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Objective In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19. Methods MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”. Results Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general. Conclusion While neurological manifestations of COVID-19 have not been studied appropriately, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations., Highlights • Some patients with COVID-19 may show nonspecific neurological symptoms, such as confusion and headache. • A few patients with COVID-19 showed more specific neurological manifestations, such as seizure or cerebrovascular problems. • Neuroinvasion of SARS-CoV2 may partially explain why some patients develop respiratory failure.

We investigated the voltage topography of interictal spikes in patients with temporal lobe epilepsy (TLE) to see whether topography was related to etiology for TLE. Adults with TLE, who had epilepsy surgery for drug-resistant seizures from 2011 until 2014 at Jefferson Comprehensive Epilepsy Center were selected. Two groups of patients were studied: patients with mesial temporal sclerosis (MTS) on MRI and those with other MRI findings. The voltage topography maps of the interictal spikes at the peak were created using BESA software. We classified the interictal spikes as polar, basal, lateral, or others. Thirty-four patients were studied, from which the characteristics of 340 spikes were investigated. The most common type of spike orientation was others (186 spikes; 54.7%), followed by lateral (146; 42.9%), polar (5; 1.5%), and basal (3; 0.9%). Characteristics of the voltage topography maps of the spikes between the two groups of patients were somewhat different. Five spikes in patients with MTS had polar orientation, but none of the spikes in patients with other MRI findings had polar orientation (odds ratio=6.98, 95% confidence interval=0.38 to 127.38; p=0.07). Scalp topographic mapping of interictal spikes has the potential to offer different information than visual inspection alone. The present results do not allow an immediate clinical application of our findings; however, detecting a polar spike in a patient with TLE may increase the possibility of mesial temporal sclerosis as the underlying etiology.

We investigated auras in patients with drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). We also investigated the clinical differences between patients with MTS and abdominal auras and those with MTS and non-mesial temporal auras. All patients with drug-resistant TLE and unilateral MTS who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center from 1986 through 2014 were evaluated. Patients with good postoperative seizure outcome were investigated. One hundred forty-nine patients (71 males and 78 females) were studied. Thirty-one patients (20.8%) reported no auras, while 29 patients (19.5%) reported abdominal aura, and 30 patients (20.1%) reported non-mesial temporal auras; 16 patients (10.7%) had sensory auras, 11 patients (7.4%) had auditory auras, and five patients (3.4%) reported visual auras. A history of preoperative tonic-clonic seizures was strongly associated with non-mesial temporal auras (odds ratio 3.8; 95% CI: 1.15-12.98; p=0.02). About one-fifth of patients who had MTS in their MRI and responded well to surgery reported auras that are historically associated with non-mesial temporal structures. However, the presence of presumed non-mesial temporal auras in a patient with MTS may herald a more widespread epileptogenic zone.

Purpose Sex-related differences have been reported in patients with neurological and psychiatric disorders. It is also plausible to assume that there might be differences between females and males with psychogenic nonepileptic seizures (PNES). Methods In this retrospective study, we investigated patients with PNES, who were admitted to the epilepsy monitoring units at centers in Iran, the USA, Canada, Brazil, Argentina, and Venezuela. Age, sex, age at seizure onset, seizure semiology, factors potentially predisposing to PNES, and video-electroencephalography recording of all patients were registered routinely. Results Four hundred and fifty-one patients had PNES-only and were eligible for inclusion; 305 patients (67.6%) were females. We executed a logistic regression analysis, evaluating significant variables in univariate analyses (i.e., age, age at onset, aura, presence of historical sexual or physical abuse, and family dysfunction). The only variables retaining significance were historical sexual abuse (p = 0.005) and presence of aura (p = 0.01); physical abuse was borderline significant (p = 0.05) (all three were more prevalent among females). Conclusion Similarities between females and males outweigh the differences with regard to the demographic and clinical characteristics of PNES. However, notable differences are that females more often report lifetime adverse experiences (sexual and probably physical abuse) and auras. While social, psychological, and genetic factors may interact with lifetime adverse experiences in the inception of PNES, the link is not yet clear. This is an interesting avenue for future studies. Fil: Asadi Pooya, Ali A.. Shiraz University of Medical Sciences; Irán. Thomas Jefferson University; Estados Unidos Fil: Myers, Lorna. Northeast Regional Epilepsy Group; Estados Unidos Fil: Valente, Kette Dualibi Ramos. Universidade de Sao Paulo; Brasil Fil: Daza Restrepo, Anilu. La Trinidad Medical Center; Venezuela Fil: D`alessio, Luciana. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Sawchuk, Tyson. Alberta Children's Hospital; Canadá. University of Nicosia; Chipre Fil: Homayoun, Maryam. Shiraz University of Medical Sciences; Irán Fil: Bahrami, Zahra. Shiraz University of Medical Sciences; Irán Fil: Alessi, Rudá. Universidade de Sao Paulo; Brasil Fil: Paytan, Angélica Aroni. La Trinidad Medical Center; Venezuela Fil: Kochen, Sara Silvia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina Fil: Buchhalter, Jeffrey. Alberta Children's Hospital; Canadá. University of Calgary; Canadá Fil: Taha, Firas. Northeast Regional Epilepsy Group; Estados Unidos Fil: Lazar, Lorraine M.. Northeast Regional Epilepsy Group; Estados Unidos Fil: Pick, Susannah. Kings' College London; Reino Unido Fil: Nicholson, Timothy. Kings' College London; Reino Unido

