Summary
Objective
The yield of epileptiform abnormalities in serial electroencephalography (EEG) studies has not been addressed in a population‐based setting for subjects with incident epilepsy or a ...single unprovoked seizure, raising the possibility of methodologic limitations such as selection bias. Our aim was to address these limitations by assessing the yield and predictors of epileptiform abnormalities for the first and subsequent EEG recording in a study of incident epilepsy or single unprovoked seizure in Rochester, Minnesota.
Methods
We used the resources of the Rochester Epidemiology Project to identify all 619 residents of Rochester, Minnesota, born in 1920 or later with a diagnosis of incident epilepsy (n = 478) or single unprovoked seizure (n = 141) between 1960 and 1994, who had at least one EEG study. Information on all EEG studies and their results was obtained by comprehensive review of medical records.
Results
Among subjects with epilepsy, the cumulative yield of epileptiform abnormalities was 53% after the first EEG study and 72% after the third. Among subjects with a single unprovoked seizure, the cumulative yield was 39% after the first EEG study and 68% after the third. Young age at diagnosis and idiopathic etiology were risk factors for finding epileptiform abnormalities across all EEG recordings.
Significance
Although the cumulative yield of epileptiform abnormalities increases over successive EEG recordings, there is a decrease in the increment for each additional EEG study after the first EEG study. This is most evident in incident epilepsy and in younger subjects. Clinically it may be worthwhile to consider that the probability of finding an epileptiform abnormality after the third nonepileptiform EEG recording is low.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine ...accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow‐up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence‐based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence‐based guidance for clinicians incorporating patients' values and preferences.
Objective
Due to significant risks to the offspring after intrauterine exposure, the European Medicines Agency issued recommendations in 2014 and 2018 restricting the use of valproate (VPA) in women ...of childbearing age (WOCA). We aimed to evaluate their impact in the Emilia‐Romagna region (ERR) of Northern Italy.
Methods
Using administrative databases, we identified all the ERR residents who received antiseizure medication (ASM) prescriptions from 2010 to 2020. Time series of incidence rates by sex and age group were evaluated for all ASMs. Focusing on VPA, an interrupted time series analysis was applied to assess the impact of the restrictions in WOCA with epilepsy (WOCA‐E) and WOCA with psychiatric disorders (WOCA‐P). We then evaluated the chronological order of ASM prescriptions with regard to the position of VPA.
Results
Incidence rates of VPA prescriptions overall decreased over time. A significant decrease was observed only for females. The effect was stronger for WOCA, after both the first (incidence rate ratio IRR = .85, 95% confidence interval CI = .75–.96) and the second restriction (IRR = .67, 95% CI = .55–.82). The decrease was significant after the second restriction both for WOCA‐E (IRR = .43, 95% CI = .27–.68) and for WOCA‐P (IRR = .49, 95% CI = .35–.70), as well as VPA as a first prescription in both populations. VPA prescriptions as further choice did not show the same trend.
Significance
After the regulatory restrictions, an overall significant decline in the use of VPA in WOCA was observed in ERR. The second restriction has been effective in consolidating the prescription trend. However, VPA appears still to be a commonly used drug in WOCA when other ASMs have failed.
Summary
Objectives
We examined the associations of lifetime and current histories of psychiatric disorders and of suicidal thoughts and behaviors with childhood‐onset epilepsies in a community‐based ...cohort of young adults.
Methods
Cases were neurotypical (normal neurologic, cognitive, and imaging examinations and no evidence of a brain insult responsible for the epilepsy) young adults with childhood‐onset epilepsy followed since the onset of their epilepsy approximately 15 years earlier and recruited as part of a community‐based study. They were compared to two different control groups: siblings and external controls from the National Comorbidity Survey‐Replication (NCS‐R). The Diagnostic Interview Survey assessed lifetime and current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR) diagnoses of mood disorders and anxiety disorders. Suicidal thoughts and suicide attempt were assessed using the Diagnostic Interview Survey for Children‐IV and the Diagnostic Interview Survey (DIS‐IV).
Results
Two hundred fifty‐seven cases and 134 sibling controls participated in the DIS‐IV portion of the young adult assessment. Comparing cases both to their sibling controls and to the controls drawn from the NCS‐R, we did not find any evidence to suggest a higher prevalence of lifetime and current mood or anxiety disorders, suicidal thoughts, and suicide attempt in young adults with childhood‐onset epilepsies.
Significance
Our findings from a community‐based sample of neurotypical young adults do not suggest a substantial or lasting association between childhood epilepsy and psychiatric disorders and suicidal behavior.
Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS), most likely autoimmune in origin, usually beginning in early adulthood. The ...aetiology of the disease is not well understood; it is viewed currently as a multifactorial disease which results from complex interactions between genetic predisposition and environmental factors, of which a few are potentially modifiable. Improving our understanding of these factors can lead to new and more effective approaches to patient counselling and, possibly, prevention and management of the disease. The 2016 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) addressed the topic of environmental, modifiable risk factors for MS, gathering experts from around the world, to collate experimental and clinical research into environmental factors that have been associated with the disease onset and, in a few cases, disease activity and progression. A number of factors, including infections, vitamin D deficiency, diet and lifestyle factors, stress and comorbidities, were discussed. The meeting provided a forum to analyse available evidence, to identify inconsistencies and gaps in current knowledge and to suggest avenues for future research.
