Tolerance of High-Dose Oral Amiodarone for Cardioversion of Atrial Flutter.

In atrial arrhythmias, amiodarone is usually given either intravenously for acute management, requiring in-hospital monitoring, or orally for chronic control, as doses given 60 times per half-life, requiring weeks to reach full effect. A high-risk, 245-kg male with heart failure exacerbated by atrial flutter was successfully cardioverted using an atypically large, 8000-mg oral amiodarone dose. The only adverse effect was transient sinus arrest, which did not require intervention, only 24 hours of inpatient monitoring. Amiodarone's unique pharmacokinetics, including its long elimination half-life and its extensive distribution into a large volume of adipose tissue, make high-dose oral amiodarone boluses a reasonable strategy for cardioversion of atrial arrhythmias.

En présence d'arythmie auriculaire, l'amiodarone est généralement administrée par voie intraveineuse dans la phase aiguë de la prise en charge, ce qui nécessite une surveillance du patient en milieu hospitalier, ou encore par voie orale dans le cadre d'un traitement au long cours à des doses représentant 60 fois la demi-vie, le plein effet du médicament n'étant obtenu qu'au bout de plusieurs semaines. Un homme de 245 kg à haut risque souffrant d'insuffisance cardiaque aggravée par un flutter auriculaire a subi avec succès une cardioversion médicamenteuse faisant appel à une dose exceptionnellement élevée d'amiodarone ­ 8000 mg ­ administrée par voie orale. Le seul effet indésirable a été une pause sinusale n'ayant pas nécessité d'intervention, seulement 24 heures de surveillance en milieu hospitalier. Vu la pharmacocinétique particulière de l'amiodarone, notamment sa longue demi-vie d'élimination et sa distribution étendue dans un grand volume de tissu adipeux, l'administration perorale de ce médicament en dose de charge constitue une stratégie raisonnable de cardioversion en cas d'arythmie auriculaire.

Treatment Decisions in Geriatric Cardiac Lymphoma Facilitated by Serial Cardiac Magnetic Resonance Imaging and Positron Emission Tomography.

A tumour encasing the right coronary was identified on computed tomography pulmonary embolism protocol in an 81-year-old man. Concerns regarding tolerability of chemotherapy in an octogenarian were addressed using cardiac magnetic resonance imaging to monitor a trial of modified-chemotherapy for his primary cardiac B-cell lymphoma. Residual activity on positron emission tomography computed tomography mandated consolidation with radiotherapy to achieve a tumor-free return to health. Despite advanced age, successful therapy in this, the oldest case of primary cardiac lymphoma reported, was facilitated by monitoring treatment effectiveness with advanced cardiac imaging and the use of standardized frailty scores in communicating his appropriate level of robustness for tolerating chemotherapy.

Une tumeur enveloppant l'artère coronaire droite a été décelée lors du protocole de tomodensitométrie à la recherche d'une embolie pulmonaire chez un homme de 81 ans. Les préoccupations relatives à la tolérance à la chimiothérapie chez un octogénaire ont été prises en considération lors de l'imagerie cardiaque par résonance magnétique pour surveiller l'essai d'une chimiothérapie modifiée de son lymphome cardiaque primitif à cellules B. L'activité résiduelle à la tomographie par émission de positons associée à la tomodensitométrie a rendu nécessaire la consolidation par radiothérapie pour un retour à la santé sans tumeur. En dépit de son âge avancé, la réussite du traitement de cet homme, le cas signalé le plus ancien de lymphome cardiaque primitif, a été facilitée par la surveillance de l'efficacité du traitement par une technique avancée d'imagerie cardiaque et l'utilisation des scores de fragilité standardisés pour connaître son degré de robustesse approprié pour tolérer la chimiothérapie.

Personalized Anticoagulation: Guided Apixaban Dose Adjustment to Compensate for Pharmacokinetic Abnormalities Related to Short-Bowel Syndrome.

