Hypothalamic hamartoma surgery in a setting with limited resources.

BACKGROUND: Three years ago (in 2020), we at the epilepsy center in Shiraz, Iran, started an endeavor to initiate a surgical program for patients with hypothalamic hamartoma (HH). We discussed that although minimally invasive techniques are desired, they are not available in the nation. We decided to proceed with open disconnection and resection surgery techniques. The current manuscript presents the results of the HH surgery program at our center as a case series. METHODS: This study included all patients with a diagnosis of HH who were referred to Shiraz Epilepsy Center with drug-resistant epilepsy and who underwent HH surgery from October 2020 to January 2023 at our epilepsy center, Namazi Hospital, Shiraz, Iran. RESULTS: Seven patients were included. All patients had gelastic seizures. Four patients (57%) underwent total resection of HH, and the lesions were disconnected and partially resected in three other patients (43%). Three patients (43%) became seizure-free after surgery, and three patients (43%) had more than 50% reduction in their seizure frequencies. Three patients (43%) had no post-operative complications. Only one patient (14.3%) suffered from a permanent postoperative complication (right hemiparesis). The mortality rate was zero. Five parents (71%) were satisfied with the surgery outcomes. CONCLUSION: Hypothalamic hamartoma surgery is feasible even in centers with limited resources if a close collaboration exists between the epileptology and neurosurgery teams. Careful planning based on the expertise of the team members and the available resources is required to foster success.

Adult epilepsy.

Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.

How to successfully establish an epilepsy care center in resource-limited countries: A scoping systematic review.

PURPOSE: The aim of the current study was to systematically review the literature on establishing epilepsy care centers in resource-limited nations in the world and to provide a comprehensive roadmap on this significantly needed endeavor. This work may provide guidance on how to develop an epilepsy care center in other resource-limited places in the world. METHODS: Web of science, Science Direct, and MEDLINE (accessed from PubMed) from inception to March 2023 were systematically searched for relevant published manuscripts. In all electronic databases, the following search strategy was implemented and these key words were used (title/abstract): epilepsy AND resource. The inclusion criteria were all original studies and articles written in English. RESULTS: We could identify nine manuscripts on how to successfully establish an epilepsy care center in resource-limited countries. Two models were identified for such an endeavor: developing a team of trained healthcare professionals (e.g., in Iran, India, China, Vietnam) or a twin affiliation between an advanced epilepsy surgery program in a developed country and a starting program in a developing country (e.g., in Georgia, Tunisia). CONCLUSION: In order to successfully establish an epilepsy care center in resource-limited countries four pillars are needed: presence of skillful healthcare professionals, having access to basic investigative technologies (i.e., MRI and EEG), a careful planning, and raising awareness.

Opinions about epilepsy surgery in adults with epilepsy.

OBJECTIVE: The goal of the current study was to investigate the opinions of adult patients with epilepsy (PWE) with regard to the application of epilepsy surgery for their condition. METHODS: We surveyed all the consecutive adult PWE with at least one year history of epilepsy who were referred to our neurology clinics (Shiraz University of Medical Sciences) from September 2022 until January 2023. Using a questionnaire, the degree of acceptance of epilepsy surgery was measured depending on the chance of seizure freedom and risk for surgery complications. RESULTS: In total, 393 adult PWE participated in the study; 180 patients (45.8%) expressed that they would be willing to have surgery if their epilepsy doctor told them that brain surgery was guaranteed to stop their seizures, without regard to the potential surgery complications. The most common reasons for the patients to be willing to have epilepsy surgery were as follows: to become seizure-free and to be able to discontinue their antiseizure medications. The most common reasons for the patients not to be willing to have epilepsy surgery were as follows: feeling of having the seizures under the control with antiseizure medications and fear of surgery complications. CONCLUSION: Many patients with epilepsy are willing to have epilepsy surgery if their physician presented epilepsy surgery to them as an established safe and effective treatment option. The important values and priorities of PWE must be considered when designing epilepsy surgery educational materials and programs for preoperative counseling for PWE with drug-resistant seizures.

