Summary
In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with ...the aim of developing clear evidence‐based and practice‐based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)–related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders.
There is a paucity of controlled treatment trials for the treatment of conversion disorder, seizures type, also known as psychogenic nonepileptic seizures (PNES). Psychogenic nonepileptic seizures, ...the most common conversion disorder, are as disabling as epilepsy and are not adequately addressed or treated by mental health clinicians.
To evaluate different PNES treatments compared with standard medical care (treatment as usual).
Pilot randomized clinical trial at 3 academic medical centers with mental health clinicians trained to administer psychotherapy or psychopharmacology to outpatients with PNES. Thirty-eight participants were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and were followed up for 16 weeks between September 2008 and February 2012; 34 were included in the analysis.
Medication (flexible-dose sertraline hydrochloride) only, cognitive behavioral therapy informed psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual.
Seizure frequency was the primary outcome; psychosocial and functioning measures, including psychiatric symptoms, social interactions, quality of life, and global functioning, were secondary outcomes. Data were collected prospectively, weekly, and with baseline, week 2, midpoint (week 8), and exit (week 16) batteries. Within-group analyses for each arm were performed on primary (seizure frequency) and secondary outcomes from treatment-blinded raters using an intention-to-treat analysis.
The psychotherapy (CBT-ip) arm showed a 51.4% seizure reduction (P = .01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning (P < .001). The combined arm (CBT-ip with sertraline) showed 59.3% seizure reduction (P = .008) and significant improvements in some secondary measures, including global functioning (P = .007). The sertraline-only arm did not show a reduction in seizures (P = .08). The treatment as usual group showed no significant seizure reduction or improvement in secondary outcome measures (P = .19).
This pilot randomized clinical trial for PNES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline. There were no improvements in the sertraline-only or treatment-as-usual arms. This study supports the use of manualized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination.
clinicaltrials.gov Identifier: NCT00835627.
Psychogenic movement disorder (PMD) and psychogenic nonepileptic seizures (PNES) are two subtypes of conversion disorder (CD). In this case-control study, we asked whether these subtypes varied as a ...function of personality and history of childhood abuse.
Fifty-nine patients with PMD from the Human Motor Control Section Clinic at the National Institutes of Health, 43 patients with PNES from the Rhode Island Hospital Neuropsychiatry and Behavioral Neurology Division, and 26 healthy volunteers (HC) received a battery of neurological, psychiatric and psychological assessments, including the NEO Personality Inventory Revised (NEO PI-R), the Childhood Trauma Questionnaire (CTQ), and the Traumatic Life Events Questionnaire (TLEQ).
One-way ANOVA between the three groups indicated significant differences in overall domains of Neuroticism (p=0.001) and Conscientiousness (p=0.009): Patients with PNES reported significantly greater levels of Neuroticism (p=0.002) and lower levels of Conscientiousness (p=0.023) than patients with PMD. Levels of Neuroticism remained significantly higher in both PMD and PNES than HC following correction for multiple comparisons. Patients with PNES reported greater levels of depressive and anxiety symptoms, overall psychopathology, greater history of sexual abuse, greater levels of alexithymia, higher levels of dissociative symptoms, and an earlier age at which they experienced their most distressing traumatic event than patients with PMD.
These findings suggest that personality traits, type of abuse and age of onset of trauma varies as a function of CD subtype. Patients with PNES rated greater Neuroticism and lower Conscientiousness than patients with PMD. These differing psychological profiles may inform differing treatment approaches such as psychological therapies for PNES and physiotherapy (with/without psychotherapy) for PMD.
•Neuroticism and Conscientiousness appear to vary by conversion disorder subtype.•PNES patients reported an earlier age of onset of trauma than PMD patients.•PNES patients reported a greater history of sexual abuse than PMD patients.
Abstract Depression is the most frequent psychiatric comorbidity in people with epilepsy (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial variables play a pathogenic ...role in the high comorbid occurrence of these two disorders. These variables were critically examined during an international symposium held in Chicago in September 2010, the results of which are presented in two companion manuscripts. The first manuscript summarizes new epidemiologic data highlighting the bidirectional relation between depression and epilepsy and related methodological issues in studying this relationship. An examination of the neurobiologic aspects of primary mood disorders, mood disorders in PWE and pathogenic mechanisms of epilepsy derived from studies in animal models and humans is allowing a better understanding of the complex relation between the two conditions. In the first manuscript, we review data from animal models of epilepsy in which equivalent symptoms of depression and anxiety disorders develop and, conversely, animal models of depression in which the kindling process is facilitated. Data from structural and functional neuroimaging studies in humans provide a further understanding of potential common pathogenic mechanisms operant in depression and epilepsy that may explain their high comorbidity. The negative impact of depression on the control of seizure disorders has been documented in various studies. In this manuscript, these data are reviewed and potential mechanisms explaining this phenomenon are proposed.
The molecular origins of second-order nonlinear effects in type I collagen fibrils have been identified with sum-frequency generation vibrational spectroscopy. The dominant contributing molecular ...groups are: 1), the methylene groups associated with a Fermi resonance between the fundamental symmetric stretch and the bending overtone of methylene; and 2), the carbonyl and peptide groups associated with the amide I band. The noncentrosymmetrically aligned methylene groups are characterized by a distinctive tilt relative to the axis perpendicular to the main axis of the collagen fiber, a conformation producing a strong achiral contribution to the second-order nonlinear effect. In contrast, the stretching vibration of the carbonyl groups associated with the amide I band results in a strong chiral contribution to the optical second-order nonlinear effect. The length scale of these chiral effects ranges from the molecular to the supramolecular.
