Long-term HIV and tuberculosis outcomes in patients hospitalised with severe cutaneous adverse reactions.

Background: Treatment-limiting severe cutaneous adverse reactions (SCAR) occur more commonly amongst persons with HIV-associated tuberculosis (TB). The impact of SCAR on long-term HIV/TB outcomes is unknown. Methods: Patients with TB and/or HIV admitted to Groote Schuur Hospital, Cape Town, South Africa with SCAR between 1/10/2018 and 30/09/2021 were eligible. Follow-up data was collected for 6- and 12-month outcomes: mortality, TB and antiretroviral therapy (ART) regimen changes, TB treatment completion, and CD4 count recovery. Results: Forty-eight SCAR admissions included: 34, 11, and 3 HIV-associated TB, HIV-only and TB-only patients with 32, 13 and 3 cases of drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis and generalised bullous fixed-drug eruption respectively. Nine (19%), all HIV-positive (eight co-infected with TB), were deceased at 12-months, and 12(25%) were lost to follow-up. Amongst TB-SCAR patients, seven (21%) were discharged on all four first-line anti-TB drugs (FLTD), while 12(33%) had regimens with no FLTDs; 24/37(65%) completed TB treatment. Amongst HIV-SCAR patients, 10/31(32%) changed ART regimen. If retained in care (24/36), median (IQR) CD4 counts increased at 12-months post-SCAR (115(62-175) vs. 319(134-439) cells/uL). Conclusion: SCAR admission amongst patients with HIV-associated TB results in substantial mortality, and considerable treatment complexity. However, if retained in care, TB regimens are successfully completed, and immune recovery is good despite SCAR.

Description and comparison of brain distribution of oxytocin receptors in Rhabdomys pumillio and Rhabdomys dilectus.

Oxytocin receptor (OXTR) distribution in the brain has been associated with different reproductive and social strategies of species. Rhabdomys pumilio (R. pumilio) and Rhabdomys dilectus (R. dilectus) are two sister rodent species that live in large/medium (but flexible) or small (mostly solitary) social groups respectively. In this study, we describe and compare the distribution of OXTR in these two species. OXTR binding in the brain of R. pumilio (8 females and 5 males) and R. dilectus (8 females and 5 males) adults was determined using autoradiography. Our results revealed significant differences in the nucleus accumbens, diagonal band, medial preoptic area, lateral habenula, superior colliculus, periaqueductal area and anterior paraventricular nucleus (higher in R. dilectus), and the dorsal lateral septum and anterior bed nucleus of the stria terminalis (higher in R. pumilio). OXTR density in other brain regions, such as the amygdala nuclei and hippocampus, did not differ between the two species. Sex differences were found in the medial preoptic area and ventral region of the lateral septum in R. pumilio (OXTR density higher in males) and in the anterior paraventricular thalamic nucleus, ventromedial nucleus of the hypothalamus and basolateral amygdala of R. dilectus (OXTR density higher in females). A sex difference in the density of OXTR was also found in the posterior region of the bed nucleus of the stria terminalis, where it was higher in males than in females of both species. This study shows species-specific brain distribution of OXTR in R. pumilio and R. dilectus that are unique, but with similarities with other polygynous or promiscuous rodent species that live in variable size groups, such as R. norvergicus, C. sociabilis, S. teguina and M. musculus.

Factors that influence parental and caregiver acceptance of routine childhood vaccination: Summary of a qualitative evidence synthesis.

We summarise a Cochrane review of qualitative evidence that explored parents' views and practices around routine childhood vaccination, and provide implications for research and practice that are relevant to the South African (SA) context. Many public health interventions to encourage vaccination are informed by an assumption that vaccine hesitancy is due to a lack of knowledge or irrational forms of thinking. The findings from this review suggest that childhood vaccination views and practices are complex social processes that are shaped by multiple factors and carry a variety of meanings. As such, we suggest that biomedical approaches must be supplemented by more nuanced and sociopolitically informed strategies for enhancing and sustaining childhood vaccination practices in SA.

CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread.

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

Pathways to school completion for young mothers: are we winning the fight?

