Rui-Juan Lv

Temporal lobe epilepsy with amygdala enlargement: a subtype of temporal lobe epilepsy

BackgroundSome recent studies suggest that some imaging-negative temporal lobe epilepsy (TLE) had significant amygdala enlargement (AE). Contradictory data were also reported in previous studies regarding the association between AE and TLE. The present study was to investigate the clinical characters of a group of TLE with AE and compare the amygdala volume of the same patient before and after antiepileptic drugs treatment by a larger sample size.MethodsThis study recruited 33 mesial TLE patients with AE and 35 healthy volunteers. The clinical history, seizure semiology, electroencephalogram (EEG), fluorodeoxyglucose-positron emission tomography (FDG-PET) and amygdala volume were investigated. The amygdala volume were compared between ipsilateral and contralateral sides, TLE patients and 35 healthy controls, and patients at first and follow-up visit by 3.0 T MRI.ResultsAverage seizure onset age was 42.0 years (SD 14.3). All patients had complex partial seizures, fourteen had occasional generalized tonic-clonic seizures which often happened during sleep. Ninety percent patients suffered from anxiety or depression. Thirty percent patients had memory decline. Interictal epileptiform discharges appeared predominantly in the anterior or inferior temporal area ipsilateral to AE. Interictal FDG-PET showed regional glucose hypometabolism in the ipsilateral temporal lobe. No hippocampal sclerosis (HS) was suspected in all patients. 22 patients demonstrated good seizure control and significantly reduced volume of the enlarged amygdala after treatment (P < 0.01). The other 11 patients showed initial response to treatment, followed by a gradual increase in seizure frequency over time, and no volume change of the enlarged amygdala after treatment.ConclusionsTLE with AE probably represents a distinct nosological and probably less homogeneous syndrome which is most likely a subtype of TLE without ipsilateral HS. The chronic and long lasting inflammatory processes or focal cortical dysplasia could lead to amygdala enlargement possibly.

ASIC1a polymorphism is associated with temporal lobe epilepsy.

Recent in vitro and in vivo data show that acid-sensing ion channel 1a (ASIC1a) activation enhances neuronal excitability in the hippocampus and neocortex, indicating that ASIC1a might play a role in the generation and maintenance of epileptic seizures. The aim of this study was to investigate association of the ASIC1a gene with temporal lobe epilepsy (TLE) for the first time. Six tag single-nucleotide polymorphisms (SNPs) of the ASIC1a gene were selected and genotyped using polymerase chain reaction-restriction fragment length polymorphism in 560 TLE patients and 401 healthy controls. There was a significant allelic and genotypic association between rs844347:A>C and TLE compared with controls. The rs844347-A allele frequency was 88.1% in the patients and 83.0% in control subjects (OR=1.516, 95% CI 1.142-2.013, p=0.004). Furthermore, the haplotype analysis revealed a significant association with TLE. The results of this study demonstrate for the first time an association between an ASC1a variant allele and TLE in a Han Chinese population.

Association of apolipoprotein E polymorphisms with temporal lobe epilepsy in a Chinese Han population

Apolipoprotein E (ApoE) has been implicated as one of the susceptibility genes for temporal lobe epilepsy (TLE). Previous studies indicate that ApoE ɛ4 is associated with several disease-related traits including the increased risk of late posttraumatic seizures, earlier onset of TLE, refractory complex partial seizures, and postictal confusion. Contradictory data were also reported regarding the association between ApoE polymorphisms and TLE. The present study was designed to investigate whether ApoE ɛ4 is a risk factor for TLE and the above clinical variables, as well as to determine whether -491A/T polymorphism may independently alter the risk for TLE in a Chinese Han population. The ApoE and -491A/T polymorphisms were genotyped in 558 controls and 735 patients including 560 TLE patients using polymerase chain reaction-restriction fragment length polymorphism. A significant association was detected between prior trauma and the ApoE ɛ4 allele in TLE patients. However, no significant differences were observed in the genotype and haplotype distributions and allele frequencies of these two polymorphisms between cases and controls. Furthermore, there were no significant associations between these two polymorphisms and the other clinical variables examined. The study illustrates that the ApoE ɛ4 allele may be involved in the development of TLE in those patients with prior trauma in the Chinese Han population.

