BACKGROUND: Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. METHODS: We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. RESULTS: The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. CONCLUSION Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
Animals ; Deep Brain Stimulation ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Macaca ; Seizures

Phantosmia is defined as the false perception of odors without any environmental odor stimulus. It is a very rare phenomenon, but it can be caused by a wide variety of conditions, such as viral or allergic rhinosinusitis, head trauma, brain tumor, migraine, temporal lobe epilepsy, stroke, and psychiatric conditions. If it is caused by a brain tumor such as glioblastoma, it can be controlled with steroids or antiepileptic drugs. Phantosmia can also be treated with surgical resection or adjuvant radiotherapy combined with chemotherapy. We report a case of glioblastoma presenting with phantosmia.
Anticonvulsants ; Brain Neoplasms ; Craniocerebral Trauma ; Drug Therapy ; Epilepsy, Temporal Lobe ; Glioblastoma* ; Migraine Disorders ; Odors ; Radiotherapy, Adjuvant ; Steroids ; Stroke

Brain tumors are the second most common type of structural brain lesion that causes chronic epilepsy. Patients with low-grade brain tumors often experience chronic drug-resistant epilepsy starting in childhood, which led to the concept of long-term epilepsy-associated tumors (LEATs). Dysembryoplastic neuroepithelial tumor and ganglioglioma are representative LEATs and are characterized by young age of onset, frequent temporal lobe location, benign tumor biology, and chronic epilepsy. Although highly relevant in clinical epileptology, the concept of LEATs has been criticized in the neuro-oncology field. Recent genomic and molecular studies have challenged traditional views on LEATs and low-grade gliomas. Molecular studies have revealed that low-grade gliomas can largely be divided into three groups : LEATs, pediatric-type diffuse low-grade glioma (DLGG; astrocytoma and oligodendroglioma), and adult-type DLGG. There is substantial overlap between conventional LEATs and pediatric-type DLGG in regard to clinical features, histology, and molecular characteristics. LEATs and pediatric-type DLGG are characterized by mutations in BRAF, FGFR1, and MYB/MYBL1, which converge on the RAS-RAF-MAPK pathway. Gene (mutation)-centered classification of epilepsy-associated tumors could provide new insight into these heterogeneous and diverse neoplasms and may lead to novel molecular targeted therapies for epilepsy in the near future.
Age of Onset ; Astrocytoma ; Biology ; Brain ; Brain Neoplasms ; Classification ; Epilepsy ; Ganglioglioma ; Glioma ; Humans ; Molecular Targeted Therapy ; Neoplasms, Neuroepithelial ; Seizures ; Temporal Lobe

BACKGROUND: Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model. METHODS: Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups. RESULTS: ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001). CONCLUSION ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.
Adenosine Monophosphate ; Anterior Thalamic Nuclei ; Cyclic AMP-Dependent Protein Kinases ; Deep Brain Stimulation ; Epilepsy/therapy* ; Epilepsy, Temporal Lobe/therapy* ; Hippocampus ; Humans ; Mossy Fibers, Hippocampal ; Signal Transduction

Epilepsy surgery that eliminates the epileptogenic focus or disconnects the epileptic network has the potential to significantly improve seizure control in patients with medically intractable epilepsy. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been an established option for epilepsy surgery since the US Food and Drug Administration cleared the use of MRgLITT in neurosurgery in 2007. MRgLITT is an ablative stereotactic procedure utilizing heat that is converted from laser energy, and the temperature of the tissue is monitored in real-time by MR thermography. Real-time quantitative thermal monitoring enables titration of laser energy for cellular injury, and it also estimates the extent of tissue damage. MRgLITT is applicable for lesion ablation in cases that the epileptogenic foci are localized and/or deep-seated such as in the mesial temporal lobe epilepsy and hypothalamic hamartoma. Seizure-free outcomes after MRgLITT are comparable to those of open surgery in well-selected patients such as those with mesial temporal sclerosis. Particularly in patients with hypothalamic hamartoma. In addition, MRgLITT can also be applied to ablate multiple discrete lesions of focal cortical dysplasia and tuberous sclerosis complex without the need for multiple craniotomies, as well as disconnection surgery such as corpus callosotomy. Careful planning of the target, the optimal trajectory of the laser probe, and the appropriate parameters for energy delivery are paramount to improve the seizure outcome and to reduce the complication caused by the thermal damage to the surrounding critical structures.
Anterior Temporal Lobectomy ; Craniotomy ; Drug Resistant Epilepsy ; Epilepsy ; Epilepsy, Temporal Lobe ; Hamartoma ; Hot Temperature ; Humans ; Laser Therapy ; Malformations of Cortical Development ; Neurosurgery ; Sclerosis ; Seizures ; Thermography ; Tuberous Sclerosis ; United States Food and Drug Administration