Background. Policy initiatives in South Africa are directed at promoting the educational and developmental outcomes of girls and young women (age 15 - 24 years). These include decreasing the incidence of HIV infection, teenage pregnancy and gender-based violence, and increasing school attendance and economic empowerment. This article explores the contexts of pregnancy, motherhood and schooling in a sample of young mothers in an urban area in Johannesburg, South Africa. Methods. This ethnographic study, based in a poor urban area in Johannesburg, South Africa, recruited 30 young mothers aged 18 - 20 years with whom open-ended interviews were conducted. Each mother was contacted 3 months after the first interview, and again 3 months later. In addition to the first round of 30 interviews, 9 young mothers were interviewed in the second round, and 6 young mothers in a third round. A total of 45 interviews were conducted. Results. The findings illustrate how young mothers mediate constraints and challenges to continue and complete their schooling when confronted with a mistimed and unintended pregnancy. A combination of factors converges to facilitate or impede school continuation and completion. Key barriers include school policy and discrimination against pregnant learners, limited options for childcare, and high levels of poverty and unemployment that strain existing scarce family resources. Conclusions. The pathway to school completion is complex and non-linear. Three particular interventions that support school attendance and completion for young mothers have value: the child support grant, the availability of crèches in the community, and a school policy that upholds the principle of inclusivity for pregnant learners and young mothers

Trade-offs between reproduction and health in free-ranging African striped mice.

Energy is limited and must be allocated among competing life-history traits. Reproduction is considered one of the most energetically demanding life-history stages. Therefore, the amount of energy an individual invests in reproduction might carry fitness costs through reduced energy allocation to other activities such as health maintenance. We investigated whether reproduction impacts health in the seasonally breeding African striped mouse (Rhabdomys pumilio). We measured health in individuals that reproduced (breeders) and individuals that did not reproduce (their adult offspring) and tested whether: (1) breeders' health before reproduction was similar to that of their offspring (representing a baseline); (2) breeders' health deteriorated after reproduction; (3) breeders' health after reproduction was worse than that of their offspring. We collected blood samples from 12 breeding females and 11 breeding males both at the onset and at the end of the breeding season and from 12 adult daughters and 11 adult sons that did not reproduce at the end of the breeding season. Health was assessed using serum biochemistry analysis with VetScan Abaxis. Breeders differed considerably in their health before and after reproduction, particularly in parameters associated with digestion (lower amylase in males), metabolism (lower albumin, alkaline phosphatase, creatinine and glucose), osmoregulation (lower potassium and phosphorous in females) and immunity (higher globulin and altered alanine aminotransferase). Our results suggest that with the onset of breeding striped mice shifted their energy allocation from maintaining health to reproduction, indicating that investment into reproduction carries significant health costs.

The pathophysiology of survival in harsh environments.

An individual's ability to survive harsh conditions might depend on its available energy, and also on its health, which is expected to decline as conditions deteriorate. Yet, we know little about how health and energy expenditure are shaped by harsh environmental conditions in free-living vertebrates. Here, we studied how African striped mice (Rhabdomys pumilio) that survived summer droughts differed in their energy expenditure and health from non-survivors. Specifically, we tested whether: (1) survivors' and non-survivors' health and energy expenditure differed before environmental conditions declined; (2) non-survivors were in poorer health and had greater energy expenditure than survivors when conditions were harshest; (3) non-survivors' health deteriorated more than that of survivors as conditions deteriorated; and (4) survivors recovered once conditions improved. Survivors and non-survivors' health was assessed using VetsScan ABAXIS, while energy expenditure was measured as resting metabolic rate (RMR). Before conditions declined, non-survivors had lower energy stores and higher globulin levels than survivors. As conditions became harsher, survivors' and non-survivors' health deteriorated but only non-survivors showed signs of permanent pathology (increased glucose and decreased globulin). Once conditions improved, survivors' health improved but was not fully restored (increased alanine aminotransferase and decreased globulin). Furthermore, while survivors and non-survivors had similar RMR before conditions became harsh; their levels diverged considerably when conditions deteriorated, with survivors having a decreased RMR and non-survivors having an increased RMR. Our results show that an individual's health before facing an environmental challenge and the way it regulates its RMR influences its ability to maintain homeostasis when conditions become more taxing.

First-in-human dose study of the novel transforming growth factor-ß receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma.

