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N Delanty

Publications and source records attributed to N Delanty.

At least 19 recordsLinked to original sources

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.

Anticonvulsants↗

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.

Adult↗

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.

Anticonvulsants↗

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.

Adult↗

Needs analysis for tele-neurophysiology in the Irish North-Western Health Board.

No clinical neurophysiology (CN) service is currently provided by the North-Western Health Board (NWHB) region in Ireland. Digital technology associated with CN is compatible with tele-neurophysiology service development and may increase the efficiency of patient care in remote areas. This study was conducted to assess the need for CN in the NWHB with a view to implementing a tele-neurophysiology service for the region. A retrospective audit of investigations performed at six CN departments in Dublin compared patient groups from regions with (Eastern Regional Health Authority--ERHA) and without (NWHB) local CN departments. 4954 records were audited. CN activity was lower than internationally expected (ERHA group 52% of expected, NWHB group 23% of expected). The 2 groups differ in the specialty of referring clinician (p < 0.0001). NWHB patients are more likely to be referred by clinicians outside their region (p < 0.0001) and wait longer for appointment (p < 0.0001). While there is an unmet demand for CN services in Ireland generally, the population of the NWHB is further disadvantaged. Tele-neurophysiology has the potential to provide fairer access to CN services across the country. The data from this study provide a baseline against which the outcome of investment in CN can be monitored and evaluated.

Chi-Square Distribution↗

Elevated extracellular levels of glutamate, aspartate and gamma-aminobutyric acid within the intraoperative, spontaneously epileptiform human hippocampus.

We report preliminary results from four patients subjected to hippocampal electrocorticography and microdialysis during temporal lobe epilepsy surgery. In two cases, spontaneously vigorous hippocampal epileptiform activity (EA) was identified; basal dialysate levels for hippocampal glutamate, aspartate, and gamma-aminobutyric acid ranged from approximately 23- to 84-fold, 19- to 33-fold and 10- to 34-fold higher, respectively, compared to the two cases of minimal hippocampal EA. These findings represent the first intraoperative evidence of elevated extracellular levels of neuroactive amino acids within the spontaneously epileptiform human hippocampus.

Adult↗

Juvenile myoclonic epilepsy: under-appreciated and under-diagnosed.

Juvenile myoclonic epilepsy (JME) is a hereditary, idiopathic, generalised epilepsy and is found in 5%-11% of patients with epilepsy. It is characterised by myoclonic jerks, occasional generalised tonic-clonic seizures, and sometimes absence seizures. JME continues to be under-appreciated and under-diagnosed. Accurate diagnosis is important as it usually responds well to treatment with appropriate anticonvulsants and misdiagnosis often results in unnecessary morbidity. In addition lifelong therapy is usually indicated as the natural history is one of relapse off treatment, even after a prolonged seizure-free period.

Adolescent↗

Patients' aims for epilepsy surgery: desires beyond seizure freedom.

PURPOSE: To evaluate prospectively patient's aims for epilepsy surgery as previously outlined theoretically by Taylor et al. (Epilepsia 1997;3:625-30). METHODS: Ninety-three consecutive patients were interviewed by a psychiatrist as part of their evaluation for epilepsy surgery. Open-ended questions about the patient were asked, and carers' aims or ambitions for change as a result of putative relief of seizures were elicited. The interviewer aimed to obtain a maximum of five aims for later follow-up purposes. These questions were part of an extensive psychiatric interview that is described. RESULTS: The aims of 69 patients or carers were analyzed. The 204 statements of aims were grouped into 59 categories initially. The five most frequently cited constituted 50% of all the aims listed. These aims were desire for work, driving of motor vehicles, independence, socializing, and freedom from drugs. The patients rarely identified a desire for improvement in cognitive functioning as an aim for epilepsy surgery. A final analysis into six categories showed that changes in social process predominated, even over changes in personal behavior. CONCLUSIONS: The social and personal aims to accompany relief of epilepsy identified by patients are consistent with the literature on psychosocial adjustment to epilepsy.

Adaptation, Psychological↗

Status epilepticus arising de novo in hospitalized patients: an analysis of 41 patients.

Most of the information on predisposing factors and mortality in status epilepticus (SE) arises from data obtained from patients presenting to the casualty department. However, another population which is frequently seen by consultative neurologists are medically ill patients who develop SE while in hospital. These patients are often notoriously difficult to treat once SE arises. We sought to characterize patients at risk for SE arising when they are hospitalized for other reasons. By doing this, risk factors for developing SE and prognostic indicators might be determined. We retrospectively reviewed records from three urban hospitals in the United States to identify hospitalized patients developing SE over a 1 year period. SE was defined as a clinical seizure lasting 30 minutes or longer, or repeated seizures without recovery. Patients who were admitted in SE or for an epilepsy-related problem, or who were less than 1 year old were excluded from the study. Forty-one patients with in-hospital SE were identified. There were 28 males and 13 females with an age range from 1 to 91 years (mean: 60 years, median: 65 years). The mean interval from hospital admission to the onset of status epilepticus was 26 days. Nineteen (46%) patients had a prior history of either epilepsy or symptomatic seizures, and of these, 10 were inadequately treated as judged by serum anticonvulsant levels at the time SE developed. Focal brain abnormality was present in 26 (63%) patients, the most common of which was stroke (17 patients ). Major metabolic derangements including hypoxia, electrolyte imbalance, hepatic encephalopathy, and sepsis were present in 23 (56%) patients. Eleven (27%) patients were being treated with theophylline preparations at the time SE developed. Mortality in this group of patients with in-hospital SE was 61% (25 deaths), with about one-third dying while in status, and two-thirds dying subsequently in hospital. In this retrospective study, there was no clear relationship between mortality and the duration of SE in this group of patients. In-hospital development of SE is usually related to underlying focal brain abnormality, especially stroke, in combination with systemic metabolic derangement. Prognosis is poor, and appears to be more related to underlying conditions rather than to status duration. More accurate prospective studies are warranted.