There are many medical causes of abdominal pain; abdominal epilepsy is one of the rarer causes. It is a form of temporal lobe epilepsy presenting with abdominal aura. Temporal lobe epilepsy is often idiopathic, however it may be associated with mesial temporal lobe sclerosis, dysembryoplastic neuroepithelial tumors and other benign tumors, arterio-venous malformations, gliomas, neuronal migration defects or gliotic damage as a result of encephalitis. When associated with anatomical abnormality, abdominal epilepsy is difficult to control with medication alone. In such cases, appropriate neurosurgery can provide a cure or, at least, make this condition easier to treat with medication. Once all known intra-abdominal causes have been ruled out, many cases of abdominal pain are dubbed as functional. If clinicians are not aware of abdominal epilepsy, this diagnosis is easily missed, resulting in inappropriate treatment. We present a case report of a middle aged woman presenting with abdominal pain and episodes of unconsciousness. On evaluation she was found to have an intra-abdominal foreign body (needle). Nevertheless, the presence of this entity was insufficient to explain her episodes of unconsciousness. On detailed analysis of her medical history and after appropriate investigations, she was diagnosed with temporal lobe epilepsy which was treated with appropriate medications, and which resulted in her pain being relieved.
Radiography, Abdominal ; Humans ; Foreign Bodies/pathology/*radiography ; Female ; Epilepsy, Temporal Lobe/*diagnosis/drug therapy ; Electroencephalography ; Anticonvulsants/therapeutic use ; Adult ; Abdominal Pain/drug therapy/*etiology/*radiography ; *Abdomen

BACKGROUNDTenidap is a liposoluble non-steroidal anti-inflammatory drug that is easily distributed in the central nervous system and also inhibits the production and activity of cyclooxygenase-2 (COX-2) and cytokines in vitro. This study aimed to evaluate the neuroprotective effect of tenidap in a pilocarpine rat model of temporal lobe epilepsy (TLE).

METHODSTenidap was administered daily at 10 mg/kg for 10 days following pilocarpine-induced status epilepticus (SE) in male Wistar rats after which prolonged generalized seizures resulted in TLE. After tenidap treatment, spontaneous recurrent seizures (SRSs) were recorded by video monitoring (for 7 hours per day for 14 days). The frequency and severity of the SRSs were observed. Histological and immunocytochemical analyses were used to evaluate the neuroprotective effect of tenidap and detect COX-2 expression, which may be associated with neuronal death.

RESULTSThere were 46.88 ± 10.70 survival neurons in tenidap-SE group, while there were 27.60 ± 5.18 survival neurons in saline-SE group at -2.4 mm field in the CA3 area. There were 37.75 ± 8.78 survival neurons in tenidap-SE group, while there were 33.40 ± 8.14 survival neurons in saline-SE group at -2.4 mm field in the CA1 area. Tenidap treatment significantly reduced neuronal damage in the CA3 area (P < 0.05) and slightly reduced damage in the CA1 area. Tenidap markedly inhibited COX-2 expression in the hippocampus, especially in the CA3 area.

CONCLUSIONTenidap conferred neuroprotection to the CA3 area in a pilocarpine-induced rat model of TLE by inhibiting COX-2 expression.

Animals ; Cyclooxygenase 2 ; metabolism ; Epilepsy, Temporal Lobe ; chemically induced ; drug therapy ; metabolism ; Indoles ; therapeutic use ; Male ; Neuroprotective Agents ; therapeutic use ; Pilocarpine ; toxicity ; Rats ; Rats, Wistar

