Jordan Dubow

Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: Final 12-month, open-label results

Motor complications in Parkinsons disease (PD) are associated with long‐term oral levodopa treatment and linked to pulsatile dopaminergic stimulation. l‐dopa‐carbidopa intestinal gel (LCIG) is delivered continuously by percutaneous endoscopic gastrojejunostomy tube (PEG‐J), which reduces l‐dopa‐plasma–level fluctuations and can translate to reduced motor complications. We present final results of the largest international, prospective, 54‐week, open‐label LCIG study. PD patients with severe motor fluctuations (>3 h/day “off” time) despite optimized therapy received LCIG monotherapy. Additional PD medications were allowed >28 days post‐LCIG initiation. Safety was the primary endpoint measured through adverse events (AEs), device complications, and number of completers. Secondary endpoints included diary‐assessed off time, “on” time with/without troublesome dyskinesia, UPDRS, and health‐related quality‐of‐life (HRQoL) outcomes. Of 354 enrolled patients, 324 (91.5%) received PEG‐J and 272 (76.8%) completed the study. Most AEs were mild/moderate and transient; complication of device insertion (34.9%) was the most common. Twenty‐seven (7.6%) patients withdrew because of AEs. Serious AEs occurred in 105 (32.4%), most commonly complication of device insertion (6.5%). Mean daily off time decreased by 4.4 h/65.6% (P < 0.001). On time without troublesome dyskinesia increased by 4.8 h/62.9% (P < 0.001); on time with troublesome dyskinesia decreased by 0.4 h/22.5% (P = 0.023). Improvements persisted from week 4 through study completion. UPDRS and HRQoL outcomes were also improved throughout. In the advanced PD population, LCIGs safety profile consisted primarily of AEs associated with the device/procedure, l‐dopa/carbidopa, and advanced PD. LCIG was generally well tolerated and demonstrated clinically significant improvements in motor function, daily activities, and HRQoL sustained over 54 weeks.

Epilepsy in Sports and Recreation

In the US, millions of people participate in physical activity on a regular basis. However, among the many people with epilepsy, few incorporate exercise into their daily routine. Whether it is because of parental or physician restriction, the fact remains that people with epilepsy are less fit and are not getting the exercise they need. For many years, patients with seizure disorders have been discouraged from participating in physical fitness and team sports due to the fear that it will exacerbate their seizure disorder. However, this overprotective attitude has been slowly changing in light of more recent data on this subject. The evidence shows that patients with good seizure control can participate in both contact and non-contact sports without adversely affecting seizure frequency. This article reviews the effects of exercise on seizure control among patients with epilepsy. It examines the morbidity and mortality associated with exercise, as well as its psychological and physiological effects. Various topics concerning antiepileptic drugs and exercise are also discussed.

Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials

Continuous administration of levodopa‐carbidopa intestinal gel (carbidopa‐levodopa enteral suspension) through a percutaneous endoscopic gastrojejunostomy is a treatment option for advanced Parkinson disease (PD) patients with motor fluctuations resistant to standard oral medications. Safety data from 4 prospective studies were integrated to assess the safety of this therapy.

Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson's disease

OFF episodes negatively impact quality of life in patients with Parkinsons disease (PD). There remains a need for an acute, effective, noninvasive treatment.

Long-Term PEG-J Tube Safety in Patients With Advanced Parkinson's Disease.

OBJECTIVES:The objectives of this study were to present procedure- and device-associated adverse events (AEs) identified with long-term drug delivery via percutaneous endoscopic gastrojejunostomy (PEG-J). Levodopa-carbidopa intestinal gel (LCIG, also known in US as carbidopa-levodopa enteral suspension, CLES) is continuously infused directly to the proximal small intestine via PEG-J in patients with advanced Parkinson’s disease (PD) to overcome slow and erratic gastric emptying and treat motor fluctuations that are not adequately controlled by oral or other pharmacological therapy.METHODS:An independent adjudication committee of three experienced (>25 years each) gastroenterologists reviewed gastrointestinal procedure- and device-associated AEs reported for PD patients (total n=395) enrolled in phase 3 LCIG studies. The rate, clinical significance, and causality of the procedure/device events were determined.RESULTS:The patient median exposure to PEG-J at the data cutoff was 480 days. Procedure- and device-associated serious AEs (SAEs) occurred in 67 (17%) patients. A total of 42% of SAEs occurred during the first 4 weeks following PEG-J placement. SAEs of major clinical significance with the highest procedural incidence were peritonitis (1.5%), pneumonia (1.5%), and abdominal pain (1.3%). The most common non-serious procedure- and device-associated AEs were abdominal pain (31%), post-operative wound infection (20%), and procedural pain (23%). In all, 17 (4.3%) patients discontinued treatment owing to an AE.CONCLUSIONS:In conclusion, incidences of PEG-J AEs with the LCIG delivery system and PEG-J longevity were compared favorably with ranges described in the PEG/PEG-J literature. A low discontinuation rate in this study suggests acceptable procedural outcomes and AE rates in PD patients treated with this PEG-J drug delivery system.

