The impact of gender, puberty, and pregnancy in patients with POLG disease

Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor.Peer reviewe

Seizure Precipitants

In the comprehensive management of epilepsy, both preventive pharmacological treatment and awareness of possible seizure precipitating factors are important. The true cause of seizure generation is often hard to disentangle, as triggers often are obscure and occur in concert. This dissertation examines possible seizure precipitants in patients admitted to Department of Neurology and Clinical Neurophysiology, St Olav's Hospital, Trondheim University Hospital, July 2006-February 2010, soon after a seizure. The results from the study are presented in three papers. In paper I, preictal caffeine intake was compared to consumption in a seizure free period as animal models and case reports have suggested caffeine to contribute to seizure development. Dietary caffeine intake 24h prior to the seizure was not different compared to habitual intake or compared to intake in a seizure free period. Therefore, caffeine does not seem to be a common seizure precipitant in a clinical setting, and patients should be accordingly advised. Non-adherence persists as a major obstacle to optimal epilepsy treatment, but its magnitude has been difficult to determine. In paper II, patients with epilepsy acutely admitted for seizures were included, and concentration/dose ratios of AEDs at admission were compared with the patiant's own steady-state, drug-fasting control values. Non-adherence was seen in 39%, and was more common in younger patients. Many patients seem to be unaware of missed drug intake. AED serum concentrations should be part of the emergency care. Efforts to improve treatment adherence is an important part of comprehensive epilepsy management. Sleep-time in the 24h prior to the seizure was assessed in paper III, and was found to be lower when compared to follow-up. Anxiety and depression did not correlate with differences in sleep time, but the interaction between alcohol and sleep was high. However, sleep loss stood out as an independent trigger. This study demonstrates that epileptic seizures usually seem to be precipitated by a combination of clinical factors

Epilepsy patients with and without perceived benefit from vagus nerve stimulation: A long-term observational single center study

Purpose: Vagus nerve stimulaton (VNS) has been used for adjunctive treatment of drug-resistant epilepsy for more than 25 years. The true efficacy has been debated, as blinded randomized controlled trials are unavailable. The aim of this study was to evaluate the patient-reported perceived benefit of VNS and to compare clinical characteristics of patients with and without benefit. Methods: Observational study of all 43 adult patients receiving VNS for > 2 years at one single center. Mean duration of treatment was 9 years. At inclusion, a semi-structured interview on VNS effectiveness was performed. In patients without benefit, the VNS was turned off. The outcome was evaluated after an observation period of one year. Results: 21 patients (49%) reported no clear benefit and stopped VNS. Only one of them resumed treatment within one year. Patients without benefit had received more new antiepileptic drugs (AEDs) during VNS treatment than those reporting benefit (p = 0.05). Other differences between the two groups were not found. Ten patients (23%) had been seizure free > 1 year at inclusion (5 in the benefit and 5 in the non-benefit group). Seizure control was attributed to the response of another new treatment in the majority of these patients. Conclusion: Half of the patients had not perceived clear benefit from VNS, and all but one terminated VNS without worsening of seizures within one year. The true outcome of long-term VNS is difficult to assess in realworld practice. The effect may be overestimated due to confounding factors, particularly the common introduction of novel AEDs and the natural course of the disorder. Patients without perceived benefit from longterm VNS should not routinely remain on treatment and be subject to undue generator re-implantations

The impact of gender, puberty, and pregnancy in patients with POLG disease

Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor

The impact of gender, puberty, and pregnancy in patients with POLG disease

Objective To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor

The impact of gender, puberty, and pregnancy in patients with POLG disease

Abstract Objective: To study the impact of gender, puberty, and pregnancy on the expression of POLG disease, one of the most common mitochondrial diseases known. Methods: Clinical, laboratory, and genetic data were collected retrospectively from 155 patients with genetically confirmed POLG disease recruited from seven European countries. We used the available data to study the impact of gender, puberty, and pregnancy on disease onset and deterioration. Results: We found that disease onset early in life was common in both sexes but there was also a second peak in females around the time of puberty. Further, pregnancy had a negative impact with 10 of 14 women (71%) experiencing disease onset or deterioration during pregnancy. Interpretation: Gender clearly influences the expression of POLG disease. While onset very early in life was common in both males and females, puberty in females appeared associated both with disease onset and increased disease activity. Further, both disease onset and deterioration, including seizure aggravation and status epilepticus, appeared to be associated with pregnancy. Thus, whereas disease activity appears maximal early in life with no subsequent peaks in males, both menarche and pregnancy appear associated with disease onset or worsening in females. This suggests that hormonal changes may be a modulating factor

Care in Europe after presenting to the emergency department with a seizure; position paper and insights from the European Audit of Seizure Management in Hospitals

info:eu-repo/semantics/publishe