sabato 31 dicembre 2016
BRESCIA NEUROLOGY UNIT RESULTS: TBK1 Mutation Spectrum in an Extended European Patient Cohort With Frontotemporal Dementia and Amyotrophic Lateral Sclerosis
Importance Every year, Ramadan fasting is practiced by many Muslim individuals. In cases of chronic disease, religious texts allow fasting to be broken. However, many believers still want to fast even at the risk of damaging their health. To our knowledge, there are no published recommendations on the medical management of Parkinson disease (PD) during Ramadan. Effective treatments exist in PD and usually require several daily drug intakes. Apart from worsening symptoms, interrupting PD treatment might lead to a severe withdrawal syndrome.
Observations Although no specific studies on this topic have led to formal recommendations, we suggest some options for adapting the treatment for patients who fast during Ramadan. The general principle is based on switching the patient’s treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch. However, such an option is only feasible for patients who require a moderate amount of PD treatment and can tolerate dopamine agonist therapy.
Conclusions and Relevance Because many patients with PD require regular multiple daily administration of dopamine-replacement medication, the management of Ramadan fasting is not easy. Switching the patient’s treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch seems to be a reasonable option to consider for patients treated with a low-to-moderate amount of PD medication.
JAMA Neurology 2016
Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations A Randomized Clinical Trial
Importance Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects.
Objective To evaluate the efficacy and safety of 25- and 50-mg/d dosages of opicapone compared with placebo as adjunct to levodopa therapy in patients with PD experiencing end-of-dose motor fluctuations.
Design This phase 3 international, multicenter outpatient study evaluated a 25- and a 50-mg/d dosage of opicapone in a randomized, double-blind, 14- to 15-week, placebo-controlled clinical trial, followed by a 1-year open-label phase during which all patients received active treatment with opicapone. Patients with PD who experienced signs of end-of-dose deterioration and had a mean total awake off-time (state of akinesia or decreased mobility) of at least 1.5 hours, not including morning akinesia, were enrolled. Data were collected from March 18, 2011, through June 25, 2013. Data from the evaluable population were analyzed from July 31, 2013, to July 31, 2014.
Main Outcomes and Measures The primary efficacy outcome of the double-blind phase was the change from baseline in absolute off-time vs placebo based on patient diaries. The open-label phase focused on maintenance of treatment effect in off-time.
Results A total of 427 patients (258 men [60.4%] and 169 women [39.6%]; mean [SD] age, 63.1 [8.8] years) were randomized to a 25-mg/d (n = 129) or a 50-mg/d (n = 154) dosage of opicapone or to placebo (n = 144). Of these, 376 patients completed the double-blind phase and entered the open-label phase, of whom 286 completed 1 year of open-label treatment. At the end of the double-blind phase, the least squares mean change (SE) in off-time was −64.5 (14.4) minutes for the placebo group, −101.7 (14.9) minutes for the 25-mg/d opicapone group, and −118.8 (13.8) minutes for the 50-mg/d opicapone group. The adjusted treatment difference vs placebo was significant for the 50-mg/d opicapone group (treatment effect, −54.3 [95% CI, −96.2 to −12.4] minutes; P = .008), but not for the 25-mg/d opicapone group (treatment effect, −37.2 [95% CI, −80.8 to 6.4] minutes; P = .11). The off-time reduction was sustained throughout the open-label phase (−126.3 minutes at 1-year open-label end point). The most common adverse events in the opicapone vs placebo groups were dyskinesia, constipation, and dry mouth. Fifty-one patients (11.9%) discontinued from the study during the double-blind phase.
Conclusions and Relevance Treatment with a 50-mg once-daily dose of opicapone was associated with a significant reduction in mean daily off-time in levodopa-treated patients with PD and motor fluctuations, and this effect is maintained for at least 1 year. Opicapone was safe and well tolerated
JAMA Neurology 2016
Association of Albumin Levels With Outcome in Intravenous Immunoglobulin–Treated Guillain-Barré Syndrome
Importance There is an urgent need for biomarkers to monitor treatment efficacy and anticipate outcome in patients with Guillain-Barré syndrome (GBS).
