Treatments for progressing Parkinson's disease: a clinical case scenario study.

OBJECTIVE: A 'case scenario' study on clinical decisions in progressing Parkinson's disease (PD) was developed to complement scientific evidence with the collective judgment of a panel of experts. METHODS: The opinions of 9 experts in movement disorders on the appropriateness of 9 common pharmacological treatments for 33 hypothetical patient profiles were compared to those of 14 general neurologists. Before rating the case scenarios, all participants received a document integrating European and US guidelines for the treatment of patients with advanced PD. Case scenarios showing disagreement or with inconsistencies in appropriateness ratings were discussed at a feedback meeting. A tool for interactive discussion on the clinical case scenarios included was developed based on the outcome of the study. RESULTS: Current guidelines are often insufficient to adequately guide the management of patients with progressing PD. The case scenario study did not reveal major differences in opinions between experts in movement disorders and general neurologists about the appropriateness of certain drug choices for specific case scenarios. However in about 1 out of 5 treatment decisions where experts stated appropriateness or inappropriateness, the general neurologists panel had no or dispersed opinions. CONCLUSIONS: This study reveals more uncertainty about treatment of advanced PD in general neurologists compared with experts in movement disorders and underlines the need for additional support for guiding treatment decisions in clinical practice.

A pilot trial with modified Atkins' diet in adult patients with refractory epilepsy.

OBJECTIVES: At Ghent University Hospital, the feasibility and efficacy of the modified Atkins' diet was evaluated in adult patients with refractory epilepsy. The Atkins' diet restricts carbohydrate intake and was originally designed for weight loss. PATIENTS AND METHODS: During a 6-month trial period, a carbohydrate restriction of 20 g/day was in place. During a 36 h hospital admission, patients were instructed about the diet. Patients underwent clinical neurological testing, EEG, ECG, blood and urine analyses and mood evaluation before and during the trial. Seizure frequency and side effects were recorded in seizure diaries and followed up at monthly clinic visits. RESULTS: Eight patients were included in the study. Three out of eight patients followed the diet for 6 months. One out of three patients showed a >50% seizure reduction, 1/3>30%, and 1/3<30%. Side effects such as constipation and diarrhoea were mild and occurred mainly during the initial week of the diet. Patients reported improved concentration and well being. This was confirmed by improved scores on the Beck Depression Inventory Scale. CONCLUSION: This pilot study shows that the modified Atkins' diet is feasible in an adult population, and that seizure frequency reduction is possible. The results need to be confirmed in larger prospective, controlled studies with comparison groups.

Standards of care for non-convulsive status epilepticus: Belgian consensus recommendations.

Non-convulsive status epilepticus (NCSE) makes up around one-third of all cases of SE, affecting approximately 1,000 to 4,000 individuals per year in Belgium. Compared with convulsive SE, NCSE has received considerably less attention, is underdiagnosed and undertreated. However, if recognised, NCSE can however be treated successfully. A workshop was convened by neurologists from major Belgian centres to review the latest information on NCSE and to make recommendations on diagnosis and treatment. These recommendations are not only intended for neurologists, but also for primary care physicians and physicians in intensive care units. NCSE should be suspected whenever cases of fluctuating consciousness or abrupt cognitive or behavioural changes are noted. Confirmation of diagnosis by EEG should be obtained wherever possible. In view of the often subtle clinical signs, EEG is also vital for monitoring treatment outcome. Non-comatose patients should generally be treated in a neurology ward since referral to an ICU is unnecessary. First-line treatment should be an intravenous benzodiazepine. For many patients who fail to respond to benzodiazepines, intravenous valproate will successfully abrogate seizure activity. Intravenous phenytoin can be used in patients with focal NCSE in whom valproate is contraindicated or ineffective. Time and care should be spent in identifying an appropriate and effective antiepileptic drug regimen without recourse to anaesthesia. For comatose patients, treatment intensity should be graded according to epilepsy history, general medical state and prognosis. In some patients, intensive remedial measures may allow rapid resolution of NSCE, whereas in more vulnerable patients, such treatment may be counterproductive.

Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease.

BACKGROUND: Restrictive valvular heart disease has been reported in patients with Parkinson's disease treated with pergolide. However, few data are available on frequency, severity, dose dependency, and reversibility of pergolide-induced disease, nor on the pulmonary pressures of these patients. We aimed to clarify these characteristics in a large group of patients. METHODS: 78 patients with Parkinson's disease treated with pergolide and 18 never treated with an ergot-derived dopamine agonist (controls) were evaluated by echocardiography. A valvular scoring system was used, ranging from 1 (proven ergot-like restrictive valvular heart disease) to 4 (no disease). For the mitral valve, tenting areas and tenting distances were measured. Systolic pulmonary artery pressures were derived from the tricuspid regurgitant jet. FINDINGS: Restrictive valvular heart disease of any type was present in 26 (33%) patients in the pergolide group and none in controls (p=0.0025). Important disease (score 1 or 2) was present in 15 (19%) patients in the pergolide group and none in controls (p=0.066). Mean tenting distances and tenting areas of the mitral valve were 1.08 cm (range 0.55-2.66) and 2.39 cm2 (0.88-4.59) in the restrictive mitral valve group versus 0.63 cm (0.22-1.20) and 1.39 cm2 (0.39-3.23) in the non-restrictive group (p=0.003 and p<0.0001, respectively). Significant correlation was noted between cumulative doses of pergolide and tenting areas of the mitral valves (r=0.412, p=0.017). Mean systolic pulmonary artery pressures were 39.3 mm Hg (range 25-71) in the high-dose group versus 38.5 mm Hg (20-65) in the low-dose group (p=0.76) and 31 mm Hg (25-40) in controls (p=0.02 vs all patients given pergolide). In six patients, pergolide treatment was stopped because of restrictive valvular heart disease, in two of whom regression of disease was shown. INTERPRETATION: Restrictive valvular heart disease is not a rare finding in patients treated with pergolide. Clinicians should consider changing to a non-ergot drug if this disease is diagnosed.

Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations.

Status epilepticus (SE) is a significant health problem, affecting approximately 1,000 to 4,000 individuals per year in Belgium. A workshop was convened by a panel of neurologists from major Belgian centers to review the latest information relating to the definition, diagnosis and treatment of convulsive SE. The panelists sought to make recommendations for practising neurologists, but also primary care physicians and physicians in intensive care units when initiating emergency measures for patients with convulsive SE. As there is an association between prolonged seizures and a poor outcome, the importance of early (within the first 5 minutes of seizure onset) and aggressive treatment is to be stressed. In addition to general systemic support (airway, circulation), intravenous administration of the benzodiazepines lorazepam or diazepam is recommended as first-line therapy. Intramuscular midazolam may also be used. If SE persists, second-line drugs include phenytoin or valproate, and third-line drugs the barbiturate phenobarbital, the benzodiazepine midazolam, or the anaesthetics thiopental or propofol, or eventually ketamine. If the patient does not recover after therapy, monitoring of seizures should involve an electroencephalogram to avoid overlooking persistence of clinically silent SE. As a general rule, the intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. If initial treatment with a benzodiazepine fails to control seizures, the patient must be referred to the emergency unit and a neurologist should be contacted immediately.

Treatment of myoclonus.

Myoclonus is a clinical term meaning a sudden, quick, involuntary muscle jerk, irregular or rhythmic, arising in the central nervous system. The most important initial step in the treatment of myoclonus is to try to subclassify the type of myoclonus and identify the underlying disease process. Metabolic derangements or other underlying conditions, if found, need to be treated. Offending drugs causing myoclonus should be removed. A number of different drugs have been used for the symptomatic control of myoclonus. They include sodium valproate, clonazepam, some other antiepileptic drugs, piracetam, and levetiracetam.

