Yolande Hanssens

Subcutaneous apomorphine: An evidence-based review of its use in Parkinson's disease

Apomorphine, a short-acting dopamine D1 and D2 receptor agonist, was the first dopamine receptor agonist used to treat Parkinson’s disease. Subcutaneous apomorphine is currently used for the management of sudden, unexpected and refractory levodopa-induced ‘off’ states in fluctuating Parkinson’s disease either as intermittent rescue injections or continuous infusions. Other indications include the challenge test for determining the dopaminergic responsiveness and finding the appropriate dose of the drug in intermittent subcutaneous administration.Except for a rapid on- and offset of the antiparkinsonian response with subcutaneous apomorphine, the magnitude and pattern of the motor response to single dose of subcutaneously administered apomorphine is qualitatively comparable to that of oral levodopa. Seventy-five percent of patients achieve a clinically significant improvement with a dose of apomorphine 4mg.The efficacy of intermittent subcutaneous apomorphine injections as an add-on to levodopa therapy in advanced Parkinson’s disease was explored in one short-term, randomised, double-blind, placebo-controlled trial, one short-term and six long-term, open-label, uncontrolled studies, including a total of 195 patients. These studies provide evidence that this mode of administration was successful in aborting ‘off’ periods and improving Parkinson’s disease motor scores, but tended to increase dyskinesias. No levodopa-sparing effect was observed.Eleven long-term, open-label, uncontrolled studies, including a total of 233 patients evaluated the efficacy of continuous subcutaneous apomorphine infusions in monotherapy or as an add-on to levodopa therapy in advanced Parkinson’s disease. These studies proved that subcutaneous apomorphine infusions are successful in aborting ‘off’ periods, reducing dyskinesias and improving Parkinson’s disease motor scores with the added benefit of a substantial levodopa-sparing effect.The apomorphine challenge test has at least 80% overall predictive ability to clinically diagnose Parkinson’s disease across the different stages of the disease and parkinsonian syndromes. Similarly, those data also indicate that the apomorphine challenge test has a >80% ability to predict dopaminergic responsiveness across all stages of Parkinson’s disease.Adverse events are usually mild and consist predominantly of cutaneous reactions and neuropsychiatric adverse effects. The incidence of adverse effects is higher in patients receiving continuous infusion than in those receiving intermittent pulsatile administration.Based on the results of these studies it is recommended that subcutaneous apomorphine either as intermittent injections or continuous infusions should be offered to any suitable Parkinson’s disease patient who has difficulties in his/her management with conventional therapy. Low-dose levodopa therapy in combination with waking-day hours subcutaneous apomorphine infusion would probably be the most efficient treatment. Continuous subcutaneous apomorphine infusions should be evaluated before more invasive measures or neurosurgical interventions are contemplated.

Tension pneumocephalus as complication of burr-hole drainage of chronic subdural hematoma: A case report.

Background: Pneumocephalus is the presence of air in the cranial cavity. When this intracranial air causes increased intracranial pressure and leads to neurological deterioration, it is known as tension pneumocephalus (TP). TP can be a major life-threatening postoperative complication, especially after evacuation of chronic subdural hematoma. We report a case of TP after evacuation of chronic subdural hematoma and review the literature. Case Description: A 70-year-old man developed right-sided weakness after being admitted with minor head trauma a few weeks earlier. He was found to have a chronic subdural hematoma and underwent burr-hole evacuation. On day 3, he suddenly deteriorated and needed intubation and ventilation. Computerized tomography (CT) of the brain showed typical Mount Fuji’s sign due to TP. Immediately, 20-30 mL of air was aspirated from the intracranial fossa, and a catheter drain was inserted. The patient became fully awake after few hours and was extubated successfully. The drain was removed on day 5, and he was transferred to the ward before being discharged home. Conclusion: TP after evacuation of a chronic subdural hematoma is a neurosurgical emergency and needs immediate resuscitation and therapy; hence it is of vital importance that all acute-care physicians, intensivists and neurosurgeons be aware of this clinical emergency.

Toluene induced postural tremor

We read with interest the article by Miyagi et al 1 and comment on the medical treatment of toluene induced tremor. Microdialysis experiments in rats have shown that inhalation of toluene increases extracellular γ-aminobutyric acid (GABA) concentrations within the cerebellar cortex2 which probably explains why GABA agonists including benzodiazepines (for example, clonazepam) are not very effective in toluene induced tremor and ataxia. Rat experiments also showed a 50% reduction in …

Peripheral Polyneuropathy Due to Chronic Use of Topical Ammoniated Mercury

BACKGROUND Despite their potentially disastrous side effects, topical mercury salts can still be found as ingredients in some over-the-counter preparations or local remedies. CASE REPORT Peripheral polyneuropathy as a result of chronic ammoniated mercury poisoning was studied and followed over 2 years. A 36-year-old man developed peripheral polyneuropathy following chronic perianal use of an ammoniated mercury ointment. Highly elevated blood and urine mercury levels were found. Sural nerve biopsy showed mixed axonal degeneration-demyelination. There was progressive improvement of his symptoms over 2 years but neurophysiological examination revealed incomplete recovery. CONCLUSION The availability of safer drugs should result in a complete ban of these dangerous compounds.

Pharmacovigilance: empowering healthcare professionals and patients

The European Union has thoroughly reformed its pharmacovigilance legislation in July 2012. Despite the changes, underreporting of adverse drug reactions remains a concern. This underreporting seems to be partially associated with incorrect customs and beliefs by healthcare professionals. Therefore, strengthening teaching and training in drug safety monitoring and reporting are essential. Sustained campaigns and education on pharmacovigilance are key elements to enhance its performance and effectiveness. In general, all healthcare professionals as well as patients should be more sensitized and empowered to contribute to pharmacovigilance programmes in order to improve drug safety.

