domenica 29 ottobre 2017

NEWS FROM BRESCIA: Postpartum Headache: A Prospective Study.

Abstract

AIMS:

To prospectively assess the incidence and etiology (ie, primary vs symptomatic) of headache in women during the first month postdelivery, with particular emphasis on the type of presentation as a clue for identifying potentially harmful etiologies. A secondary aim was to evaluate the relative frequency of migraine- vs tension-type headache in cases of primary headache.

METHODS:

A total of 900 consecutive women were enrolled in the study and examined within 3 days of delivery, both clinically and with transcranial color-coded sonography (TCCS). During the course of follow-up, all subjects presenting with headache suspected of being secondary to intracranial pathology underwent a complete clinical and instrumental assessment with TCCS and magnetic resonance imaging (MRI) and angiography. A telephone interview was administered to all subjects 1 month after delivery. Two-tailed t test, Mann-Whitney test, Pearson chi-square test, and multiple logistic regression were used to analyze the data.

RESULTS:

At the end of the follow-up period, 241 women (26.8% of the sample) reported at least one headache attack. In 88 of these 241 cases (9.8%), the headache attack occurred soon after delivery and was already recorded at the first visit. Thunderclap headache occurred in 34 (3.8%) of the subjects. In all but one of these subjects, the course was spontaneously benign. None of the recorded variables allowed discrimination of the subjects with thunderclap headache from those without headache. Three subjects had thunderclap headache following dural anesthesia, and one subject was found to have reversible cerebral vasoconstriction syndrome. Headache with gradual onset was recorded in 207 subjects (23%). Three of these subjects fulfilled the criteria for pre-eclampsia, and 13 had postural headache after dural anesthesia. Migraine history and urinary protein were independent predictors of gradual onset headache, and migraine history and parity were significant independent predictors of pulsating pain with gradual onset headache.

CONCLUSION:

Headache appeared early in the first days postdelivery, and its incidence increased in the first month thereafter. Predictors were different according to whether the headache had a gradual onset or a thunderclap presentation. Primary headache accounted for the overwhelming majority of the recorded cases.

J Oral Facial Pain Headache 2017 

NEWS FROM THE WORLD: PRAC Further Restricts Daclizumab (Zinbryta) in MS

Because of the risk for liver damage, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has recommended further restrictions on daclizumab (Zinbryta, Biogen/AbbVie), used to treat adults with relapsing forms of multiple sclerosis (MS).
A safety review by the committee found that "unpredictable and potentially fatal immune-mediated liver injury" can occur during treatment with daclizumab and for up to 6 months after discontinuation of the drug, the PRAC said today.
"In order to reduce the risks, doctors should now only prescribe Zinbryta for relapsing forms of multiple sclerosis in patients who have had an inadequate response to at least two disease modifying therapies (DMTs) and cannot be treated with other DMTs," the PRAC advised.
The committee launched a safety review of daclizumab back in June following the death from fulminant liver failure of a patient who was treated with daclizumab in an ongoing observational study, as well as the occurrence of four cases of serious liver injury.
One month later, amid their ongoing review, the PRAC issued provisional recommendations restricting use of the drug to patients who experience highly active relapsing MS despite having undergone a full and adequate course of treatment with at least one DMT or patients with rapidly evolving severe relapsing MS who are unsuitable for treatment with other DMTs. 
Today, the PRAC adopted final measures aimed to improve liver monitoring and limit use of daclizumab to patients who have had an inadequate response to at least two DMTs and cannot be treated with other such therapies.
Daclizumab, given as a once-monthly injection for adults with relapsing forms of MS, was first authorized for use in the European Union in July 2016.
Daclizumab was approved by the US Food and Drug Administration (FDA) for relapsing forms of MS in May 2016. The FDA cautioned, however, that daclizumab should be used only in patients who have not responded to one or two prior therapies because it carries serious safety risks, including potentially severe liver damage and immune conditions. In clinical trials, 1.7% of patients treated with daclizumab had a serious liver reaction.

font: Medscape

NEWS FROM THE WORLD- Peripheral nerve involvement in multiple sclerosis: Demonstration by magnetic resonance neurography

Objective

To detect and quantify peripheral nerve lesions in multiple sclerosis (MS) by magnetic resonance neurography (MRN).

