Fractures in people with epilepsy: A nationwide population-based cohort study.

OBJECTIVE: The objective of this study was to determine the age, gender, and site-specific prevalence of fractures in people with epilepsy (PWE) and matched general population comparators in a nationwide study in North Macedonia between 2015 and 2018. METHODS: PWE and matched controls were selected through a systematic search of the electronic National Health System (eNHS). We determined the period prevalence (PP) of all site-specific fractures. We also calculated gender and age-specific incidence rate ratios (IRR) for various fractures. Odds ratios (ORs) and risk ratios (RR) were estimated for the number and type of ASM as well as comorbid conditions. RESULTS: Out of 13 818 prevalent epilepsy cases, 6383 (46.2%) were females, and 7435 (53.8%) were males. 109 PWE out of 1000 had at least one fracture during the study period and ~8 people out of 1000 in the general population. The most frequent sites in terms of PP both in PWE and controls, were fractures of the lower arm, hip and femur, and lower leg. Significant differences in PP for all fracture locations were observed between PWE and controls (P < 0.001). The noticeable differences of ∼100 times higher PP were observed for fractures of the skull and jaw in PWE. IRR of any fracture in PWE was 272.84/10 000 person-years; higher in the older age groups and among people who received >2 ASM. Fracture risk was increased with the use of >2 ASM (OR: 1.56; 95% CI: 1.32-1.84 and RR: RR: 1.32). The presence of comorbidities also increased fractures risk (OR: 1.24; 95% CI: 1.10-1.38). SIGNIFICANCE: This population-based study depicts a higher fracture prevalence in PWE compared to the general population. A higher number of ASM and the presence of comorbidities increase the risk of fractures and targeted prevention might be needed in those subgroups of PWE.

Prevalence of various risk factors associated with new-onset epilepsy after the age of 50: a retrospective population-based study.

Population-based studies of epilepsy risk factors are rare. We aimed to evaluate the prevalence of various risk factors associated with new-onset epilepsy after the age of 50 years. We included all incident cases in North Macedonia between 2015 and 2018. Study participants were ascertained from the national healthcare platform. We performed a retrospective analysis of Electronic Health Records of 2,367 patients (1,017 females and 1,350 males) whose epileptic seizures started after the age of 50 years. Patients were stratified into 10-year age groups. The most common risk factor for new-onset epilepsy in our cohort was stroke, which was associated with new-onset epilepsy in 20% of patients aged 50-59 years and almost 50% of patients aged 70-79 years. The second most frequent risk factor was neoplasm in patients aged 50-69 years and dementia in patients older than 70 years. The other pre-existing conditions included: metabolic disorders, traumatic brain injury, and postencephalitic and inflammatory diseases. Chronic alcoholism was the most common metabolic risk factor associated with new-onset epilepsy and accounted for 84% of cases in this subgroup. Only metabolic disorders were significantly more frequent in males than in females (p<0.00001). We did not identify any epilepsy risk factor in 967 patients (41%). Systemic vascular risk factors were frequent in our cohort: 1,574 patients had hypertension (66%) and 449 patients had diabetes (19%), and 339 had both conditions (14%). We found that structural lesions were the most prevalent risk factor associated with new-onset epilepsy in middle-aged and elderly patients. Recognition of possibly modifiable factors associated with late-onset epilepsy could have a positive impact on reducing the risk of developing epilepsy.

Risk factors associated with new-onset epilepsy in young adults: Population-based study.

OBJECTIVE: Risk factors for childhood and late-onset epilepsy are thoroughly described in existing literature, while they are less defined and ambiguous for young adults. We aimed to evaluate the prevalence of various risk factors associated with new-onset epilepsy in adults aged 20-49 years. We included all incident cases in North Macedonia between 2015 and 2018. METHODS: Study participants were ascertained through the nationwide healthcare platform. We performed a retrospective analysis of their Electronic Health Records and identified associated conditions which are considered putative risk factors for epilepsy. RESULTS: Of 1691 included patients, 694 (41%) had at least one putative risk factor. The most common were neoplasms and cerebrovascular diseases (8% of cases, respectively), followed by intellectual disability (6%), alcohol/substance abuse (5%), and traumatic brain injury (4%). Infective and inflammatory diseases were infrequent in our cohort (1%). Other very rare risk factors included degenerative and metabolic disorders and malformations of cortical development (2%). Idiopathic (genetic) generalized epilepsies accounted for 7% of incident cases. Chronic alcoholism and illicit drugs abuse (dominantly opioids) were significantly more frequent in males than in females (p < 0.00001). CONCLUSION: Brain neoplasms and stroke were the most prevalent risk factors associated with new-onset epilepsy in young adults. Furthermore, adult-onset IGE were common in our cohort. The majority of patients did not have any of conventional risk factors and probably specific genetic causes might become increasingly recognized in adult-onset epilepsies in the future.

