Exploring shared triggers and potential etiopathogenesis between migraine and idiopathic/genetic epilepsy: Insights from a multicenter tertiary-based study.

INTRODUCTION: Migraine and epilepsy are two episodic disorders that share common pathophysiological mechanisms. The aim of our research was to assess the possible shared etiopathogenesis by analyzing the relations of headache, and seizure triggers, based on information obtained from a national cohort surveying the headache characteristics of 809 patients who had been diagnosed with idiopathic/genetic epilepsy. MATERIAL AND METHODS: Our study utilized data from a multi-center, nationwide investigation of headaches in 809 patients with idiopathic/genetic epilepsy. Out of these, 508 patients reported complaints related to any type of headache (333 Migraines, 175 Headaches of other types). In the initial phase of the study encompassing the entire sample of 809 epilepsy patients, differences in seizure triggers were assessed between the migraine group (n = 333) and the non-migraine group (n = 476). Additionally, the subsequent part of the study pertains to a subgroup of the entire patient group, namely those affected by all types of headaches (n = 508), and differences in headache triggers were assessed among migraine patients (n = 333) and those with other types of headaches (n = 175). Similar differences were observed between epilepsy patients with and without a family history of epilepsy. RESULTS: The most frequently reported seizure triggers in all I/GE group (n = 809) were stress (23%), sleep deprivation (22%) and fatigue (18%), respectively. The most frequently reported headache triggers in migraine patients were stress (31%), sleep deprivation (28%), and noise (26%). The occurrence of menstruation-triggered seizures in individuals with migraine and I/GE was found to be considerably higher than those without migraine. The most common triggers for seizure and headache among the individuals with a positive family history of epilepsy were determined to be light stimuli and sleep deprivation. CONCLUSION: In conclusion, our study provides valuable insights into the overlapping triggers including sleep patterns, stress levels, and menstrual cycles, etc. and potential shared etiology of migraine and I/GE. Recognizing these connections may facilitate the development of more precise therapeutic strategies and underscore the significance of adopting a holistic, multidisciplinary approach to the management of these intricate neurological conditions. Further research is essential to explore in greater depth the shared mechanisms underpinning these associations and their implications for clinical practice.

Peri-ictal headache: An underestimated prognostic finding associated with idiopathic epilepsies.

OBJECTIVE: There are a handful of studies investigating peri-ictal headache (PIH) and its clinical associations in patients with idiopathic/genetic epilepsies (I/GE). This multi-center study aimed to investigate PIH, which is an ignored comorbid condition in patients with I/GE, by headache experts and epileptologists working together. METHODS: The data were collected from a cross-sectional large study, using two structured questionnaires for headache and epilepsy features, fulfilled by neurologists. Headaches were classified according to the International Classification of Headache Disorders, third edition, whereas seizure and syndrome types were diagnosed according to International League Against Epilepsy criteria. The patients with a headache starting 24 hours before the onset of the seizure (preictal) or within 3 hours after the seizure (postictal) were defined as patients with PIH. We compared demographic and clinical differences between two groups of patients with and without PIH statistically and used ROC curves to determine a threshold of the total number of seizure triggers associated with the occurrence of PIH. RESULTS: Among 809 (531 females, 65.6%) consecutive patients with I/GE, 105 (13%) patients reported PIH (22 preictal, 82 postictal headaches, and one with both types). Peri-ictal headache was more frequently reported by females and those having a family history of migraine or epilepsy, and it was significantly associated with lower rates of seizure freedom for more than five years, drug resistance, and use of polytherapy, remarkably. Moreover, ROC curves showed that having more than 3 seizure triggers was associated with the presence of PIH. CONCLUSION: Our findings revealed that PIH may be linked to poor outcomes in I/GEs and seems to be related to a lower ictal threshold precipitated by multiple triggers. Future prospective studies will illuminate the unknown underlying mechanisms and appropriate management strategies for PIH to improve the prognosis.

European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

BACKGROUND AND PURPOSE: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. METHODS: A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. RESULTS: The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. CONCLUSIONS: This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Clinical findings, etiological factors, and prognosis markers in status epilepticus: a university hospital experience.

