Prediction of cognitive worsening in de novo Parkinson's disease: Clinical use of biomarkers.

BACKGROUND: Cognitive impairment is a frequent and disabling feature of Parkinson's disease. Identifying the factors able to predict cognitive worsening since the early stage may improve disease management. The objective of this study was to define the best predictors of future cognitive worsening in a group of patients with newly diagnosed PD and to propose cutoff values potentially useful at the individual level. METHODS: Fifty-four consecutive drug-naive patients with de novo PD were prospectively evaluated by clinical and neuropsychological assessment, resting EEG, and 123 I-FP-CIT-SPECT and clinically classified into mainly motor, diffuse/malignant, and intermediate PD subtypes; they were then followed up for an average of 5 years. Cognitive outcome was defined by identifying cognitively stable or worsened patients. RESULTS: Step-wise logistic regression selected the posterior qEEG mean frequency and 123 I-FP-CIT-SPECT uptake at caudate level (P < 0.0001). The posterior qEEG mean frequency (cut point, 8.3 Hz) and the caudate 123 I-FP-CIT-SPECT uptake (cut point, 2.3, specific to nondisplaceable binding ratio) achieved 82% and 80% of accuracy, respectively, in predicting cognitive outcome. Survival analysis showed decreasing expected time to cognitive worsening associated with scores below the established thresholds for qEEG and 123 I-FP-CIT-SPECT and with the presence of a malignant clinical phenotype. CONCLUSIONS: Resting EEG and 123 I-FP-CIT-SPECT are good predictors of future cognitive worsening, in de novo drug-naive PD patients. Wherever available, these biomarkers could add valuable prognostic information to classification into different clinical phenotypes. © 2017 International Parkinson and Movement Disorder Society.

Mapping brain morphological and functional conversion patterns in predementia late-onset bvFTD.

PURPOSE: The diagnosis of behavioural variant frontotemporal dementia (bvFTD) is challenging during the predementia stage when symptoms are subtle and confounding. Morphological and functional neuroimaging can be particularly helpful during this stage but few data are available. METHODS: We retrospectively selected 25 patients with late-onset probable bvFTD. Brain structural MRI and FDG PET were performed during the predementia stage (mean MMSE score 27.1 ± 2.5) on average 2 years before. The findings with the two imaging modalities were compared (SPM8) with those in a group of 20 healthy subjects. The bvFTD patients were divided into two subgroups: those with predominant disinhibition (bvFTD+) and those with apathy (bvFTD-). RESULTS: Hypometabolism exceeded grey matter (GM) density reduction in terms of both extension and statistical significance in all comparisons. In the whole bvFTD group, hypometabolism involved the bilateral medial, inferior and superior lateral frontal cortex, anterior cingulate, left temporal and right parietal cortices and the caudate nuclei. GM density reduction was limited to the right frontal cortex and the left medial temporal lobe. In bvFTD+ patients hypometabolism was found in the bilateral medial and basal frontal cortex, while GM reduction involved the left anterior cingulate and left inferior frontal cortices, and the right insula. In bvFTD- patients, atrophy and mainly hypometabolism involved the lateral frontal cortex and the inferior parietal lobule. CONCLUSION: These findings suggest that hypometabolism is more extensive than, and thus probably precedes, atrophy in predementia late-onset bvFTD, underscoring different topographic involvement in disinhibited and apathetic presentations. If confirmed in a larger series, these results should prompt biomarker operationalization in bvFTD, especially for patient selection in therapeutic clinical trials.

Parkinson's Disease Sleep Scale 2: application in an Italian population.

Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients.

Neuroimaging features in C9orf72 and TARDBP double mutation with FTD phenotype.