Methods

Thirty-six patients diagnosed with MS based on the 2010 McDonald criteria (34 with the relapsing–remitting form, 2 with clinically isolated syndrome) with and without disease-modifying treatment were compared to 35 healthy age-/sex-matched volunteers. All patients underwent detailed neurological and electrophysiological examinations. Three Tesla MRN with large anatomical coverage of both legs and the lumbosacral plexus was performed by using 2-dimensional (2D) fat-saturated, T2-weighted (T2w) and dual echo turbo spin echo sequences as well as a 3D T2-weighted, fat-saturated SPACE sequence. Besides qualitative visual nerve assessment, a T2w signal quantification was performed by calculation of proton spin density and T2 relaxation time. Nerve diameter was measured as a morphometric criterion.

Results

T2w hyperintense nerve lesions were detectable in all MS patients, with a mean lesion number at thigh level of 151.5 ± 5.7 versus 19.1 ± 2.4 in controls (p < 0.0001). Nerve proton spin density was higher in MS (tibial/peroneal: 371.8 ± 7.7/368.9 ± 8.2) versus controls (tibial/peroneal: 266.0 ± 11.0/276.8 ± 9.7, p < 0.0001). In contrast, T2 relaxation time was significantly higher in controls (tibial/peroneal: 82.0 ± 2.1/78.3 ± 1.7) versus MS (tibial/peroneal: 64.3 ± 1.0/61.2 ± 0.9, p < 0.0001). Proximal tibial and peroneal nerve caliber was higher in MS (tibial: 52.4 ± 2.1mm2, peroneal: 25.4 ± 1.3mm2) versus controls (tibial: 45.2 ± 1.4mm2p < 0.0015; peroneal: 21.3 ± 0.7mm2p = 0.0049).

Interpretation

Peripheral nerve lesions could be visualized and quantified in MS in vivo by high-resolution MRN. Lesions are defined by an increase of proton spin density and a decrease of T2 relaxation time, indicating changes in the microstructural organization of the extracellular matrix in peripheral nerve tissue in MS. By showing involvement of the peripheral nervous system in MS, this proof-of-concept study may offer new insights into the pathophysiology and treatment of MS. 

Ann Neurol 2017

NEWS FROM THE WORLD- Prediction of phenotypic severity in mucopolysaccharidosis type IIIA

Objective

Mucopolysaccharidosis IIIA or Sanfilippo disease type A is a progressive neurodegenerative disorder presenting in early childhood, caused by an inherited deficiency of the lysosomal hydrolase sulfamidase. New missense mutations, for which genotype–phenotype correlations are currently unknown, are frequently reported, hampering early prediction of phenotypic severity and efficacy assessment of new disease-modifying treatments. We aimed to design a method to determine phenotypic severity early in the disease course.

Methods

Fifty-three patients were included for whom skin fibroblasts and data on disease course and mutation analysis were available. Patients were phenotypically characterized on clinical data as rapidly progressing or slowly progressing. Sulfamidase activity was measured in fibroblasts cultured at 37 °C and at 30 °C.

Results

Sulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a combination of known severe mutations remained below the limit of quantification under both culture conditions. In contrast, sulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a known mild mutation increased above the limit of quantification when cultured at 30 °C. With division on the basis of the patients' phenotype, fibroblasts from slowly progressing patients could be separated from rapidly progressing patients by increase in sulfamidase activity when cultured at 30 °C (p < 0.001, sensitivity = 96%, specificity = 93%).

Interpretation

Phenotypic severity strongly correlates with the potential to increase sulfamidase activity in fibroblasts cultured at 30 °C, allowing reliable distinction between patients with rapidly progressing or slowly progressing phenotypes. This method may provide an essential tool for assessment of treatment effects and for health care and life planning decisions. 

Ann Neurol 2017

NEWS FROM THE WORLD- Comprehension of an Elevated Amyloid Positron Emission Tomography Biomarker Result by Cognitively Normal Older Adults