OBJECTIVE: To determine the factors affecting mortality and disability in status epilepticus (SE) and to evaluate the prediction ability of the Status Epilepticus Severity Score (STESS) for disability and mortality. MATERIALS AND METHOD: The demographic and clinical characteristics, prognosis and prognosis predictors of 72 patients who were diagnosed with SE between 2013 and 2018 were retrospectively evaluated. The STESS was used to predict prognosis, and the modified Rankin scale (mRS) was used to determine the disability at discharge. RESULTS: The study population had a mean age of 45.4 ± 20.7, and it was found that mortality was 22.2% and acute symptomatic etiology played a 54.1% role in etiology. Advanced age, refractory SE or super-refractory SE, acute symptomatic etiology, and a history of epilepsy were related to mortality, symptomatic etiology (acute, progressive, remote), a history of hospitalization and epilepsy in intensive care or in other departments other than the neurology department were associated with disability. The sensitivity of STESS in predicting mortality was 100%, specificity was 69%, accuracy was 76.4%, positive predictive value (PPV) was 48.5%, and the negative predictive value (NPV) was 100%. The sensitivity of STESS in predicting mobilization during discharge was 55.6% with a 63.9% specificity and 59.7% accuracy, PPV was 60.6%, and NPV was 59%. CONCLUSION: It was observed that STESS strongly predicts a good prognosis; however, it was not found to be useful in predicting motor disability during discharge. Thus, new studies should be conducted to predict and evaluate mobility in SE patients at discharge.

Diagnosis of comorbid migraine without aura in patients with idiopathic/genetic epilepsy based on the gray zone approach to the International Classification of Headache Disorders 3 criteria.

Background: Migraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert. Methods: In this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis. Results: Longer headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone. Conclusion: Longer headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.

Electroencephalogram abnormalities in patients with NREM parasomnias.

OBJECTIVE: Electroencephalographic (EEG) changes in patients with NREM parasomnias (NRP) occur in sleep architecture as changes in slow wave sleep or cyclic pattern, which are not considered abnormal. However, abnormalities in EEG in these patients have recently been reported, indicating that EEG patterns in NRPs are not definitive. Moreover, most of the polysomnography (PSG) findings in NRP patients were reported in the adult population requiring data from pediatric population to avoid bias in conclusion. METHODS: In sum, 39 patients with a NRP were undergone comprehensive assessments including a PSG with additional EEG montages. EEG recordings were evaluated in patients without a history of epilepsy and further compared between pediatric and adult patients. RESULTS: Twenty-three (59%) of the patients were pediatric and 77% were male. The mean age was 18.4 (±13.1) years. Of the patients, 19 (49%) had somnambulism, 13 (33%) had confusional arousal and seven (18%) had sleep terrors. Macrostructure of sleep detected by PSG was normal in all patients. After excluding 11 (28%) patients with a positive history of epilepsy, seven (25%) of 28 showed EEG abnormalities within K-complexes in NREM-II stage, six of whom were pediatric patients compared to only one adult (p < 0.05). CONCLUSION: This study showed that patients with NRP may display EEG abnormalities in NREM-II stage. These abnormalities were more frequent in pediatric patients compared to adults. In NRP patients, utmost care should be taken in EEG evaluations to prevent false diagnosis of epilepsy.

Assessment of genes involved in behavior, learning, memory, and synaptic plasticity following status epilepticus in rats.

OBJECTIVE: In this study, it was aimed to evaluate cognitive and behavioral changes after status epilepticus (SE) induced by pentylenetetrazole in immature rats via Morris water maze and open-field area tests and to assess alterations in expression of 84 key genes involved in synaptic plasticity after SE. METHOD: The study was conducted on 30 immature rats (12-days old). The rats were assigned into groups as control and experiment (SE) groups. The SE was induced by pentylenetetrazole in 12-days old rats. In addition, experiment group was divided into two groups as mature (n = 8) and immature SE (n = 8) subgroups. Again, the control group was divided into two groups as mature (n = 7) and immature control (n = 7) subgroups. Hippocampal tissue samples were prepared, and expression of 84 key genes involved in synaptic plasticity was assessed in Genome and Stem Cell Center of Erciyes University before behavioral tests in immature rats (22-days old) and after open-filed area and Morris water maze tests in mature rats (72-days old) in both experiment and control groups. RESULTS: No significant difference was detected in behavioral tests assessing spatial memory and learning among groups. Significant differences were detected, ARC (activity-regulated cytoskeleton-associated protein), BDNF (brain-derived neurotrophic factor), MAPK1 (mitogen-activated protein kinase 1), NR4A1 (nuclear receptor subfamily 4 group A member 1), PPP3CA (protein phosphatase 3 catalytic subunit alpha), RGS2 (regulator of G protein signaling 2), and TNF (tumor necrosis factor) gene expressions between control and experiment groups in immature rats whereas in ADCY8 (adenylate cyclase 8), BDNF (brain-derived neurotrophic factor), EGR4 (early growth response 4), and KIF17 (kinesin family member 17) gene expressions between control and experiment groups in mature rats. DISCUSSION: In this study, differences detected in gene expressions of synaptic plasticity after SE indicate in which steps of synaptic plasticity may be problematic in epileptogenesis. The gene expressions in this study may be considered as potential biomarkers; however, epileptogenesis is a dynamic process and cannot be explained through a single mechanism. Future studies on epileptogenesis and studies specifically designed to evaluate genes detected in our study will further elucidate synaptic plasticity in epilepsy and epileptogenesis.

