Tuberous Sclerosis: A Rare Disease with an Orphan Complex.

Introduction In the Republic of Ireland, there are no tuberous sclerosis complex (TSC) specialist clinics. Methods A clinical audit was carried out to assess the care received by patients attending two specialist adult epilepsy specialist centres, measuring their care against the UK guidelines. Results Although many baseline investigations are carried out, only one-third of patients had diagnostic genetic testing results available. Neuropsychiatry is largely neglected, and the completion of neuropsychiatric assessments checklists is inadequate. Discussions concerning SUDEP are not happening and access to treatment is limited. Reporting of radiological findings in TSC is inconsistent and the number of adults with TSC accessing specialist epilepsy services appear to be low. Discussion TSC care in the Republic of Ireland is fragmented, difficult to navigate and wasteful of resources due to the complex nature of the disease and no formal clinical setting to manage it. The service gaps echo the demand for an improved care system including consistent radiological reporting of TSC pathology. The absence of a specialist TSC clinic compounds the complexity of navigating care for individuals with TSC, families and healthcare professionals. Extending this audit nationally will give a more complete picture and highlight the resources required to bring care of these patients in line with recommended guidelines.

Changing Trends in Life Expectancy in Intellectual Disability over Time

Decreased life expectancy (LE) has historically been found among people with intellectual disability (ID) compared to the general population. Several recent studies have looked into ageing and cause of death in ID. Results of many of these studies suggest that, although LE in ID remains lower than the general population, it has increased across many Western societies in recent decades. Increases in LE in the general and ID populations appear to follow similar trends. Some major causes of mortality in ID are similar to the general population, and therefore may be amenable to similar preventative healthcare interventions. In this article, we have outlined possible reasons for improved LE in ID, and potential areas that may require further intervention. However, more detailed studies on mortality in ID may provide more accurate insight into areas requiring intervention in ID populations.

Perampanel: An audit of clinical experience using the epilepsy electronic patient record.

Perampanel is a non-competitive antagonist of AMPA glutamate receptors on post synaptic neurons. The aim of this study was to conduct an audit of the experience of perampanel treatment in Ireland based on the interrogation of the national epilepsy electronic patient record (EPR). A retrospective audit was compiled which reviewed the progress of patients who had been treated across two regional epilepsy centres. The EPR was used to identify patients and collect information relevant to their perampanel therapy. Collected data was entered into a statistical package for social sciences for analysis using descriptive statistics. Seventy patients were identified for inclusion in this audit. Partial onset epilepsy was the predominant epilepsy syndrome treated with perampanel. Eight milligrams daily was the maximum dose achieved in 31.45% (n=22). Complex partial seizures demonstrated the best seizure response to perampanel, which was optimal at doses of 4mgs to 8mgs once daily. Treatment was discontinued primarily due to side effect profile (28.5%; n=20). The common side effects reported were behavioural alteration, sedation and dizziness. Abnormal thoughts were identified in 4.2% (n=3). Overall perampanel has been shown to be an effective adjunct. The EPR was demonstrated as an effective tool for audit and research.

Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.

OBJECTIVES: Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine. METHODS: Fifteen-year prospective observational study from 1996 until 2012. The main outcome measure is the MCM rate. RESULTS: Informative outcomes were available for 5206 cases. 1290 women were exposed to valproate monotherapy, 1718 to carbamazepine monotherapy and 2198 to lamotrigine monotherapy. The MCM risk with valproate monotherapy exposure in utero was 6.7% (95% CI 5.5% to 8.3%) compared with 2.6% with carbamazepine (95% CI 1.9% to 3.5%) and 2.3% with lamotrigine (95% CI 1.8% to 3.1%). A significant dose effect was seen with valproate (p=0.0006) and carbamazepine (p=0.03) exposed pregnancies. A non-significant trend towards higher MCM rate with increasing dose was found with lamotrigine. MCM rate for high-dose lamotrigine (>400 mg daily) was lower than the MCM rate for pregnancies exposed to <600 mg daily of valproate, but this was not significant (3.4% vs 5.0%, p=0.31). CONCLUSIONS: In utero exposure to valproate carries a significantly higher MCM risk than lamotrigine (p=0.0001) and carbamazepine (p=0.0001) monotherapy. In contrast to prior findings, high-dose lamotrigine was associated with fewer MCMs than all doses of valproate. While lamotrigine has a favourable profile compared with valproate for adverse pregnancy outcomes, the requirements for seizure control should not be overlooked.

The economic cost of nonepileptic attack disorder in Ireland.