Status epilepticus-related etiology, incidence and mortality: A meta-analysis

Status epilepticus (SE) is a severe medical condition. To determine its epidemiology and outcome of SE, we performed a meta-analysis to investigate the etiology, incidence and mortality of SE. We searched PubMed and Embase between Jan 1, 2000, and Oct 31, 2016, with no regional restrictions, for observational studies of the etiology, incidence and mortality of SE. Forty-three studies were included in the meta-analysis. The pooled crude annual incidence rate, the pooled case fatality rate and the pooled crude annual mortality rate of SE were 12.6/100,000 (95% CI: 10.0-15.3), 14.9% (95% CI: 11.7-118.7) and 0.98/100,000 (95% CI: 0.74-1.22), respectively. Elderly subjects with SE had a higher case fatality rate (28.4% (95% CI: 17.7-42.3)) and crude annual incidence rate (27.1% (95% CI: 15.8-38.2)). The most important etiology-specific attributable fraction of patients with SE was acute symptomatic etiology (OR 0.411, 95% CI: 0.315-0.507). Age and economic income contributed to differences in SE incidence and short-term case fatality rate.

A polymorphism in CALHM1 is associated with temporal lobe epilepsy.

A recent study suggests that the P86L polymorphism (rs2986017) in the calcium homeostasis modulator 1 (CALHM1) gene interferes with calcium homeostasis and increases amyloid β (Aβ) levels. Moreover, in vitro and in vivo data show that both calcium homeostasis and high levels of Aβ play an important role in the induction and maintenance of epileptic seizures in hippocampus, indicating CALHM1 might play a potential role in pathophysiological pathways involved in temporal lobe epilepsy (TLE). The aim of this study was to investigate the genetic contribution of CALHM1 to TLE. Five single-nucleotide polymorphisms (SNPs) of CALHM1 were selected and genotyped using polymerase chain reaction restriction fragment length polymorphism in 560 patients with TLE and 401 healthy controls. We found a positive association between rs11191692 and TLE, but a negative result between rs2986017 and TLE. The rs11191692-A allele frequency was found in 32.4% of the patients and in 26.2% of control subjects (OR=1.35, 95% CI=1.10-1.65, uncorrected P=0.003, corrected P=0.015). Furthermore, the positive association between rs11191692 and TLE independent of apolipoprotein E ε4 was supported by five SNPs haplotype analysis. The results of this study provide the first evidence that the SNP rs11191692 in CALHM1 confers highly increased susceptibility to TLE.

Seizure semiology and electroencephalography in young children with lesional temporal lobe epilepsy

PURPOSE This study aimed to discuss the clinical features of seizure semiology and electroencephalography (EEG) in young children with lesional temporal lobe epilepsy (TLE). METHOD Children with lesional TLE received presurgical evaluation for intractable epilepsy. They were followed up for more than one year after temporal lobectomy. We reviewed the medical history and video-EEG monitoring of children with TLE to analyze the semiology of seizures and EEG findings and compared the semiology of seizures and EEG findings of childhood TLE and adult TLE. RESULTS A total of 84 seizures were analyzed in 11 children (aged 23-108 months). The age of seizure onset was from 1 month to 26 months (a mean of 17.6 months). All of the patients exhibited prominent motor manifestations including epileptic spasm, tonic seizure, and unilateral clonic seizure. Seven children manifested behavioral arrest similar to an automotor seizure in adult TLE but with a shorter duration and higher frequency. The automatisms were typically orofacial, whereas manual automatisms were rarely observed. The EEG recordings revealed that diffuse discharge patterns were more common in younger children, whereas focal or unilateral patterns were more typical in older children. All of the patients were seizure-free after temporal lobectomy with more than one-year follow-up. All of the children had a mental development delay or regression; however, there was improvement after surgery, especially in those with surgery performed early. CONCLUSION In contrast to TLE in adults, young children with lesional TLE probably represent a distinct nosological and probably less homogeneous syndrome. Although they had generalized clinical and electrographic features, resective epilepsy surgery should be considered as early as possible to obtain seizure control and improvement in mental development.