Rare Genetic Variation and Outcome of Surgery for Mesial Temporal Lobe Epilepsy.

OBJECTIVE: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. METHODS: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug-resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2-year postsurgical follow-up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. RESULTS: Nine centers from 3 continents contributed 206 patients operated for drug-resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss-of-function (LoF) variants (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.9-3.5, p = 1.3E-09) and in genes encoding voltage-gated cation channels (OR = 2.4, 95% CI = 1.4-3.8, p = 2.7E-04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between-group differences. INTERPRETATION: Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision-making and counseling. ANN NEUROL 2022.

Parents' opinions about epilepsy surgery in children with epilepsy.

OBJECTIVE: This survey aimed to investigate the opinions of the parents of children with epilepsy with regard to the application of epilepsy surgery for their children. METHODS: We surveyed all the parents of children with epilepsy referred to our neurology clinic (Shiraz University of Medical Sciences) in April-July 2022. We collected their opinions about epilepsy surgery based on a predesigned questionnaire. The inclusion criteria included parents of all children with epilepsy (1 to 16 years of age, with at least one-year history of epilepsy, and with at least one drug used in the past 12 months). RESULTS: In total, 472 people participated in the study; 277 participants (58.7%) were willing to have epilepsy surgery for their child; the most common reason was to be able to discontinue the drugs. Sex (male), age (younger), and education (college) of the parents had significant associations with the parental willingness to have surgery for their children. The patient's drug regimen (polytherapy) and history of ictal injury (in the child) also had significant associations with the parental willingness to have surgery for the children. CONCLUSION: Most parents of children with epilepsy are willing to have epilepsy surgery for their children if their physician presents epilepsy surgery to them as an established, safe, and effective treatment option. Patient and parental-related factors should be considered when designing educational materials and programs for preoperative counseling for the parents of children with drug-resistant seizures.

Physicians' beliefs about brain surgery for drug-resistant epilepsy: A global survey.

PURPOSE: To investigate the opinions of physicians about brain surgery for drug-resistant epilepsy worldwide. METHODS: Practicing neurologists, psychiatrists, and neurosurgeons from around the world were invited to participate in an online survey. The survey anonymously collected data about demographics, years in clinical practice, discipline, nation, work setting, and answers to the questions about beliefs and attitudes about brain surgery for drug-resistant epilepsy. RESULTS: In total, 1410 physicians from 20 countries and different world regions participated. The propensity to discuss brain surgery with patients, who have drug-resistant seizures, was higher among men (versus women) [Odds Ratio (OR) 1.67, 95% CI 1.20-2.31; p = 0.002]. In comparison to neurologists, psychiatrists were less likely (OR 0.28, 95% CI 0.17-0.47; p < 0.001) and neurosurgeons were more likely (OR 2.00, 95% CI 1.08-3.72; p = 0.028) to discuss about it. Survey participants working in Africa, Asia, the Middle East, and the Former Union of Soviet Socialist Republics showed a lower propensity to discuss epilepsy surgery with patients. CONCLUSION: This study showed that on an international level, there is still a knowledge gap concerning epilepsy surgery and much needs to be done to identify and overcome barriers to epilepsy surgery for patients with drug-resistant seizures worldwide.

Epilepsy management during difficult times

Major disruption in the delivery of healthcare services can occur in exceptional situations such as natural disasters, conflicts, periods of severe economic hardship, and epidemics. These disruptions typically affect to the greatest extent the most vulnerable segments of the population, including people with epilepsy. Inability to access healthcare services can lead to failure to undergo necessary diagnostic investigations, or to receive needed therapeutic interventions, including epilepsy surgery. Stress and other factors associated with the nature or the cause of the disruption can adversely affect seizure control status, or precipitate the occurrence of psychiatric disorders and other comorbid conditions. Failure to access antiseizure medications is a common occurrence in these situations and can result in loss of seizure control, withdrawal seizures, and status epilepticus. In this article, we provide examples of recent disruptions in healthcare and their implications for people with epilepsy. We discuss the consequences of natural disasters, conflicts, economic sanctions, and focus in greater detail on lessons learnt during the COVID-19 pandemic. We also discuss possible mitigation procedures, focusing in particular on the application of telemedicine to epilepsy care. Finally, we underline the need for governments, healthcare authorities, and international organizations to improve their preparedness to deal with exceptional situations that may arise in the future.

