Zonisamide safety in pregnancy: Data from the UK and Ireland epilepsy and pregnancy register.

BACKGROUND: Animal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight. OBJECTIVE: To calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight. METHODS AND MATERIALS: Data were obtained from the UK and Ireland Epilepsy and Pregnancy register (UKIEPR) which is an observational, registration, and follow up study from December 1996 to July 2020. Eligibility criteria were use of zonisamide and to have been referred to the UKIEPR before the outcome of the pregnancy was known. Primary outcome was evidence of MCM. RESULTS: From December 1996 through July 2020 there were 112 cases of first trimester exposure to zonisamide, including 26 monotherapy cases. There were 3 MCM for monotherapy cases (MCM rate 13.0% (95% confidence interval 4.5-32.1)), and 5 MCM for polytherapy cases (MCM rate 6.9% (95% confidence interval 3.0-15.2)). While the median birth weight was on 71st and 44th centile for monotherapy and polytherapy cases respectively, there was a high rate of infants born small for gestational age (21% for both). CONCLUSION: These data raise concerns about a signal for potential teratogenicity with zonisamide in human pregnancy. Given the low numbers reported, further data will be required to adequately counsel women who use zonisamide in pregnancy.

The reliable measurement of temporal trends in mortality attributed to epilepsy and status epilepticus in Northern Ireland between 2001-2015.

PURPOSE: Epilepsy mortality is of considerable public health concern, as a leading cause of premature neurological death. Recent English and Welsh mortality data suggests a falling mortality rate where epilepsy was the underlying cause of death, predominantly due to a reduction in status epilepticus (SE) mortality. We sought to validate this finding in Northern Ireland. METHODS: Officially recorded death certificate data related to epilepsy and SE were obtained from the Northern Ireland statistics and research agency. Data were analysed from 2001 to 2015. The outcomes were the age-adjusted mortality rate for epilepsy and SE. External validation of SE deaths was carried out using data from an intensive care national audit and research centre database. RESULTS: From 2001 until end of 2015, epilepsy was recorded at death certification in 1484 cases. 458 deaths were considered due to epilepsy. Among 75 in whom SE was recorded, SE was the cause of death in 46 patients. External validation found 103 total deaths related to SE in ICU departments in Northern Ireland, suggesting an overall under-ascertainment of officially recorded statistics. With respect to the 2013 European Standard Population, the mean age-adjusted mortality rate for epilepsy was 1.9 (95% C.I. 1.73-2.07) per 100,000 person years. For SE the mean age-adjusted mortality rate was 2.1 (95% C.I. 0.15-0.27) per 100,000 person years. CONCLUSIONS: Death certification in SE is likely to be an underestimate of the reality. Further efforts are urgently needed to determine the extent of SE-related deaths and all deaths in patients with epilepsy.

Hidden in plain sight: Non-convulsive status epilepticus-Recognition and management.

Non-convulsive status epilepticus (NCSE) is an electroclinical state associated with an altered level of consciousness but lacking convulsive motor activity. It can present in a multitude of ways, but classification based on the clinical presentation and electroencephalographic appearances assists in determining prognosis and planning treatment. The aggressiveness of treatment should be based on the likely prognosis and the underlying cause of the NCSE.

Pregnancy and epilepsy; meeting the challenges over the last 25 years: The rise of the pregnancy registries.

PURPOSE: Women with epilepsy (WWE), of all ages, have much to consider if their care is to be optimised and they are not to be denied the choices open to those without epilepsy. At no time is this more critical than during their child-bearing years when treatment decisions are complex. METHODS: In this article we will provide a personal commentary and review of the pertinent literature on how the management of WWE of childbearing years has changed over the last 25 years. As well as reflecting on the state of knowledge at the start of the 1990s and the approach to managing WWE at this time, we will demonstrate that in addition to much more information now being available that there has also been an attempt to standardise how WWE should be managed. RESULTS: As a means of achieving this increase in knowledge and standardisation of care, we argue that the various pregnancy registries have played a significant part in these positive developments. As vehicles for collecting clinically relevant data, they have provided information that has helped empower women and their health care providers to make sound clinical decisions, as well as highlighting the difficulties and unknowns. CONCLUSIONS: Still being active the pregnancy registries maintain a continued focus on the relevant issues relating to WWE.

The palmar metric: A novel radiographic assessment of the equine distal phalanx.

Digital radiographs are often used to subjectively assess the equine digit. Recently, quantitative and objective radiographic measurements have been reported that give new insight into the form and function of the equine digit. We investigated a radio-dense curvilinear profile along the distal phalanx on lateral radiographs we term the Palmar Curve (PC) that we believe provides a measurement of the concavity of the distal phalanx of the horse. A second quantitative measurement, the Palmar Metric (PM) was defined as the percent area under the PC. We correlated the PM and age from 544 radiographs of the distal phalanx from the left and right front feet of various breed horses of known age, and 278 radiographs of the front feet of Quarter Horses. The PM was negatively correlated with age and decreased at a rate of 0.28 % per year for horses of various breeds and 0.33 % per year for Quarter Horses. Therefore, veterinarians should be aware of age related change in the concave, parietal solar aspect of the distal phalanx in the horse.

