Pharmacodynamics, Efficacy, and Safety of IPX203 in Parkinson Disease Patients With Motor Fluctuations Objectives IPX203 is an investigational oral extended-release capsule formulation of carbidopa and levodopa. The pharmacodynamics and efficacy of IPX203 were compared with immediate-release carbidopa-levodopa (IR CD-LD) in this open-label, rater-blinded, multicenter, crossover study in patients with advanced Parkinson disease (PD). Methods Twenty-eight patients were randomized to 2 weeks of treatment with IR CD-LD followed by IPX203 or IPX203 followed by IR CD-LD. Pharmacokinetic and motor assessments were conducted on days 1 and 15 of each treatment period. Efficacy was assessed using a 3-day PD diary. Pharmacodynamics were assessed by rater-blinded Movement Disorder Society—Unified Parkinson's Disease Rating Scale Part III and Investigator Assessment of Subject's Motor State. Results After a single dose, levodopa concentrations were sustained above 50% of peak concentration for 4.6 hours with IPX203 versus 1.5 hours with IR CD-LD (P < 0.0001). Based on the PD diary, patients experienced significantly less Off time with IPX203 as a percentage of waking hours than IR CD-LD (mean 19.3% vs 33.5%, respectively; P < 0.0001), translating into 2.3 hours less Off time than IR CD-LD with most of this improvement (1.9 hours) being Good On time. There was no significant difference in the amount of On time with troublesome dyskinesia between treatments. Pharmacodynamic assessments demonstrated similar outcomes in favor of IPX203 on day 1 and a significant predose benefit on motor examination after multiple dosing. Conclusions IPX203 demonstrated a sustained effect to reduce Off time and improve Good On time in patients with PD and motor fluctuations. Both treatments were well tolerated.

Cerebrospinal Fluid Concentrations of Nimodipine Correlate With Long-term Outcome in Aneurysmal Subarachnoid Hemorrhage: Pilot Study Objectives The aim was to evaluate plasma and cerebrospinal fluid (CSF) nimodipine concentrations in patients with aneurysmal subarachnoid hemorrhage and their correlation with clinical outcome. Methods Nimodipine infusion was started at 1 mg/h and increased up to 2 mg/h and continued up to 21 days in surviving patients. Arterial and CSF samples were collected at least after 24 hours of stable nimodipine dosing. Delayed cerebral ischemia and vasospasm were documented by new neurological deficits and neuroimaging. The clinical outcome was assessed at 9 months by the modified Rankin scale. Results Twenty-three patients were enrolled. Nimodipine dose was 13 to 38 μg/kg per hour. Nimodipine arterial and CSF concentrations were 24.9 to 71.8 ng/mL and 37 to 530 pg/mL, respectively. Dose did not correlate with arterial or CSF concentrations. Arterial concentrations did not correlate with corresponding CSF concentrations. Doses and arterial concentrations did not correlate with the clinical outcome and were not associated with the occurrence of delayed cerebral ischemia. However, patients with no significant disability after 9 months of hemorrhage showed significantly higher CSF nimodipine concentrations (P = 0.015) and CSF-to-plasma ratios (P = 0.011) compared with patients who showed some degree of disability or who died. Conclusions Cerebrospinal fluid nimodipine concentrations measured during hospital drug infusion showed a correlation with long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. These very preliminary data suggest that CSF concentrations monitoring may have some value in managing these patients.

Real-World Effectiveness and Safety of Fingolimod in Patients With Relapsing Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina Objectives The aim of this prospective observational postmarketing study was to evaluate fingolimod effectiveness in a real-world setting in Buenos Aires, Argentina. Methods Relapsing remitting multiple sclerosis patients who had been prescribed fingolimod owing to treatment failure and had at least greater than or equal to 24 months of follow-up were included during August 2013 and June 2018. Three-monthly clinical evaluations and 12-monthly magnetic resonance were performed. Demographic and clinical variables were described as well as the safety and the effectiveness outcomes that included the proportion of patients free from clinical relapses, from disability progression, from new or enlarging T2 or T1 gadolinium-enhancing lesions on annual magnetic resonance imaging, and from any disease activity during the follow-up. Results A total of 97 patients were included (68% female [n = 66]; mean ± SD age, 30 ± 10.5 years; mean ± SD disease duration, 6.5 ± 3.1 years; mean ± SD Expanded Disability Status Scale, 3.5 ± 1; mean ± SD fingolimod use, 30 ± 13 months [range, 18–56 months]). One hundred percent (97) used previous disease-modifying therapy, mainly interferons (87%; n = 84). Fourteen patients (14.4%) discontinued/withdrew fingolimod (10 owing to disease activity and 4 owing to tolerance and personal decisions). Eighty-two percent were free from clinical relapses, and 85% were free from disability progression; 75% of patients remained free from new or newly enlarging T2 lesions, and 78% of patients were free from gadolinium enhancing lesions. The proportion of patients free from any disease activity was 54%. Conclusions The effectiveness of fingolimod in a newly real-world setting was consistent with information provided from phase III clinical trials.