Importance  The goal of Alzheimer disease (AD) prevention together with advances in understanding the pathophysiology of AD have led to clinical trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data are needed to inform the processes of describing AD biomarkers to cognitively normal adults and assessing their understanding of this knowledge.
Objective  To determine the comprehension of an elevated amyloid positron emission tomographic (PET) biomarker result by cognitively unimpaired adults.
Design, Setting, and Participants  The Study of Knowledge and Reactions to Amyloid Testing, a substudy of an AD prevention trial, involved 2 semistructured telephone interviews with 80 participants recruited from 9 study sites: 50 received elevated and 30 received not elevated amyloid PET scan results. Interviews were conducted 4 to 12 weeks after result disclosure and again 1 year later. Data presented here were collected from November 5, 2014, through December 10, 2015. The 50 participants included in this study were cognitively normal, aged 65 to 85 years, evenly distributed by gender, and had elevated amyloid PET results. Subsequent reports will examine persons with “not elevated” results and compare the influence of the different results.
Main Outcomes and Measures  Participant comprehension of an elevated amyloid result was assessed by analyzing their responses to the following questions: “What was the result of your amyloid PET scan?” (followed by “Can you tell me in your own words what that means?” or “How would you explain it to a friend?”), “Was it the result you expected?” and “Did the result teach you anything or clarify anything for you?”
Results  Of the 50 participants aged 65 to 85 years, 49 (98%) were white, 40 (80%) reported a family history of AD, and 30 (60%) had a postgraduate educational level. Most participants (31 [62%]) understood that elevated amyloid conferred an increased but uncertain risk of developing AD. Some desired understanding of the term elevated other than its being a categorical result enabling trial entry eligibility; they wanted information regarding how elevated their amyloid was, how close to the study threshold they were, or percentages, numbers, or a scale to help them make sense of the result.
Conclusions and Relevance  Including an explanation of how and why a dimensional biomarker is converted to a categorical classification would enhance future AD biomarker clinical trials and educational materials.
JAMA Neurology 2017

NEWS FROM THE WORLD- Kinetics of Human Mutant Tau Prion Formation in the Brains of 2 Transgenic Mouse Lines

Importance  Accumulation of the protein tau is a defining characteristic of several neurodegenerative diseases. Thorough assessment of transgenic (Tg) mouse lines that replicate this process is critical for establishing the models used for testing anti-tau therapeutics in vivo.
Objective  To define a consistent mouse model of disease for use in future compound efficacy studies.
Design, Setting, and Participants  In this time course study, cohorts of Tg and control mice were euthanized at defined intervals. Collected brains were bisected down the midline. One half was frozen and used to measure the tau prion content, while the other half was fixed for immunostaining with anti-tau antibodies. All mice were maintained at the Hunters Point Animal Facility at the University of California, San Francisco, and all experiments were performed at the Mission Bay Campus of the University of California, San Francisco. Study animals were PS19, homozygous and hemizygous Tg(MAPT*P301S), and B6/J mice. The study dates were August 9, 2010, to October 3, 2016.
Main Outcomes and Measures  Tau prions were measured using a cell-based assay. Neuropathology was measured by determining the percentage area positive for immunostaining in defined brain regions. A separate cohort of mice was aged until each mouse developed neurological signs as determined by trained animal technicians to assess mortality.
Results  A total of 1035 mice were used in this time course study. These included PS19 mice (51.2% [126 of 246] male and 48.8% [120 of 246] female), Tg(MAPT*P301S+/+) mice (52.3% [216 of 413] male, 43.8% [181 of 413] female, and 3.9% [16 of 413] undetermined), Tg(MAPT*P301S+/−) mice (51.8% [101 of 195] male and 48.2% [94 of 195] female), and B6/J mice (49.7% [90 of 181] male and 50.3% [91 of 181] female). While considerable interanimal variability in neuropathology, disease onset, and tau prion formation in the PS19 mice was observed, all 3 measures of disease were more uniform in the Tg(MAPT*P301S+/+) mice. Comparing tau prion formation in Tg(MAPT*P301S+/+) mice with B6/J controls, the 95% CIs for the 2 mouse lines diverged before age 5 weeks, and significant (P < .05) neuropathology in the hindbrain of 24-week-old mice was quantifiable.
Conclusions and Relevance  The assessment of disease progression using 3 criteria showed that disease onset in PS19 mice is too variable to obtain reliable measurements for drug discovery research. However, the reproducibility of tau prion formation in young Tg(MAPT*P301S+/+) mice establishes a rapid assay for compound efficacy in vivo.
JAMA Neurology 2017

NEWS FROM THE WORLD- Disability Trajectories Before and After Stroke and Myocardial Infarction The Cardiovascular Health Study