Purpose The aim of this study was to investigate the frequency and characteristics of auras in patients with psychogenic nonepileptic seizures (PNES) and to characterize the patients’ historical and clinical risk factors that may be associated with such manifestations. Methods In this retrospective database study, all patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center at Shiraz University of Medical Sciences, from 2008 until 2018, were studied. Results During the study period, 258 patients were investigated. One hundred and seventy-three patients (67.1%) reported having auras. Auras were associated with multiple variables, including sex ratio, history of head injury, ictal injury, and taking antiepileptic drugs, in univariate analyses. We then performed a logistic regression analysis, assessing these four variables. The model that was generated by the regression analysis was significant (p = 0.0001) and could predict the possibility of auras in 72% of the patients. Within the model, sex ratio (OR: 0.498; 95% CI: 0.282−0.878; p = 0.01) and a history of head injury (OR: 0.096; 95% CI: 0.020−0.465; p = 0.004) retained their significance. Conclusion Patients with PNES may frequently report auras including some auras which are often seen in patients with focal epilepsies; as a result, they are at great risk of receiving wrong diagnosis and unnecessary treatments. Health care professionals involved in the management of patients with seizures should be aware of this risk and prescribe an antiepileptic drug only after making a definite diagnosis of epilepsy in a patient with a paroxysmal event.

Purpose To classify patients with psychogenic nonepileptic seizures (PNES) according to a recently proposed classification system and investigate the variability of PNES semiology. Methods We retrospectively investigated all patients with PNES admitted at the Jefferson Comprehensive Epilepsy Center from 2012 through 2016. We classified their seizures after retrospectively reviewing their recorded videos during their video-EEG monitoring admission and investigated the seizure variability. We extracted all the clinical data from their medical records. We also studied factors potentially associated with seizure variability. Results Forty nine patients were studied and 220 seizures were reviewed and classified. Mean number of seizures per patient was 4.5. Twenty seven (55%) patients had subjective seizures, 26 (53%) had generalized motor, 14 (29%) had akinetic and five (10%) had focal motor seizures. Twenty eight (57%) patients had only one seizure class, while 19 (39%) patients had two different seizure classes and two (4%) patients had three seizure classes. Among 28 patients with one seizure class, 14 (50%) patients had variable semiologies from one seizure to the other. Hence, 71.5% of the patients showed either inter- or intra-class variability, whereas seizures were stereotypical in 28.5%. No demographic or clinical factors were significantly associated with variability of PNES semiology. Conclusion Neither the stereotypy nor the variability of PNES can or should be used as a marker of the disease and to differentiate PNES from epilepsy. The variability of the episodes of PNES does not hinder an appropriate classification of these seizures.