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register.

OBJECTIVE: In the general population, folic acid supplementation during pregnancy has been demonstrated to reduce the frequency of neural tube defects (NTDs) and other major congenital malformations (MCMs). It is recommended that women with epilepsy contemplating pregnancy take supplemental folic acid because of the known antifolate effect of some antiepileptic drugs (AEDs). Here the aim was to determine the effectiveness of this practice. METHODS: This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant and who are referred before outcome of the pregnancy is known. The main outcome measure is the MCM rate. Outcomes were analysed against folic acid exposure, malformation type and drug group for the most commonly used monotherapy AEDs. RESULTS: In 1935 cases reported to have received preconceptual folic acid, 76 MCMs (3.9%; 95% CI 3.1 to 4.9) and eight NTDs (0.4%; 95% CI 0.2 to 0.8) were identified. For 2375 women who were reported to have received folic acid but not until later in the pregnancy (n = 1825) or not at all (n = 550), there were 53 outcomes with an MCM (2.2%; 95% CI 1.7 to 2.9) and eight NTDs (0.34%; 95% CI 0.2 to 0.7). CONCLUSIONS: The study supports the view that extrapolation from studies carried out in the general population to groups of women with epilepsy may be questionable. It may be that the increased risk of MCM recorded in this group occurs through mechanisms other than that of folic acid metabolism.

Idiopathic intracranial hypertension; incidence, presenting features and outcome in Northern Ireland (1991-1995).

OBJECTIVES: To determine the age and sex specific incidence rates, presenting features, and visual outcome of idiopathic intracranial hypertension in Northern Ireland. METHODS: A case-note review of all patients with idiopathic intracranial hypertension, diagnosed at the Royal Victoria Hospital, Belfast between 1991 and 1995. RESULTS: Forty-two patients were identified corresponding to an average annual incidence rate per 100,000 persons of 0.5 for the total and 0.9 for the female population. The commonest presenting symptoms were headache (84%), transient visual obscurations (61%) and sustained visual loss (34%). Impaired Snellen visual acuity and visual field loss were documented in 21% and 62% of patients respectively at presentation, and in 24% and 39% at last follow-up. One patient suffered deterioration in visual functioning sufficient to interfere with normal daily activities. CONCLUSIONS: The age and sex specific incidence rates of IIH in Northern Ireland are lower than have been reported in previous population-based series. Disabling visual loss occurs in a small number of patients despite all interventions.

Vagal nerve stimulation in patients with refractory epilepsy. Effect on seizure frequency, severity and quality of life.

Vagal nerve stimulation using an NCP (Cyberonics) device has been suggested as a potential treatment for patients with epilepsy that has previously proven refractory. Ten patients in Northern Ireland have had this device implanted and been fully audited pre- and post-operatively. Twelve months post-implantation, five patients have demonstrated a greater than 50% reduction in seizure frequency. A statistical reduction in seizure severity of the ictal phase of the major seizures has also been shown. Improvement in the patients' overall quality of life has, however, not been demonstrated in parallel to seizure reduction.

Bilateral astrocytoma involving the limbic system precipitating disabling amnesia and seizures.

Astrocytomas involving the limbic system are usually unilateral in nature. We report a very unusual case where a low-grade astrocytoma originating in the left temporal lobe spread to the right hippocampus through the hippocampal commissure to cause disabling amnesia and seizures. Some improvement in the memory deficit was facilitated by identification of complex partial status epilepticus. EEG should be performed in all patients with lesions of the limbic system and neuropsychological problems if ongoing seizure activity is not to be missed.

Non-convulsive status epilepticus: a treatable cause of confusion in pituitary apoplexy.

Confusion occurring in pituitary apoplexy is well described. We describe a case of pituitary apoplexy associated with confusion, occurring as a result of non-convulsive status epilepticus. Electroencephalography should be performed in pituitary apoplexy associated with confusion if this treatable and potentially serious complication is not to be missed.

Effective diagnosis of spinal cord compression using telemedicine.

We report the case of a man with an acute cervical cord lesion which was diagnosed after a teleconsultation with a neurologist at a distant neurological centre. We show that the ability to assess patients clinically using real-time videolinks is also of use in detecting those patients who would benefit from specialist neurosurgical intervention, but who might otherwise be denied it because of their location.

Prevalence of the Chiari/hydrosyringomyelia complex in adults with spina bifida: preliminary results.