BACKGROUNDS: Since the advent of MRI, cavernous angioma has been recognized as an important cause of chronic epilepsy. However, the natural course or optimal treatment strategies of chronic epilepsy with cavernous angioma have not been established yet. METHODS: We conducted a retrospective review of the Yonsei Epilepsy Data Bank and found 13 patients with characteristic MR findings of cavernous angioma who have been followed at the Yonsei Epilepsy Clinics for longer than one year. The clinical variables and outcome of the patients were analyzed. RESULTS: The subjects consisted of 7 men and 6 women. The age of seizure-onset was approximately 21 years old and the duration of seizure were 9 years. All patients in this study had small(< 2cm) and single cavernous angioma and the majority of lesions(9/13) were located in the temporal lobe. One patient also had hippocampal atrophy and another two had combined venous malformations. After adequate trials of antiepileptic drug therapy, 5 patients became seizure free, 2 patients showed worthwhile improvement and the remaining 6 patients did not have any improvement. The withdrawal of antiepileptic drugs was tried in two patients after seizure free period of 3 years but seizure recurred in all patients. Epilepsy surgery had been performed in two patients. One patient who had the left hippocampal atrophy has been remain seizure free after a standard anterior temporal lobectomy but the other patient who had performed a lesionectomy alone did not improve after surgery. During the period of follow up for about 36 months, no symptomatic bleeding had been occurred in any patiet included to the study. CONCLUSION: The incidence of hemorrhagic events in chronic epilepsy patients with cavernous angioma is extremely low. About half of the patients can be adequately managed by antiepileptic drugs therapy but the chance of successful withdrawal of AEDs seems slim.
Anterior Temporal Lobectomy ; Anticonvulsants ; Atrophy ; Drug Therapy ; Epilepsy* ; Female ; Follow-Up Studies ; Hemangioma, Cavernous* ; Hemorrhage ; Humans ; Incidence ; Magnetic Resonance Imaging ; Male ; Prognosis* ; Retrospective Studies ; Seizures ; Temporal Lobe ; Young Adult

An 81-year-old woman with a history of temporal lobe epilepsy-induced psychotic episodes was initially admitted to a general hospital where she was started on a course of oral antibiotics for community-acquired pneumonia, and ciprofloxacin eye drops to treat nasolacrimal duct obstruction. After one week, the patient was discharged back to a nursing home with these medications. However, she was admitted to our psychiatric ward two days later due to a relapse of psychosis. Another six days later, she developed breakthrough seizures associated with subtherapeutic serum phenytoin levels. Having explored all possible causes of reduced serum phenytoin levels, ciprofloxacin eye drops was discontinued in the patient, resulting in gradual return of phenytoin levels to the therapeutic range, with no further seizures observed in the patient.
Administration, Oral ; Aged, 80 and over ; Anti-Bacterial Agents ; administration & dosage ; Ciprofloxacin ; administration & dosage ; adverse effects ; Drug Interactions ; Epilepsy, Temporal Lobe ; drug therapy ; Female ; Hospitalization ; Humans ; Ophthalmic Solutions ; adverse effects ; Phenytoin ; blood ; Psychotic Disorders ; drug therapy ; Seizures ; chemically induced

To investigate the effect of crocin on the progression and generalized seizure of temporal lobe epilepsy in mice.Hippocampus rapid kindling model was established in C57BL/6J mice. The effects of crocin on seizure stage, afterdischarge duration (ADD), number of stimulation in each stage and final state, the incidence of generalized seizure (GS), average seizure stage and ADD were observed.Crocin (20 mg/kg) significantly retarded behavioral seizure stages (<0.05) and shortened cumulative ADD (<0.01) during hippocampus rapid kindling acquisition in mice compared with vehicle group. Meanwhile, number of stimulations in stage 1-2 was significantly increased (<0.05) and the incidence of fully kindled animals was significantly decreased (<0.01). However, 10 or 50 mg/kg crocin showed no significant effect on the above indexes (all>0.05). Crocin (100 or 200 mg/kg) significantly decreased the incidence of GS (all<0.01) and reduced average seizure stages (all<0.01) in fully-kindled mice compared with vehicle group; Fifty mg/kg crocin only reduced average seizure stages (<0.05).Low-dose crocin can retard the progression in hippocampus rapid kindling acquisition in mice, while high-dose crocin relieves the GS in fully-kindled mice, which suggests that crocin may be a potential anti-epileptic compound.
Animals ; Anticonvulsants ; pharmacology ; Carotenoids ; pharmacology ; therapeutic use ; Dose-Response Relationship, Drug ; Electric Stimulation ; Epilepsy, Temporal Lobe ; chemically induced ; drug therapy ; Hippocampus ; drug effects ; physiopathology ; Kindling, Neurologic ; drug effects ; physiology ; Mice ; Mice, Inbred C57BL ; Seizures ; classification ; drug therapy