Fatal dialysis disequilibrium syndrome: A tale of two patients

Dialysis disequilibrium syndrome (DDS) is a central nervous system disorder, which occurs during hemodialysis (HD) or within 24 h following the first HD. DDS commonly occurs in patients suffering from end-stage renal failure undergoing HD for the first time. In a critically ill patient suffering from severe sepsis or septic shock, the combined effects of post-HD brain edema and changes in the brain due to septic encephalopathy, may become amplified leading to DDS. Here we report 2 cases with acute renal failure (ARF), undergoing HD for more than a week and being ventilated and who developed DDS. DDS might have contributed to the sudden deterioration and death in these septic patients. The first case was a 31-year-old male, involved in a motor vehicle accident and had a severe abdominal injury. Underwent laparotomy and hemostasis was achieved. On day 4, the patient developed hemorrhagic shock associated with ARF, which prompted daily HD. On day 8, he went into septic shock. On day 16, 1 h after his daily HD, he became unresponsive and his pupils became dilated and fixed and he expired 2 days later. The second case was a young male who suffered severe abdominal and chest injury after a fall from a height. He developed ARF on day 3 and required HD. On day 9, he had septic shock. Three days later, during his daily HD, he became unconscious and his pupils were not reacting to light and the patient died on day 12. Conclusion: In patients with severe sepsis/septic shock, DDS may occur even after repeated sessions of HD. The acute care physicians, intensivists, and nephrologists should be aware of the risks of DDS.

Efficacy and tolerability of antiepileptic drugs in an Omani epileptic population.

OBJECTIVE The aim of this hospital-based study is to get an insight into the efficacy and tolerability of antiepileptic drugs (AED) in Omani epileptic patients. PATIENTS AND METHODS All Omani patients (aged 14 years and above) suffering from epileptic seizures for at least 2 years and followed-up by board-certified neurologists in Sultan Qaboos University Hospital (SQUH) were evaluated. The treatment retention rate since first visit at SQUH and over the last 2 years was used as primary efficacy measure of AED therapy. Change in seizure-frequency and side effect profiles were also assessed. RESULTS In this population of 203 confirmed epileptic patients, generalized tonic-clonic (40%) and partial seizures (39%) were most commonly observed, idiopathic/cryptogenic origin (81%) being the most frequent encountered origin. Sixty one percent of the patients were controlled with an AED in monotherapy and overall 34% of patients could be successfully maintained on monotherapy during the whole follow-up period at SQUH (median 6 years). The treatment retention rates for carbamazepine (CBZ) at a daily dose of 400-600 mg, sodium valproate (VPA) at a daily dose of 500-1000 mg, and phenytoin (PHT) at a daily dose of 300 mg, in monotherapy over the total follow-up period was 51, 50, and 21%, respectively. In contrast, over the last 2 years these rates were highest for VPA (91%) followed by CBZ (83%) and PHT (73%). Adverse drug reactions were recorded in 67% of patients, and were most commonly encountered with VPA. CONCLUSIONS Despite a higher adverse effect profile for VPA, long-term treatment with CBZ and VPA appeared to be equally effective in terms of treatment retention rates and seizure control.

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview

Abstract Background: The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. Review: This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995–January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012–2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. Conclusions: Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

Optimization and stratification of multiple sclerosis treatment in fast developing economic countries: a perspective from Qatar

Abstract Objective: The introduction of disease-modifying therapies (DMTs) – with varying degrees of efficacy for reducing annual relapse rate and disability progression – has considerably transformed the therapeutic landscape of relapsing–remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS that conform to the healthcare system in a fast-developing economic country such as Qatar. Research design and methods: We conducted a systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane Database of Systematic Reviews (1 January 1990 through 30 September 2016). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites to obtain relevant safety information on these DMTs. Results: For each of the DMTs, the mode of action, efficacy, safety and tolerability are briefly discussed. To facilitate the interpretation, the efficacy data of the pivotal phase III trials are expressed by their most clinically useful measure of therapeutic efficacy, the number needed to treat (NNT). In addition, an overview of head-to-head trials in RRMS is provided as well as a summary of the several different RRMS management strategies (lateral switching, escalation, induction, maintenance and combination therapy) and the potential role of each DMT. Finally, algorithms were developed for CIS, active and highly active or rapidly evolving RRMS and subsequent breakthrough disease or suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the DMTs, taking into account patient preference, allowed the provision of rational and safe patient-tailored treatment algorithms. Conclusions: Recommendations and algorithms for the management of CIS and RRMS have been developed relevant to the healthcare system of this fast-developing economic country.

Remifentanil apnea: Case report and review of the literature.

Remifentanil is an opioid analgesic frequently used in intensive care patients because of its rapid onset of action, potency, and ultra-short duration. If an excessive dose is given, it leads to rapid, short lasting, potentially life-threatening side effects such as apnea, bradycadia, hypotension, and rigidity, following rapid peak serum levels. We report a 36-year-old woman developing apnea with bradycardia and hypotension, following an infusion in the central venous catheter lumen that had been used for remifentanil till tracheal extubation. The patient was immediately ventilated with bag-valve-mask and improved within 8 minutes. She became fully awake, heart rate and blood pressure returned to normal, and oxygen saturation improved to 100%. Acute care physicians, intensivists, anesthesiologists, and critical care nurses should be aware of this clinical problem in order prevent it as much as possible and to initiate immediate resuscitative measures.