PURPOSE: TGFß signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFß signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer. EXPERIMENTAL DESIGN: Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria. RESULTS: In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥ 6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥ 6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events. CONCLUSIONS: On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation.

Cardiac Safety of TGF-ß Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study.

Transforming growth factor-beta (TGF-ß) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-ß signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-ß inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ≥6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-ß inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials.

Pharmacokinetic, pharmacodynamic and biomarker evaluation of transforming growth factor-ß receptor I kinase inhibitor, galunisertib, in phase 1 study in patients with advanced cancer.

Purpose Transforming growth factor-beta (TGF-ß) signaling plays a key role in epithelial-mesenchymal transition (EMT) of tumors, including malignant glioma. Small molecule inhibitors (SMI) blocking TGF-ß signaling reverse EMT and arrest tumor progression. Several SMIs were developed, but currently only LY2157299 monohydrate (galunisertib) was advanced to clinical investigation. Design The first-in-human dose study had three parts (Part A, dose escalation, n = 39; Part B, safety combination with lomustine, n = 26; Part C, relative bioavailability study, n = 14). Results A preclinical pharmacokinetic/pharmacodynamic (PK/PD) model predicted a therapeutic window up to 300 mg/day and was confirmed in Part A after continuous PK/PD. PK was not affected by co-medications such as enzyme-inducing anti-epileptic drugs or proton pump inhibitors. Changes in pSMAD2 levels in peripheral blood mononuclear cells were associated with exposure indicating target-related pharmacological activity of galunisertib. Twelve (12/79; 15%) patients with refractory/relapsed malignant glioma had durable stable disease (SD) for 6 or more cycles, partial responses (PR), or complete responses (CR). These patients with clinical benefit had high plasma baseline levels of MDC/CCL22 and low protein expression of pSMAD2 in their tumors. Of the 5 patients with IDH1/2 mutation, 4 patients had a clinical benefit as defined by CR/PR and SD ≥6 cycles. Galunisertib had a favorable toxicity profile and no cardiac adverse events. Conclusion Based on the PK, PD, and biomarker evaluations, the intermittent administration of galunisertib at 300 mg/day is safe for future clinical investigation.

Defining a therapeutic window for the novel TGF-ß inhibitor LY2157299 monohydrate based on a pharmacokinetic/pharmacodynamic model.

AIMS: To identify prospectively a safe therapeutic window for administration of a novel oral transforming growth factor ß (TGF-ß) inhibitor, LY2157299 monohydrate, based on a pharmacokinetic/pharmacodynamic (PK/PD) model. Simulations of population plasma exposures and biomarker responses in tumour were performed for future trials of LY2157299 in glioblastoma and other cancer populations. METHODS: The model was updated after completion of each cohort during the first-in-human dose (FHD) study. The flexible design allowed continuous assessment of PK variability by recruiting the required number of patients in each cohort. Based on 30% inhibition of TGF-ß RI kinase phosphorylates (pSMAD), biologically effective exposures were anticipated to be reached from 160 mg onwards. The therapeutic window was predicted, based on animal data, to be between 160 and 360 mg. RESULTS: No medically significant safety issues were observed and no dose limiting toxicities were established in this study. Observed plasma exposures (medians 2.43 to 3.7 mg l⁻¹ h, respectively) with doses of 160 mg to 300 mg were within the predicted therapeutic window. Responses, based on the MacDonald criteria, were observed in these patients. CONCLUSIONS: A therapeutic window for the clinical investigation of LY2157299 in cancer patients was defined using a targeted PK/PD approach, which integrated translational biomarkers and preclinical toxicity. The study supports using a therapeutic window based on a PK/PD model in early oncology development.

NDM-1 imported from India--first reported case in South Africa.

Carbapenem-resistant Enterobacteriaceae have been increasingly reported throughout the world. The first South African report of a New Delhi metallo-beta-lactamase was from Gauteng in August 2011. Despite maintaining a high degree of vigilance, the first such case was seen in KwaZulu-Natal almost a year later. Other cases have been unable to confirm a definite link to any other affected areas; this is the first case in South Africa showing this direct epidemiological link.

Early maternal separation leads to down-regulation of cytokine gene expression.

