A PET imaging study of the brain changes of glucose metabolism in patients with temporal lobe epilepsy and depressive disorder.

BACKGROUND: This study aims to compare the difference of the brain changes of glucose metabolism between temporal lobe epilepsy patients (TLE) with major depressive disorder and temporal TLE without major depressive disorder. METHODS: A total of 24 TLE patients, who met the inclusion criteria of our hospital, were enrolled in this study. They were divided into a TLE with depression group (n = 11) and a TLE without depression group (n = 13), according to the results of the HAMD-24 Scale. Two groups patients were examined using 18F-FDG PET brain imaging. RESULTS: The low metabolic regions of the TLE with depression group were mainly found in the left frontal lobe, temporal lobe and fusiform gyrus, while the high metabolic regions of the TLE with depression group were mainly located in the right frontal lobe, visual joint cortex and superior posterior cingulate cortex. Both of the TLE groups had high metabolic compensation in the non-epileptic area during the interictal period. CONCLUSIONS: There is an uptake difference of 18F-FDG between TLE patients with depression and TLE patients without depression in multiple encephalic regions.

Electroclinical and Multimodality Neuroimaging Characteristics and Predictors of Post-Surgical Outcome in Focal Cortical Dysplasia Type IIIa.

Focal cortical dysplasia (FCD) type IIIa is an easily ignored cause of intractable temporal lobe epilepsy. This study aimed to analyze the clinical, electrophysiological, and imaging characteristics in FCD type IIIa and to search for predictors associated with postoperative outcome in order to identify potential candidates for epilepsy surgery. We performed a retrospective review including sixty-six patients with FCD type IIIa who underwent resection for drug-resistant epilepsy. We evaluated the clinical, electrophysiological, and neuroimaging features for potential association with seizure outcome. Univariate and multivariate analyses were conducted to explore their predictive role on the seizure outcome. We demonstrated that thirty-nine (59.1%) patients had seizure freedom outcomes (Engel class Ia) with a median postsurgical follow-up lasting 29.5 months. By univariate analysis, duration of epilepsy (less than 12 years) (p = 0.044), absence of contralateral insular lobe hypometabolism on PET/MRI (p Log-rank = 0.025), and complete resection of epileptogenic area (p Log-rank = 0.004) were associated with seizure outcome. The incomplete resection of the epileptogenic area (hazard ratio = 2.977, 95% CI 1.218-7.277, p = 0.017) was the only independent predictor for seizure recurrence after surgery by multivariate analysis. The results of past history, semiology, electrophysiological, and MRI were not associated with seizure outcomes. Carefully included patients with FCD type IIIa through a comprehensive evaluation of their clinical, electrophysiological, and neuroimaging characteristics can be good candidates for resection. Several preoperative factors appear to be predictive of the postoperative outcome and may help in optimizing the selection of ideal candidates to benefit from epilepsy surgery.

The efficacy and safety of a ketogenic diet for children with refractory epilepsy in China: a retrospective single-center cohort study.

BACKGROUND: The ketogenic diet (KD) has been implemented in many different counties. However, in China, study concerning the efficacy of the KD is still at an early-stage of evaluation. Furthermore, the KD is thought to be incompatible with Chinese children because of its lack of palatability, especially for the Asian population. In addition, its substantial antiepileptic effect remains to be confirmed. METHODS: To evaluate the efficacy and safety of the KD treatment of refractory childhood epilepsy in China, we prospectively enrolled 147 children with refractory epilepsy for KD treatment in Guangdong 999 Brain Hospital and followed up the children for 6 months. Outcome was measured by seizure frequencies before and after the KD diet and adverse effects. We also evaluated influences of different variables (starting age, duration of epilepsy, and others) on the outcome. RESULTS: We found after 1 month, 3 months, and 6 months of KD treatment, 28.0%, 55%, and 67.9% of the subjects remained on diet with a >50% seizure reduction and seizure-free rates of 6.5%, 13.2%, and 23.3%, respectively. Gender, starting age, duration, etiology, classification, and seizure type of epilepsy showed no significant influence on efficacy. Anorexia, diarrhea, and gravel were the main side-effects of the KD treatment. CONCLUSIONS: In conclusion, the KD is a safe and efficacious method for childhood refractory epilepsy treatment.

Surgical treatment of low-grade brain tumors associated with epilepsy.

