 31 (67.3%) had late onset seizures. The early onset post-stroke seizures occurred more frequently after hemorrhagic stroke, while the late onset were more often seen in ischemic stroke. Ischemic strokes occurred mostly in the middle cerebral artery area, whereas lobar cortical hematomas were observed in the hemorrhagic stroke patients. The early onset seizures had statistically significant left hemisphere lesions, while those which were late onset had right hemisphere lesions (p<0.038). Secondary generalized seizures were the most common type in both groups. The seizures were well controlled with monotherapy in both groups, but seizure recurrence was found to be higher in the late onset seizure group. Conclusion: This study found significant left hemisphere lesions in the patients with early onset seizures, while in those with late onset seizures, lesions were present in the right hemisphere. In both groups, cortical involvement played an important role. Secondary generalized seizures were the most frequently occurring, and these were treated with antiepileptic monotherapy.