Initial Diagnosis Of Epilepsy Research Articles

Association between anti-seizure medication and the risk of lower urinary tract infection in patients with epilepsy

PurposeThe aim of this retrospective study was to analyze the incidence of lower urinary tract infections (LUTI) and antibiotic prescriptions within 12 months after initial prescription of anti-seizure medication (ASM) between January and December 2020 (index date) and to investigate the association between a broad spectrum of ASMs and the risk of LUTI in patients with epilepsy. MethodsThis retrospective cohort study included a total of 9186 adult patients (≥18 years) with an initial diagnosis of epilepsy and a prescription of an ASM treated in 1284 general practices in Germany between January 2010 and December 2020 (index date). Six frequently prescribed ASMs with at least 1000 available patients were analyzed. Patients treated with one of six ASMs were matched to each other by propensity scores based on sex, age, and secondary diagnoses. Cox regression models were used to analyze the association between the use of ASM and LUTI risk. ResultsThe cumulative LUTI incidence 12 months after the start of therapy was highest in patients treated with pregabalin (16.7%), followed by valproate (11.6%) and gabapentin (10.2%). A similar trend was observed for LUTI with antibiotic prescription (9.2% pregabalin, 6.8% valproate, 6.8% gabapentin). Conditional regression analyses revealed that pregabalin therapy was significantly positively associated with LUTI (HR: 1.76; 95% CI 1.29–2.39) and LUTI-based antibiotic prescription (HR: 2.16; 95% CI 1.43–3.27). Carbamazepine was associated with a significantly lower incidence of LUTI in women (HR: 0.47; 95% CI: 0.30–0.75), but not in men. No significant associations were observed for other ASMs. ConclusionThe present study identifies a significant positive association between ASM and LUTI incidence and antibiotic prescriptions in patients with epilepsy treated with pregabalin, whereas a protective effect was found for carbamazepine in women only. No significant associations were observed for the four remaining ASMs.

Severity of Epilepsy and Response to Antiseizure Medications in Individuals With Multiple Sclerosis: Analysis of a Real-World Dataset.

Epilepsy is an important comorbidity that affects outcomes for people with multiple sclerosis (MS). However, it is unclear whether seizure severity among individuals with coexistence of MS and epilepsy (MS + E) is higher than in those with other focal epilepsies. Our goal was to compare the overall severity of epilepsy in individuals with MS + E vs those with focal epilepsy without MS (E - MS), as defined by seizure-related health care utilization, frequency and duration of status epilepticus, and frequency of antiseizure medication (ASM) regimen changes. In this hypothesis-generating study, we analyzed a US commercial nationwide deidentified claims data set with >86 million individuals between January 1, 2008, and August 31, 2019. Using validated algorithms, we identified adults with E - MS and those with MS + E. We compared the number and length of seizure-related hospital admissions, the number of claims and unique days with claims for status epilepticus, and the rates of ASM regimen changes between the MS + E and E - MS groups. During the study period, 66,708 individuals with E - MS and 537 with MS + E had ≥2 years of coverage after their initial diagnosis of epilepsy. There was no difference between the MS + E and E - MS groups in the percentage of individuals admitted for seizures and/or status epilepticus. However, MS + E with seizure-related admissions had more admissions and longer hospital stays than those with E - MS. MS + E who experienced status epilepticus had more unique days with status epilepticus claims compared with E - MS. MS + E were more likely to have ASM regimen changes in 2 years after the initial diagnosis of epilepsy and had more ASM changes during 2 years compared with E - MS. Among individuals with MS + E, there were no differences in our measures of seizure severity for those treated with sodium channel blockers/modulators vs other ASM classes. This study supports the notion that individuals with MS + E can have more severe epilepsy than those with E - MS. Seizure severity among individuals with MS + E treated with sodium channel blockers/modulators vs other ASM classes shows no significant differences. This study provides Class III evidence that individuals with MS + E can have more severe epilepsy than those with E - MS.