A 45-year-old woman who required lifelong anticoagulation for recurrent thrombosis had her therapeutic choices limited by heparin-induced thrombocytopenia and abnormal pharmacokinetics (greatly reduced absorption) resulting from short gut syndrome from extensive gut resection after mesenteric thrombosis. As an alternative to inconvenient and expensive injections of fondaparinux, personalized dosing of a direct oral anticoagulant was sought using clinical pharmacology techniques. Enteral absorption was ascertained with small test doses of apixaban, and the ability of supraconventional doses to deliver effective concentrations was verified.

Therapeutic Differences in 24-h Ambulatory Blood Pressures in Patients Switched Between Bioequivalent Nifedipine Osmotic Systems With Differing Delivery Technologies.

Comparing modified-release formulations can be difficult using current bioequivalence criteria. Two 60-mg-once-daily nifedipine formulations are deemed bioequivalent in Canada. This study examined the validity of the assumption that these interchangeable, but different, delivery technologies are therapeutically equivalent in maintaining systolic blood pressure (SBP) control throughout the entire dosing interval. We used 24-h Ambulatory Blood Pressure Monitoring to objectively examine whether formulation switches changed population SBP >2 mmHg (reflecting 6% increased stroke mortality) and in what proportion of patients SBP changed ≥6 mmHg (risking unnecessary therapeutic alterations). When 20 patients, previously receiving 60-mg-once-daily Nifedipine-GITS, were switched to Mylan-Nifedipine-XL, population-mean ± SE 24-h SBP increased 3 ± 1.1 mmHg (P = 0.0173) and 8-h nocturnal SBP increased 4 ± 1.6 mmHg (P = 0.0098). Thus, interchange of nifedipine formulations can affect therapeutic consistency. These data support existing calls to improve criteria for establishing bioequivalence between formulations employing differing modified-release technologies.

Evaluation of electrode position in deep brain stimulation by image fusion (MRI and CT).

INTRODUCTION: Imaging has an essential role in the evaluation of correct positioning of electrodes implanted for deep brain stimulation (DBS). Although MRI offers superior anatomic visualization of target sites, there are safety concerns in patients with implanted material; imaging guidelines are inconsistent and vary. The fusion of postoperative CT with preoperative MRI images can be an alternative for the assessment of electrode positioning. The purpose of this study was to assess the accuracy of measurements realized on fused images (acquired without a stereotactic frame) using a manufacturer-provided software. METHODS: Data from 23 Parkinson's disease patients who underwent bilateral electrode placement for subthalamic nucleus (STN) DBS were acquired. Preoperative high-resolution T2-weighted sequences at 3 T, and postoperative CT series were fused using a commercially available software. Electrode tip position was measured on the obtained images in three directions (in relation to the midline, the AC-PC line and an AC-PC line orthogonal, respectively) and assessed in relation to measures realized on postoperative 3D T1 images acquired at 1.5 T. RESULTS: Mean differences between measures carried out on fused images and on postoperative MRI lay between 0.17 and 0.97 mm. CONCLUSION: Fusion of CT and MRI images provides a safe and fast technique for postoperative assessment of electrode position in DBS.

Low-frequency versus high-frequency stimulation of the pedunculopontine nucleus area in Parkinson's disease: a randomised controlled trial.

OBJECTIVE: To compare the influence of low-frequency (10-25 Hz) versus higher (60-80 Hz) frequency stimulation of the pedunculopontine nucleus area (PPNa) on akinaesia, freezing of gait and daytime sleepiness. METHOD: We included nine patients with Parkinson's disease (PD) and severe gait disorders. In this double-blind randomised cross-over study, patients were assessed after 24 h of PPNa stimulation. Assessments included the motor part of the Unified Parkinson's Disease Rating Scale, the Epworth Sleepiness Scale and a behavioural gait assessment. RESULTS: Compared with 60-80 Hz, 10-25 Hz PPNa stimulation led to decreased akinaesia, gait difficulties and daytime sleepiness in 7/9 patients. In one patient, these symptoms were aggravated under 10-25 Hz stimulation compared with 60-80 Hz. CONCLUSION: These results are in keeping with the benefits of chronic PPNa stimulation for gait and postural difficulties in patients with PD, and with regard to the influence of patients' clinical characteristics, differential neuronal loss in the PPNa and electrode location. We conclude that in patients with PPNa stimulation, low frequency provides a better outcome than high-frequency stimulation.