Importance  Ischemic strokes may accelerate long-term functional decline apart from their acute effects on neurologic function.
Objective  To test whether the increase in long-term disability is steeper after than before the event for ischemic stroke but not myocardial infarction (MI).
Design, Settings, and Participants  In the population-based, prospective cohort Cardiovascular Health Study (1989-2013), longitudinal follow-up was conducted for a mean (SD) of 13 (6.2) years. Follow-up data were used until September 1, 2013; data analysis was performed from August 1, 2013, to June 1, 2016. Models based on generalized estimating equations adjusted for baseline covariates and included a test for different slopes of disability before and after the event. Participants included 5888 Medicare-eligible individuals 65 years or older who were not institutionalized, expected to reside in the area for 3 or more years, and able to provide informed consent. Exclusions were needing a wheelchair, receiving hospice care, and undergoing radiotherapy or chemotherapy.
Exposures  Ischemic stroke and MI.
Main Outcomes and Measures  Annual assessments with a disability scale (measuring activities of daily living [ADLs] and instrumental ADLs). The number of ADLs and instrumental ADLs (range, 0-12) that the participant could not perform was analyzed continuously.
Results  The mean (SD) age of the entire cohort (n = 5888) was 72.8 (5.6) years; 2495 (42.4%) were male. During follow-up, 382 (6.5%) participants had ischemic stroke and 395 (6.7%) had MI with 1 or more disability assessment after the event. There was a mean of 3.7 (2.4) visits before stroke and 3.7 (2.3) visits after stroke; there was a mean of 3.8 (2.5) visits before MI and 3.8 (2.4) visits after MI. The increase in disability near the time of the event was greater for stroke (0.88 points on the disability scale; 95% CI, 0.57 to 1.20; P < .001) than MI (0.20 points on the disability scale; 95% CI, 0.06 to 0.35; P = .006). The annual increase in disability before stroke (0.06 points per year; 95% CI, 0.002 to 0.12; P = .04) more than tripled after stroke (0.15 additional points per year; 95% CI, 0.004 to 0.30; P = .04). The annual increase in disability before MI (0.04 points per year; 95% CI, 0.004 to 0.08; P = .03) did not change significantly after MI (0.02 additional points per year; 95% CI, −0.07 to 0.11; P = .69).
Conclusions and Relevance  In this large, population-based study, a trajectory of increasing disability became significantly steeper after stroke but not after MI. Thus, in addition to the acute brain injury and consequent impairment, ischemic stroke may also be associated with potentially treatable long-term adverse effects on the brain that lead to accelerated functional decline.
JAMA Neurology 2017

NEWS FROM THE WORLD- PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer’s disease

Abstract

Mitochondrial dysfunction and synaptic damage are early pathological features of the Alzheimer’s disease-affected brain. Memory impairment in Alzheimer’s disease is a manifestation of brain pathologies such as accumulation of amyloid-β peptide and mitochondrial damage. The underlying pathogenic mechanisms and effective disease-modifying therapies for Alzheimer’s disease remain elusive. Here, we demonstrate for the first time that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with Alzheimer’s disease pathology. Restoring neuronal PINK1 function strikingly reduces amyloid-β levels, amyloid-associated pathology, oxidative stress, as well as mitochondrial and synaptic dysfunction. In contrast, PINK1-deficient mAPP mice augmented cerebral amyloid-β accumulation, mitochondrial abnormalities, impairments in learning and memory, as well as synaptic plasticity at an earlier age than mAPP mice. Notably, gene therapy-mediated PINK1 overexpression promotes the clearance of damaged mitochondria by augmenting autophagy signalling via activation of autophagy receptors (OPTN and NDP52), thereby alleviating amyloid-β-induced loss of synapses and cognitive decline in Alzheimer’s disease mice. Loss of PINK1 activity or blockade of PINK1-mediated signalling (OPTN or NDP52) fails to reverse amyloid-β-induced detrimental effects. Our findings highlight a novel mechanism by which PINK1-dependent signalling promotes the rescue of amyloid pathology and amyloid-β-mediated mitochondrial and synaptic dysfunctions in a manner requiring activation of autophagy receptor OPTN or NDP52. Thus, activation of PINK1 may represent a new therapeutic avenue for combating Alzheimer’s disease.

