Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model.

Status epilepticus (SE) refers to a single seizure that lasts longer than typical seizures or a series of consecutive seizures. The hippocampus, which is vulnerable to the effects of SE, has a critical role in memory storage and retrieval. The trisynaptic loop in the hippocampus connects the substructures thereof, namely the dentate gyrus (DG), CA3, and CA1. In an animal model of SE, abnormal neurogenesis in the DG and aberrant neural network formation result in sequential neural degeneration in CA3 and CA1. Photobiomodulation (PBM) therapy, previously known as low-level laser (light) therapy (LLLT), is a novel therapy for the treatment of various neurological disorders including SE. However, the effects of this novel therapeutic approach on the recovery process are poorly understood. In the present study, we found that PBM transformed SE-induced abnormal neurogenesis to normal neurogenesis. We demonstrated that PBM plays a key role in normal hippocampal neurogenesis by enhancing the migration of maturing granular cells (early neuronal cells) to the GCL, and that normal neurogenesis induced by PBM prevents SE-induced hippocampal neuronal loss in CA1. Thus, PBM is a novel approach to prevent seizure-induced neuronal degeneration, for which light devices may be developed in the future.

Seizure control after radiosurgery for cerebral arteriovenous malformations: a 25-year experience.

OBJECTIVE: Seizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control. METHODS: Patients with AVM who presented with a history of seizure and underwent SRS at the authors' institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6-295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up. RESULTS: Seizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0-27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4-23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15-0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16-0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test). CONCLUSIONS: This study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

Radiosurgery with a Rotating Gamma System: A Very Effective Treatment for Symptomatic Cerebral Cavernomas.

AIM: To evaluate the value of radiosurgery with a rotating gamma-system (RGS) for cerebral cavernomas. PATIENTS AND METHODS: Seventy-nine patients with symptomatic cerebral cavernomas underwent RGS radiosurgery at the Bach Mai Hospital, Hanoi, Vietnam. Median dose (single fraction) was 20 Gy (range=14-26 Gy). Endpoints included effect on headache, seizures and tumor size. RESULTS: Of 60 patients with headache, 17% had complete response, 82% partial response and 2% stable disease (best response). Of 39 patients with seizures, 31% had complete response, 64% partial response and 5% stable disease. Four patients developed recurrent seizures after 1 year. Regarding the size of cavernoma at 15 months, complete response was observed in 6%, partial response in 75%, stable disease in 15%, progression in 1% and pseudo-progression in 3% of patients. Bleeding within 2 years after RGS radiosurgery occurred in only five patients (6%). RGS dose had no significant impact on outcomes. CONCLUSION: RGS radiosurgery provided very high rates of symptom relief in patients with cerebral cavernomas.

Radiosurgery for the management of cerebral arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are rare, unstable vascular lesions which spontaneously rupture at a rate of approximately 2-4% annually. Stereotactic radiosurgery is a minimally invasive treatment for AVMs, with a favorable risk-to-benefit profile in most patients, with respect to obliteration, hemorrhage, and seizure control. Radiosurgery is ideally suited for small to medium-sized AVMs (diameter <3cm or volume <12cm3) located in deep or eloquent brain regions. Obliteration is ultimately achieved in 70-80% of cases and is directly associated with nidus volume and radiosurgical margin dose. Adverse radiation effects, which appear as T2-weighted hyperintensities on magnetic resonance imaging, develop in 30-40% of patients after AVM radiosurgery, are symptomatic in 10%, and fail to clinically resolve in 2-3%. The risk of AVM hemorrhage may be reduced by radiosurgery, but the hemorrhage risk persists during the latency period between treatment and obliteration. Delayed postradiosurgery cyst formation occurs in 2% of cases and may require surgical treatment. Radiosurgery abolishes or ameliorates seizure activity in the majority of patients with AVM-associated epilepsy and induces de novo seizures in 1-2% of those without preoperative seizures. Strategies for the treatment of large-volume AVMs include neoadjuvant embolization and either dose- or volume-staged radiosurgery.

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas.

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 µm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Seizure outcome after radiotherapy and chemotherapy in low-grade glioma patients: a systematic review.