Adolescent↗

Statin therapy and stroke prevention.

Hypercholesterolemia has not traditionally been considered an important risk factor in the pathogenesis of stroke. However, recent studies show that statin therapy significantly reduces ischemic stroke for patients with established coronary artery disease. Statin therapy may reduce stroke through amelioration of precerebral atherosclerosis in the carotid artery and the aorta. Anti-atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur within the blood and in plaque. Statins may also protect against cerebral ischemia through beneficial modulation of the brain endothelial nitric oxide system. Ongoing studies are exploring the role of statin therapy in the primary prevention of stroke and in the prevention of cognitive decline and multi-infarct cerebrovascular disease.

Anti-Inflammatory Agents↗

Antiplatelet agents for secondary prevention of ischemic stroke.

OBJECTIVE: To review and summarize the efficacy, mechanisms of action, and cost of the options available when choosing antiplatelet agents for secondary stroke prevention. DATA SOURCES: This article is based on a review of the literature found with MEDLINE, CINAHL, and Cochrane Reviews (1980-June 2000) and abstracts from relevant international scientific meetings. We searched for the terms aspirin, ticlopidine, dipyridamole, antiplatelet, and clopidogrel. STUDY SELECTION: English-language articles, both reviews and original studies, were evaluated, and all information considered relevant was included in this review. In addition, guidelines from the American Heart Association are included. DATA SYNTHESIS: Aspirin is a relatively inexpensive and effective agent for secondary stroke prevention, and lower doses of aspirin appear as effective as higher doses. Ticlopidine has been used alone or in combination with aspirin, but serious adverse effects have limited its use. Clopidogrel has emerged as a safe and effective alternative to ticlopidine and lacks some of the serious adverse effects associated with ticlopicine, but is not superior to aspirin in secondary stroke prevention. Unlike previous studies, one recent trial showed that dipyridamole in combination with aspirin is superior to aspirin alone. CONCLUSIONS: Antiplatelet therapy is a key component of secondary prevention strategies in ischemic stroke. While aspirin has been the cornerstone in the management of stroke, other classes of antiplatelet drugs present new opportunities to optimize antiplatelet therapy.

Aspirin↗

Statins and neuroprotection.

The beneficial effect of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in primary prevention of coronary artery disease in those with hypercholesterolaemia and in secondary prevention in those with established coronary vascular disease are now well known. A growing body of evidence suggests that statins also possess important additional clinical benefits, such as stroke risk reduction. In this article we review the evidence that statins may be neuroprotective, especially in the brain parenchyma during stroke. We also review the observational data that statins may prevent the onset of dementia.

Animals↗

Do statins afford neuroprotection in patients with cerebral ischaemia and stroke?

An emerging body of evidence indicates that beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or 'statins', provide neuroprotection in addition to reducing ischaemic stroke. Statins reduce the incidence of ischaemic stroke by stabilising atherosclerotic plaques in the precerebral vasculature and through antithrombotic actions, and the neuroprotective effects of statins may confer significant clinical benefit. Some of these neuroprotective effects are likely to be cholesterol independent and mediated by the interruption of isoprenoid biosynthesis. Therapy with statins may modulate endothelial function and preserve blood flow to regions exposed to an ischaemic insult. In particular, statin-mediated preservation of endothelial nitric oxide synthase activity in cerebral vasculature, especially in the ischaemic penumbra, may limit neurological deficit. Moreover, putative anti-inflammatory and antioxidant properties of statins may confer additional neuroprotection. Further large clinical trials are necessary to address the role of statin therapy in the primary prevention of stroke, small vessel cerebrovascular disease and vascular dementia.

Antioxidants↗

Hypertensive emergencies.

A hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage. Most patients presenting with hypertensive emergency have chronic hypertension, although the disorder can present in previously normotensive individuals, particularly when associated with pre-eclampsia or acute glomerulonephritis. The pathophysiological mechanisms causing acute hypertensive endothelial failure are complex and incompletely understood but probably involve disturbances of the renin-angiotensin-aldosterone system, loss of endogenous vasodilator mechanisms, upregulation of proinflammatory mediators including vascular cell adhesion molecules, and release of local vasoconstrictors such as endothelin 1. Magnetic resonance imaging has demonstrated a characteristic hypertensive posterior leucoencephalopathy syndrome predominantly causing oedema of the white matter of the parietal and occipital lobes; this syndrome is potentially reversible with appropriate prompt treatment. Generally, the therapeutic approach is dictated by the particular presentation and end-organ complications. Parenteral therapy is generally preferred, and strategies include use of sodium nitroprusside, beta-blockers, labetelol, or calcium-channel antagonists, magnesium for pre-eclampsia and eclampsia; and short-term parenteral anticonvulsants for seizures associated with encephalopathy. Novel therapies include the peripheral dopamine-receptor agonist, fenoldapam, and may include endothelin-1 antagonists.

Antihypertensive Agents↗

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.

Antioxidants↗