Incidence and prevalence of epilepsy in the Republic of North Macedonia: Data from nationwide integrated health care platform.

PURPOSE: This study aimed to evaluate the incidence and period prevalence of epilepsy in the Republic of North Macedonia, an upper-middle-income country with universal access to healthcare, based on a nationwide healthcare platform (NHP). METHODS: NHP contains reports from all inpatient and outpatient medical encounters and procedures, and all electronic medical records are linked together with a unique patient number. We performed the analysis of the data maintained at the Macedonian Ministry of Health, concerning the five years of the study (2014 through 2018). Population and demographic data for each year were obtained from the State Statistical Office. RESULTS: The period prevalence was 6.67 per 1,000 inhabitants. There were 6383 (46.2%) females and 7435 (53.8%) males; the gender difference was significant: 6.17 per 1,000 females and 7.16 per 1,000 males (p = 0.0000). Between 2015 and 2018 the median annual incidence of epilepsy was 68 new epilepsy patients per 100,000, with an upward trend over time. The age-specific incidence was high in childhood and adolescence, was constant (and low) in the adult years, and gradually increased in each successive age group after the age of 50 years. The greatest incidence was found in group 70-79 years of age. The incidence in childhood and adolescence tends to gradually decrease from 2015 to 2018, while it progressively increased in population over 50 years of age, which may explain a rise in overall incidence. We found a statistically significant higher incidence in males than in females, a ratio consistently being 1.2: 1. CONCLUSION: The data from the study provides accurate findings on the prevalence and incidence of epilepsy in the upper-middle-income Southeastern European country.

Patients' attitude toward AED withdrawal: A survey among individuals who had been seizure-free for over 2 years.

OBJECTIVE: The study aimed to evaluate the attitudes of seizure-free patients toward the antiepileptic drug (AED) withdrawal and to highlight the factors that affect their perspectives. METHODS: The study participants were recruited among the individuals attending the epilepsy outpatient clinic of a university hospital in Skopje between January 2018 and April 2019. Patients with epilepsy who had been seizure-free for at least 2 years on stable monotherapy were included. RESULTS: Among the 90 participants, 43 were female, and the mean age was 36.3 years. The mean duration of active epilepsy before remission was 7.9 years, and the length of the seizure-free period at the time of evaluation was 2-20 years. Forty-four percent of participants aimed to taper their antiseizure medications because of concerns about the potential long-term side effects and teratogenicity, the burden of taking medication daily, stigma, as well as the impression of no longer having a chronic disease after withdrawal. The majority of them preferred slow versus rapid withdrawal. On the other side, 55% of patients choose to continue AED treatment, mainly feeling well-adjusted to it and being concern about possible seizure recurrence after withdrawal and subsequent loss of driving license or even their jobs. Previous unsuccessful attempts to discontinue AED together with previously uncontrolled seizures were additional motives against withdrawal. The patients' views toward stopping or withholding AED were significantly associated with their gender and marital status (male patients as well as single ones favored medication withdrawal). Patients' age to some extent, though not significantly, affected their viewpoints (younger participants tended to question the further necessity of AEDs and were more concerned about the potential adverse consequences). No other demographic or epilepsy-related data considerably predisposed the decisions. CONCLUSIONS: More than half of the patients with epilepsy preferred to continue their AED after 2 years of seizure freedom. Male gender, being single, and somewhat younger age were associated preferences to withdraw AED.

Widespread frontal lobe cortical dysplasia or partial hemimegalencephaly: a continuum of the spectrum.

Focal cortical dysplasia (FCD) type II and hemimegalencephaly (HME) are currently considered as a continuum of pathology, the most important distinction being the extent or the size/volume of the lesion. While partial HME involving the posterior cortex has been well described, we present an unusual case with a dysplastic lesion of the whole frontal lobe. A 17-year-old boy had focal seizures from the age of nine years. Apart from diminished right-hand dexterity, his neurological and cognitive status were unremarkable. The course of his epilepsy exhibited a relapsing-remitting pattern, with prolonged periods of remission. Imaging showed dysplastic left frontal lobe (including paracentral lobule) thickened cortex with an abnormal gyration pattern resembling polymicrogyria, as well as dystrophic calcifications and hypodensity scattered throughout the white matter. This patient represents an intermediate case within the FCD type II/HME spectrum. Localization of the lesion in the frontal lobe as well as clinical characteristics (childhood onset, relapsing-remitting epilepsy, without hemiparesis and overt cognitive impairment) are more consistent with FCD type II, while a range of MRI features is shared between HME and FCD type II.

Levetiracetam-Induced Seizure Aggravation in Patients With Focal Cortical Dysplasia.

