Yang Lü

Photosensitivity in epileptic syndromes of childhood and adolescence

PURPOSE Photosensitivity, a reaction of the brain to external photic stimulation, can be graded from 1 to 4, and is most frequently seen in the first decades of life. This study investigated photosensitivity in children with epilepsy. METHODS A retrospective study performed in the neuropaediatric department of the largest paediatric hospital in Kiel, treating patients at all medical care levels. The clinical data and EEG records of 566 patients with the most common epileptic syndromes were analyzed, in particular regarding photosensitivity. Their EEGs included application of intermittent light stimulation using standard techniques at twice the minimum. RESULTS The proportion of photosensitive patients was significantly higher in the paediatric cohort than in adult patients, as published in the literature: 46% of patients with generalized epilepsies showed photosensitivity as compared to 20% with focal epilepsies. Photosensitivity was more common in idiopathic generalized epilepsy (IGE), (epilepsy with grand mal on awakening, 74%; juvenile absence epilepsy, 56%; juvenile myoclonic epilepsy, 50%; childhood absence epilepsy, 44%) than in focal types (idiopathic partial - Rolandic epilepsy, 23%; symptomatic/cryptogenic type of epilepsy, 16%), while in patients who experienced occasional seizures (neonatal/febrile seizures), this ranged between 40% and 23%, respectively. The generalized photoparoxysmal response, (PPR), grades 3 and 4 were found significantly more often in patients with IGE (92%) than in patients with focal epilepsies. Finally, the female preponderance was confirmed (37% to 27% of all epilepsies). CONCLUSIONS Photosensitivity can be detected both in patients with IGE, with idiopathic and symptomatic/cryptogenic types of focal epilepsies, and with epileptic (occasional) seizures. PPR grades 3 and 4 are the most common in IGE.

Efficacy and Safety of Adjunctive Zonisamide in Adult Patients with Refractory Partial-Onset Epilepsy: A Randomized, Double-Blind, Placebo-Controlled Trial

AbstractBackground and Objective: Clinical studies have reported that zonisamide is effective for a wide range of seizure types, including refractory partial-onset seizures. However, there have been no reported studies of the efficacy of zonisamide in the Chinese population to date. The aim of the present study was to evaluate the efficacy and safety of zonisamide in the treatment of adult Chinese patients with refractory partial-onset epilepsy. Methods: This was a randomized, double-blind, placebo-controlled trial conducted over a 16-week period. 104 patients with refractory partial-onset epilepsy were enrolled. Participants were randomly assigned to receive addon zonisamide or placebo. Zonisamide was titrated to a target dosage of 300 or 400 mg/day. Seizure frequency and adverse effects were documented. Results: 102 patients completed the trial. Zonisamide showed significantly greater efficacy compared with placebo (responder rate 55.8% vs 36.0%, p < 0.05), including 55.2% (16 of 29 patients) in the zonisamide 300 mg/day arm and 56.5% (13 of 23 patients) in the zonisamide 400 mg/day arm. Zonisamide 300 and 400 mg/day showed similar efficacy (p > 0.05). Moreover, similar efficacy of zonisamide was found in the control of complex partial seizures, simple partial seizures and secondary generalized seizures. There was no difference in the incidence of adverse effects between zonisamide and placebo. Reported adverse effects in the zonisamide group involved the digestive system (32.5% of total adverse effects in the group) [including transient increases in liver enzymes (27.8%)], weight changes (30.2%), the haematological system (15.1%), neurological/psychiatric effects (10.3%), the urinary system (7.9%) and the cardiovascular system (4.0%). Only digestive system adverse effects constituted a significantly higher proportion of adverse effects in the zonisamide group than in the placebo group (32.5% vs 30.2%, p < 0.05). Conclusion: Zonisamide 300–400 mg/day is effective and well tolerated as an adjunctive drug in adult Chinese patients with refractory partial-onset epilepsy.

Clinical value of decreased superoxide dismutase 1 in patients with epilepsy

PURPOSE Our previous study using proteomic analysis showed that superoxide dismutase 1 (SOD1) was significantly decreased in cerebrospinal fluid (CSF) of patients with epilepsy. However, the relevance of CSF-SOD1 alterations for the pathophysiology of epilepsy is currently unknown. The present study was intended to add to our understanding of this issue by measuring SOD1 levels in the CSF of patients with resistant epilepsy and non-resistant epilepsy. METHODS A total of 52 patients with epilepsy were recruited. 29 were non-resistant, 23 drug-resistant. 20 individuals with no evidence of any neurological diseases were used as control. The concentration of CSF and serum SOD1 was measured by enzyme-linked immunosorbent assay. RESULTS The concentration of CSF-SOD1 was decreased in both the drug-resistant (0.13 ± 0.12 ng/ml) and the non-resistant epilepsy subgroups (0.29 ± 0.23 ng/ml) compared to the control group (0.40 ± 0.35 ng/ml). SOD1 was significantly lower in the drug-resistant than the non-resistant epilepsy subgroup (P<0.05). CONCLUSION SOD1 levels are decreased in the CSF of patients with epilepsy, especially of patients with intractable epilepsy. Low CSF-SOD1 levels may be a predictor of antiepileptic drug resistance in patients with epilepsy.