The present study endeavored to calculate a conservative estimate of both incidence- and prevalence-based costs of nonepileptic attack disorder (NEAD) in Ireland by applying previously identified prevalence figures to Irish population figures. Variables related to the economic cost of NEAD were identified based on a retrospective chart review of patients diagnosed with NEAD at Beaumont Hospital, Dublin. The annual cost per patient of undiagnosed NEAD was calculated as €20,995.30. The combined cost of diagnosis and psychological treatment of NEAD was estimated at €8728. Although it is difficult to determine precise economic costings, early diagnosis and intervention would result in a significant economic saving to the exchequer, a reduction in hospital waiting-list times, and a better prognosis for patients.

Psychiatric and psychosocial morbidity 1 year after epilepsy surgery.

OBJECTIVES: There is a high rate of psychiatric comorbidity in patients with epilepsy. However, the impact of surgical treatment of refractory epilepsy on psychopathology remains under investigation. We aimed to examine the impact of epilepsy surgery on psychopathology and quality of life at 1-year post-surgery in a population of patients with epilepsy refractory to medication. METHODS: This study initially assessed 48 patients with refractory epilepsy using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life in Epilepsy Inventory 89 (QOLIE-89) on admission to an Epilepsy Monitoring Unit (EMU) as part of their pre-surgical assessment. These patients were again assessed using the SCID-I, QOLIE-89 and HADS at 1-year follow-up post-surgery. RESULTS: There was a significant reduction in psychopathology, particularly psychosis, following surgery at 1-year follow-up (p < 0.021). There were no new cases of de novo psychosis and surgery was also associated with a significant improvement in the quality of life scores (p < 0.001). CONCLUSIONS: This study demonstrates the impact of epilepsy surgery on psychopathology and quality of life in a patient population with refractory surgery. The presence of a psychiatric illness should not be a barrier to access surgical treatment.

The health care journeys experienced by people with epilepsy in Ireland: what are the implications for future service reform and development?

Opportunities exist to significantly improve the quality and efficiency of epilepsy care in Ireland. Historically, epilepsy research has focused on quantitative methodologies that often fail to capture the invaluable insight of patient experiences as they negotiate their health care needs. Using a phenomenological approach, we conducted one-to-one interviews with people with epilepsy, reporting on their understanding of their health care journey from onset of symptoms through to their first interaction with specialist epilepsy services. Following analysis of the data, five major themes emerged: delayed access to specialist epilepsy review; uncertainty regarding the competency and function of primary care services; significant unmet needs for female patients with epilepsy; disorganization of existing epilepsy services; and unmet patient information needs. The findings reveal important insights into the challenges experienced by people with epilepsy in Ireland and identify the opportunities for future service reorganization to improve the quality and efficiency of care provided.

Towards the development of integrated epilepsy services: an audit of documented epilepsy care.

Effective chronic disease management (CDM) requires the ready availability and communication of accurate, clinical disease specific information. Using epilepsy as a probe into CDM, we report on the availability and reliability of clinical information in the primary care records of people with epilepsy (PWE). The medical records of 374 PWE from 53 general practices in the Mid-West region of Ireland were examined. Confirmation of an epilepsy diagnosis by a neurologist was documented for 132 (35%) patients. 282 (75%) patients had no documented evidence of receiving specialist neurology review while 149 (40%) had not been reviewed by their GP in the previous two years for their epilepsy. Significant variation in documentation of epilepsy specific information together with an inadequacy and inconsistency of existing epilepsy services was highlighted.

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.

An outcome analysis of seventeen patients treated surgically for intractable extratemporal epilepsy.

We studied the outcomes of seventeen patients treated surgically for extratemporal lobe epilepsy. A retrospective case review of medical charts was performed. Seizure freedom post surgery was appraised using the Engel classification system. Post-operatively seven patients (41%) were seizure free (Engel class I), four patients were class II (23.5%), two in class III (11.76%) and four in class IV (23.5%). Three patients (17.6%) suffered traumatic injuries due to seizures. The mean duration of epilepsy prior to surgery was 12.2 years and the mean number of anti-epileptic medications given was 6.5. Seizure freedom rates for surgical treatment of extratemporal epilepsy in this centre are similar to those of other centres. Post-operative morbidity in this centre was similar to other centres. Any complications resolved with no lasting impairment.

Analysis of the aetiology of epilepsy in 3,216 adult patients attending a tertiary referral center enabled by an electronic patient record.