Role of Pregabalin in Treatment of Polyneuropathy in Multiple Myeloma Patients: A Retrospective Study Objectives Polyneuropathy (PN) is a frequent and significant clinical manifestation of multiple myeloma that may be observed at onset of disease or induced during treatment as a therapy-related complication. Polyneuropathy may be a relevant issue in myeloma patients owing to its significant impact on the quality of life, considering that it may lead to dose reduction or treatment discontinuation. The present retrospective study intended to evaluate efficacy of pregabalin (PGB) in treatment of PN in multiple myeloma patients. Materials and Methods Medical charts of 108 consecutive PN myeloma patients were reviewed. Data regarding the tumor history and therapy as well as the clinical and neurophysiological examinations 6 months before and after initiation of PGB therapy were collected. Results Thirty-eight medical charts had all the requested information. All patients (n = 38) underwent bortezomib-based treatment; 19 were previously treated and 19 were treatment naive. At first neurologic visit, all patients had PN symptoms (grade 2 of National Cancer Institute—Common Toxicity Criteria) without relevant pain. Neurophysiological evaluation showed a significant decrease in sensory nerve action potential amplitude (P = 0.006), conduction velocity (P = 0.006), and distal latency (P = 0.03) of sensory nerves between the first and the last neurological examination, in all patient population. Similar results were observed in treatment-naive patients, when the study cohort was stratified according to previous treatment. On the contrary, no significant differences were found between the first and the last neurophysiological follow-up evaluation in previously treated patients. Six months after PGB treatment, all patients reported disappearance of neurological symptoms (grade 0 National Cancer Institute—Common Toxicity Criteria). Conclusions In this retrospective study, improvement in neurological symptoms during PGB therapy was observed in the total population, despite the presence of a distal, sensory axonal neuropathy, as evidenced by neurophysiological examination.

Long-term Apomorphine Infusion Users Versus Short-term Users: An International Dual-center Analysis of the Reasons for Discontinuing Therapy Objectives A retrospective analysis at 2 specialist centers was undertaken to determine the long-term efficacy of subcutaneous apomorphine infusion (APO), rates and reasons for discontinuation, and factors that might contribute to discontinuation. Methods Demographics, clinical outcomes data, and reasons for discontinuation were collected for patients treated with APO at Chulalongkorn Centre of Excellence for Parkinson's Disease and Related Disorders, Bangkok, Thailand (n = 36) and Fundacion Jimemez Diaz Universidad Autonoma de Madrid, Spain (n = 16). Results There were 19 (52.7%) patients in the Thai cohort and 10 (62.5%) patients in the Spanish cohort who discontinued treatment within around 6 months of initiation, most commonly due to skin nodules (Thai cohort) and perceived lack of efficacy (Spanish cohort). Those who continued APO tended to stay on treatment. In both cohorts, APO resulted in significant reductions in Unified Parkinson's Disease Rating Scale 3 motor scores, daily OFF time, and levodopa-equivalent dose in patients who subsequently stopped therapy, suggesting APO is clinically effective even when “lack of efficacy” is stated as a reason for discontinuing. Daily OFF hours after APO therapy was found to be a significant predictive factor for APO discontinuation with an odds ratio of 5.952 (P = 0.040). The cutoff point that determined APO discontinuation was calculated to be 1.75 or more OFF hours (sensitivity, 84.6%; specificity, 63.2%). Conclusions Apomorphine infusion is a minimally invasive therapy and therefore very easy to discontinue if difficulties arise. This fact might explain the high dropout rate of this technique. Successful long-term adherence to APO therapy requires a multidisciplinary health care team approach including regular patient follow-up and assessment and prompt resolution of queries and concerns.