Nutritional status of an elderly population in Southwest China: A cross-sectional study based on comprehensive geriatric assessment

ObjectiveFew data is available on the nutritional status of old Chinese. The present study aimed to describe the nutritional status and clinical correlates for malnutrition risk in the older people.DesignCross-sectional study.SettingHospital- and community-based older people were recruited in the region of Chongqing, China.Participants558 individuals aged 60 years old or over between April 2011 and October 2012.MeasurementsComprehensive geriatric assessment was performed and nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF). Nutrition-associated factors were analyzed, including health status (chronic diseases, depression, cognition, function impaired), social factors (education status, marital status, the type of work before 60 years old) and life style factors (smoking, drinking, diet).ResultsThe mean age was 73.1±8.0 years and 43.9% were men. Prevalence of malnutrition and risk for malnutrition were 3.2% and 19.3 %, respectively. Several factors increased poor nutrition independently including self-rated health, comorbidity, chronic obstructive pulmonary disease, gastrointestinal disease and cognitive impairment. Fish decreased the risk of poor nutrition.ConclusionsThe prevalence was relatively low in older people of Chongqing, Southwest China. Poor nutrition was found to be increased due to the common health problems. Thus the patients with these problems should pay more attention on nutritional status. The older people should often have fish because of their nutritional benefit.

Vascular Risk Factors and Mild Cognitive Impairment in the Elderly Population in Southwest China

Objectives: Increasing evidence has demonstrated that vascular risk factors (VRFs) contribute to cognitive impairment in the elderly population. Prevention and administration of VRFs can be a vital strategy for delaying cognitive impairment. This study aimed to determine the impact of VRFs on cognitive function of the aged people from Chongqing, Southwest China. Methods: A total of 597 participants (≥60 years) from hospital and community population were enrolled in the cross-sectional study. Participants were screened for hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD). Blood pressure (BP) and blood lipid were also measured. Cognitive function was assessed with Mini-Mental State Examination and Clinical Dementia Rating. Logistic regression analysis was used to look for VRFs impacting mild cognitive impairment (MCI). Then we investigated the relationship between different types of vascular diseases and MCI. Results: A total of 457 participants showed normal cognitive function and 140 participants showed MCI. After adjusting for age, gender, and education, logistic regression analysis demonstrated that hypertension, CHD, systolic BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were independently associated with MCI; however, CVD, diastolic BP, triglyceride, and high-density lipoprotein cholesterol were not associated with MCI. Moreover, vascular diseases significantly contributed to MCI compared with no vascular disease; however, no significant difference in incident MCI was found among different combinations of vascular diseases. Conclusions: Hypertension, CHD, TC, and LDL-C are independent risk factors for MCI. Moreover, patients with vascular diseases have a higher risk of MCI; however, the amount of vascular diseases does not increase the risk of MCI.

Expression pattern of sorting nexin 25 in temporal lobe epilepsy: A study on patients and pilocarpine-induced rats

PURPOSE The transforming growth factor β (TGF-β) signaling pathway is involved in the epileptogenesis. Sorting Nexin 25 (SNX25) has been recently proposed to modulate TGF-β signaling through endosomal sorting of TGF-β receptors for lysosomal degradation. The aim of the present study was to determine the expression pattern of SNX25 in brains of epilepsy patients and in animal model of epilepsy. METHODS We investigated the expression of SNX25 in the brain tissues of patients with temporal lobe epilepsy (TLE) and in the pilocarpine-induced rat model of epilepsy using western blotting, real-time quantitative RT-PCR, and double-label immunofluorescence. RESULTS The expression of SNX25 was significantly increased in TLE patients in comparison to controls (0.21±0.07 vs. 0.11±0.03, P<0.05). In the lithium-pilocarpine induced epileptic rats, significant elevation of SNX25 levels was detected in the chronic phase, while no SNX25 alteration occurred in the acute and latent phases. Moreover, SNX25 localized to astrocytes and neurons, in both human samples and animal models. CONCLUSION Our results indicate that upregulation of SNX25 might be involved in the development of temporal lobe epilepsy.

Tolerability and safety of topiramate in Chinese patients with epilepsy : an open-label, long-term, prospective study.