Seizure is a rare presenting manifestation of COVID-19.

OBJECTIVE: The aim of the current study was to investigate whether seizure is among the presenting manifestations of COVID-19. METHODS: All patients referred to emergency rooms anywhere in Iran between 12 and 25 April 2020 and who were sufficiently ill to require hospital admission with COVID-19, confirmed by a positive COVID-19 test, were studied. Data on the presenting manifestations were collected. RESULTS: Of 5872 people, who were admitted to hospitals in Iran with COVID-19 during the study period, 45 came to the emergency room with seizures. This makes seizure as the presenting manifestation of COVID-19 in 0.8 % of all patients with a severe illness. 93 % of the patients were 15 years of age and older. Four of the individuals presenting with seizures (9%) had a past history of epilepsy. Fifteen of these individuals (33 %) had other chronic medical conditions (e.g., cancer, diabetes mellitus, heart disease, etc.). CONCLUSION: This case series provides evidence that seizures are among the presenting manifestations of COVID-19 in 0.8 % of the patients who are admitted to hospital due to a severe illness.

Stem cell therapy in patients with epilepsy: A systematic review.

PURPOSE: The existing evidence of the potential applications and benefits of stem cell transplantation (SCT) in people with epilepsy and also its adverse effects in humans were systematically reviewed. METHODS: MEDLINE (accessed from PubMed), Google Scholar, and Scopus from inception to August 17, 2020 were systematically reviewed for related published manuscripts. The following key words (in the title) were used: "stem cell" AND "epilepsy" OR "seizure". Articles written in English that were human studies on stem cell transplantation in people with epilepsy were all included. RESULTS: We could identify six related articles. Because of their different methodologies, performing a meta-analysis was not feasible; they included 38 adults and 81 pediatric patients together. Five studies were single-arm human studies; there were no serious adverse events in any of the studies. CONCLUSION: While stem cell transplantation seems like a promising therapeutic option for patients with drug-resistant epilepsy, data on its application is scarce and of low quality. For now, clinical stem cell-based interventions are not justified. Perhaps, in the future, there will be a rigorous and intensely scrutinized clinical trial protocol with informed consent that could provide enough scientific merit and could meet the required ethical standards.

Prevention and treatment of temporal lobe epilepsy: lessons from hepatitis B story!

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and hippocampal sclerosis (HS) is the most common pathological substrate of TLE. Considering the significant consequences of uncontrolled seizures (e.g. increased morbidity and mortality), epilepsy prevention remains a necessity that potentially could save many lives. Human herpes virus-6 (HHV-6) has been linked to TLE in humans. The relationship between HHV-6 and HS-TLE could be attributed to a neuro-inflammatory cascade triggered by the infection, involving direct neuronal damage and production of several pro-inflammatory cytokines under certain conditions that are still incompletely understood. Hepatitis B virus (HBV) infection is another chronic viral infection with a life-long latency. HBV infection is linked to various clinical conditions, including liver cirrhosis. There are currently three ways to fight HBV infection and its consequences; primary prevention (by vaccination), secondary prevention (by drug therapy), and tertiary prevention (by liver transplantation). Considering the similarities between the natural histories of HHV-6 and HBV infections, and also the successful strategies which are currently available to fight HBV infection and its long-term consequences, here, we propose three strategies to fight HHV-6 and its possible long-term consequence (i.e. HS-TLE): Primary prevention: by developing vaccines to prevent HHV-6 infection; Secondary prevention: by considering trials of antiviral drugs to treat HHV-6 infection, when it happens in the childhood to hopefully prevent its long-term consequences; and, Tertiary prevention: by stem cell therapy for drug-resistant epilepsy.

Structural brain abnormalities in patients with psychogenic nonepileptic seizures.

