Illness representations of people with later-onset functional seizures.

PURPOSE: Although functional seizures can start at any age, little is known about the individuals for whom onset occurs after the age of 40. It has been proposed that health-related traumatic events are more relevant causal factors for people with 'later-onset functional seizures' than for those whose functional seizures begin earlier in life, however, the illness representations of people with later-onset functional seizures have not yet been investigated. This study aimed to understand the experiences and illness representations of people with later-onset functional seizures. METHODS: This was a mixed-methods study. People with later-onset functional seizures were recruited via a neurologist's caseload and online membership-led organisations. Semi-structured interview transcripts were analysed using Template Analysis according to the Common-Sense Model (CSM). Self-report measures of demographic and clinical details were collected to characterise the sample and verify themes. RESULTS: Eight people with later-onset functional seizures participated in the study. Illness representations relating to all domains of the CSM as well as an additional theme of 'Triggers' were identified. Functional seizures were characterised as a mysterious brain disorder analogous to a computer malfunction and involving involuntary movements associated with alterations in consciousness. Perceptions of duration were indefinite, and triggers were unknown or at the extremes of autonomic arousal. Half of the sample identified health-related events/trauma as causal. Opinions were divided on 'cumulative life stress' as a causal factor. Most perceived themselves to have limited or no control but having 'control' over seizures was conceptualised as different to reducing their likelihood, frequency, or impact. Later-onset functional seizures were viewed as being more detrimental for caring and financial responsibilities but to have advantages for acceptance. CONCLUSIONS: This is the first study to assess the illness representations of people with later-onset functional seizures. Many themes were similar to those identified in samples including people with earlier-onset functional seizures. Health-related trauma or events were the most strongly endorsed perceived causal factor, but with the exception of 'consequences', all representations were characterised by uncertainty. Clinicians should hold in mind the interaction between life stage and the consequences of later-onset functional seizures.

An antenatal marker of neurodevelopmental outcomes in infants with congenital heart disease.

OBJECTIVE: Prenatal exposures are known to alter fetal neurodevelopment and autonomic control. We aimed to explore the correlation between fetal autonomic activity, measured by fetal heart rate variability, and 18-month developmental outcome in subjects with congenital heart disease. STUDY DESIGN: From 2010 to 2013, 5 fetuses with hypoplastic left heart syndrome, 9 with transposition of the great arteries and 9 with tetralogy of Fallot were included in this prospective cohort study. A maternal abdominal fetal electrocardiogram monitor recorded fetal heart rate at 34 to 38 weeks gestational age. We assessed associations between fetal heart rate parameters including interquartile range and s.d. of the fetal RR intervals and 18-month Bayley Scales of Infant Development-III scores using Pearson's correlation coefficient. Multivariable regression modeling identified predictors of neurodevelopmental scores. RESULTS: Fetal heart rate variability parameters at 34 to 38 weeks gestational age correlated with 18-month Cognition (r=0.47, P=0.03) and Motor scores (r=0.66, P=0.001). The interquartile range of the fetal RR intervals predicted Cognition (ß=0.462, P=0.028, R2=0.282) and Motor (ß=0.637, P<0.001, R2=0.542) scores. CONCLUSIONS: In fetuses with congenital heart disease, low heart rate variability at 34 to 38 weeks gestational age predicts diminished 18-month Cognitive and Motor performance. Prenatal autonomic activity may serve as a marker of early childhood development in these high-risk patients.

Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses.

OBJECTIVE: To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject. METHODS: We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression. RESULTS: The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (ß = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (ß = 10.6, P = 0.04 and ß = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (ß = -14.7, P = 0.03). CONCLUSION: In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cerebrovascular resistance and neonatal EEG predict 18-month neurodevelopmental outcome in infants with congenital heart disease.

OBJECTIVES: The purpose of this study was to investigate early markers of risk for neurobehavioral compromise in survivors with congenital heart disease (CHD). METHODS: Pregnant women in whom a fetal CHD had been diagnosed before 24 weeks' gestational age (GA) were enrolled in this prospective pilot study for serial Doppler ultrasound assessment of the fetal middle cerebral artery (MCA) and umbilical arteries. The cerebral-to-placental resistance ratio (CPR) and MCA pulsatility index (PI) Z-scores for GA were calculated. After birth, subjects underwent high-density (128-lead) electroencephalography (EEG), and beta frequency (12-24 Hz) band EEG power, a measure of local neural synchrony, was analyzed. Neurodevelopment was assessed at 18 months with the Bayley Scales of Infant Development (BSID)-III. RESULTS: Thirteen subjects were enrolled: four with hypoplastic left heart syndrome (HLHS), four with transposition of the great arteries (TGA) and five with tetralogy of Fallot (TOF). Compared with subjects with normal CPR, those with CPR < 1 (n = 7) had lower mean BSID cognitive scores (91.4 ± 4.8 vs. 99.2 ± 3.8, P = 0.008). Fetal MCA-PI Z-score also correlated with BSID cognitive score (r = 0.589, P = 0.03) as did neonatal EEG left frontal polar (r = 0.58, P = 0.037) and left frontal (r = 0.77, P = 0.002) beta power. Furthermore, fetal Doppler measures were associated with EEG power: fetuses with CPR < 1 had lower left frontal polar (t = 2.36, P = 0.038) and left frontal (t = 2.85, P = 0.016) beta power as newborns than did fetuses with normal CPR, and fetal MCA-PI Z-score correlated with neonatal EEG left frontal polar (r = 0.596, P = 0.04) and left frontal (r = 0.598, P = 0.04) beta power. CONCLUSION: In fetuses with HLHS, TGA and TOF, abnormal cerebrovascular resistance predicts decreased neonatal EEG left frontal beta power and lower 18-month cognitive development scores.