PURPOSE: The aim of this study was to review the causes of the epilepsies in our institution, an adult tertiary referral center for neurology and neurosurgery in Dublin, Ireland. Data was obtained from a bespoke epilepsy electronic patient record (EPR). METHODS: Predetermined search parameters of well-established broad categories of epilepsy aetiology were used to identify patients with a diagnosis of epilepsy attending Beaumont Hospital, Dublin. There were 3216 patients that met the inclusion criteria for this study. We included living patients with epilepsy attending our institution. We then excluded patients with a diagnosis of pure non-epileptic attack disorder and patients found to have idiopathic generalised epilepsy (IGE) (n = 382) from our final cohort. We excluded IGE due to the complex polygenic basis underlying this patient group. RESULTS: An aetiology was identified in 54.3 % (n = 1747) of the total number of patients studied. Of the symptomatic epilepsies, 41.08 % (n = 1321) were acquired and 13.3 % (n = 426) were predominantly of genetic or developmental aetiology. The most common causes of the acquired epilepsies were hippocampal sclerosis (n = 380; 28.75 %), cerebral tumor (n = 279; 21.06 %), traumatic brain injury (n = 248; 18.77 %), stroke and cerebrovascular disease (n = 151; 11.43 %) and perinatal causes (n = 138; 10.45 %). The leading causes in the genetic / developmental category included cavernous haemangiomas (n = 62, 22.22 %), arteriovenous malformations (n = 59; 21.15 %) and cortical dysplasia (n = 55; 19.71 %). The aetiology of a patient's epilepsy was undetermined in 45.68 % (n = 1469) of individuals. CONCLUSION: This study emphasizes the clinical utility of the ILAE's 2017 revised classification of the epilepsies and highlights the evolving dynamic nature of attributing causality in epilepsy. This is the largest single centre analysis of the aetiology of the epilepsies described in the literature. It is also the first large scale study examining aetiology utilising a bespoke electronic patient record in epilepsy.

Location-specific reflex epilepsy: a novel reflex epilepsy phenotype.

Reflex epilepsies are rare syndromes where seizures are triggered by particular stimuli or activities that may be motor, sensory or cognitive in nature. Triggers are diverse, may be extrinsic or intrinsic in nature and heterogeneous phenotypes have been described over the years. We give an account of a case of location-specific reflex epilepsy which we suggest is a novel reflex epilepsy phenotype relating to higher cortical function (HCF), and review the literature in relation to features of HCF reflex epilepsies described to date.

Felbamate in an adult population with severe refractory epilepsy.

Felbamate (FBM) is efficacious in treating patients with refractory epilepsy but was withdrawn due to cases of aplastic anaemia, hepatic failure and five reported deaths. FBM is currently used in specialist centres and is only being used in one Irish centre to date. This papers aim is to review the efficacy and safety experience of FBM in Irish adult patients with refractory epilepsy. A retrospective chart review was done on patients' medical records. Patients were subdivided into responders and non responders based on change in seizure frequency and side effects were recorded for all. Of the 13 patients on FBM nine patients responded to FBM, four patients did not. FBM is a safe and efficacious alternative in an Irish adult population with refractory epilepsy. However close monitoring is still required given the potential fatal side effects that are possible with this anticonvulsant.

Epilepsy care in general practice.

Epilepsy care in Ireland is shared between primary, secondary and tertiary care services with the General Practitioner (GP) managing the process. Barriers to effective epilepsy care in Irish general practice remain undocumented although sub-optimal and fragmented services are frequently anecdotally reported. This survey of Irish GPs reports on such barriers to epilepsy care and on the Information & Communication Technology (ICT) issues potentially relevant to the use of an epilepsy specific Electronic Patient Record (EPR). The response rate was 247/700 (35.3%). Respondents supported the concept of shared care for epilepsy 237 (96%) however they were very dissatisfied with existing neurology services, including pathways of referral 207 (84%) and access to specialist neurology advice and investigations 232 (94%). They reported that neurology services and investigations may be accessed more expeditiously by patients with private health insurance than those without 178 (72%). Consequently many patients are referred to the emergency department for assessment and treatment 180 (73%). A deficit in epilepsy care expertise among GPs was acknowledged 86 (35%). While computerisation of GP practices appears widespread 230 (93%), just over half the respondents utilise available electronic functionalities specific to chronic disease management. GP specific electronic systems infrequently link or communicate with external electronic sources 133 (54%). While the current pathways of care for epilepsy in Ireland appear fragmented and inadequate, further investigations to determine the quality and cost effectiveness of the current service are required.

Potential efficacy of zonisamide in refractory juvenile myoclonic epilepsy: retrospective evidence from an Irish compassionate-use case series.

To retrospectively evaluate the efficacy of zonisamide as adjunctive therapy in the treatment of refractory juvenile myoclonic epilepsy. We retrospectively reviewed the records of seven patients with refractory juvenile myoclonic epilepsy, commenced on a compassionate-use basis on zonisamide as adjunctive treatment between October 2001 and September 2004. We found significant response rates (>50% reduction in seizure frequency) of 83.3%, 100% and 100% for generalised convulsions, myoclonus, and absence seizures respectively. These results were sustained over more prolonged follow-up in five of seven patients, with one patient improving further over time. Two patients became seizure free with the introduction of zonisamide. Two patients were able to reduce the number of anti-epileptic medications and maintain >75% and 100% reduction in seizure frequency respectively. Four patients initially had minor side-effects that resolved during the maintenance period. In this retrospective study, zonisamide was effective and well-tolerated as adjunctive therapy in patients with refractory juvenile myoclonic epilepsy.