Awareness of Migraine Among Primary Care Physicians in Turkey: A Regional Study.

INTRODUCTION: Migraine is a primary headache that involves genetic and environmental factors. In studies conducted in different countries, migraine was shown to be underdiagnosed, treated insufficiently, and highly related to disability. The primary aim of this study was to identify the competence in making a diagnosis of migraine by primary care physicians who provide basic health care to patients. METHODS: Primary care physicians (266 individuals) working in the primary health service centers located within the borders of Kayseri province were included in our study. The research was conducted by using techniques such as face-to-face meetings with the primary care physicians and by participants filling in questionnaires. A neurologist evaluated the questionnaire form. The information provided by the participants was evaluated according to the migraine without aura diagnostic criteria prepared by the International Headache Society (ICHD-3 Beta). RESULTS: Only 10.5% participants were able to give the complete diagnostic criteria of migraine without aura. The most well-known properties were unilateral (53.4%) and pulsating headaches (47%). CONCLUSION: This study showed that educational programs are required regarding migraines for primary care physicians, supported by complete educational material.

A rare entity in ED: posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome is a clinico-neuroradiologic entity with typical symptoms and symmetric high-signal intensity lesions in the bilateral parietooccipital lobes on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging. In this presentation, we report a case of posterior reversible encephalopathy syndrome who was admitted to our emergency department because of seizure and deterioration of consciousness. The aim of this presentation is to alert the emergency physicians about one of the hypertensive emergencies with neurologic symptoms associated with hypertension.

Prevalence of and influencing factors for chronic headaches among pregnant women.

OBJECTIVE: To determine the prevalence of headaches and their influencing factors among pregnant women. METHODS: A cross-sectional study was conducted from January 3 to April 29, 2005, with 1357 women receiving routine pregnancy check-ups at the obstetric clinics of the community health institutions of Kayseri, Turkey. A structured questionnaire and the Zung Depression Scale were used to collect data. RESULTS: Overall, 24.6% (95% confidence interval, 22.3%-26.9%) of the participants had headaches before pregnancy, whereas only 17.9% (95% confidence interval, 15.9%-20.1%) had headaches during pregnancy. Although the headache prevalence was lower during than before pregnancy, it was high among the participants aged 35 years or older, those who received help in their housework, and those who were multiparous. Moreover, the Zung depression score was significantly high among those experiencing headaches. CONCLUSION: The significant decrease in headache prevalence observed during pregnancy may be the result of a pregnancy-specific hormonal status. However, the most significant factors influencing the frequency of headaches in the participants were related to their socioeconomic status and the severity of depression.

Different seizure types and skin lesions in oculocerebrorenal syndrome of Lowe.

Oculocerebrorenal syndrome of Lowe is an X-linked recessive disorder localized to Xq24-26.1. The phenotypic features of this disorder are Fanconi-type renal failure, mental retardation, and various eye abnormalities. Seizures may accompany the disease, and the skin-related findings are poorly defined. This case of a 9-year-old patient, diagnosed as having and followed for oculocerebrorenal syndrome of Lowe, has been presented for his seizures, which were initially myoclonic but subsequently atonic, and for his skin findings, understood to be trichoepithelioma, cystic in nature, and stemming from mature hair follicles. In monitoring the disease, the manifestation of the seizures as atonic seizures accompanied by focally initiated secondary generalized epileptic discharges is a finding previously undefined in oculocerebrorenal syndrome of Lowe. Moreover, the presence of dermal findings of a cystic nature is reported in few cases of this syndrome. In this rare syndrome, it is necessary to be aware of the presence of atonic seizures, which have an association with the progression of the disease that has not been previously reported in the literature, and of the cystic dermal lesions as part of the syndrome.

The relationship between fatigue and depression, and event-related potentials in epileptics.

The aim of the present study was to establish the rate of fatigue and the relationship between fatigue, depression, and P300 in people with epilepsy. We compared Fatigue Severity Scale (FSS) and Beck Depression Inventory (BDI) scores and event-related potentials (ERPs) of people with epilepsy (n=73) with those of controls (n=31). The rate of fatigue was found to be 42.4%, and fatigue and depression were positively correlated. There was an interaction between fatigue and ERPs, but the effect of ERPs on fatigue was greater. While polytherapy was a major factor affecting ERPs, depression had no effect on ERPs in people with epilepsy. The data suggest that fatigue is an important finding and is strongly correlated with cognitive processes and depression. Polytherapy contributed to cognitive disturbances and, hence, fatigue, whereas depression had no effect on cognitive processes in people with epilepsy.

A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures.

