Roderick Duncan

Dose-dependent Safety and Efficacy of Zonisamide: A Randomized, Double-blind, Placebo-controlled Study in Patients with Refractory Partial Seizures

Summary:  Purpose: To evaluate the safety and efficacy of zonisamide (ZNS) as adjunctive treatment in patients with refractory localization‐related epilepsy.

Newly presenting psychogenic nonepileptic seizures: incidence, population characteristics, and early outcome from a prospective audit of a first seizure clinic.

There are few published population-based data for psychogenic nonepileptic seizures (PNES). We prospectively identified first presentations of PNES from a population of 367,566, over 3 years. PNES were diagnosed in 68 patients, in 54 of whom the diagnosis was confirmed by video/EEG recording, indicating an incidence of 4.90/100,000/year. Median diagnostic delay was 0.6 ± 0.2 year. At presentation with PNES, our patients already had high rates of psychological morbidity, medically unexplained symptoms other than PNES, and economic dependence. At 3 months postdiagnosis, 27 of 54 patients (50.0%) were spell free. For 24 of the 27 patients (88.9%), spells ceased immediately on communication of the diagnosis. At 6 months, 24 of 54 patients (44.4%) were spell free. Poor early outcome was predicted by unemployment. Our data suggest that early outcome is good in patients with recent-onset PNES, but some patients relapse quickly.

Late onset psychogenic nonepileptic attacks

Objective: To investigate differences between groups of patients with early vs late onset psychogenic nonepileptic attacks (PNEA). Methods: The authors compared patients with onset of PNEA after age 55 years (n = 26) to patients whose onset of PNEA was before age 55 years (n = 241). The authors examined sociodemographic variables, factors potentially predisposing to PNEA, clinical semiology, and medical and psychiatric background. Results: Patients with late onset PNEA were more likely to be male (p = 0.029) (p values are quoted uncorrected for multiple comparisons). They were less likely to report antecedent sexual abuse (p = 0.008), and more likely to have severe physical health problems (p < 0.001) and to report health-related traumatic experiences (p < 0.0001). There were no clear differences in PNEA clinical semiology. There was a trend to better baseline mental health in the late onset group. Conclusions: The data suggest a distinct subgroup of patients with late onset psychogenic nonepileptic attacks, in whom psychological trauma related to poor physical health plays a prominent role.

Psychopathology in people with epilepsy and intellectual disability; an investigation of potential explanatory variables

Objectives:There are few studies on epilepsy and psychopathology in people with intellectual disability (mental retardation) despite epilepsy prevalence rates that are thirty times higher than in the general population. The aims of this study, therefore, were to identify reliable, epilepsy-specific predictors of psychiatric and behavioural disorder in these patients, and to investigate reliable predictors of carer stress. Methods:A database of 685 patients was compiled, from which 250 were randomly selected. Structured interviews were completed on 186 of these 250 patients (74%) (108 men, 78 women; mean age (SD) 35.5 (10.1)) comprising descriptive, clinical and functional components, and validated measures of psychopathology for which comparative data were available. Logistic and linear regression methods were used to identify predictors. Results:One-third of patients with epilepsy and intellectual disability met criteria for possible psychiatric disorder, particularly affective/neurotic disorder; twice the comparison rates for intellectual disability alone. Behavioural problem levels, however, were lower than population norms. Regression models explaining modest amounts of variance (R2⩽24%) suggested certain seizure phenomena (greater seizure severity, more seizures in past month, lesser tendency to loss of consciousness during seizures) as particular risk factors for psychiatric disorder. General disability factors such as level of intellectual, sensory or motor disability and side effects of medication, however, contributed more to explaining behavioural problems. Around half of the family carers reported significant stress, and one-third exhibited clinically significant anxiety symptoms. Younger carers were more stressed, and side effects from patients’ medication also contributed to carer stress. Conclusions:Although epilepsy in itself may be a risk factor for psychopathology in a minority of people with intellectual disability, some epilepsy-specific factors may predict psychiatric disorder. Behavioural problems need to be considered separately from psychiatric disorder because general factors, more closely associated with disability, are stronger predictors of their occurrence.

