Fan-Gang Meng

Selective amygdalohippocampectomy versus anterior temporal lobectomy in the management of mesial temporal lobe epilepsy: a meta-analysis of comparative studies

OBJECT Whether selective amygdalohippocampectomy (SelAH) has similar seizure outcomes and better neuropsychological outcomes compared with anterior temporal lobectomy (ATL) is a matter of debate. The aim of this study was to compare the 2 types of surgery with respect to seizure outcomes and changes in IQ scores. METHODS PubMed, Embase, and the Cochrane Library were searched for relevant studies published between January 1990 and September 2012. Studies comparing SelAH and ATL with respect to seizure and intelligence outcomes were included. Two reviewers assessed the quality of the included studies and independently extracted the data. Odds ratios and standardized mean deviations with 95% confidence intervals were used to compare pooled proportions of freedom from seizures and changes in IQ scores between the SelAH and ATL groups. RESULTS Three prospective and 10 retrospective studies were identified involving 745 and 766 patients who underwent SelAH and ATL, respectively. The meta-analysis demonstrated a statistically significant reduction in the odds of seizure freedom for patients who underwent SelAH compared with those who underwent ATL (OR 0.65 [95% CI 0.51-0.82], p = 0.0005). The differences between the changes in all IQ scores after the 2 types of surgery were not statistically significant, regardless of the side of resection. CONCLUSIONS Selective amygdalohippocampectomy statistically reduced the odds of being seizure free compared with ATL, but the clinical significance of this reduction needs to be further validated by well-designed randomized trials. Selective amygdalohippocampectomy did not have better outcomes than ATL with respect to intelligence.

Predictors of seizure freedom after surgical management of tuberous sclerosis complex: a systematic review and meta-analysis.

PURPOSE To evaluate the rate of seizure freedom in surgical management of tuberous sclerosis complex (TSC) and to identify factors associated with postoperative seizure outcome. METHODS A comprehensive literature search identified articles published since 1990 that described seizure outcomes in patients with TSC who underwent resective surgery. Two reviewers assessed article eligibility and independently extracted the data. Eleven potential prognostic variables were identified and dichotomized for analyses. Random or fixed effects meta-analyses were used depending on the presence or absence of heterogeneity. RESULTS Among 229 patients in 13 studies, the pooled rate of postoperative seizure freedom was 59%. Seizure onset later than 1 year of age, unilateral focality in interictal or ictal electroencephalography, and lobectomy were significantly associated with a higher rate of seizure freedom. CONCLUSIONS Our findings indicate that surgery is an effective treatment modality for TSC patients. The meta-analyses provided useful evidence-based information for identifying TSC candidates for epilepsy surgery and planning surgical strategy.

A Macaque Model of Mesial Temporal Lobe Epilepsy Induced by Unilateral Intrahippocampal Injection of Kainic Acid

Objective In order to better investigate the cause/effect relationships of human mesial temporal lobe epilepsy (mTLE), we hereby describe a new non-human primate model of mTLE. Methods Ten macaques were studied and divided into 2 groups: saline control group (n = 4) and kainic acid (KA) injection group (n = 6). All macaques were implanted bilaterally with subdural electrodes over temporal cortex and depth electrodes in CA3 hippocampal region. KA was stereotaxically injected into the right hippocampus of macaques. All animals were monitored by video and electrocorticography (ECoG) to assess status epilepticus (SE) and subsequent spontaneous recurrent seizures (SRS). Additionally, in order to evaluate brain injury produced by SE or SRS, we used both neuroimaging, including magnetic resonance image (MRI) & magnetic resonance spectroscopy (MRS), and histological pathology, including Nissl stainning and glial fibrillary acid protein (GFAP) immunostaining. Results The typical seizures were observed in the KA-injected animal model. Hippocampal sclerosis could be found by MRI & MRS. Hematoxylin and eosin (H&E) staining and GFAP immunostaining showed neuronal loss, proliferation of glial cells, formation of glial scars, and hippocampal atrophy. Electron microscopic analysis of hippocampal tissues revealed neuronal pyknosis, partial ribosome depolymerization, an abnormal reduction in rough endoplasmic reticulum size, expansion of Golgi vesicles and swollen star-shaped cells. Furthermore, we reported that KA was able to induce SE followed by SRS after a variable period of time. Similar to human mTLE, brain damage is confined to the hippocampus. Accordingly, hippocampal volume is in positive correlations with the neuronal cells count in the CA3, especially the ratio of neuron/glial cell. Conclusions The results suggest that a model of mTLE can be developed in macaques by intra-hippocampal injection of KA. Brain damage is confined to the hippocampus which is similar to the human mTLE. The hippocampal volume correlates with the extension of the hippocampal damage.