OBJECTIVE: To explore the strategy of surgical treatment of low-grade brain tumors associated with epilepsy. METHODS: Clinical data of 158 patients with low-grade brain tumors were collected from January 2011 to December 2017 in Guangdong Sanjiu brain hospital. All patients received Preoperative evaluation. Lesion site: 18 cases were located in multiple cerebral lobes, 10 cases were in the functional zones, 130 cases were in the non-functional zones (including 74 cases were in the medial of temporal lobe). The surgical strategy included subtotal resection, gross-total resection and enlarged resection. Postoperative effects were evaluated by Engel classification. RESULTS: A total of 158 patients underwent surgical treatment, among these patients, only 1 patient underwent intracranial electrode implantation. Surgical methods: 34 cases of subtotal resection, 3 cases of gross-total resection, 119 cases of enlarged resection (including Anterior temporal lobectomy in 74 cases) and 2 case of Selective hippocampal amygdalectomy. The final pathology suggested that there are 74 cases of ganglionglioma, 25 cases of dysembryoplastic neuroepithelial tumors, 9 cases of pilocytic astrocytoma, 16 cases of oligodendroglioma, 10 cases of pleomorphic xanthoastrocytoma, 4 case of diffuse astrocytoma, 9 cases of unclassified astrocytoma, 11 case of oligoastrocytoma. The follow-up time was between 1 and 7 years, with an average of 3.44±1.77 years. Postoperative recovery: 147 patients had an Engel Class I outcome, 10 patients were in Engel Class II, 1 patient was in Class IV. CONCLUSION: The strategy of surgical treatment of low-grade brain tumors associated with epilepsy should pay more attention to the preoperative assessment of the epileptogenic zone. The tumor is not exactly the same as the epileptogenic zone, and the strategy of surgical treatment depends on the tumor feature as well as whether it was located in temporal lobe or involved in functional areas.

Oxcarbazepine oral suspension in young pediatric patients with partial seizures and/or generalized tonic-clonic seizures in routine clinical practice in China: a prospective observational study.

BACKGROUND: This study aimed to assess efficacy and safety of oxcarbazepine (OXC) oral suspension in pediatric patients aged 2-5 years with partial seizures (PS) and/or generalized tonic-clonic seizures (GTCS) in real-world clinical practice in China. METHODS: This 26-week, prospective, single-arm, multicenter, observational study recruited pediatric patients aged 2-5 years with PS or GTCS suitable for OXC oral suspension treatment based on physicians' judgments from 11 medical centers in China. Enrolled subjects started OXC oral suspension treatment as monotherapy or in combination with other antiepileptic drugs. Primary efficacy outcome was the percentage of pediatric subjects achieving ≥ 50% seizure frequency reduction at the end of the 26-week treatment. Secondary efficacy-related parameters and safety parameters such as adverse events (AEs) and serious AEs (SAEs) were also monitored during the 26-week treatment period. RESULTS: Six hundred and six pediatric patients were enrolled and 531 (87.6%) completed the study. After 26 weeks of treatment, 93.3% subjects achieved ≥ 50% seizure frequency reduction, and 81.8% achieved 100% seizure frequency reduction compared to baseline. Among different seizure types, OXC was effective in all subjects with simple PS and in > 90% of subject with other type of seizure present in the study. AEs were observed in 49 (8.1%) subjects. Only three subjects experienced SAE. Rash (n = 18, 2.97%) was the most common AE. Only 17 subjects discontinued due to AEs. CONCLUSION: This study, reporting the real-world data, further confirms the efficacy and good safety profile of OXC oral suspension in Chinese pediatric patients aged 2-5 years with PS and/or GTCS.

HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.

OBJECTIVE: To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug-induced cutaneous adverse reactions. METHODS: A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug-induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes. RESULTS: HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10-15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10-5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association. CONCLUSIONS: HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

[Clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy].