Objectives:This study focused on (i) evaluating the long-term tolerability and safety of topiramate in Chinese patients with epilepsy, and (ii) comparing the tolerability and safety of topiramate monotherapy versus polytherapy in the same population.Methods:This was a prospective, open-label, long-term (36 months) clinical trial. 320 patients (275 adults and 45 children) with epilepsy were recruited into the study; of these, 156 patients had generalised seizures, 151 patients had partial seizures and 13 patients had unclassifiable seizures. All patients received topiramate ∼200 mg/day either as monotherapy or as adjunctive therapy. At each visit, a physical examination and routine laboratory analysis were performed, and the adverse event (AE) profile was obtained by face-to-face interview.Results:268 patients received topiramate ≤100 mg/day and 52 patients received topiramate 100–200 mg/day. Topiramate-associated AEs occurred in 98 patients (30.6%). The most common AEs were weight loss in 18 patients (8.4%), paraesthesias in 17 (7.2%), poor memory in ten (3.8%), and dizziness in six (2.8%). Most AEs were mild to moderate and transitory; discontinuation of topiramate was observed in 13 patients (4.1%) as a result of AEs such as impaired memory (seven patients [54%]), paraesthesias (four patients [31%]), and weight loss and cutaneous reaction (each one patient [7.5% each]). The rate of AEs was significantly higher with use of topiramate as monotherapy than as adjunctive therapy (68 patients vs 30 patients [47.8% vs 16.4%], respectively).Conclusions:Topiramate is well tolerated in Chinese patients with epilepsy in clinical practice. Compared with its use as adjunctive therapy, topiramate monotherapy is associated with a significantly higher frequency of adverse events.

Chitinase1 contributed to a potential protection via microglia polarization and Aβ oligomer reduction in D-galactose and aluminum-induced rat model with cognitive impairments

Chitinase activity is increased in Alzheimers disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimers pathology and microglia function. Artificial chitinase1 and chitinase inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on inflammatory factors and β-amyloid (Aβ) oligomers deposition in D-galactose/AlCl3-induced rat model with cognitive impairments. Aβ-treated N9 microglia cells were analyzed to further verify whether the changes in inflammatory factors following chitinase1 treatment were associated with microglia alternative activation. Our data displayed that the activity of chitinase1 was both improved in D-galactose/AlCl3-injected rats and Aβ-pretreated microglia. Moreover, there was an improvement in cognitive function in chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1, Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation factors (tumor necrosis factor alpha, TNFα, interleukin 1 beta, IL-1β) were decreased in D-galactose/AlCl3-induced AD rats with chitinase1 treatment. A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype. We also detected that chitnase1 could weaken the deposition of Aβ oligomers in the brain of D-galactose/ AlCl3-induced AD rats. In conclusion, Chitinase1 might exert protective effects against AD by polarizing microglia to an M2 phenotype and resisting Aβ oligomer deposition.

Time-Dependent Decrease of Clusterin as a Potential Cerebrospinal Fluid Biomarker for Drug-Resistant Epilepsy

Our previous study on proteomic analysis has shown that clusterin (CLU) is significantly decreased in the cerebrospinal fluid (CSF) of patients with epilepsy. Therefore, the present study aimed to confirm CLU concentration reduction in the CSF of patients with drug-resistant epilepsy and drug-responsive epilepsy. Fifty-two patients with epilepsy (23 drug resistance and 29 drug effectivity) and 20 control individuals were recruited. The concentrations of CSF and serum CLU were detected. Moreover, alteration of CLU was detected in the rat hippocampus over time after pilocarpine-induced status epilepticus (SE). Our results showed that human CSF-CLU levels were decreased in patients with both drug-resistant epilepsy and drug-responsive epilepsy compared to controls, and concentration of CSF-CLU was obviously lower in drug-resistant epilepsy than in drug-responsive epilepsy. In the pilocarpine-induced seizure rats, expression of neuronal CLU was gradually decreased in a time-dependent manner from acute phase to chronic phase after the onset of SE. In conclusion, CLU level is decreased in the CSF of human epilepsy and the similar alteration is confirmed in a rat model with epilepsy. Therefore, CLU might contribute to the development of epilepsy and be a potential CSF biomarker for resistant epilepsy.

Hypoxia-Up-Regulated Mitochondrial Movement Regulator Does Not Contribute to the APP/PS1 Double Transgenic Mouse Model of Alzheimer's Disease

Background/Aims: It has been demonstrated that mitochondrial dysfunction is associated with Alzheimers disease (AD); meanwhile, hypoxia-up-regulated mitochondrial movement regulator (HUMMR) plays an important role in regulating mitochondrial function. The present study aimed to confirm the association between HUMMR and mitochondrial function in AD. Methods: We detected the expression of HUMMR at transcriptional and translational levels in APP/PS1 double transgenic mice using real-time quantitative RT-PCR and Western blotting. Age- and gender-matched wild-type (WT) littermates were used as controls. Mitochondrial morphology was observed in the hippocampus and cortex of APP/PS1 double transgenic mice using transmission electron microscopy. Results: Damage to mitochondrial morphology in the hippocampus and cortex of APP/PS1 double transgenic mice was found, including swelling and cavitations. Our analysis showed no statistical differences in the expression of HUMMR between APP/PS1 double transgenic mice and WT littermates (p > 0.05). These results showed that there was no association between HUMMR and mitochondrial dysfunction in APP/PS1 transgenic mice. Conclusion: These results indicate that HUMMR does not play a key role in mitochondrial dysfunction in the APP/PS1 double transgenic AD mouse.