OBJECTIVES: We assessed the relationship between the clinical features of patients with psychogenic nonepileptic seizures (PNES) and referrals for brain imaging tests. We also hypothesized that some clinical factors might be associated with structural brain imaging abnormalities in these patients. METHODS: In this retrospective study, patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2019, were studied. RESULTS: One hundred thirty-two patients had a brain magnetic resonance imaging (MRI) study available. Forty-seven patients (36%) had abnormal finding(s) in their MRI. Age (odds ratio = 1.040, p = 0.02), and comorbid epilepsy (odds ratio = 3.006, p = 0.005) were significantly associated with having an abnormal brain MRI. In a subanalysis, we excluded the patients with comorbid epilepsy (46 patients). From the remaining 86 patients (with PNES only), 23 patients (26.7%) had abnormal findings on their MRIs. Common epileptogenic structural brain abnormalities (e.g., tumors, mesial temporal sclerosis, encephalomalacia, and developmental anomalies) were common in patients with comorbid PNES and epilepsy (in 19 out of 46 patients; 41%), but not in those with PNES only (in 4 out of 86 patients; 5%) (p = 0.00001). CONCLUSION: While the evidence is convergent on the relatively high prevalence of structural brain abnormalities in patients with PNES, the data so far is suboptimal. In order to investigate the significance of structural brain abnormalities in the development of PNES, future well-designed multicenter studies, which include a large number of patients with a unified methodology of imaging, are desirable.

Attention-deficit hyperactivity disorder in adults with epilepsy.

PURPOSE: We investigated the prevalence of attention-deficit hyperactivity disorder (ADHD) in adult people with epilepsy (PWE). We hypothesized that ADHD is common among adult PWE and, some clinical factors may be associated with ADHD. METHODS: In this cross-sectional study, 200 adult PWE referred to our neurology clinic at Shiraz, Iran were recruited (consecutively sampled). Validated Persian versions of Adult ADHD Self-Report Scale (ASRS v1.1) and Addenbrooke's Cognitive Examination-Revised (ACE-R) tests were used. We performed univariate analyses and also a logistic regression analysis. RESULTS: Eighty-two patients (41%) were male, and 118 (59%) were female. Seventy patients (35%) had a positive screen for ADHD. There was a significant association between cognitive function and the prevalence of positive screening for ADHD in the whole group; 19 (18%) of the patients with a normal cognition, 23 (42%) of those with mild impairment, and 28 (70%) of those with severe cognitive impairment screened positive for ADHD (p = 0.0001). One hundred and five patients had normal cognition and were studied separately. Nineteen patients (18%) had screened positive for ADHD. Attention-deficit hyperactivity disorder was not associated with any of the tested variables in these patients. CONCLUSION: About one-fifth of adults with epilepsy and normal cognitive function may have a positive screen for ADHD. Routine screening of all PWE for early detection and appropriate management of ADHD would be a reasonable approach.

Electroencephalography in epilepsy: look for what could be beyond the visual inspection.

Since its starting point in 1929, human scalp electroencephalography (EEG) has been routinely interpreted by visual inspection of waveforms using the assumption that the activity at a given electrode is a representation of the activity of the cerebral cortex under it, but such a method has some limitations. In this review, we will discuss three advanced methods to obtain valuable information from scalp EEG in epilepsy using innovative technologies. Authors who had previous publications in the field provided a narrative review. Spike voltage topography of interictal spikes is a potential way to improve non-invasive EEG localization in focal epilepsies. Electrical source imaging is also a complementary technique in localization of the epileptogenic zone in patients who are candidates for epilepsy surgery. Quantitative EEG simplifies the large amount of information in continuous EEG by providing a static graphical display. Scalp electroencephalography has the potential to offer more spatial and temporal information than the traditional way of visual inspection alone in patients with epilepsy. Fortunately, with the help of modern digital EEG equipment and computer-assisted analysis, this information is more accessible.

Novel therapies for epilepsy in the pipeline.