Exposure to stressors may lead to subsequent alterations in the immune response. The precise mechanisms underlying such vulnerability are poorly understood, but may be hypothesized to include changes in cytokine systems. Maternal separation was used as a model of exposure to early life stressors. Subsequent cytokine gene expression was studied using a cytokine gene expression array. Maternal separation resulted in significant down-regulation of the expression of 6 cytokine genes; chemokine ligand 7, chemokine receptor 4, interleukin 10, interleukin-1beta, interleukin 5 receptor alpha and integrin alpha M. Specific cytokines may be involved in mediating the effects of early adversity on subsequent immunosuppression. Further work is needed to delineate fully the relationship between early adversity, immune alterations, and behavioural changes.

Subacute seizure incidence in thrombolysis-treated ischemic stroke patients.

BACKGROUND: To assess the incidence of seizures in acute ischemic stroke patients treated with chemical (tPA) thrombolysis. METHODS: Retrospective study including all thrombolysis patients treated in Calgary between January 1, 2001, and October 31, 2006. Descriptive statistics and age/sex-adjusted P values were calculated. RESULTS: Of 400 eligible patients (median age 74.0 years, range: 24-77), 16 (4%) developed post-stroke seizures: 10 (62.5%) within one week (early) and 6 (37.5%) after 1 week but within the hospital stay (late). Single-vessel anterior circulation involvement (93.8% vs. 87%, P = 0.34) and hemorrhage (37.5% vs. 20%, P = 0.15) were more common in those with compared to without seizures but did not reach statistical significance. Atrial fibrillation was more common in those with (56.3%) than without (36.1%) seizures (P = 0.04). Death during admission was more likely (P = 0.03) in those who sustained seizures (37.5%) compared to those without seizures (17.6%). CONCLUSIONS: In this cohort of tPA-treated patients, post-stroke seizures were associated with atrial fibrillation and early mortality.

Cooperative breeding in groups of synchronously mating females and evolution of large testes to avoid sperm depletion in african striped mice.

Testis size has been related to the mating system of both vertebrates and invertebrates. These differences are regarded as adaptive responses to sperm competition in promiscuously mating species. However, not all variation in testis size can be explained by sperm competition. Here, we test the hypothesis that the evolution of large testes occurs when synchronously breeding females must be fertilized within a short period of time to avoid reproductive competition among the females. African striped mouse (Rhabdomys pumilio) males of a polygynous population with cooperative breeding and high risk of sperm depletion had testes and cauda epididymis twice as large as those of males of four different promiscuous populations with high risk of sperm competition. When paired with three females simultaneously in captivity, males of the polygynous population bred with three females within 8 days, leading to synchronous births in their harems, thereby potentially reducing the risk of infanticide. Males from the promiscuous population reproduced with only one or two females within 8 days, and births were not synchronous. We conclude that large testes are selected for in species with synchronously mating females, which is ultimately beneficial for the evolution of cooperative breeding.

Adult-onset epilepsy associated with dysembryoplastic neuroepithelial tumors.

RATIONALE: Dysembryoplastic neuroepithelial tumors (DNET) are benign, localized lesions that typically cause localization-related epilepsy of childhood onset. Although excellent seizure outcomes are expected following surgical resection of focal, benign lesions, reports in pediatric epilepsy series suggest that this may not be the case with DNETs, which may exhibit complex and often multifocal epileptogenesis. We report the characteristics and surgical outcome of an adult- and childhood-onset cohort with this condition. METHODS: Retrospective cohort of 23 patients seen at two major epilepsy centers, with localization-related epilepsy associated with histopathologically demonstrated DNETs. We assessed clinical, electrographic and surgical outcome features in patients with adult- and childhood-onset epilepsy. We were particularly interested in the level of congruence of EEG and MRI data and the need for intracranial recordings. We evaluated seizure outcomes at last follow-up. RESULTS: The mean age was 33.3 years (range: 5-56 years). Ten patients had adult-onset epilepsy. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. Status epilepticus did not occur. Non-enhancing lesions on MRI were located in the temporal lobe in 17 patients, the frontal lobe in 3 patients and the parietal/occipital region in 2 patients. One patient had a DNET that involved both frontal and temporal areas. Ictal scalp EEG and MRI were congruent in 17 patients (74%). Eleven patients (48%) underwent lesionectomies, while the rest required some resection of extralesional cortex as well. Five patients required intracranial EEG. There was no association with cortical dysplasia. Seventeen patients (74%) had an Engel class 1 outcome, in a follow-up period that ranging from 5 to 98 months. CONCLUSIONS: We found no difference in outcomes between adult- and childhood-onset cases. Although epileptogenicity was complex, congruence between electro-clinical and neuroimaging studies was high and allowed good surgical outcomes at 1 year of follow-up.