POST-COVID 19 ENCEPHALITIS IN PATIENT WITH DE NOVO MUTATION IN THE SCN1A GENE, A CASE REPORT

Seizures are defined as a transient occurrence of signs and symptoms due to an abnormal, excessive or synchronous neuronal activity in the brain, characterized by abrupt and involuntary skeletal muscle activity. The presence of cephalgic syndrome, infectious-toxic encephalopathy, hypo- and anosmia and ageusia are pathognomonic conditions in COVID-19 infected patients. Post-Covid 19 encephalitis develops to encephalopathy in children with epilepsy. Based on the clinical appearance and the parameters that showed past Covid-19 infection, a diagnosis of post-COVID19 encephalopathy was confirmed. To confirm the diagnosis, clinical examinations, MRI of the brain, electroencephalography, lumbar puncture, laboratory tests (including CBC, CRP, basic metabolic panel, liver panel, hemostasis with D-dimer) are necessary. Based on the brain changes registered on the EEG record, the physical findings and the presence of SARS CoV 2 IgG antibodies, it was concluded that a child with an initial diagnosis of epilepsy, developed encephalopathy after asymptomatic COVID 19 infection. Keywords: Post-COVID19 complications, encephalitis, Dravet syndrome, epilepsy, de novo mutation, children

Sensitivity of long-term EEG monitoring as a second diagnostic step in the initial diagnosis of epilepsy.

In this retrospective study, we aimed to evaluate the sensitivity and negative predictive value of long-term EEG (L-EEG) in patients being assessed for epilepsy, who had already undergone non-specific standard EEG(s) (S-EEG). Secondary endpoints of this study were: (1) the correlation of non-specific changes on EEG with epileptiform patterns on L-EEG; and (2) the correlation of clinical parameters such as subjective frequency of seizures or epileptogenic lesions on cerebral imaging with epileptiform changes on L-EEG. We retrospectively analysed clinical and electrophysiological data of 75 patients, assessed for epilepsy at the University Hospital Zurich, who had undergone an L-EEG for at least 48 hours, between 2010 and 2015. All patients had already undergone S-EEG(s) before L-EEG, which showed no epileptic changes. Furthermore, the association with clinical parameters, such as frequency of presumptive seizures, abnormalities on standard-EEG, AED intake and cerebral imaging with the final diagnosis, was analysed. Out of 75 patients, 14 (19%) patients were finally diagnosed with epilepsy. In eight of these patients, L-EEGs showed typical ictal/interictal patterns, with a sensitivity of 57% and negative predictive value of 91%. Neither the subjective frequency of seizures nor potentially epileptogenic lesions on cerebral imaging were associated with a positive epilepsy diagnosis. In this preselected cohort of patients, who had already undergone a non-diagnostic S-EEG, the sensitivity of L-EEG remained considerable. Nonetheless, our study also revealed a significant false-negative rate. Based on the high negative predictive value in this study, L-EEG appears to be most useful at excluding epilepsy. Nevertheless, thorough evaluation of seizure history and clinical findings remain crucial for a reliable diagnosis.

Predicting the risk of stroke in patients with late-onset epilepsy: A machine learning approach

BackgroundThe goal of this cohort study was to estimate the predictors for ischemic stroke in patients with epilepsy in a large database containing data from general practitioners in Germany using machine learning methods. MethodsThis retrospective cohort study included 11,466 patients aged ≥ 60 years with an initial diagnosis of epilepsy in 1182 general practices in Germany between January 2010 and December 2018 from the IQVIA Disease Analyzer database. The Sub-Population Optimization and Modeling Solutions (SOMS) tool was used to identify subgroups at a higher risk of stroke than the overall population with epilepsy based on 37 different variables. ResultsA total of seven variables were considered important. Four co-diagnoses (diabetes, hypertension, heart failure, and alcohol dependence) were by far the strongest predictors with a combined predictive ability of more than 90%, whereby diabetes (41.4%) was the strongest predictor, followed by hypertension (35.0%) and heart failure (11.8%). The predictive importance of male gender was only 1.5%, and age was not recognized as an important predictor. Finally, the prescribed AEDs levetiracetam, with a predictive importance of 5.0%, and valproate, with 2.7%, were found to be weak predictors. ConclusionThe stroke risk in patients with epilepsy was relatively high and could be predicted based on comorbidities such as diabetes mellitus, hypertension, heart failure, and alcohol dependence. Knowing and addressing these factors may help reduce the risk of stroke in patients with epilepsy.

Occurrence of status epilepticus in persons with epilepsy is determined by sex, epilepsy classification, and etiology: a single center cohort study

BackgroundStatus epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality.MethodsThis survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study.Results87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time.ConclusionSE is frequent among persons with epilepsy and there remain unmet needs regarding patient education.