Neuroimaging of diving-related decompression illness: current knowledge and perspectives.

Diving-related decompression illness is classified into 2 main categories: arterial gas embolism and decompression sickness. The latter is further divided into types 1 and 2, depending on the clinical presentation. MR imaging is currently the most accurate neuroimaging technique available for the detection of brain and spinal cord lesions in neurologic type 2 decompression sickness. Rapid bubble formation in tissues and the bloodstream during ascent is the basic pathophysiologic mechanism in decompression illness. These bubbles can damage the central nervous system through different mechanisms, namely arterial occlusion, venous obstruction, or in situ toxicity. Neuroimaging studies of decompression sickness have reported findings associated with each of these mechanisms: some typical results are summarized and illustrated in this article. We also review the limitations of previous work and make practical methodologic suggestions for future neuroimaging studies.

Levodopa-resistant freezing of gait and executive dysfunction in Parkinson's disease.

We examined executive functioning in patients with Parkinson's disease exhibiting, or not, levodopa-resistant freezing of gait (L-FOG). 38 advanced-stage patients with L-FOG were identified in a consecutive series of 400 patients. They were matched with 38 patients without L-FOG. All patients underwent prospective evaluations of cognitive and motor functioning before subthalamic nucleus surgery, and 1 year after. A composite frontal score, a measure of executive functioning, was compared between the two groups. We also examined correlations between the frontal score and the score on the FOG item of the Unified Parkinson Disease Rating Scale II. Results show that after surgery, patients with L-FOG, as a group, were more impaired in executive functioning than control patients. However, individual data analysis showed preserved executive functions in 11 patients with L-FOG. In addition, there was no correlation between L-FOG severity and the degree of executive impairment. Therefore, frontal dysfunction may be one mechanism underlying L-FOG in a number of patients with Parkinson's disease. However, since some patients develop L-FOG despite the preservation of executive functions, lesions or dysfunction of other neuronal structures are likely to be involved.

Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers.

OBJECTIVE: Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with Gaucher disease (GD), is unknown. Our objective was to estimate PD penetrance in a familial study of GBA mutation carriers. METHODS: Probands with familial PD were recruited through the French Parkinson Disease Genetic Study Group. All GBA exons were sequenced in probands and their relatives. To estimate the age-specific cumulative PD risk (i.e., penetrance) in GBA mutation carriers, we used the proband's phenotype exclusion likelihood method and corrected for selection of familial cases by considering the status of one affected relative per family as unknown. RESULTS: Of 525 probands with familial PD, 24 (4.6%) were GBA mutation carriers. Of their 256 relatives, 43 (16.8%) had PD and 26 of 32 affected relatives tested for GBA mutations were mutation carriers; 213 relatives did not have PD and 31 of 71 of unaffected relatives tested for GBA mutations were mutation carriers. Under a dominant model, penetrance was estimated as 7.6%, 13.7%, 21.4%, and 29.7% at 50, 60, 70, and 80 years, respectively. There was no significant difference in penetrance at 70 years between N370S carriers, L444P carriers, and carriers of rarer mutations. CONCLUSION: The relatively high penetrance estimate in GBA carriers obtained in this study should lead to consideration of GBA as a dominant causal gene with reduced penetrance and should be taken into account for genetic counseling in relatives of patients with GD and patients with GBA-associated PD.