There is growing evidence that antitumor treatment contributes to better seizure control in low-grade glioma patients. We performed a systematic review of the current literature on seizure outcome after radiotherapy and chemotherapy and evaluated the association between seizure outcome and radiological response. Twenty-four studies were available, of which 10 described seizure outcome after radiotherapy and 14 after chemotherapy. All studies demonstrated improvements in seizure outcome after antitumor treatment. Eight studies reporting on imaging response in relation to seizure outcome showed a seizure reduction in a substantial part of patients with stable disease on MRI. Seizure reduction may therefore be the only noticeable effect of antitumor treatment. Our findings demonstrate the clinical relevance of monitoring seizure outcome after radiotherapy and chemotherapy, as well as the potential role of seizure reduction as a complementary marker of tumor response in low-grade glioma patients.

Cryptochrome-dependent magnetic field effect on seizure response in Drosophila larvae.

The mechanisms that facilitate animal magnetoreception have both fascinated and confounded scientists for decades, and its precise biophysical origin remains unclear. Among the proposed primary magnetic sensors is the flavoprotein, cryptochrome, which is thought to provide geomagnetic information via a quantum effect in a light-initiated radical pair reaction. Despite recent advances in the radical pair model of magnetoreception from theoretical, molecular and animal behaviour studies, very little is known of a possible signal transduction mechanism. We report a substantial effect of magnetic field exposure on seizure response in Drosophila larvae. The effect is dependent on cryptochrome, the presence and wavelength of light and is blocked by prior ingestion of typical antiepileptic drugs. These data are consistent with a magnetically-sensitive, photochemical radical pair reaction in cryptochrome that alters levels of neuronal excitation, and represent a vital step forward in our understanding of the signal transduction mechanism involved in animal magnetoreception.

nNOS inhibition during profound asphyxia reduces seizure burden and improves survival of striatal phenotypic neurons in preterm fetal sheep.

Basal ganglia injury after hypoxia-ischemia remains common in preterm infants, and is closely associated with later cerebral palsy. In the present study we tested the hypothesis that a highly selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10, would improve survival of striatal phenotypic neurons after profound asphyxia, and that the subsequent seizure burden and recovery of EEG are associated with neural outcome. 24 chronically instrumented preterm fetal sheep were randomized to either JI-10 (3 ml of 0.022 mg/ml, n = 8) or saline (n = 8) infusion 15 min before 25 min complete umbilical cord occlusion, or saline plus sham-occlusion (n = 8). Umbilical cord occlusion was associated with reduced numbers of calbindin-28k-, GAD-, NPY-, PV-, Calretinin- and nNOS-positive striatal neurons (p < 0.05 vs. sham occlusion) but not ChAT-positive neurons. JI-10 was associated with increased numbers of calbindin-28k-, GAD-, nNOS-, NPY-, PV-, Calretinin- and ChAT-positive striatal neurons (p < 0.05 vs. saline + occlusion). Seizure burden was strongly associated with loss of calbindin-positive cells (p < 0.05), greater seizure amplitude was associated with loss of GAD-positive cells (p < 0.05), and with more activated microglia in the white matter tracts (p < 0.05). There was no relationship between EEG power after 7 days recovery and total striatal cell loss, but better survival of NPY-positive neurons was associated with lower EEG power. In summary, these findings suggest that selective nNOS inhibition during asphyxia is associated with protection of phenotypic striatal projection neurons and has potential to help reduce basal ganglia injury in some premature babies.

Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study.

BACKGROUND: Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. METHODS: In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. RESULTS: At 3 months after radiotherapy, seizure reduction was significant (≥ 50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. CONCLUSIONS: This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy.

Norovirus gastroenteritis and seizures: an atypical case with neuroradiological abnormalities.

We describe an 8-year-old boy admitted because of prolonged seizures during norovirus gastroenteritis without any signs of encephalopathy. Blood tests were normal and cerebrospinal fluid examination resulted negative for both bacteria and viruses. A reverse transcriptase polymerase chain reaction revealed norovirus RNA in a stool sample. A cerebral computed tomography turned out to be normal whereas subsequent cerebral magnetic resonance imaging showed transitory signal abnormalities consistent with vasogenic edema. The post-ictal electroencephalogram revealed normal background activity with sporadic left posterior delta waves. The child was discharged after 10 days with an unremarkable physical examination. A cerebral magnetic resonance imaging and an electroencephalogram after 1 month were both negative. We report a new case of benign infantile convulsions due to norovirus gastroenteritis with neuroradiological abnormalities to the pertinent literature in order to improve knowledge about this disorder and increase the possibility of clarifying its pathogenesis.