Bilateral subthalamic nucleus stimulation in the treatment of neurodegeneration with brain iron accumulation type 1.

Background: Neurodegeneration with brain iron accumulation type 1 (NBIA1), previously called Hallervorden-Spatz disease, is a rare neurodegenerative condition with abnormal brain iron accumulation. There have been some reports of deep brain stimulation (DBS) in the treatment of NBIA1. However, the target was usually the globus pallidus internus or thalamus. Objectives/Methods: We present a case of NBIA1 in a 16-year-old male who was treated with bilateral subthalamic nucleus (STN)-DBS and explored its efficacy in the treatment of NBIA1. The patient presented with severe generalized dystonia and marked dysarthria and had previously had unsuccessful ablation surgery. MRI confirmed the diagnosis of NBIA1. Results: He had significant improvement postoperatively, and the benefit of surgery was maintained for 3 years during follow-up. Burke-Fahn-Marsden Dystonia Rating Scale score was 114/120 preoperatively, and dropped to 60/120 at 14 days, 35/120 at 1 month, 28/120 at 3 months, 14/120 at 1 year and 18/120 at 3 years postoperatively. Conclusions: Our results suggest that bilateral STN-DBS might be considered as an effective treatment for selective NBIA1 patients.

High-frequency stimulation of the hippocampus protects against seizure activity and hippocampal neuronal apoptosis induced by kainic acid administration in macaques

Kainic acid (KA) administration is known to cause seizures and neuronal death in the hippocampus. High-frequency stimulation (HFS) of the hippocampus can be a promising method in the treatment of epilepsy while the mechanism of action is unknown yet. It remains unknown whether HFS is neuroprotective for hippocampal neurons following KA-induced seizures in macaques, although HFS has neuroprotective effects in animal models of Parkinsons disease. We therefore examined the effects of HFS on KA-induced seizures and neuronal survival in macaques hippocampus. Seizure frequency following KA that led to seizures in macaques was strongly reduced by HFS of the hippocampus. In addition, administration of KA led to marked neuronal apoptosis in the hippocampus, accompanied by increased levels of Bax, activated caspase-3 and decreased levels of Bcl-2. HFS was found to attenuate changes in apoptosis-related proteins and robustly decreased neuronal loss following KA administration. These data indicate that hippocampal HFS can protect hippocampal neurons against KA neurotoxicity, and that HFS neuroprotection is likely to operate with inhibition of apoptosis.

Heart rate changes in partial seizures: analysis of influencing factors among refractory patients

BackgroundWe analyzed the frequency of heart rate (HR) changes related to seizures, and we sought to identify the influencing factors of these changes during partial seizures, to summarize the regularity of the HR changes and gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. To date, detailed information on influencing factors of HR changes related to seizures by multiple linear regression analysis remains scarce.MethodsUsing video-electroencephalograph (EEG)-electrocardiograph (ECG) recordings, we retrospectively assessed the changes in the HR of 81 patients during a total of 181 seizures, including 27 simple partial seizures (SPS), 110 complex partial seizures (CPS) and 44 complex partial seizures secondarily generalized (CPS-G). The epileptogenic focus and the seizure type, age, gender, and sleep/wakefulness state of each patient were evaluated during and after the seizure onset. The HR changes were evaluated in the stage of epilepsy as time varies.ResultsOf the 181 seizures from 81 patients with ictal ECGs, 152 seizures (83.98%) from 74 patients were accompanied by ictal tachycardia (IT). And only 1 patient was accompanied by ictal bradycardia (IB). A patient has both IT and IB. We observed that HR difference was independently correlated with side, type and sleep/wakefulness state. In this analysis, the HR changes were related to the side, gender, seizure type, and sleep/wakefulness state. Right focus, male, sleep, and CPS-G showed more significant increases than that were observed in left, female, wakefulness, SPS and CPS. HR increases rapidly within 10 seconds before seizure onset and ictus, and typically slows to normal with seizure offset.ConclusionCPS-G, sleep and right focus led to higher ictal HR. The HR in the stage of epilepsy has regularly been observed to change to become time-varying. The risk factors of ictal HR need to be controlled along with sleep, CPS-G and right focus. Our study first explains that the HR in seizures has a regular evolution varying with time. Our study might help to further clarify the basic mechanisms of interactions between heart and brain, making seizure detection and closed-loop systems a possible therapeutic alternative in refractory patients.