Predicting drug-resistant patients who respond to add-on therapy with levetiracetam.

INTRODUCTION: Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients. METHODS: We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'. RESULTS: 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders. DISCUSSION: A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.

Imaging in patients with a first seizure.

Neuroimaging has important applications in the diagnosis and treatment of patients with seizures and epilepsy and can contribute to the proper classification of certain epileptic disorders. When a patient presents to the Accident and Emergency Department with a first seizure, the clinician may request brain imaging to determine the cause of the seizure. In new onset seizures or epilepsy with suspected focal pathology, computed tomography (CT) of the brain should be performed if the patient has not fully recovered or if magnetic resonance imaging (MRI) is not available within a reasonable time period. Otherwise, it is reasonable to forego CT and perform MRI. This report emphasises the need for appropriate imaging for accurate diagnosis of suspected new-onset partial epilepsy.

July 2004: 40-year-old man with headaches and dyspnea.

A 40-year-old man had a 6-week history of severe frontal headaches and dry cough. Chest x-ray showed hilar adenopathy with bilateral parenchymal infiltrates. A diagnosis of atypical pneumonia was made. Four weeks later he was admitted with persistent headache. Infectious screen was negative. Brain MR post contrast, revealed cerebellar enhancement and swelling with moderate tonsillar herniation; findings which precluded the performance of a lumbar puncture. High resolution CT thorax confirmed hilar abnormalities; shown by microscopy to represent non caseating granulomata. A presumptive diagnosis of sarcoidosis was reached. Despite an initial symptomatic improvement his headache persisted. Repeat MRI, eleven days after admission, showed reduced cerebellar enhancement and swelling with no change in the degree of tonsillar herniation. He deteriorated acutely and died two weeks after admission. Autopsy revealed cerebral oedema with tonsillar herniation secondary to cryptococcal meningitis variety neoformans. There was no evidence of neurosarcoid. Active and inactive sarcoid was identified in the lungs and hilar nodes with no evidence of systemic sarcoid. Focal evidence of cryptococcal pneumonitis was present in the lung as a necrotic focus. A strong index of clinical suspicion is necessary to diagnose the rare association of cryptococcus complicating sarcoidosis.

Safety of newer generation anti-epileptic drugs in non-accidental overdose: an Irish population study.

UNLABELLED: Seven new anti-epileptic drugs (AEDs) have become available in Ireland over the last 10 years; data from animal models and clinical trials suggest that they have a superior safety profile to older AEDs. A specific relationship between epilepsy and psychiatric co-morbidity has long been recognised, including the relationship between epilepsy and suicide. AEDs are common agents taken in intentional drug overdoses. We undertook a study to review the frequency and outcome of non-accidental overdose with seven new AEDS in an Irish population from 1996 to 2000. METHOD: All reported cases of drug overdoses with AEDs from 1996 to 2000 were reviewed. Data was provided by the National Poisons Information Centre, Beaumont Hospital and the Central Statistics Office. Medical records from Beaumont Hospital were reviewed in specific cases of serious drug toxicities. An extensive review of published literature reviewing the safety profile of these AEDs was performed and medical literature retrieved from the databases of the pharmaceutical industry was similarly reviewed. RESULTS: Of the 164 reported cases of newer AEDs, there were no fatalities among the cases followed up. CONCLUSION: The absence of mortalities and serious consequences from deliberate self-poisoning with the newer agents is supportive evidence for the superior safety profile of the newer AEDs.

Antioxidant therapy in neurologic disease.

Free radical or oxidative injury may be a fundamental mechanism underlying a number of human neurologic diseases. Therapy using free radical scavengers (antioxidants) has the potential to prevent, delay, or ameliorate many neurologic disorders. However, the biochemistry of oxidative pathobiology is complex, and optimum antioxidant therapeutic options may vary and need to be tailored to individual diseases. In vitro and animal model studies support the potential beneficial role of various antioxidant compounds in neurologic disease. However, the results of clinical trials using various antioxidants, including vitamin E, tirilazad, N-acetylcysteine, and ebselen, have been mixed. Potential reasons for these mixed results include lack of pretrial dose-finding studies and failure to appreciate and characterize the individual unique oxidative processes occurring in different diseases. Moreover, therapy with antioxidants may need to be given early in chronic insidious neurologic disorders to achieve an appreciable clinical benefit. Predisease screening and intervention in at-risk individuals may also need to be considered in the near future.