Somatosensory reflex seizures in a patient with hypertrophic cranial pachymeningitis

Somatosensory-evoked reflex epilepsy is characterized by seizures in response to specific stimuli. It is highly uncommon for somatosensory-evoked focal seizures to be caused by movement or a change in posture. Reflex epilepsy induced by both somatosensory and proprioceptive stimulations has not been previously reported. In this study, we present a case of reflex epilepsy evoked by somatosensory and proprioceptive stimulation in a patient with hypertrophic cranial pachymeningitis. After comparing our patient with other cases of previously reported somatosensory-evoked reflex epilepsy, we determined that our patient had an unusual cause of reflex epilepsy.

The role of the microRNA-146a/complement factor H/interleukin-1β-mediated inflammatory loop circuit in the perpetuate inflammation of chronic temporal lobe epilepsy

ABSTRACT Increasing evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of temporal lobe epilepsy (TLE). However, it is unclear how the perpetuate inflammation develops. Some recent studies have suggested the possible involvement of microRNA-146a (miR-146a) in the modulation of inflammatory signaling occurring in TLE. To understand how miR-146a modulates inflammatory signaling in TLE, we investigated the role of interleukin-1β (IL-1β), miR-146a and human complement factor H (CFH) in the perpetuate inflammation in rat models of chronic TLE and U251 cells. We found that enhancive miR-146a could upregulate the expression of IL-1β and downregulate the expression of CFH, whereas reductive miR-146a could downregulate the expression of IL-1β and upregulate the expression of CFH, in hippocampi of chronic TLE rat models. Meanwhile, enhancive miR-146a could increase the abnormal wave forms in the chronic TLE rat models. Additionally, enhancive IL-1β could feedback downregulate the expression of CFH, upregulate the expression of miR-146a and increase the abnormal wave forms in chronic TLE rat models. After CFH gene knockdown in U251 cells, enhancive miR-146a did not upregulate the expression of IL-1β. In summary, this study shows that enhancive miR-146a can upregulate the inflammatory factor IL-1β in chronic TLE by downregulating CFH, and that upregulation of IL-1β plays an important feedback-regulating role in the expression of miR-146a and CFH, forming a miR-146a–CFH–IL-1β loop circuit that initiates a cascade of inflammation and then leads to the perpetuate inflammation in TLE. Therefore, modulation of the miR-146a–CFH–IL-1β loop circuit could be a novel therapeutic target for TLE. Summary: The microRNA-146a–complement factor H–interleukin-1β loop circuit might initiate a cascade of inflammation, leading to the perpetuate inflammation in temporal lobe epilepsy.

Seizure as the unique clinical manifestation of cerebral metastases in a 27-year-old man with non-small cell lung cancer