Predictors and course of medically intractable epilepsy in young children presenting before 36 months of age: A retrospective, population‐based study

To determine the prevalence and identify predictors of medical intractability in children presenting with epilepsy before 36 months of age, and to assess the effect of medical intractability on long-term mortality and intellectual function. Children with newly diagnosed epilepsy before 36 months between 1980 and 2009 while resident in Olmsted County, MN, were identified. Medical records were reviewed to collect epilepsy-specific variables and long-term outcome data. Medically intractable epilepsy was defined as either (1) seizure frequency greater than every 6 months at final follow-up and failure of two or more antiepileptic drugs for lack of efficacy, or (2) having undergone epilepsy surgery after failure to respond to two or more antiepileptic drugs. One hundred twenty-seven children with new-onset epilepsy were identified and followed for a median of 78 months. Medically intractable seizures occurred in 35%, and significant predictors on multivariate analysis were age ≤12 months at diagnosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 2.00, 22.84, p = 0.002), developmental delay at initial diagnosis of epilepsy (OR 20.03, 95% CI 3.49, 114.83, p = 0.0008), neuroimaging abnormality (OR 6.48, 95% CI 1.96, 21.40, p = 0.002), and focal slowing on initial EEG (OR 5.33, 95% CI 1.14, 24.88, p = 0.03). Medical intractability occurred early in the course in most children, being seen in 61% by 1 year, and 93% by 5 years after initial diagnosis. Mortality was higher (20% vs. 0%, p < 0.001) and intellectual outcome poorer (p < 0.001) if epilepsy was medically intractable. One third of children presenting with epilepsy before 36 months will be medically intractable, and significant predictors are identified. Medically intractable epilepsy is associated with increased mortality risk and significant intellectual disability.

Differences in Child versus Parent Reports of the Child's Health-Related Quality of Life in Children with Epilepsy and Healthy Siblings

Objectives Self versus proxy perspectives may produce different results that are important for clinical decision-making and for assessing outcomes in research studies. We examined differences in child versus parent report of the child's health-related quality of life (HRQOL) in a large prospective, community-based study of newly diagnosed childhood epilepsy that included children with epilepsy (case) and sibling controls. Methods HRQOL was assessed 8 to 9 years after initial diagnosis of epilepsy in a subset of 143 case-control matched pairs using the Child Health Questionnaire (CHQ), a generic HRQOL measure with child (CHQ-CF87), and parent (CHQ-PF50) versions. Results There were no significant differences between self-reported case and sibling control HRQOL scores on 9 of 11 scales or 2 global items. Nevertheless, parent ratings were significantly better (higher HRQOL) for sibling controls compared with epilepsy cases on 10 of 12 scales, global behavior and general health items, and the physical and psychosocial summary scores ( P ≤ 0.05). Parent–child agreement was low for cases and controls (kappa 0.27–0.33) for three single-item questions with the same wording on parent and child versions. Parent ratings of the case's HRQOL were often significantly associated with 5-year remission status and current antiepileptic drug use, but the case's self-reported HRQOL scores were not. In contrast, current pharmacoresistance was often associated with the child and parent ratings of the child's HRQOL. Conclusion Children with epilepsy report HRQOL that is comparable to that of sibling controls, while parents rate children with epilepsy as having lower HRQOL than sibling controls. Measuring outcomes in studies of this population should incorporate both perspectives.

Pearls: Epilepsy

Technology plays a greater and expanding role in the evaluation, diagnosis, and treatment of epilepsy and seizure disorders with the use of electroencephalography and video electroencephalography (EEG) monitoring. However, the history and clinical examination of the patient will always be the most important parts of the evaluation of patients with seizures, epilepsy, and other similar disorders. Clinical pearls for the differential diagnosis of seizures, psychogenic nonepileptic seizures, initial diagnosis of epilepsy, epilepsy evaluation, and use of anticonvulsants are provided.

Remission of epilepsy after two drug failures in children: A prospective study

Determine the probability of a more than 1-year remission after failure of a second drug in children prospectively followed from initial diagnosis of epilepsy and then from time of second drug failure. Identify prognostic factors for remission after second drug failure. Of 613 children, 128 did not respond favorably to 2 drugs, had a trial of at least a third drug (median, 3), and were followed for more than 1 year (median, 10.1 years) since second drug failure. Product limit and proportional hazards techniques were used to analyze predictors of any 1-year remission (Rem1) and 1- and 3-year remission at last contact (Rem1/3-LC). Seventy-three patients (57%) had a remission. Repeated remissions and relapses were common. Only 48 (37.5%) achieved Rem1-LC and 28 (23%) Rem3-LC. Idiopathic epilepsy (Rem1: rate ratio [RR], 3.64, p < 0.0001; Rem1-LC: RR, 2.57, p = 0.008) and seizure frequency (Rem1: RR, 0.76, p = 0.003; Rem1-LC: RR, 0.82, p = 0.04 per increase in category) were the most robust predictors. Symptomatic cause was the only correlate of Rem3-LC. Remission before second drug failure did not predict remission after second drug failure. Remission after second drug failure is common but often temporary. Children who have not responded to two appropriate drugs should be carefully evaluated to maximize therapy and possibly considered for more aggressive treatments.

Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1 deficiency syndrome in Japan

We report the first two Japanese children diagnosed with glucose transporter type 1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial diagnosis of epilepsy and were reinvestigated for previously unexplainable hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1 (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum glucose levels determined simultaneously showed a CSF/serum glucose ratio of below 0.4 in both patients. In mildly affected Patient #1, the postprandial waking EEG showed improvement in the background activity, as compared to that recorded after overnight fasting, while no significant changes were observed in severely affected Patient #2. In both patients, the functional GLUT1 defect was confirmed by 3- O-methyl- d-glucose uptake into erythrocytes. Molecular analyses identified heterozygous novel mutations in both patients, within exons 6 and 2 of the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but started in Patient #2 with significant clinical benefit. Fasting CSF analysis and pre-/postprandial EEG changes in children with epileptic seizures and unexplainable neurological deterioration help in diagnosing this potentially treatable disorder.

Risk of Status Epilepticus in Epilepsy

The occurrence of status epilepticus (SE) after the initial diagnosis of epilepsy was determined in a prospective community-based cohort study of 613 children at Montefiore Medical Center, Bronx, NY; Yale Medical School, New Haven, CT; and BIOS/NIU, DeKalb, IL.

Status epilepticus after the initial diagnosis of epilepsy in children.

To determine the risk and predictors of status epilepticus in children after they have been diagnosed with epilepsy. In a prospective community-based cohort study of 613 children, the occurrence of status epilepticus after the initial diagnosis of epilepsy was ascertained. Parents were called every 3 months, and interval medical records were reviewed every 6 months. Predictors of primary interest included a history of status before the diagnosis of epilepsy, age at onset, underlying etiology, and epilepsy syndrome. Data were analyzed with chi2 tests, Kaplan-Meier analyses, and Cox proportional hazards models. Of 613 children followed a median of 8.0 years, 58 (9.5%) had > or =1 episode of status epilepticus during follow-up evaluation. The first episode occurred a median of 2.5 years after initial diagnosis (range, <1 month to 8.8 years). A history of previous status epilepticus was strongly associated with subsequent status epilepticus (18/56 [32.1%] vs 40/557 [7.2%]; p < 0.0001). Younger age at onset and symptomatic etiology contributed independently to the risk of status epilepticus. Mortality was higher in children with status epilepticus before diagnosis, largely secondary to underlying cause. Status epilepticus occurs in approximately 10% of children after initial diagnosis of epilepsy. Status epilepticus before initial diagnosis, young age at onset, and symptomatic etiology independently influence the risk of status epilepticus. In those without status epilepticus before diagnosis, the risk is modest and is realized over a prolonged period. For children at highest risk, maintaining abortive therapy in the home may be a reasonable precaution.

The accuracy of the diagnosis of paroxysmal events in children.

To assess the accuracy of the diagnosis of epileptic seizures in children. The Dutch Study of Epilepsy in Childhood is a prospective hospital-based study of 881 children referred because of possible seizures. The diagnosis was based on predefined descriptive criteria, as applied by a panel of three pediatric neurologists. Children with a definite other diagnosis were excluded. All children with unclear events were followed up for 1 year and children with seizures were followed up for 2 years to assess the accuracy of the diagnosis. In 170 of 224 children seen after a single event, the incident was classified initially as epileptic, in 54 as unclear. In none of the 170 children did the diagnosis prove to be wrong. In four of the 54 children, recurrent episodes enabled a definite diagnosis of epilepsy. In 412 of the 536 children seen with multiple events, an initial diagnosis of epilepsy was made. After follow-up, this initial diagnosis was probably incorrect in 19. In contrast, seven of 124 children with multiple unclear episodes at intake later received the diagnosis epilepsy. A false-positive diagnosis of epilepsy was made in 4.6%, whereas a definite diagnosis of epilepsy or seizure was delayed in 5.6% of children with multiple unclear events and in 7.4% of children with one unclear event.

Neuroimaging in children with newly diagnosed epilepsy: A community-based study.