Despite the availability of many antiepileptic drugs (AEDs) (old and newly developed) and, as recently suggested, their optimization in the treatment of patients with uncontrolled seizures, more than 30% of patients with epilepsy continue to experience seizures and have drug-resistant epilepsy; the management of these patients represents a real challenge for epileptologists and researchers. Resective surgery with the best rates of seizure control is not an option for all of them; therefore, research and discovery of new methods of treating resistant epilepsy are of extreme importance. In this article, we will discuss some innovative approaches, such as P-glycoprotein (P-gp) inhibitors, gene therapy, stem cell therapy, traditional and novel antiepileptic devices, precision medicine, as well as therapeutic advances in epileptic encephalopathy in children; these treatment modalities open up new horizons for the treatment of patients with drug-resistant epilepsy.

History of surgery for temporal lobe epilepsy.

The history of epilepsy and its treatment goes back to ancient times when it included medicinal herbs, lifestyle modifications, and even surgery. Trepanation is considered the oldest surgical procedure for the treatment of epilepsy. The first series of temporal lobectomies for the treatment of drug-resistant epilepsy were reported by Penfield and Flanigin (1950). During the years since then, neuroimaging and other technologies have had remarkable and revolutionary progress. This progress has resulted in tremendous advancements in understanding the underlying causes and pathophysiology of epilepsies. With the help of these technologies and advancements, we may now offer surgery as a safer therapeutic option to more patients who are suffering from drug-resistant temporal lobe epilepsy. However, the degree of improvement in surgery outcome has not been proportionate to the technological progress.

Drug-resistant parietal lobe epilepsy: clinical manifestations and surgery outcome.

We reviewed a large surgical cohort to investigate the clinical manifestations, EEG and neuroimaging findings, and postoperative seizure outcome in patients with drug-resistant parietal lobe epilepsy (PLE). All drug-resistant PLE patients, who were investigated for epilepsy surgery at Jefferson Comprehensive Epilepsy Center between 1986 and 2015, were identified. Demographic data, seizure data, EEG recordings, brain MRI, pathological findings, and postsurgical seizure outcome were reviewed. In total, 18 patients (11 males and seven females) were identified. Sixteen patients (88%) had tonic-clonic seizures, 12 (66%) had focal seizures with impaired awareness, and 13 (72%) described auras. Among 15 patients who had brain MRI, 14 patients (93%) had parietal lobe lesions. Only three of 15 patients (20%) who had interictal scalp EEG recordings showed parietal interictal spikes. Of 12 patients with available ictal surface EEG recordings, only three patients (25%) had parietal ictal EEG onset. After a mean follow-up duration of 8.6 years, 14 patients (77.7%) showed a favourable postoperative seizure outcome. In patients with PLE, semiology and EEG may be misleading and brain MRI is the most valuable tool to localize the epileptogenic zone. Postsurgical seizure outcome was favourable in our patients with drug-resistant parietal lobe epilepsy.

Epilepsy surgery in drug resistant temporal lobe epilepsy associated with neuronal antibodies.

We assessed the outcome of patients with drug resistant epilepsy and neuronal antibodies who underwent epilepsy surgery. Retrospective study, information collected with a questionnaire sent to epilepsy surgery centers. Thirteen patients identified, with antibodies to GAD (8), Ma2 (2), Hu (1), LGI1 (1) or CASPR2 (1). Mean age at seizure onset: 23 years. Five patients had an encephalitic phase. Three had testicular tumors and five had autoimmune diseases. All had drug resistant temporal lobe epilepsy (median: 20 seizures/month). MRI showed unilateral temporal lobe abnormalities (mainly hippocampal sclerosis) in 9 patients, bilateral abnormalities in 3, and was normal in 1. Surgical procedures included anteromesial temporal lobectomy (10 patients), selective amygdalohippocampectomy (1), temporal pole resection (1) and radiofrequency ablation of mesial structures (1). Perivascular lymphocytic infiltrates were seen in 7/12 patients. One year outcome available in all patients, at 3 years in 9. At last visit 5/13 patients (38.5%) (with Ma2, Hu, LGI1, and 2 GAD antibodies) were in Engel's classes I or II. Epilepsy surgery may be an option for patients with drug resistant seizures associated with neuronal antibodies. Outcome seems to be worse than that expected in other etiologies, even in the presence of unilateral HS. Intracranial EEG may be required in some patients.