Hypoplastic left heart syndrome with restrictive atrial septum and advanced heart block documented with a novel fetal electrocardiographic monitor.

Hypoplastic left ventricle with congenital heart block has been reported previously in a fetus with concurrent left atrial isomerism and levo-transposition of the great arteries. We present the unusual case of an infant diagnosed in utero with hypoplastic left heart syndrome, a restrictive atrial septum and advanced heart block but with D-looping of the ventricles and no atrial isomerism. In addition, fetal heart rhythm was documented with the assistance of a new fetal electrocardiographic monitor.

Is hydrops fetalis a manifestation of fetal pulmonary edema caused by impaired lymphatic drainage?

Hydrops fetalis is the final common hemodynamic pathway for a variety of fetal cardiovascular pathologies, including high-output states associated with fetal anemia or arteriovenous fistulas, and abnormalities of both cardiac structure and rhythm. Hydrops fetalis secondary to cardiovascular decompensation is usually accompanied by increases in fetal systemic venous pressure as evidenced by alterations in venous Doppler blood flow velocities. We present two cases of severe fetal aortic stenosis with left ventricular fibroelastosis and mitral regurgitation, and in-utero closure or stenosis of the foramen ovale, with severe hydrops fetalis, despite normal systemic venous Doppler flow profiles. These cases have led us to reconsider the presumed etiology of cardiovascular-based hydrops fetalis in fetuses with severely impaired left ventricular pump function and secondary mitral regurgitation. We hypothesize that raised pulmonary venous pressure, with only mildly increased central venous pressure, may impact negatively on pulmonary lymphatic flow, decrease serum oncotic pressure, increase venous hydrostatic pressure, and lead to hydrops fetalis.

Discordant anatomically corrected malposition of the great vessels and Ebstein's malformation: fetal and neonatal findings.

Discordant anatomically corrected malposition of the great vessels (ACM) is a rare congenital cardiac malformation that is often associated with other cardiac lesions. To our knowledge, a fetal diagnosis of this lesion has not yet been reported in the literature. We present a case of ACM associated with Ebstein's malformation, diagnosed by fetal echocardiography.

Meningitis associated with sulphasalazine in a patient with Sjögren's syndrome and polyarthritis.

A case of meningitis occurring in a 37 year old woman with Sjögren's syndrome, seropositive arthritis, and a possible overlap syndrome soon after starting sulphasalazine and after subsequent rechallenge is reported.

A comparison of nafarelin acetate and danazol in the treatment of endometriosis.

Nafarelin 400 micrograms daily and danazol 600 mg daily were compared in a double-blind randomized study. Eighty-two patients with endometriosis were treated for 6 months after an initial laparoscopy and 74 had a second laparoscopy. Twenty-two (30%) patients had complete disease regression, 42 (57%) patients had a partial regression, and in 10 (13%) patients disease was unchanged or worse. Both treatments led to significant regression of active disease but not of adhesions. At 3 months follow-up, 34 (64%) patients reported their symptoms were improved, 15 (28%) reported no change, and 4 (8%) were worse. Nafarelin was associated with more hot flushes and headaches, and danazol with more weight gain. No significant differences, however, were noted in treatment efficacy between the two groups.

Effect of nafarelin on uterine fibroids measured by ultrasound and magnetic resonance imaging.

Administration of the LHRH agonist, Nafarelin (D-(Nal2)6 GnRH), at a dosage of 200 micrograms twice daily intranasally in 13 patients with uterine leiomyomata resulted in a reduction in uterine volume to a mean of 55.1% at 3 months and 44.5% at 6 months as measured using ultrasound. Re-enlargement occurred on discontinuing therapy and the uterus was back to the original volume at three months. Magnetic resonance imaging (MRI) performed in five patients showed advantages over ultrasound in identification of fibroid number in two patients. Mean reduction in uterine area measured using MRI was 61.3%, and mean reduction of fibroid area 57%. Oestradiol was suppressed with treatment to a mean of 69 pmol/l.

An attempt to alter the pathophysiology of polycystic ovary syndrome using a gonadotrophin hormone releasing hormone agonist--Nafarelin.