Objectives Tonic-clonic seizures are associated with greater chance of seizure relapse after anterior temporal lobectomy. We investigated whether the interval between the last preoperative tonic-clonic seizure and surgery relates to seizure outcome in patients with drug-resistant mesial temporal lobe epilepsy (MTLE). Methods In this retrospective study, patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was categorized as seizure freedom or relapse. The relationship between surgical outcome and the interval between the last preoperative tonic-clonic seizure and surgery was investigated. Results One-hundred seventy-one patients were studied. Seventy nine (46.2%) patients experienced tonic-clonic seizures before surgery. Receiver operating characteristic curve of timing of the last preoperative tonic-clonic seizure was a moderate indicator to anticipate surgery failure (area under the curve: 0.657, significance; 0.016). The best cutoff that maximizes sensitivity and specificity was 27 months; with a sensitivity of 0.76 and specificity of 0.60. Cox-Mantel analysis confirmed that the chance of becoming free of seizures after surgery in patients with no or remote history of preoperative tonic-clonic seizures was significantly higher compared with patients with a recent history (i.e., in 27 months before surgery) (p = 0.0001). Conclusions The more remote the occurrence of preoperative tonic-clonic seizures, the better the postsurgical seizure outcome, with at least a two year gap being more favorable. A recent history of tonic-clonic seizures in a patient with MTLE may reflect more widespread epileptogenicity extending beyond the borders of mesial temporal structures.

Purpose Among different seizure types, tonic–clonic seizures are more significant because they are more often associated with morbidity. No prior study has been done to investigate risk factors associated with tonic–clonic seizures in patients with mesial temporal epilepsy. Methods In this retrospective study, all drug-resistant mesial temporal epilepsy patients in the database of patients who underwent epilepsy surgery at Jefferson comprehensive epilepsy center were recruited. These patients were prospectively registered in a database from 1986 till 2014. Patients' age, gender, epilepsy risk factors, age at seizure onset, and preoperative seizure type(s) were registered routinely. Potential risk factors associated with experiencing preoperative tonic–clonic seizures were investigated. Results Two hundred seventy-five patients (132 males and 143 females) were studied. Aura type was associated with experiencing perioperative tonic–clonic seizures. Patients with epigastric auras less frequently reported having tonic–clonic seizures compared with those who had other types of auras (odds ratio: 0.37 and 95% confidence interval: 0.19–0.70; p = 0.001) and those who did not have any auras (odds ratio: 0.35 and 95% confidence interval: 0.16–0.77; p = 0.008). Conclusion Epigastric auras may indicate that a specific anatomic location is involved in epileptogenesis from which generalization is harder because of that location's poor connections with other brain regions.

Purpose Psychogenic non-epileptic seizures (PNES) are more prevalent among women. We investigated the potential differences in demographic and clinical characteristics of PNES between women and men. Methods In this prospective study, all patients with a clinical diagnosis of PNES (based on ictal recordings) were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 through 2012. The epileptologist interviewed all the patients. We compared the demographic and clinical characteristics and seizure semiology of PNES between women and men. Results Two hundred and twenty-two patients were diagnosed as having PNES. One hundred and eighty-eight patients had video-EEG recordings available and included in the study. One hundred and twenty-nine (69%) were female and 59 (31%) were male. There were no significant differences between women and men with PNES with regard to demographic, clinical and semiological characteristics. Conclusion We did not observe any significant demographic differences between women and men with PNES. Likewise, seizure characteristics and semiology were very similar in both genders. It appears that an Islamic lifestyle (in Iran) has little influence on the sex ratio and clinical manifestations of PNES compared with the Western studies.

Objectives Epidemiologic data concerning idiopathic generalized epilepsies (IGEs) are scarce or often unreliable. In the current study, we specifically analyzed the syndromes of IGE based on their demographic, clinical, and EEG findings to determine if other than the seizure type(s) and age of onset, there are any other distinctive features to distinguish these syndromes of IGEs from one another. Materials and methods In this retrospective study, all patients with a clinical diagnosis of IGE were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, from 2008 to 2011. Demographic variables and relevant clinical and EEG variables were summarized descriptively. Statistical analyses were performed using Chi square and Fisher's exact tests. Results 2190 patients with epilepsy were registered at our epilepsy clinic and 442 patients (20.2%) were diagnosed as having IGE. Age of seizure onset was 12 ± 7 years. Juvenile myoclonic epilepsy was the most frequent syndrome, followed by epilepsy with generalized tonic–clonic seizures only and juvenile absence epilepsy. Epilepsy risk factors, physical examination, MRI and even EEG could not differentiate various syndromes of IGE. Conclusion The key element in making the correct diagnosis of an IGE syndrome is obtaining a detailed clinical history. However, other than the seizure type(s) and age of onset, there are no any other distinctive features to distinguish these syndromes of IGEs from one another. Besides, sometimes these syndromes have overlapping features.