Neuroimaging is generally considered a part of the evaluation of seizures and epilepsy. There is limited information about its current use in the initial evaluation of pediatric epilepsy and about its yield during the initial diagnosis of epilepsy. We describe the patterns in the use and yield of diagnostic imaging in children with newly diagnosed epilepsy in a community-based study. Children were recruited when first diagnosed with epilepsy by participating physicians in Connecticut (1993-1997). Definitions for etiology and underlying epilepsy syndromes are as published by the International League Against Epilepsy. Of 613 children, 488 (79.6%) had imaging: 388 (63. 3%) magnetic resonance imaging, 197 (32.1%) computed tomography scans, and 97 (15.8%) both. Half of children with idiopathic generalized epilepsy had imaging studies compared with 70% to 100% of children with other forms of epilepsy, depending on the specific type. Etiologically relevant abnormalities were found in 62 (12.7% of those imaged). Fourteen of these children had otherwise completely normal presentations and histories. Their abnormalities included tuberous sclerosis (N = 4), tumors (N = 2), an arteriovenous malformation later diagnosed as a tumor, a cavernous angioma, cerebral malformations (N = 3), and other abnormalities (N = 3). Thirteen of the 14 had partial seizures and 12 had focal electroencephalographic (EEG) findings. Only 1 had neither. In children with newly diagnosed epilepsy, neuroimaging reveals a small but significant number of serious abnormalities not previously suspected. Most of these children have partial seizures or focal EEG abnormalities. Neuroimaging should be considered during the evaluation of children with newly diagnosed epilepsy, especially for those with neurologic deficits or partial seizures or focal EEG abnormalities that are not part of an idiopathic localization-related epilepsy syndrome.

Heart disease mortality and morbidity in patients with epilepsy.

All-cause and heart disease mortality and ischemic heart disease incidence among patients with an initial diagnosis of epilepsy while residents of Rochester, MN, from 1935 through 1979 were determined. Death rates from heart disease were slightly elevated for persons with epilepsy. The increased death rate from heart disease was confined to persons less than 65 years of age. The incidence of ischemic heart disease and of sudden cardiac death as the initial manifestation of ischemic heart disease was significantly increased in persons with epilepsy, but the increase was primarily limited to those with symptomatic epilepsy attributed to cerebrovascular disease. The occurrence of ischemic heart disease and sudden cardiac death was not related to anticonvulsant medication status.

Remission of seizures and relapse in patients with epilepsy.

In a longitudinal study of patients with epilepsy in Rochester, Minnesota, we found that the probability of being in remission (at least 5 consecutive years seizure-free, and continuing) at 20 years after diagnosis was 70%. The rates for remission we encountered were generally higher than those previously reported. We believe that the better prognosis in our series results from inclusion of all incidence cases in a defined population, beginning at the initial diagnosis of epilepsy. Prognosis for remission of epilepsy is poor in patients with associated neurologic dysfunction identified from birth. Patients with idiopathic seizures and survivors of postnatally acquired epilepsy have better prospects for eventual remission. The probability of remission is highest in patients with generalized-onset seizures diagnosed before 10 years of age. Prognosis is less favorable for those with partial complex seizures and adult-onset epilepsy.

Cardiogenic syncope and epilepsy.

SYNCOPE has been defined as 'a failure of the heart's action resulting in loss of consciousness or sometimes in death' (O.E.D.). Since Gower's discussion of vaso-vagal attacks (1907) many forms of reflex syncope have been described and studied, among them cough syncope (Baker, 1949), carotid sinus syncope (Weiss, 1935) and micturition syncope (Coggins, Lillington & Gray, 1964). The sudden and transient interruption of consciousness seen in a syncopal attack is not uncommonly associated with organic heart disease-cardiogenic syncope (Brigden, 1966)-occurring as it may with sudden changes of rhythm, heart block, paroxysmal tachycardia, myocardial infarction, aortic or pulmonary stenosis, ball-valve obstruction of the mitral valve and lesions associated with severe pulmonary hypertension. The physiological mechanisms involved are reviewed in detail by Wayne (1961). That syncope, if prolonged more than 15-20 sec, may be followed by epileptiform convulsions and incontinence is well attested (Spens, 1793; Campbell, Symonds & Williams, 1950) occurring particularly often in the dentist's chair (Symonds, 1950). The differentiation between epilepsy and syncope in certain cases therefore may be difficult, for although implicit in a diagnosis of epilepsy is a consideration of a primary disorder of brain (Williams, 1958), variants of focal epilepsy, possibly with a hypothalamic excitatory point, may produce apparent syncopal attacks with reflex cardiovascular changes (Kinnier Wilson, 1928; Kershman, 1949). The establishment of a not immediately apparent cardiac cause for syncope in four patients who were referred to a neurological clinic with an initial diagnosis of epilepsy was felt to warrant drawing further attention to this diagnostic problem, particularly as three were seen within the space of I month.