Depression is considered one of the prodromal symptoms of Parkinson's disease (PD) along with sleep disorders, hyposmia and constipation. Prodromal symptoms refer to the stage wherein early motor ...symptoms and signs allowing a diagnosis of PD are not yet present. The objective of this study was to investigate the association between the use of antidepressants, as indirect measure of depression, and subsequent PD onset, clinically diagnosed, in the Local Health Trust of Bologna, Italy.
Historical cohort study with use of antidepressants as exposure and PD onset as outcome. The cohort considered consisted of inhabitants of Bologna aged ≥35 years in 2005; those who had used antidepressants in the previous 3 years were excluded. Subjects were followed up from 2006 and until PD onset, migration out of Bologna, death or end of the study period (2017), whichever came first. “The ParkLink Bologna” system was used to detect disease onset. “ParkLink Bologna” is a research study including patients with a clinical diagnosis of PD residing in Bologna. Residents that used antidepressants for at least 180 consecutive days within 1 year were considered exposed. Hazard ratios (HR) and 95% confidence interval (CI) were estimated with Cox proportional hazards models, using exposure as time-dependent variable and adjusting for potential confounders: age, gender, use of medical care and comorbidities.
From 2006 to 2017 199,093 person-years were exposed and 4,286,470 not exposed. Fifty-one subjects with PD were identified in the exposed group and 556 subjects in the non-exposed showing an association of adjusted HR = 1.7 (CI 1.3–2.3). The association was stronger for males (HR 2.2, CI 1.5–3.2) compared to females (HR 1.2, CI 0.8–1.9), for subjects ≤65 years of age (HR 2.4, CI 1.6–3.6) vs. >65 years (HR 1.3, CI 0.8–1.9) and for those with less comorbidities. Age and gender were confounders in the associations between antidepressant use and PD onset.
The use of antidepressants as indirect measure of depression is associated with the subsequent development of PD. Our findings confirm that depression may precede the onset of motor symptoms in PD. The association is stronger for younger subjects, who are males and with fewer comorbidities.
•The use of antidepressants is associated with the development of Parkinson's disease.•The association is stronger for younger subjects, who are males and with fewer comorbidities.•Depression may precede the onset of motor symptoms in Parkinson's disease.
No previous population-based study has addressed the contribution of activation procedures to the yield of epileptiform abnormalities on serial EEGs. We assessed yield of activation-related ...epileptiform abnormalities and predictors of finding an activation-related abnormality with multiple EEGs in a population-based study of newly diagnosed epilepsy.
We used the resources of the Rochester Epidemiology Project to identify 449 residents of Rochester, Minnesota with a diagnosis of newly diagnosed epilepsy at age 1 year or older, between 1960 and 1994, who had at least one EEG. Information on all activation procedures (i.e., sleep, hyperventilation, and photic activation) and seizure/epilepsy characteristics was obtained by comprehensive review of medical records.
At the first EEG, the yield of epileptiform abnormalities was greatest for individuals 1 to 19 years of age at diagnosis, for each activation procedure. The yield in patients aged 1 to 19 versus ≥20 years was 21.6% versus 10.3% for sleep, 6.5% versus 3.3% for photic stimulation, and 10.3% versus 5% for hyperventilation. Among young people (aged 1-19 years), sleep was associated with an increased likelihood of finding an activation-related abnormality on any EEG. The likelihood of finding an activation-related abnormality on any EEG was decreased for postnatal symptomatic and for unknown etiology.
Among activation procedures, sleep showed the highest yield of epileptiform abnormalities. There was a low yield for photic stimulation and hyperventilation. Within each activation procedure, younger age at diagnosis had the greatest yield. Sleep is the most effective activation procedure, especially in younger patients, and should be performed when possible.
Background and purpose
The patterns of long‐term risk of SARS‐CoV‐2 infection, hospitalization for COVID‐19, and related death are uncertain in people with Parkinson disease (PD) or parkinsonism ...(PS). The aim of the study was to quantify these risks compared to a control population cohort, during the period March 2020–May 2021, in Bologna, Northern Italy.
Methods
ParkLink Bologna cohort (759 PD, 192 PS) and controls (9226) anonymously matched (ratio = 1:10) for sex, age, district, and comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March–May 2020 and October 2020–May 2021).
Results
Adjusted hazard ratio of SARS‐CoV‐2 infection was 1.3 (95% confidence interval CI = 1.04–1.7) in PD and 1.9 (95% CI = 1.3–2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID‐19 was 1.1 (95% CI = 0.8–1.7) in PD and 1.8 (95% CI = 0.97–3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30‐day mortality risk after hospitalization was higher (p = 0.048) in PS (58%) than in PD (19%) and controls (26%).
Conclusions
Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS‐CoV‐2 infection throughout the first 15 months of the pandemic. COVID‐19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.
Compared with controls, people with Parkinson disease and parkinsonism showed a higher risk of SARS‐CoV‐2 infection throughout the first 15 months of the pandemic. COVID‐19 hospitalization risk was increased only in people with parkinsonism and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.
The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated.
The aim of this study was to map and assess the evidence on MS occurrence after drug ...exposure, in order to identify possible signals of causal association.
A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies.
After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results.
A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes.
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