Objective To assess whether there is an association between serum albumin levels, a widely used and relatively easily measurable biomarker of health and inflammation, and the clinical course and outcome of GBS in patients treated with intravenous immunoglobulin (IVIG).
Design, Setting, and Participants We used serum samples derived from a cohort of patients with GBS admitted to hospitals across the Netherlands participating in national GBS studies from May 5, 1986, through August 2, 2000. Serum albumin was measured from January 13 to 20, 2011. Analysis was performed from February 25, 2013, to September 6, 2016. All patients fulfilled the criteria for GBS and had severe disease (defined as not being able to walk unaided >10 m). Patients misdiagnosed as having GBS were retrospectively excluded from the study. Serum samples were obtained before and after IVIG treatment at 4 standardized time points from 174 patients. Albumin levels were determined by routine diagnostic turbidimetry and related to demographics and clinical course during a follow-up of 6 months.
Main Outcomes and Measures Serum albumin concentration was determined before and after treatment with IVIG and related to clinical outcome: muscle weakness (measured by Medical Research Council sum score), respiratory failure (measured by requirement and duration of mechanical ventilation), and ability to walk (measured by GBS disability score).
Results Serum albumin levels were determined in 174 patients with GBS (mean [SD] age, 49.6 [20.1] years; 99 males [56.9%]). Before treatment, the median serum albumin level was 4.2 g/dL (interquartile range, 3.8-4.5 g/dL), with hypoalbuminemia (albumin, <3.5 g/dL) in 20 (12.8%) of 156 patients. Two weeks after commencing treatment with IVIG (2 g/kg), the median serum albumin level decreased to 3.7 g/dL (interquartile range, 3.2-4.1 g/dL) (P < .001), and the number with hypoalbuminemia increased to 60 (34.5%) of 174 (P < .001). Hypoalbuminemia was associated with an increased chance of respiratory failure before (16 [36.4%] of 44, P = .001) or after (29 [54.7%] of 53, P < .001) IVIG treatment, inability to walk unaided (21 [35.0%] of 60 vs 6 [5.3%] of 114, P < .001), and severe muscle weakness at 4 weeks (Medical Research Council sum score, 31.8 vs 52.9, P < .001) and 6 months (Medical Research Council sum score, 49.4 vs 58.4, P < .001).
Conclusions and Relevance Patients with GBS may develop hypoalbuminemia after treatment with IVIG, which is related to a more severe clinical course and a poorer outcome. Further studies are required to confirm that serum albumin can be used as a biomarker to monitor disease activity and treatment response to IVIG in patients with GBS.
JAMA Neurology 2016
Focal temporal pole atrophy and network degeneration in semantic variant primary progressive aphasia
A wealth of neuroimaging research has associated semantic variant primary progressive aphasia with distributed cortical atrophy that is most prominent in the left anterior temporal cortex; however, there is little consensus regarding which region within the anterior temporal cortex is most prominently damaged, which may indicate the putative origin of neurodegeneration. In this study, we localized the most prominent and consistent region of atrophy in semantic variant primary progressive aphasia using cortical thickness analysis in two independent patient samples ( = 16 and 28, respectively) relative to age-matched controls ( = 30). Across both samples the point of maximal atrophy was located in the same region of the left temporal pole. This same region was the point of maximal atrophy in 100% of individual patients in both semantic variant primary progressive aphasia samples. Using resting state functional connectivity in healthy young adults ( = 89), we showed that the seed region derived from the semantic variant primary progressive aphasia analysis was strongly connected with a large-scale network that closely resembled the distributed atrophy pattern in semantic variant primary progressive aphasia. In both patient samples, the magnitude of atrophy within a brain region was predicted by that region’s strength of functional connectivity to the temporopolar seed region in healthy adults. These findings suggest that cortical atrophy in semantic variant primary progressive aphasia may follow connectional pathways within a large-scale network that converges on the temporal pole.
sabato 24 dicembre 2016
Association of Periodic and Rhythmic Electroencephalographic Patterns With Seizures in Critically Ill Patients
Importance Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear.
Objective To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures.
Design, Setting, and Participants We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures.
Interventions Continuous electroencephalography.
Main Outcomes and Measures Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures.
Results Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10).
Conclusions and Relevance In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.
JAMA Neurology 2016