APOE-ɛ4 Carrier Status and Donepezil Response in Patients with Alzheimer’s Disease

Abstract Background: Previous studies have investigated associations between apolipoprotein E (APOE)-ɛ4 allele status and acetylcholinesterase inhibitor treatment response in patients with Alzheimer’s disease. The ability to draw definitive conclusions regarding the effect of APOE-ɛ4 genotype on treatment response has been hindered by inconsistent results among studies and methodological limitations that restrict interpretation of study findings. Objective: To determine whether APOE-ɛ4 carrier status influences the magnitude of change in 13-item Alzheimer’s Disease Assessment Scale−Cognitive Subscale (ADAS-cog) score associated with acetylcholinesterase inhibitor treatment (i.e., donepezil). Methods: Analyses were performed using pooled data from the donepezil and placebo treatment arms of three consecutive, similarly designed, 12-week, multi-national, randomized clinical studies that enrolled patients with mild-to-moderate Alzheimer’s disease. Correlations between APOE-ɛ4 carrier status and ADAS-cog scores were evaluated using analysis of covariance. Results: No appreciable interaction between donepezil response and APOE-ɛ4 carrier status or copy number was detected. Both carriers and non-carriers of APOE-ɛ4 who received donepezil experienced significant improvements from baseline in ADAS-cog score versus placebo (p <  0.05). Change from baseline to final observation in the donepezil treatment group was – 2.95 for APOE-ɛ4 carriers and – 4.09 for non-carriers (p = 0.23). In contrast, non-carriers of APOE-ɛ4 in the placebo treatment group exhibited a greater improvement from baseline versus carriers (–2.38 versus – 0.60, p = 0.05). Conclusion: Within this population, APOE genotype had no statistically significant effect on cognitive response to donepezil treatment; however, APOE-ɛ4 allele status was associated with a difference in the magnitude of the change in ADAS-cog of placebo-treated patients.

Status epilepticus due to tiagabine ingestion.

Tiagabine, in excess dosing scenarios, has been rarely documented to cause status epilepticus. We describe such a case that was not responsive to benzodiazepines, but only to propofol infusion.

Acute Dystonic Reaction Associated With Foscarnet Administration

Drug-induced movement disorders are commonly seen in the inpatient setting and outpatient movement disorders centers. The most common acute reactions are dystonia, parkinsonism, and akathisia. Drug-induced movement disorders are classically associated with dopamine receptor blocking agents, most notably typical and atypical antipsychotic medications. However, extrapyramidal side effects can also be seen with antiemetics, promotility drugs, serotonergic agents, and opioid agonists. We describe a patient who developed an acute dystonic reaction shortly after the administration of intravenous foscarnet, an antiviral agent. Her work-up for secondary causes of dystonia was otherwise negative, and her symptoms resolved after receiving intravenous anticholinergic treatment.

The relation of brain ouabain-like compounds and idiopathic intracranial hypertension

Objectives.—To determine the relationship between levels of ouabain‐like compounds (OLC) in the cerebrospinal fluid (CSF) and the occurence of idiopathic intracranial hypertension (IIH).

Visual system side effects caused by parasympathetic dysfunction after botulinum toxin type B injections

Botulinum toxin type B (BTX‐B) has been approved by the Food and Drug Administration for the treatment of cervical dystonia. However, as with botulinum toxin type A (BTX‐A) it has off‐label uses, such as for hyperhidrosis, focal dystonias, spasticity, and facial wrinkles. BTX‐B has also been shown to be a safe and effective alternative for patients who are resistant to BTX‐A. The most commonly reported side effects include dry mouth and dysphagia. To date, there have been few reports of visual disturbances associated with BTX‐B use. In this study, we report on three individual patients who received BTX‐B and who subsequently developed parasympathetic dysfunction of the visual system after injections of BTX‐B at remote sites.