OBJECTIVE: To explore the clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy (DRPLA). METHODS: DNA analysis for DRPLA gene was performed in two patients. Clinical features and genetic testing of Chinese DRPLA patients reported in the literature were reviewed in terms of initial symptoms, CAG repeat and age of onset. RESULTS: Both families were confirmed by genetic analysis. In family 1, the number of CAG repeat in the proband, his brother and his mother was determined respectively as 8/65, 8/53 and 8/18. In family 2, the number of CAG repeat was respectively 13/63, 13/18, 18/52 and 13/13 in the proband, his brother, his father and his mother. The size of the expanded CAG repeats has inversely correlated with the age at onset (P<0.05, r=- 0.555). The age at onset of epilepsy was 10 and that for the onset of ataxia is forty years in initial symptom. CONCLUSION: The clinical characteristics of DRPLA include epilepsy, ataxia and cognitive impairment. The initial symptoms are epilepsy in adolescence and ataxia in adults. The size of expanded CAG repeats inversely correlates with the age at onset. The initial symptoms are different with different age of onset. It is difficult to diagnose DRPLA at an early stage.

Graph theoretical analysis reveals disrupted topological properties of whole brain functional networks in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common forms of drug-resistant epilepsy. Previous studies have indicated that the TLE-related impairments existed in extensive local functional networks. However, little is known about the alterations in the topological properties of whole brain functional networks. METHOD: In this study, we acquired resting-state BOLD-fMRI (rsfMRI) data from 26 TLE patients and 25 healthy controls, constructed their whole brain functional networks, compared the differences in topological parameters between the TLE patients and the controls, and analyzed the correlation between the altered topological properties and the epilepsy duration. RESULTS: The TLE patients showed significant increases in clustering coefficient and characteristic path length, but significant decrease in global efficiency compared to the controls. We also found altered nodal parameters in several regions in the TLE patients, such as the bilateral angular gyri, left middle temporal gyrus, right hippocampus, triangular part of left inferior frontal gyrus, left inferior parietal but supramarginal and angular gyri, and left parahippocampus gyrus. Further correlation analysis showed that the local efficiency of the TLE patients correlated positively with the epilepsy duration. CONCLUSION: Our results indicated the disrupted topological properties of whole brain functional networks in TLE patients. SIGNIFICANCE: Our findings indicated the TLE-related impairments in the whole brain functional networks, which may help us to understand the clinical symptoms of TLE patients and offer a clue for the diagnosis and treatment of the TLE patients.

Outcomes of sustained-release formulation of valproate and topiramate monotherapy in patients with epilepsy: a multi-centre, cohort study.

BACKGROUND: New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR). Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49-0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62-0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84-1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88-1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70). CONCLUSIONS: The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

[Neovascularization after ischemic stroke].

After ischemic stroke, there is neovascularization around the infarcted area, which is called penumbra. Angiogenesis and arteriogenesis are responsible for the new vessel formation. Until recently, vasculogenesis has been proved to involve mechanisms in postischemic neovascularization, which was thought to be restricted to embryonic development. New blood vessels' formation is a complex pathologic process after ischemic stroke, in which many factors are properly involved. There are factors stimulating neovascularization, such as vascular endothelial growth factor, platelet-derived growth factor, basic fibroblast growth factor and angiopoietin; there are also factors inhibiting neovascularization, such as thrombospondin. Functional recovery was found after stroke, which may contribute to angiogensis in the periinfarct tissue. Thus, therapeutic angiogenesis has been initially studied in animal models, but there is still a long way to go for therapeutic angiogenesis to be used in the treatment of stroke patient.

[Effectiveness of urokinase used in combination with batroxobin (DF-521) in rat model of focal cerebral ischemia-reperfusion].

OBJECTIVE: This study was designed to use urokinase (UK) in combination with batroxobin in thrombolytic therapy so as to see whether batroxobin(DF-521) would be effective for neuroprotection. METHODS: The model of right middle cerebral artery occlusion (MCAO) in male SD rats was established. 120 rats were randomized into 9 groups, namely control group, sham control group, and groups that were treated with batroxobin and urokinase together or separately. Each group comprised 15 rats. Intracranial bleeding, infarct volume ratio and neurological function were observed. RESULTS: Intracranial bleeding was found in 5 rats of the UK 5000 U/kg group, in 4 rats of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (2 h) group, and in only 1 rat of the UK 5000 U/kg (2 h) + DF-521 5 BU/kg (1 h) group. Cerebral infarct volume ratio was obviously reduced in 5 BU/kg batroxobin group. No difference was observed in neurological deficit scores. CONCLUSION: 5000 U/kg urokinase increased the risk of intracranial hemorrhage in rat MCAO model. Batroxobin either used separately or in combination with urokinase would not increase the risk of intracranial hemorrhage in rat MCAO model.