Development of an electronic decision tool to support appropriate treatment choice in adult patients with epilepsy--Epi-Scope(®).

BACKGROUND: Given the continuous knowledge progression and the growing number of available antiepileptic drugs (AEDs), making appropriate treatment choices for patients with epilepsy is increasingly difficult. While published guidelines help for separate clinical aspects, patients with a combination of specific characteristics may escape proper guidance. This study aimed to determine the appropriateness of AEDs for particular clinical variables and to offer treatment recommendations for adult patients with epilepsy in a user-friendly format for practicing neurologists. METHODS: Using the RAND/UCLA Appropriateness Method, the appropriateness of AEDs as initial/second mono-therapy and combination therapy was assessed in relation to selected clinical variables by a Belgian panel of 13 experts in epilepsy. Panel recommendations for particular patient profiles were determined by the outcome of these separate ratings. RESULTS: The appropriateness outcome of individual AEDs was not substantially different between first and second mono-therapy; valproate was considered appropriate for all types of generalised and partial seizures. The outcome for combination therapy was highly dependent on the type of AED and seizures. With respect to co-morbidities and co-treatments, levetiracetam and pregabalin proved to have the least contra-indications. For the elderly and with respect to factors related to the female reproductive system the appropriateness of AEDs showed a more diffuse pattern. Although caution was deemed necessary for some combinations, the AEDs were never considered inappropriate regarding their drug interaction profile. CONCLUSIONS: The Epi-Scope(®) tool that displays appropriateness recommendations for highly specific, possibly complex cases, supports optimal treatment choices for adult patients with epilepsy in daily practice.

Predictive factors for outcome of invasive video-EEG monitoring and subsequent resective surgery in patients with refractory epilepsy.

OBJECTIVE: This is a descriptive study of patients who underwent invasive video-EEG monitoring (IVEM) at Ghent University Hospital. The aim of the study is to identify predictive factors for outcome of IVEM and resective surgery (RS). These factors may optimize the patient flow following the non-invasive presurgical evaluation towards IVEM and RS or other treatments. PATIENTS AND METHODS: Over the past 16 years, 68/710 refractory epilepsy patients included in the presurgical evaluation protocol (M/F 41/27, mean age 33 years) underwent IVEM at Ghent University Hospital. Patient features and follow-up data were collected from the patients' medical files and the electronic patient database at the neurology and neurosurgery department. Predictive factors for IVEM outcome were identified by comparing features of patients with a positive IVEM outcome (i.e. ictal onset zone identification) and patients with a negative IVEM outcome. Predictive factors for RS outcome were identified by comparing features of patients with Engel class I and patients with Engel class II-IV outcome. RESULTS: In 56/68 patients (82%) IVEM outcome was positive. The occurrence of a seizure-free interval in the patient's history and a non-localizing ictal scalp EEG in patients with a structural abnormality on MRI (p<0.05) were predictive factors for a negative IVEM outcome. 32/68 patients underwent RS. In 22/32 (70%) patients RS resulted in an Engel class I outcome. A structural abnormality on MRI was a predictive factor for a positive RS outcome in patients in whom a focal or regional focus was resected (p<0.05). CONCLUSION: This study shows that IVEM identifies one or more ictal onset zone(s) in up to 80% of patients. The potential of IVEM to identify the ictal onset zone is unlikely in patients with a seizure-free interval in their medical history and a non-localizing ictal scalp EEG during the non-invasive presurgical evaluation. Half of these patients underwent RS with long-term seizure freedom in 70%. Patients with structural MRI lesions have the highest chance of seizure freedom. These findings may contribute to the optimization of patient management during both the invasive and non-invasive presurgical work-up.

Deep brain stimulation in patients with refractory temporal lobe epilepsy.

PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of > or =50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.