Increasing evidence has shown that morphological and functional neuroimaging may help to understand the pathophysiological mechanisms leading to behavioral disturbances in patients with genetic or sporadic frontotemporal dementia (FTD). The C9orf72 expansion was found in association with the N267S TARDBP mutation in two siblings with behavioral-variant FTD (bvFTD). In one of them with very mild dementia, MRI showed symmetric atrophy of temporal, inferolateral and orbital frontal cortex, while [18F]FDG-PET disclosed more extended hypometabolism in dorsolateral and inferolateral frontal cortex, anterior cingulate, and caudate nucleus. Hypometabolism in right lateral and orbital frontal cortex was confirmed also in comparison with a group of sporadic bvFTD patients. These findings appear as the neuroimaging hallmark of double C9orf72 and TARDBP gene mutation with a bvFTD phenotype.

Sleep, epilepsy, and autism.

The purpose of this review article is to explore the links between sleep and epilepsy and the treatment of sleep problems in children with autism spectrum disorder (ASD). Epilepsy and sleep have bidirectional relationships, and problems with both are highly prevalent in children with ASD. Literature is reviewed to support the view that sleep is particularly important to address in the context of ASD. Identification and management of sleep disorders may improve seizure control and challenging behaviors. In closing, special considerations for evaluating and treating sleep disorders in children with ASD and epilepsy are reviewed. This article is part of a Special Issue entitled "Autism and Epilepsy".

Pulses of South Atlantic water into the tropical North Atlantic since 1825 from coral isotopes.

Decadal and multidecadal changes in the meridional overturning circulation may originate from either the subpolar North Atlantic or the Southern Hemisphere. New records of carbon and oxygen isotopes from an eastern Martinique Island (Lesser Antilles) coral reveal irregular, decadal, double-step events of low ∆14C and enhanced vertical mixing, high δ18O and high δ13C values starting in 1885. Comparison of the new and published ∆14C records indicates that the last event (1956-1969) coincides with a widespread, double-step ∆14C low of South Atlantic origin from 32°N to 18°S, associated with a major slowdown of the Caribbean Current transport between 1963 and 1969. This event and the past Martinique ∆14C lows are attributed to pulses of northward advection of low ∆14C Sub-Antarctic Mode Waters into the tropical Atlantic. They are coeval with changes of the tropical freshwater budget and likely driven by meridional overturning circulation changes since ~1880.

Practical Approaches and Knowledge Gaps in the Care for Children With Leukodystrophies.

Leukodystrophies are a group of neurodegenerative genetic disorders that affect approximately 1 in 7500 individuals. Despite therapeutic progress in individual leukodystrophies, guidelines in neurologic care are sparse and consensus among physicians and caregivers remains a challenge. At patient advocacy meetings hosted by Hunter's Hope from 2016-2018, multidisciplinary experts and caregivers met to conduct a literature review, identify knowledge gaps and summarize best practices regarding neurologic care. Stages of severity in leukodystrophies guided recommendations to address different levels of need based on a newly defined system of disease severity. Four core neurologic domains prioritized by families were identified and became the focus of this guideline: sleep, pain, seizures/epilepsy, and language/cognition. Based on clinical severity, the following categories were used: presymptomatic, early symptomatic, intermediate symptomatic, and advanced symptomatic. Across the leukodystrophies, neurologic care should be tailored to stages of severity while accounting for unique aspects of every disease and multiple knowledge gaps present. Standardized tools and surveys can help guide treatment but should not overburden families.

Differences in overnight polysomnography scores using the adult and pediatric criteria for respiratory events in adolescents.