Abstract
Background
Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.
Methods
This nationwide cohort study comprises 30 625 women who received ovarian ...stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided.
Results
After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio SIR = 1.43, 95% confidence interval CI = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio HR = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time.
Conclusions
Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.
Abstract The clinical manifestations of depression in people with epilepsy (PWE) are pleomorphic, often associated with anxiety symptoms and anxiety disorders. The ongoing debate of whether the ...clinical presentation of depression in PWE is unique to this neurologic disorder is reviewed. Comorbid depression can impact the recruitment of PWE for pharmacologic trials with antiepileptic drugs (AEDs). Yet, the impact of depression on the response of the seizure disorder to pharmacotherapy with AEDs and its impact on worse adverse events may bias the interpretation of the trial findings, particularly when depressed patients are included in the AED trials. PWE have a greater suicidal risk than the general population. This risk is mediated by multiple factors, and recent data from the FDA have imputed a potential pathogenic role to all AEDs. The recognition of patients at risk is reviewed. Yet, the validity of the FDA data has been questioned, and the status of this controversial question is analyzed. As in the case of epilepsy, depression and pain syndromes have a relatively high comorbidity. The negative impact of depression on pain is reminiscent of that of depression in PWE; furthermore, the high comorbidity may be also associated with the existence of common pathogenic mechanisms. Neurologists and in particular, epileptologists establish the diagnosis of psychogenic non-epileptic seizures (PNES) in whom a comorbid depressive disorder is very often identified. The role of depression in the course of PNES and its treatment are discussed. Scarce data are available on the treatment of depression in PWE. Thus, clinicians have had to adopt data from patients with primary depressive disorders. We outline a consensus strategy on the identification and treatment of depressive disorders in adult and pediatric patients with epilepsy.
Abstract Objective: We sought to compare the diagnostic and treatment practices for psychogenic nonepileptic seizures (PNES) in the United States (US) to Chile. Methods: A survey on the diagnostic ...and treatment practices for PNES was administered to practicing clinicians in Chile. Results from 96 Chilean respondents were compared to results from 307 US clinicians. Type I error (alpha) was set to 0.005 for multiple comparisons. Results: Diagnosis : The diagnosis of PNES is made by inpatient video‐EEG/LTM in 89% of the US respondents compared to 25% of the Chilean respondents (p < 0.0001). The diagnosis of PNES is made by history and exam alone at twice the rate in Chile (38%) than in the US (16%; p < 0.0001). Treatment : A higher proportion of the Chilean respondents (65%) endorsed psychopharmacotherapy as potentially beneficial compared to the US respondents (31%; p < 0.0001). Discussion: This cross-cultural multi‐site survey reveals some differences in PNES evaluation and management between neurologists and other clinicians in the US and in Chile. Access to video EEG may improve PNES diagnosis and treatment.
Abstract Objective Psychogenic movement disorder (PMD) and psychogenic non-epileptic seizures (PNES) are two subtypes of conversion disorder (CD). In this case-control study, we asked whether these ...subtypes varied as a function of personality and history of childhood abuse, using the NEO Personality Inventory Revised (NEO PI-R). Methods Fifty-nine patients with PMD from the Human Motor Control Section Clinic at the National Institutes of Health, 43 patients with PNES from the Rhode Island Hospital Neuropsychiatry and Behavioral Neurology Division, and 26 healthy volunteers (HC) received a battery of neurological, psychiatric and psychological assessments. Results One-way ANOVA between the three groups indicated significant differences in overall domains of Neuroticism (p = 0.001) and Conscientiousness (p = 0.009): Patients with PNES reported significantly greater levels of Neuroticism (p = 0.002) and lower levels of Conscientiousness (p = 0.023) than patients with PMD. Levels of Neuroticism remained significantly higher in both PMD and PNES than HC following correction for multiple comparisons. Patients with PNES reported greater levels of depressive and anxiety symptoms, overall psychopathology, greater history of sexual abuse, greater levels of alexithymia, higher levels of dissociative symptoms, and an earlier age at which they experienced their most distressing traumatic event than patients with PMD. Conclusions These findings suggest that personality traits, type of abuse and age of onset of trauma varies as a function of CD subtype. Patients with PNES rated greater Neuroticism and lower Conscientiousness than patients with PMD. These differing psychological profiles may inform differing treatment approaches such as psychological therapies for PNES and physiotherapy (with/without psychotherapy) for PMD.
Abstract The increasing miscarriage rate with advancing female age is attributed to a decline in oocyte quality. A poor response to ovarian hypestimulation is often an expression of a decrease in ...oocyte quantity. Although oocyte quality and quantity both decrease as a result of ovarian ageing, it is unclear whether these two processes are related to each other. To investigate the relationship between oocyte quantity and quality, we compared miscarriage rates between IVF treated women with a poor and normal response, respectively. Data were studied from a retrospective nationwide cohort of Dutch women undergoing IVF treatment from 1983 to 1995. Women achieving an ongoing pregnancy after their first complete IVF cycle ( n = 1468) were compared with those experiencing miscarriage ( n = 357) with respect to their ovarian response. Logistic regression analysis showed a statistically significant association between poor response (fewer than four retrieved oocytes) and miscarriage ( P = 0.001). Due to interaction, this association became stronger with increasing female age. Among women <36 years, miscarriage rates between poor and normal responders did not differ, whereas among women ⩾36 years poor responders had a statistically significant increased miscarriage rate compared with normal responders ( P = 0.001). These results support the hypothesis of a relationship between quantitative ovarian reserve and oocyte quality.
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