Using electroacupuncture at acupoints to predict the efficacy of hippocampal high-frequency electrical stimulation in pharmacoresistant temporal lobe epilepsy patients

Hippocampal high-frequency electrical stimulation (HFS) shows long-term efficiency in some pharmacoresistant temporal lobe epilepsy patients. However, the success of the procedure varies from patient to patient and neither neurologists nor neurosurgeons are currently unable to pre-operatively predict which patients will respond to the stimulation. Just like electrical stimulation of the hippocampus in the brain, electroacupuncture (EA) at acupoints involves electrical stimulation and is also efficient in treating epilepsy. However, the stimulation targets are acupoints, which are located outside of the brain, and we presume that electrical stimulation of both targets can activate therapeutic neuronal networks, which explains why both stimulations are effective in treating epilepsy. Despite the involvement of different activated positions, the neurotransmitters, including both excitatory and inhibitory amino acids, generated from the stimulation are similar. It has been shown that both hippocampal HFS and EA at acupoints are related to the metabolism of amino acids and thus, we propose the hypothesis that EA at acupoints can predict the curative effect of hippocampal HFS: if EA at acupoints is effective, HFS of hippocampus will also be effective.

Responsive neurostimulation for the treatment of medically intractable epilepsy

With an annual incidence of 50/100,000 people, nearly 1% of the population suffers from epilepsy. Treatment with antiepileptic medication fails to achieve seizure remission in 20-30% of patients. One treatment option for refractory epilepsy patients who would not otherwise be surgical candidates is electrical stimulation of the brain, which is a rapidly evolving and reversible adjunctive therapy. Therapeutic stimulation can involve direct stimulation of the brain nuclei or indirect stimulation of peripheral nerves. There are three stimulation modalities that have class I evidence supporting their uses: vagus nerve stimulation (VNS), stimulation of the anterior nuclei of the thalamus (ANT), and, the most recently developed, responsive neurostimulation (RNS). While the other treatment modalities outlined deliver stimulation regardless of neuronal activity, the RNS administers stimulation only if triggered by seizure activity. The lower doses of stimulation provided by such responsive devices can not only reduce power consumption, but also prevent adverse reactions caused by continuous stimulation, which include the possibility of habituation to long-term stimulation. RNS, as an investigational treatment for medically refractory epilepsy, is currently under review by the FDA. Eventually systems may be developed to enable activation by neurochemical triggers or to wirelessly transmit any information gathered. We review the mechanisms, the current status, the target options, and the prospects of RNS for the treatment of medically intractable epilepsy.

High-frequency electrical stimulation in the nucleus accumbens of morphine-treated rats suppresses neuronal firing in reward-related brain regions

Summary Background Previous studies have reported that high-frequency stimulation (HFS) in the nucleus accumbens (NAc) is a potential treatment modality for drug craving and relapse. We aimed to explore the electrophysiological changes in reward-related brain regions during NAc stimulation and reveal the effects of stimulation frequency and target changes on NAc neuronal activities. Material/Methods Twenty-eight rats were randomized into saline (n=8) and morphine (n=20) groups. The morphine group was further divided into core (n=10, only the core of the NAc was stimulated) and shell (n=10, only the shell of the NAc was stimulated) subgroups. Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days. We recorded NAc neuronal responses to NAc core stimulation at different frequencies, as well as changes in VP and VTA neuronal firing during NAc core stimulation, and changes in NAc neuronal firing during NAc shell stimulation. Results The results indicate that high frequency stimulation was more effective in suppressing NAc neuronal activities than low frequency stimulation and that core stimulation was more effective than shell stimulation. Most VP neurons were inhibited by NAc core stimulation, while VTA neurons were not. Conclusions The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions. The stimulation might be frequency- dependent in suppressing neuronal firing. The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.

Subthalamic Deep Brain Stimulation With a New Device in Parkinson's Disease: An Open-Label Trial

We aimed to evaluate the safety and efficacy of subthalamic nucleus deep brain stimulation (STN‐DBS) with a new stimulator (Beijing PINS Medical Co., Ltd, PNS 1101) in Parkinsons disease (PD).