The gut morphology of the African ice rat, Otomys sloggetti robertsi, shows adaptations to cold environments and sex-specific seasonal variation.

We studied the gut morphology of the ice rat Otomys sloggetti robertsi, a non-hibernating murid rodent endemic to the sub-alpine and alpine regions of the southern African Drakensberg and Maluti mountains. The gut structure of O. s. robertsi is well adapted for a high fibre, herbivorous diet, as is the case with other members of its subfamily Otomyinae. Despite the broad similarity in gross gut morphology with mesic- and arid-occurring otomyines, O. s. robertsi has a larger small intestine, caecum, stomach volume and parts of the colon, which we suggest are adaptations for increased energy uptake and/or poor diet quality in alpine environments. However, O. s. robertsi has a smaller larger intestine than other otomyines, perhaps because it occupies a mesic habitat. Seasonal sexual differences occurred, with females increasing dimensions of the stomach, small intestine length, caecum, and large intestine in summer. Sexual asymmetry in gut morphology may be related to increased energy requirements of females during pregnancy and lactation, indicating phenotypic plasticity in response to poor quality vegetation and a shorter growing season in alpine habitats.

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 800 mg/day) in a B.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive NMDA receptor channel blocker under investigation for the treatment of epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of adjunctive remacemide hydrochloride or placebo, in adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients (n= 262) were randomized to one of three doses of remacemide hydrochloride (300, 600 or 800 mg/day) or placebo, in a B.I.D. regimen, for up to 14 weeks. Plasma concentrations of carbamazepine (CBZ) and phenytoin (PHT) were controlled throughout. Patients recorded their seizures on a diary card. There was an increase in the percentage of responders (defined as a reduction in seizure frequency from baseline > or = 50 %), from 15 % (9/60) with placebo, to 30 % (18/60) in the 800 mg/day group. A pairwise comparison between remacemide hydrochloride 800 mg/day and placebo was statistically significant (P = 0.049). Most reported adverse events (mainly CNS and gastrointestinal) were mild or moderate in severity and dose-dependent. Adjunctive remacemide hydrochloride treatment was associated with a higher, dose-related responder rate compared with placebo. The difference reached significance at the highest dose tested (800 mg/day). Remacemide hydrochloride was well tolerated.

Family functioning in subjects with pseudoseizures and epilepsy.

The purpose of this study was to identify differences in family functioning between subjects with pseudoseizures and their families, and control subjects with epilepsy. Thirty-one adult subjects with pseudoseizures and 31 controls with intractable epilepsy, whose diagnoses were confirmed using video-EEG, were recruited from the epilepsy unit of a tertiary care hospital over a 4-year period. Each study participant and their first-degree adult family members completed two standardized questionnaires designed to measure family functioning: the McMaster Family Assessment Device (FAD) and the Beavers Self-Report Family Inventory (SFI). Individuals with pseudoseizures, when compared with epileptic subjects, exhibited significantly elevated scores in three scales of the FAD and in one scale of the SFI, indicating greater psychopathology within the family, as perceived by the individual. Statistically significant differences with the FAD were on measures of affective involvement (p = .044), communication (p = .004), and general functioning (p = .013). The SFI revealed significantly greater difficulty with conflict (p = .050). No differences were noted between subjects with both pseudoseizures and epilepsy and subjects with pseudoseizures alone. In comparison with the families of the epileptic group, the families of subjects with pseudoseizures displayed statistically significant elevations in their responses on the roles scale (p = .003) of the FAD. The responses of the family members did not differ in regard to the role they assumed within the family unit (i.e., spouse, parent). In summary, individuals with pseudoseizures view their families as being more dysfunctional, particularly in the area of communication, whereas their family members perceived difficulties in defining roles. This suggests that family education and interventions focusing on these areas, may be an important aspect of the treatment of patients with pseudoseizures.