Hypothermia Associated With Melatonin Ingestion in a Child With Autism Autism spectrum disorder is a neurodevelopmental disorder characterized by social interaction and communication disorder and restrictive and repetitive behaviors. Sleep disorders are frequently observed in children with autism spectrum disorder. We present a case of hypothermia in an autistic child with a sleep disorder whose body temperature decreased to 34°C after a single dose of melatonin. Hypothermia continued for 2 more days, but her nighttime sleeping problems decreased. This case is important because it demonstrates the possible risk of hypothermia with melatonin use in children with autism with a sleep disorder.

Bupropion Causes Misdiagnosis in Brain Dopamine Transporter Imaging for Parkinsonism Objective The objective of this study was to report long-lasting effects of bupropion on brain dopamine transporter (DAT) in a patient with depression and parkinsonism. Methods The patient was a 52-year old man who had been treated with 150 mg/d of bupropion for depression. The patient developed cognitive problems, bradykinesia, and reduced stride length for which he was scanned with [123I]FP-CIT single photon emission computed tomography after the recommended 1-week discontinuation of bupropion. Levodopa treatment trial was initiated without a response. Eleven months later, the patient was scanned for a second time after a 1-month stoppage of bupropion. Results The first scan was abnormal with left putamen specific binding ratio of 1.99 (SDs from the reference value mean, −2.40), right putamen of 2.27 (SD, −1.84), left caudate of 2.33 (SD, −2.26), and right caudate of 2.29 (SD, −2.18). The second scan (after 1-month discontinuation) was normal, and specific binding ratios had increased from 5.2% to 31.7% in all striatal regions as compared with the first scan. Brain magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography imaging were normal, and there was no levodopa response or other features supporting neurodegenerative parkinsonism. Conclusions Bupropion has previously generally been discontinued 1 week prior DAT imaging, which meets the recommended, albeit arbitrary, time interval of 5 plasma clearance half-lives before the scan. One-week discontinuation of bupropion before DAT imaging may be insufficiently short. Our case shows that longer medication washout and rescan may be needed when there is contradiction between the imaging result and clinical outcome in patients with medications affecting DAT binding.

Priapism With Methylphenidate Use in a Preschool-Aged Boy Resolved With Switching to Atomoxetine Background Priapism is a persistent unwanted erection that is not linked with sexual stimulation. A number of previous case reports have shown priapism with methylphenidate (MPH) use, especially in adolescence and preadolescence period. In all of these cases, the unwanted erections ceased after the medication was discontinued and no further attention-deficit hyperactivity disorder medication was initiated. Hereby, we present the case of a boy who had priapism episodes with MPH, which resolved with switching to atomoxetine (ATX). Case Report A 5-year, 10-month-old medically healthy boy was diagnosed with attention-deficit hyperactivity disorder and was prescribed methylphenidate immediate-release (10 mg/d). Two weeks later, his family communicated and reported penile erection episodes since the initiation of MPH. With the suspect of a medication-induced adverse reaction, MPH was discontinued and priapism resolved within a week. Thereafter, 10 mg/d of ATX was initiated. Four-week follow-up with ATX treatment revealed that the medication was tolerated well, and priapism or any other adverse effect was not reported. Conclusions This case report suggests that ATX may be safely used in some children who experienced priapism with MPH. Future studies are needed to clarify the risk factors and etiologic mechanisms of this adverse reaction.

Treatment of Catatonia in Frontotemporal Dementia: A Lesson From Zolpidem Test Background During recent years, zolpidem presents a potential but transient treatment option for a large variety of neurologic conditions. Although most cases had disorders of consciousness or movement disorders, there are few reports of beneficial effects of zolpidem on language function. Case We present a case of frontotemporal dementia who developed catatonia during her disease course and her refractory speech problem showed dramatic response to zolpidem. Conclusions In dementia patients, different catatonic symptoms may show differential responses to the therapeutic agents and, if verbal symptoms are dominant, it is worthy to try zolpidem in the early stage.

The Naranjo Scale and Tardive Syndromes, a Historical Perspective No abstract available