Functional (conversion) neurological symptoms: research since the millennium

Functional neurological symptoms (FNS) are commonly encountered but have engendered remarkably little academic interest. ‘UK-Functional Neurological Symptoms (UK-FNS)’ was an informal inaugural meeting of UK based clinicians in March 2011 with a variety of research and clinical interests in the field. This narrative review reflects the content of the meeting, and our opinion of key findings in the field since the turn of the millennium.

Blindness in eclampsia: CT and MR imaging.

Three cases of cortical blindness complicating eclampsia are described, with magnetic resonance imaging (MRI) and X-ray computed tomography (CT). The correspondence of MRI lesions (hyperintense on T2 weighted, and hypointense on T1 weighted sections) and low attenuation lesions on CT scan indicated ischaemia rather than haemorrhage as the pathological mechanism.

Disability, distress and unemployment in neurology outpatients with symptoms ‘unexplained by organic disease’

Objectives To determine the disability, distress and employment status of new neurology outpatients with physical symptoms unexplained by organic disease and to compare them with patients with symptoms explained by organic disease. Methods As part of a cohort study (the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patients symptoms were explained by organic disease. Patients whose symptoms were rated as ‘not at all’ or only ‘somewhat’ explained by disease were considered cases, and those whose symptoms were ‘largely’ or ‘completely’ explained by disease were considered controls. All patients completed self-ratings of disability, health status (Medical Outcomes Study Short Form 12-Item Scale (SF-12)) and emotional distress (Hospital Anxiety and Depression Scale) and also reported their employment and state financial benefit status. Results 3781 patients were recruited: 1144 (30%) cases and 2637 (70%) controls. Cases had worse physical health status (SF-12 score 42 vs 44; difference in means 1.7 (95% CI –2.5 to 0.9)) and worse mental health status (SF-12 score 43 vs 47; difference in means –3.5 (95% CI –4.3 to to 2.7)). Unemployment was similar in cases and controls (50% vs 50%) but cases were more likely not to be working for health reasons (54% vs 37% of the 50% not working; OR 2.0 (95% CI 1.6 to 2.4)) and also more likely to be receiving disability-related state financial benefits (27% vs 22%; (OR 1.3, 95% CI 1.1 to 1.6)). Conclusions New neurology patients with symptoms unexplained by organic disease have more disability-, distress- and disability-related state financial benefits than patients with symptoms explained by disease.

Clinical differences between patients with nonepileptic seizures who report antecedent sexual abuse and those who do not

Purpose: To investigate clinical differences between patients with psychogenic nonepileptic seizures (PNES) who report antecedent sexual abuse, and patients who do not.

CT, MR and SPECT imaging in temporal lobe epilepsy.

Cranial computed tomography (CT) with modified temporal lobe technique, 0.15T magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were carried out on 30 patients with intractable temporal lobe epilepsy. Lateralising abnormalities were detected in 21/30 patients overall. Specific lesions were detected by CT in one patient and by MRI in seven patients (in one case bilateral). In addition CT detected asymmetry of the sylvian fissures or temporal horns in 10 patients, and MRI in eight patients. SPECT detected lateralising abnormalities in 19 patients (in five cases bilateral). It is concluded that low field MRI is superior to modified CT in demonstrating subtle structural lesions of the temporal lobe. Functional scanning with SPECT supports the evidence of origin of an epileptic focus in a substantial proportion of cases and may improve the selection of patients for surgery.

The safety of antiepileptic drug withdrawal in patients with non-epileptic seizures.

Background: To determine whether withdrawal of anticonvulsant drugs (AED) can be carried out safely in patients with non-epileptic seizures (NES). Methods: Prospective evaluation of safety and outcome in 78 patients with NES who satisfied a standardised set of criteria for excluding the diagnosis of coexisting or underlying epilepsy. Findings: The patients were taking from one to three AED. Sixty four patients were withdrawn as outpatients, 14 as inpatients. Five patients stopped their drugs abruptly, and two had AED restarted and had to be withdrawn again. Otherwise all patients adhered to withdrawal schedules. A new type of attack in addition to NES was seen in three patients (complex partial seizures in all three cases). NES frequency declined in the group as a whole over the period of the study (follow up 6–12 months) in all individuals except for eight patients in whom there was a transient increase. Fourteen patients reported new physical symptoms after withdrawal; however, no serious adverse events were reported. Conclusions: With appropriate diagnostic investigation and surveillance during follow up withdrawal of AED can be achieved safely in patients with NES.