OBJECTIVES: The choice of antiepileptic drug is typically based on seizure type, and there is no evidence for superior effectiveness or potential deterioration of particular antiepileptic drug in specific etiologic subgroups. The aim of the study was to identify etiological factor(s) associated with increased risk of seizure aggravation with levetiracetam (LEV). METHODS: A retrospective analysis of 139 patients treated with LEV was performed. Seizure aggravation was defined as a 100% or greater increase in seizures frequency, which occurred within 1 month of drug introduction. RESULTS: Five patients who fulfilled the selection criteria were identified. Seizure aggravation occurred with low doses (500-1000 mg) of LEV. In addition to increased frequency and duration, 2 patients developed new seizure types. Withdrawal of LEV resulted in seizure return to background frequency in all patients. Four of 5 patients have distinctive magnetic resonance imaging finding of focal cortical dysplasia. No patients with paradoxical effect of LEV were detected in the idiopathic epilepsy group or other types of symptomatic epilepsies. CONCLUSIONS: Our results suggest that LEV may possibly induce seizure exacerbation in a subset of patients with focal cortical dysplasia-related epilepsy, although large studies are needed to establish the relation. Underlying causes of epilepsy could impact the treatment choice because electroclinical semiology might be the "final common pathway" of different epileptogenic mechanisms in diverse etiologies.

Phenotypic spectrum in families with mesial temporal lobe epilepsy probands.

PURPOSE: The traditional perception of mesial temporal lobe epilepsy (MTLE) as a predominantly acquired disorder is challenged due to emerging evidence of familial aggregation. In this study, we ascertained the extent of familial occurrence of epilepsy in MTLE patients, as well as phenotypic heterogeneity in affected relatives. METHODS: We identified and reevaluated patients with MTLE, treated at Epilepsy Department for a period of two years. All eligible putatively affected relatives were asked to participate in the study. In addition to comprehensive epilepsy interview, they underwent EEG and MRI studies. RESULTS: 52 patients with MTLE were included; nine of them (17%) had at least one family member with epilepsy. Subsequently, we analyzed nine probands with MTLE and a total of 15 relatives with seizures. Among affected relatives, spectrums of clinical manifestations were observed. Typical MTL seizures were described in five individuals, while other types of focal or generalized tonic-clonic seizures were reported in other ten relatives. A total of seven individuals had febrile seizures. Hippocampal sclerosis was found in three probands and none of the relatives. Two of affected family members had a traumatic brain injury in addition to febrile seizures, prior to the occurrence of their epilepsy. CONCLUSION: We demonstrate that familiar occurrence of epilepsy and subsequently putative genetic background, accounts for a substantial proportion MTLE patients. In addition, we foreground the remarkable intra- and interfamilial phenotypic heterogeneity than usually described, displaying the complexity of the genotype-phenotype correlations.

Seizure outcome following medical treatment of mesial temporal lobe epilepsy: Clinical phenotypes and prognostic factors.

OBJECTIVE: Surveys on mesial temporal lobe epilepsy (MTLE) repeatedly demonstrate that seizures are commonly resistant to antiepileptic drugs (AED), but patients usually came from third-level epilepsy centers, making the medically refractory population larger. The aim of our study is to evaluate patterns of seizure control and prognostic factors of general population of MTLE patients observed in clinical practice. METHODS: Sixty five MTLE patients were evaluated for demographic data, family history, febrile convulsions, detailed descriptions of auras and seizures, presence of secondarily generalized seizures, age at seizure onset, duration of epilepsy, epileptiform discharges in EEG, neuroradiological findings and AED schedules with therapeutic response. According to seizure frequency, patients were divided into three groups: (1) seizure-free (SF) patients at the time of evaluation, (2) patients considered as having infrequent seizures (IS) if they presented only auras or up to three dyscognitive (complex partial) seizures per year and (3) patients with higher rate were regarded as having frequent seizures i.e. being drug-resistant (DR). For each clinical parameter, the three groups were compared statistically. In addition, following the patterns of evolution over time, patients were categorized into two groups: continuous pattern, with no period of remission, and intermittent pattern, in which patients had at least one period of remission. RESULTS: Ten patients (15.4%) were seizure free, 19 (29.2%) had infrequent seizures, while 36 patients (55.4%) had frequent uncontrolled seizures. Ten (52.6%) IS patients and ten (27.7%) DR patients had a intermittent i.e. relapse-remitting pattern with at least one period of two years without seizures. Female patients dominated SF group and the gender difference with other groups reached statistical significance (p=0.02). Comparing the groups, DR group had longer seizure duration than IS group (12.6±10.9years vs. 22.8±10.6years, p=0.006). Number of tried AEDs (p<0.00006) was significantly lower in the seizure-free patients. Other variables are not related to course of the epilepsy. CONCLUSION: MTLE is a heterogeneous syndrome, 45% of patients in our series were having either rare auras or seizures or were seizure-free. The factors associated with drug resistance were longer duration of epilepsy, higher number of previously tried AED and male gender.