Dear editor, Brain metastases (BM) occur in 20–40% of patients with non-small cell lung cancer (NSCLC) at some point during the disease course [1]. NSCLC is heterogeneous in terms of its histological subtypes and distinct driving oncogenes [2], which may affect the development of BM. Adenocarcinoma, identified through histology, has been reported to be associated with BM from NSCLC. Patients with BM from NSCLC often present with headaches, nausea and vomiting, seizures, and meningeal irritation. However, patients with BM from NSCLC who only present with seizures without any evidence of lung cancer are very rare. In this report, we describe a 27year-old man with BM from NSCLC whose only presenting symptom was seizure. A 27-year-old man presented to the emergency department during Chinese spring festival with a history of seizures that had been occurring for the previous 5 days. The seizures were described by the paramedics as well as by bystanders as a Jacksonian seizure affecting the right limb, followed by a generalized tonic-clonic seizure lasting approximately 3 min. The patient had Todd’s paralysis of the right limb following each seizure. He did not exhibit any confusion between episodes and suffered approximately four seizures per day. The patient had previously been healthy. The family history was negative for seizures, endocrine disorders, or neoplasms. On physical examination, his vital signs were within normal limits, and he did not exhibit any focal neurological signs. Results of laboratory diagnostic tests performed on admission were within normal limits. Electroencephalogram (EEG) was performed at another hospital and demonstrated a few amount of spikes in the left temporal and frontal regions. Brain magnetic resonance imaging (MRI) without enhancement was performed at the same hospital as the EEG and did not reveal any abnormalities. A thoracic Xray showed normal results. Following these initial tests, the patient was diagnosed as epilepsy without known cause. We then performed a lumbar puncture for routine tests that included testing for autoantibodies of autoimmune encephalitis and cytology on the cerebrospinal fluid (CSF) to further investigate the cause of the seizures. The intracranial pressure was approximately 200 mmH2O, and white blood cells (WBCs) measured in the CSF were 13/μL (normal range is less than 10/μL). The autoantibodies of autoimmune encephalitis were negative. Herpes simplex virus IgM antibodies (1 and 2) were positive in the blood but negative in the CSF. CSF cytology revealed heterocysts. Furthermore, CSF cytopathology revealed cells that were identified as adenocarcinoma. We then performed a contrast enhanced brain MRI scan and an enhanced CT scan of the patient’s thorax. The enhanced brain MRI demonstrated clear enhancement in the right thalamus and midline meninges (Fig. 1). The enhanced thoracic CT scan revealed a mass in the inferior lobe of the right lung (Fig. 2). The histopathology of the sample obtained by percutaneous lung biopsy identified the mass as adenocarcinoma, and the final diagnosis was BM from NSCLC. The lesion in right thalamus was thought to be caused by implantation metastasis through the CSF circulation. Written informed consent was obtained from the patient prior to this report. This patient was diagnosed with leptomeningeal carcinomatosis (LC) characterized by multifocal seeding of the Rui-Juan Lv and Pu Yin contributed equally to this work.

Correlation between tumor necrosis factor alpha mRNA and microRNA-155 expression in rat models and patients with temporal lobe epilepsy

Accumulative evidence demonstrates that there is an inseparable connection between inflammation and temporal lobe epilepsy (TLE). Some recent studies have found that the multifunctional microRNA-155 (miR-155) is a key regulator in controlling the neuroinflammatory response of TLE rodent animals and patients. The aim of the present study was to investigate the dynamic expression pattern of tumor necrosis factor alpha (TNF-α) as a pro-inflammatory cytokine and miR-155 as a posttranscriptional inflammation-related miRNA in the hippocampus of TLE rat models and patients. We performed real-time quantitative PCR (qRT-PCR) on the rat hippocampus 2 h, 7 days, 21 days and 60 days following kainic acid-induced status epilepticus (SE) and on hippocampi obtained from TLE patients and normal controls. To further characterize the relationship between TNF-α and miR-155, we examined the effect of antagonizing miR-155 on TNF-α secretion using its antagomir. Here, we found that TNF-α secretion and miR-155 expression levels were correlated after SE. The expression of TNF-α reached peak levels in the acute phase (2h post-SE) of seizure and then gradually decreased; however, it rose again in the chronic phase (60 days post-SE). miR-155 expression started to increase 2 h post-SE, reached peak levels in the latent phase (7 days post-SE) of seizure and then gradually decreased. The variation in the trend of miR-155 lagged behind that of TNF-α. In patients with TLE, the expression levels of both TNF-α and miR-155 were also significantly increased. Furthermore, antagonizing miR-155 inhibited the production of TNF-α in the hippocampal tissues of TLE rat models. Our findings demonstrate a critical role for miR-155 in the physiological regulation of the TNF-α pro-inflammatory response and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, regulation of the miR-155/TNF-α axis may be a new therapeutic target for TLE.