The aim of this study was to see whether the pathophysiology of polycystic ovary syndrome could be altered by suppressing the abnormal cycle of events associated with abnormal gonadotrophins and androgens. Fifteen women with polycystic ovary syndrome were treated with the GnRH agonist Nafarelin at a dosage of 200 micrograms twice daily intranasally for a period of 3 or 6 months. Eight of these women also had a dexamethasone suppression test 0.5 mg four times daily for 48 h before and after treatment with Nafarelin, in order to differentiate between an adrenal and ovarian source for the excess androgens. Gonadotrophins and androgens were well suppressed, LH to a mean of 1.5 IU/l, testosterone to 1.1 nmol/l and androstenedione to 6.4 nmol/l. Three months after discontinuing Nafarelin, all these hormones had returned to pretreatment levels. The ultrasound appearance of the ovaries showed no consistent reduction in ovarian volume or the disappearance of ovarian follicles. Hirsutism showed slight improvement in four out of seven patients. After treatment one patient out of the eight complaining of infertility, conceived spontaneously and one patient ovulated on a reduced dosage of clomiphene. There was no change in the menstrual pattern of the others. Despite the achievement of good hormonal suppression, there was no change in the condition after therapy was discontinued suggesting that whatever the cause of the condition it remains a permanent situation.

Survey of the long term incidence of osteonecrosis of the hip and adverse medical events in rheumatoid arthritis after high dose intravenous methylprednisolone.

A prospective, randomised, double blind, matched cohort survey using retrospective data was undertaken to assess the long term incidence of osteonecrosis of the hip and adverse medical effects occurring after intravenous pulsed methylprednisolone used in the treatment of rheumatoid arthritis over the period 1977-86. One hundred and forty three patients were matched for age, sex, duration and severity of the disease, erosive and serological status. Information was obtained by direct questioning and from hip x rays, the latter being read independently by two 'blind' radiologists. Two definite cases of osteonecrosis were identified, one in both the treated and control groups and three possible cases (radiological disagreement) in the treated group. Adverse medical events, when analysed by systems, were similar in both groups. This study did not provide evidence of increased osteonecrosis of the hip or adverse medical events in the treated group compared with the control group.

Pulsed methylprednisolone in active early rheumatoid disease: a dose-ranging study.

A dose-ranging, double-blind study of pulsed methylprednisolone in 71 patients with active classical or definite RA is reported. Single pulses of 40 mg, 500 mg or 1 g were administered during a 24-h admission. All patients benefited transiently, but only in those who received 1 g was this prolonged beyond 3 weeks. Laboratory measurements showed no significant change in any group. Significantly more patients in the 1 g group felt the treatment worthwhile than in the other groups. The drop-out rates in the 40 mg and 500 mg groups differed significantly from that seen in the 1 g group and were such that statistical analysis beyond 3 weeks was difficult to interpret. Side-effects were mild. Three patients subsequently developed avascular necrosis, one in the 1 g and two in the 40 mg groups. The study suggests that single doses of MP below 1 g are not helpful in the management of acute RA.

Alteration of plasma prednisolone levels by indomethacin and naproxen.

Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P less than 0.001) increase in free prednisolone levels after concurrent therapy with either indomethacin or naproxen for 2 weeks. Total prednisolone levels were unchanged. These results could provide an explanation for clinical reports that these two NSAI drugs possess a steroid-sparing effect.

A double-blind placebo-controlled trial of methylprednisolone pulse therapy in active rheumatoid disease.

To confirm the findings of uncontrolled trials that methylprednisolone pulse therapy (MPPT) is a safe treatment for active rheumatoid disease, a double-blind trial was conducted in which 20 patients with active rheumatoid disease were randomly allocated to receive an infusion of either 1 g methylprednisolone or placebo. Methylprednisolone produced significant improvement in all clinical variables measured, a benefit which was sustained for at least 6 weeks. The placebo produced only transient improvement in some of the clinical variables measured. when the 10 placebo groups patients were later given an infusion of 1 g methylprednisolone, they too showed significant clinical benefit. The methylprednisolone also gave rise to improvements in some haematological and biochemical variables.

High dose intravenous methylprednisolone "pulse" therapy in patients with rheumatoid disease. Plasma methylprednisolone levels and adrenal function.

Twenty seven patients with acute rheumatoid disease who had not previously received systemic corticosteroid therapy were given a pulse(s) of high dose methylprednisolone sodium succinate (MPS) intravenously. Of the 27 patients 22 received 1 g MPS once and 5 were given the drug on three consecutive days. Plasma "MP" (total MPS plus hydrolysed methylprednisolone) and cortisol levels were measured at various intervals post infusion. Clinical assessments were made before and at 2 week intervals after each infusion for 12 weeks. Patients showed objective improvement for up to 12 weeks post infusion. Maximum "MP" levels ranging between 16 and 72 mumol/l were obtained after single infusions. In a majority of the patients "MP" concentrations in plasma were reduced to values between 0.12-3.4 mumol/l in 24 h, 0.06 to 0.13 mumol/l in 48 h. Plasma cortisol levels were incompletely suppressed for a few days in all patients, but the drug was removed from plasma and normal adrenal function restored within a fortnight after steroid infusion at the latest.