The aim of the present work was to assess serum melatonin levels and melatonin circadian rhythm in patients with diurnal and nocturnal complex partial epilepsy. Daily rhythms of melatonin were studied in patients with diurnal complex partial epilepsy (n=10), patients with nocturnal complex partial epilepsy (n=10), and a control group (n=10). All patients were under carbamazepine treatment. Serum melatonin samples were taken at 1000, 2200, 0100, and 0500 hours. We found that melatonin circadian rhythm was normal in all patients when compared with controls. Melatonin levels were low in both patients with nocturnal and patients with diurnal complex partial epilepsy compared with the control group at 1000, 2200, 0100, and 0500 hours; a statistically significant decrease in melatonin levels was observed in the patients with epilepsy at 1000 hours only. These findings suggest that melatonin levels and circadian rhythm of melatonin do not differ between patients with nocturnal and patients with diurnal complex partial epilepsy. Further detailed research is necessary to determine the factors that govern the nocturnal or diurnal occurrence of complex partial seizures.

Ketamine reduces lidocaine-induced seizures in mice.

Systemic toxic reactions to local anesthetics are brought about by absolute overdosage, and, most commonly, inadvertent intravascular injections. The anti-convulsant action of ketamine has been studied. However, the effect of ketamine on lidocaine-induced convulsions has not been reported. This study investigated the effect of ketamine on lidocaine-induced seizures in mice. Mice (32-41 g) were divided into 2 groups, 15 in each group, and were pretreated with intraperitoneal normal saline solution or intraperitenoeal (ip) ketamine before lidocaine. Group 1 (N = 15) received 75 mg kg ip lidocaine; Group 2 (N = 15) received 20 mg kg ketamin ip; 5 min later 75 mg kg lidokaine ip were applied. Clinical features, incidences, latencies, durations, and mortality rate of convulsions were recorded. After 75 mg kg lidocaine injection, ataxia, loss of righting reflex, and generalized tonic-clonic convulsions were seen within 2-5 min in Group 1. Generalized tonic-clonic convulsions were seen in 8 mice and deep sedation was seen in 7 mice in Group 2 (p < .05). Generalized status epilepticus occurred in one mouse in both groups. Three mice from Group l and one mouse from Group 2 died during convulsions. There were no differences between the two groups with regard to the onset and duration of seizures (p > .05). It was concluded that ketamine significantly prevented lidocaine-induced generalized tonic-clonic seizures; on the other hand, the lethality of lidocaine was least reduced by ketamine.

EMX2-independent familial schizencephaly: clinical and genetic analyses.

Schizencephaly is a human brain malformation distinguished by full-thickness unilateral or bilateral clefts through the neocortex. Heterozygous mutations in the EMX2 locus are reported to give rise to schizencephaly. However, the comprehensive identification of causative genetic loci is precluded by a lack of large pedigrees and genome-wide linkage analyses. We present here a large Turkish pedigree with three individuals with schizencephaly. The similarity of clinical signs in affected individuals strongly suggests an underlying genetic cause; however, genome-wide linkage analysis rules out EMX2 linkage and instead suggests additional candidate loci. These results indicate that genetic forms of schizencephaly are likely to be heterogeneous.

Effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory and learning in immature rats.

Status epilepticus (SE) can be harmful to the developing brain. Our knowledge of the emotional and behavioral consequences of generalized SE in developing animals remains limited. Therefore, we investigated the short- and long-term effects of pentylenetetrazole (PTZ)-induced SE on emotional memory and learning and behavioral parameters in immature rats. SE was induced in 16- to 20-day-old rats (P16-P20) using intraperitoneal injections of PTZ (n=21); control rats received saline (n=10). All animals were tested using an elevated T-maze and open-field test 2, 14, 30, and 180 days after SE, to evaluate emotional memory and learning and behavior. Anxiety levels decreased 2 and 14 days after SE, and conditioned learning of PTZ-treated immature rats was better than that of the control rats. These results indicate that a decreased anxiety level facilitates conditioned learning. Behavioral changes are transient, and no emotional memory or learning deficits occur following PTZ-induced SE in immature rats.

A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease.

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.

The effects of pentylenetetrazole-induced status epilepticus on behavior, emotional memory, and learning in rats.

Status epilepticus (SE) can cause spatial learning, memory, and behavioral deficits; however, little information is available, especially regarding the effects of such seizures on emotional memory and learning functions. We investigated the effects of SE on emotional memory, learning, and behavior in mature rats over short and long periods. SE was induced in 50- to 60-day-old rats (P50-P60) using intraperitoneal injections of pentylenetetrazole (PTZ, n = 20); control rats received saline (n = 10). All animals were tested with elevated T-maze and open-field tests on the 1st, 7th, 14th, and 180th days after SE to evaluate emotional memory, learning, and behavior. The number of fecal boli increased, and one-way escape latency was long in a short period after SE. PTZ-induced SE causes transient memory deficits, which is related to unconditioned fear, but it did not cause any persistent abnormalities of behavior, emotional memory, and learning in mature rats.