AIM: To establish the prevalence of Chiari malformations and hydrocephalus (HS) in adults with spina bifida (SB). INTRODUCTION: Adults with SB have recently been shown to be at risk from significant deterioration arising from the C/HS complex. Little is known about the prevalence of these malformations in adulthood, their natural history, risk factors for deterioration and optimum management. MATERIALS AND METHODS: Patients are recruited from a clinic for adults with SB and hydrocephalus, routinely questioned about recent changes in neurological symptoms and a full neurological examination performed. Functional assessments include: Barthel Index; Nottingham EADL; Nine Hole Peg Test; 10 metre timed walk test. Sagittal T1 and TSE (turbo spin-echo) magnetic resonance images (MRI) of the cranio-cervical junction and spinal cord are obtained using a 1.0-T MRI system with a phased-array surface coil. Scans are reported blindly. RESULTS: 76 patients have been assessed, 40 female, 36 male, mean age 27.5 years. Of these, 48 (63.2%) have symptoms +/- signs compatible with C/HS, but only 18 (23.7%) have reported new, potentially relevant, neurological symptoms over the previous 12 months. Of 25 patients undergoing MRI so far, 19 (76%) have had Chiari malformations and 12 (48%) have had HS. None of those with a negative scan have had signs/symptoms suggestive of the C/HS complex but a negative clinical evaluation has been unable to exclude such pathology. CONCLUSIONS: These early results suggest that the prevalence of the C/HS complex is high in adults with SB and cannot be predicted by neurological examination alone. Given past experience, the need for continued neurological follow up in a large proportion of the SB population throughout adulthood is likely to be essential.

The Chiari/hydrosyringomyelia complex presenting in adults with myelomeningocoele: an indication for early intervention.

OBJECTIVE: To determine how adults with myelomeningocoele who develop the Chiari/hydrosyringomyelia complex present, and to determine if surgical intervention influences outcome in these patients. METHODS: A chart review of the 220 patients who attend a clinic for adults with spina bifida and hydrocephalus (CASBAH), and follow-up of the five cases with myelomeningocoele who had surgical intervention for associated symptomatic Chiari/hydrosyringomyelia complex. RESULTS: Bilateral upper limb weakness and wasting were the commonest presenting symptoms (four patients). Sensory disturbance (three patients) was also common, dysphagia (one) and ataxia (one) occurring less often. The median time to surgical intervention was 36 months. Two patients had a shunting procedure performed in isolation, two foramen magnum decompression in addition to a shunting procedure and one a foramen magnum decompression. Surgical intervention did not completely reverse problems attributed to the Chiari/hydrosyringomyelia complex in any of the cases. One patient died post-operatively. Of the four who survived one had some improvement in function post-operatively, two remained static and one had further mild deterioration. CONCLUSION: All adults with myelomeningocoele should be questioned about changes in upper limb function for early detection of Chiari/hydrosyringomyelia complex. Our results suggest that early intervention is needed if further deterioration is to be avoided, and to improve the chances of neurological and functional recovery.

Neurological examination is possible using telemedicine.

To compare the reliability of neurological examination performed by telemedicine and face to face, a junior doctor examined 23 patients face to face, these examinations being witnessed either by one or by two telemedicine observers using a telemedicine video-link at 384 kbit/s. The gold standard was a face-to-face examination from a panel of six consultant neurologists. Power, deep tendon reflexes, plantar responses, coordination, sensation, eye movements, facial strength, tongue movements, sitting balance and gait were studied. Seventeen patients satisfied the inclusion criteria, and a total of 1,084 matched pairs of observations were made. The reliability of the telemedicine examination ranged from fair to moderate for deep tendon reflexes, coordination and eye movement, to near perfect for plantar responses. Overall, examination by telemedicine compared favourably with face-to-face examination. Telemedicine examination was more sensitive in detecting abnormalities than face-to-face examination for all the neurological tests studied and more specific for all but one (plantar responses). The study showed that neurological examination using telemedicine is at least as good as face-to-face examination performed by a junior doctor.

Use of scanning laser ophthalmoscopy to monitor papilloedema in idiopathic intracranial hypertension.

AIMS: To determine the sensitivity of confocal scanning laser ophthalmoscopy (SLO) in detecting clinically significant changes in papilloedema secondary to idiopathic intracranial hypertension (IIH) and the correlation with visual field loss. METHODS: Eight patients--three new, two recurrent, and three chronic cases of IIH--were examined over a 9 month period with SLO (Heidelberg retina tomograph) of optic nerve head and 30-2 Humphrey visual fields (six cases). Optic disc swelling (volume) was assessed in each eye using a circular contour line placed around the swollen optic nerve head on the mean image of three topographic images. Nine volume measurements from single images in each eye of every patient were performed on one occasion to assess repeatability. RESULTS: In the five acute cases optic disc volumes (range 1-16 mm3) decreased with treatment to stable, normal levels. Three of these had mild, reproducible, field defects which resolved. Two chronic cases had stable or fluctuating disc volume with no detectable change in grade of papilloedema and mild field loss. In one case which underwent theco-peritoneal shunting both disc volume and field worsened, indicating therapeutic failure. Both improved postoperatively. CONCLUSIONS: SLO has a high sensitivity for detecting small changes in disc volumes and correlates closely with visual field change in the short term. It can confirm therapeutic failure by detecting stable or increasing disc volume. Decreasing volume may indicate resolution of papilloedema or secondary optic atrophy, so accompanying funduscopy and visual fields remain essential.

Headaches in the accident and emergency department.

Serious illness is not uncommon in patients attending accident and emergency departments with headache. Careful clinical assessment, focusing on characteristics of the headache, associated symptoms and certain examination findings, helps to identify those at risk, and permits the efficient management of everybody else.