STUDY OBJECTIVES: There was no consensus in the 2007 American Academy of Sleep Medicine scoring manual on whether pediatric or adult respiratory criteria should be used in adolescents due to lack of data. Our objective was to compare pediatric and adult criteria in adolescents referred for obstructive sleep apnea (OSA). We hypothesized that pediatric criteria would capture more respiratory events than adult criteria. DESIGN: Retrospective cross-sectional analysis. SETTING: Clinical sleep laboratory. PARTICIPANTS: 101 subjects aged 13-18 years clinically referred for OSA. INTERVENTIONS: Overnight polysomnogram. Data were scored using both adult and pediatric AASM criteria. For adult criteria, data were scored using both AASM hypopnea rule A, defined by > or = 4% desaturation, and B, defined by > or = 3% desaturation or arousal. RESULTS: Median (range) apnea hypopnea index (AHI) by pediatric criteria was 1.7 events/hour (0-42.9). AHI using rule A was 0.4 (0-35.6); rule B, 1.4 (0-38.4). A higher pediatric AHI was associated with greater differences between pediatric and adult AHI using either rule A or B. There was no significant discordance in OSA classification comparing pediatric and adult criteria rule B (P = 0.3), but there was a significant rate of discordance classification comparing pediatric and adult criteria rule A(P < 0.001). CONCLUSIONS: Either pediatric or adult criteria rule B can be used in adolescents as few subjects change diagnostic category between these 2 criteria. Use of adult rule A results in fewer children meeting criteria for OSA. Further research into the clinical relevance of the scoring metric in adolescents is warranted.

Nocturnal enuresis: a suggestive endophenotype marker for a subgroup of inattentive attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) and enuresis co-occur at a higher rate than expected; the cause for this is unclear. STUDY DESIGN: Diagnostic and demographic variables were compared in 344 children ages 6 to 12 years, with and without enuresis, recruited in an ADHD genetic study. Sleep variables were investigated in a subgroup of 44 enuretic children with age- and sex-matched nonenuretic controls. The association of enuresis with single nucleotide polymorphisms located in regions reported in linkage with enuresis was explored. RESULTS: The prevalence rate of nocturnal enuresis was 16.9% for the entire cohort. There were no differences in sex, age, socioeconomic status, intelligence quotient, medication treatment, or comorbidities. The enuresis group had a higher likelihood of inattentive symptoms than the nonenuretic group. Night wakings and ability of children to wake themselves in the morning were both significantly decreased in children with enuresis compared with control children in the Child Sleep Habits Questionnaire Night Wakings subscale. No significant association was found with chromosomal regions previously reported in linkage with enuresis. CONCLUSIONS: Deficits in arousal may contribute to both enuresis and inattentive ADHD. Nocturnal enuresis may be a useful clinical marker in identifying a subgroup of the inattentive phenotype in ADHD genetic studies.

The role of polysomnography in decannulation of children with brain and spinal cord injuries.

OBJECTIVE: The objective of this retrospective review was to determine the utility of polysomnography (PSG) in influencing the decision to decannulate pediatric patients with brain and spinal cord injuries in an inpatient rehabilitation hospital setting. METHODS: Between 2010 and 2016, data were collected on pediatric patients with brain and/or spinal cord injuries who had PSG performed with the goal of decannulation. Patients underwent a decannulation protocol involving toleration of continuous tracheostomy capping and bedside tracheoscopy by otolaryngology. Decision to decannulate was determined with input from multiple disciplines. Associations were examined between decannulation success and findings on PSG as well as demographic factors, injury characteristics, otolaryngology findings, and timeline from initial injury to selected events. RESULTS: A total of 46 patients underwent PSG, after which 38 (83%) were deemed appropriate and eight (17%) were deemed inappropriate for decannulation. Individuals who were deemed ready for decannulation had significantly lower obstructive apnea hypopnea indexes (AHI) (1.7 vs 5.4 events/h, P = 0.03), respiratory disturbance indexes (RDI) (2.4 vs 7.6 events/h, P = 0.006), and peak end tidal carbon dioxide (CO2 ) levels (50.0 vs 58.7 torr, P = 0.009) on PSG compared to those who were not decannulated. There were no complications following decannulation prior to discharge. CONCLUSION: PSG provided important additional information as part of a multidisciplinary team assessment of clinical readiness for decannulation in pediatric patients with brain and spinal cord injuries who underwent a decannulation protocol. Obstructive AHI, RDI, and peak end tidal CO2 level were associated with successful decannulation prior to discharge from inpatient rehabilitation.