Surgical treatment and radiation therapy of frontal lobe meningiomas in 7 dogs.

The cases of 7 adult dogs with generalized seizures managed by surgical excision and radiation therapy for frontal lobe meningiomas were reviewed. The neurological examination was unremarkable in 6 of the 7 dogs. Five dogs were operated on using a bilateral transfrontal sinus approach and 2 using a unilateral sinotemporal approach to the frontal lobe. One dog was euthanized 14 d after surgery; radiation therapy was initiated 3 wk after surgery in the remaining 6 dogs. Long-term follow-up consisted of neurological examination and magnetic resonance imaging (MRI) and/or computed tomography (CT) scan after radiation therapy. The mean survival time for dogs that had surgery and radiation therapy was 18 mo after surgery. Frontal lobe meningiomas have been associated with poor prognosis. However, the surgical approaches used in these cases, combined with radiation therapy, allow a survival rate for frontal lobe meningiomas similar to that for meningiomas located over the cerebral convexities.

Distinct FGFs promote differentiation of excitatory and inhibitory synapses.

The differential formation of excitatory (glutamate-mediated) and inhibitory (GABA-mediated) synapses is a critical step for the proper functioning of the brain. An imbalance in these synapses may lead to various neurological disorders such as autism, schizophrenia, Tourette's syndrome and epilepsy. Synapses are formed through communication between the appropriate synaptic partners. However, the molecular mechanisms that mediate the formation of specific synaptic types are not known. Here we show that two members of the fibroblast growth factor (FGF) family, FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. FGF22 and FGF7 are expressed by CA3 pyramidal neurons in the hippocampus. The differentiation of excitatory or inhibitory nerve terminals on dendrites of CA3 pyramidal neurons is specifically impaired in mutants lacking FGF22 or FGF7. These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. FGF22-deficient mice are resistant to epileptic seizures, and FGF7-deficient mice are prone to them, as expected from the alterations in excitatory/inhibitory balance. Differential effects of FGF22 and FGF7 involve both their distinct synaptic localizations and their use of different signalling pathways. These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help to organize specific presynaptic terminals in the mammalian brain.

Does albendazole affect seizure remission and computed tomography response in children with neurocysticercosis? A Systematic review and meta-analysis.

A recent trial suggested that albendazole reduces seizures in adults with neurocysticercosis. There is still no consensus regarding optimal management of neurocysticercosis in children. The authors conducted a systematic review and meta-analysis to assess the efficacy of albendazole in children with neurocysticercosis, by searching the Cochrane Databases, MEDLINE, EMBASE, and LILACS. Three reviewers extracted data using an intent-to-treat analysis. Random effects models were used to estimate relative risks. Four randomized trials were selected for meta-analysis, and 10 observational studies were selected for qualitative review. The relative risk of seizure remission in treatment versus control was 1.26 (1.09, 1.46). The relative risk of improvement in computed tomography in these trials was 1.15 (0.97, 1.36). Review of observational studies showed conflicting results, likely owing to preferential administration of albendazole to sicker children.

Electromagnetic waves of 900 MHz in acute pentylenetetrazole model in ontogenesis in mice.

The purpose of this study was to measure the effects of electromagnetic waves (EMW) at 900 MHz. EMW were produced by a signal generator and were administered to mice via an antenna. The frequency of the waves was tested by a spectrum analyser and a frequency-meter. The emitted power was 0.25 mW. A total of 117 mice (59 prepubertal and 58 adult) was used. Mice were exposed to EMW or sham radiation for 2 h and 20 h before an injection of pentylenetetrazole (PTZ). A statistically significant difference was found between the latency measurements within 20 h for prepubertal mice in stages 1 and 2 ( p<0.05). The effects on prepubertal mice of long-term 900 MHz EMW in a PTZ model may be an indication of possible problems in developing brains.

[The delayed effects of modulated and non-modulated electromagnetic field on epileptiformic activity in rats]. / Otdalennye posledstviia deistviia modulirovannogo i nemodulirovannogo elektromagnitnogo polia na epileptiformnuiu aktivnost' krys.

The modifying influence of the weak electromagnetic field on the development of the audiogenic spasmodic activity in rats was shown. The decrease of lifetime of experimental rats exposed to electromagnetic fields with different parameters and development of tumours (in one set of experiments) was found.