Brain 2017

NEWS FROM THE WORLD- Epidemiology of recurrent traumatic brain injury in the general population A systematic review

ABSTRACT

Objective: To comprehensively assess recurrent traumatic brain injury (rTBI) risk and risk factors in the general population.
Methods: We systematically searched MEDLINE, EMBASE, and the references of included studies until January 16, 2017, for general population observational studies reporting rTBI risk or risk factors. Estimates were not meta-analyzed due to significant methodologic heterogeneity between studies, which was evaluated using meta-regression.
Results: Twenty-two studies reported recurrence risk and 11 reported on 27 potential risk factors. rTBI risk was heterogeneous and varied from 0.43% (95% confidence interval [CI] 0.19%–0.67%) to 41.92% (95% CI 34.43%–49.40%), with varying follow-up periods (3 days–55 years). Median time to recurrence ranged from 0.5 to 3.8 years. In studies where cases were ascertained from multiple points of care, at least 5.50% (95% CI 4.80%–6.30%) of patients experienced a recurrence after a 1-year follow-up. Studies that used administrative data/self-report surveys to ascertain cases tended to report higher risk. Risk factors measured at time of index traumatic brain injury (TBI) that were significantly associated with rTBI in more than one study were male sex, prior TBI before index case, moderate or severe TBI, and alcohol intoxication. Risk factors reported in a single study that were significantly associated with rTBI were epilepsy, not seeking medical care, and multiple factors indicative of low socioeconomic status.
Conclusions: rTBI is an important contributor to the general population TBI burden. Certain risk factors can help identify individuals at higher risk of these repeated injuries. However, higher quality research that improves on rTBI surveillance methodology is needed.
Neurology 2017

NEWS FROM THE WORLD- Evolution of DWI lesions in cerebral amyloid angiopathy Evidence for ischemia

ABSTRACT

Objective: To address the pathophysiologic nature of small diffusion-weighted imaging (DWI) lesions in patients with cerebral amyloid angiopathy (CAA) who underwent serial MRI. Specifically, we tested (1) whether DWI lesions occurred preferentially in individuals with prior DWI lesions, (2) the cross-sectional association with chronic cortical cerebral microinfarcts (CMIs), and (3) the evolution of DWI lesions over time.
Methods: Patients with probable CAA (n = 79) who underwent at least 2 MRI sessions were included. DWI lesions were assessed at each available time point. Lesion appearance and characteristics were assessed on available structural follow-up images. Presence and burden of other neuroimaging markers of small vessel disease (white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, and chronic cortical CMIs) were assessed as well.
Results: Among 221 DWI scans (79 patients with 2 DWI scans; 40 with ≥3), 60 DWI lesions were found in 28 patients. Patients with DWI lesions at baseline were not more likely to have additional DWI lesions on follow-up compared to patients without DWI lesions at baseline. DWI lesions were associated with chronic cortical CMIs and cortical superficial siderosis, but not with other markers. For 39/60 DWI lesions, >1 MRI sequence was available at follow-up to determine lesion evolution. Twenty-four (62%) were demarcated as chronic lesions on follow-up MRI. Five appeared as cavitations, 18 as noncavitated infarcts, and 1 underwent hemorrhagic transformation.
Conclusions: Based on their neuroimaging signature as well as their association with chronic cortical CMIs, DWI lesions appear to have an ischemic origin and represent one part of the CMI spectrum.

Neurology 2017

NEWS FROM THE WORLD- Cortical superficial siderosis multifocality in cerebral amyloid angiopathy A prospective study

ABSTRACT

Objective: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci.
Methods: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0–4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH.
Results: The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9–5.1 years), the annual ICH recurrence rates per cSS scores (0–4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77–5.75; p < 0.0001).
Conclusions: The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

Neurology 2017

NEWS FROM THE WORLD- Serum neurofilament light in familial Alzheimer disease A marker of early neurodegeneration

ABSTRACT

Objectives: To investigate whether serum neurofilament light (NfL) concentration is increased in familial Alzheimer disease (FAD), both pre and post symptom onset, and whether it is associated with markers of disease stage and severity.
Methods: We recruited 48 individuals from families with PSEN1 or APP mutations to a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using an ultrasensitive immunoassay on the single molecule array (Simoa) platform. Cognitive testing and MRI were performed; 33 participants had serial MRI, allowing calculation of atrophy rates. Genetic testing established mutation status. A generalized least squares regression model was used to compare serum NfL among symptomatic mutation carriers, presymptomatic carriers, and noncarriers, adjusting for age and sex. Spearman coefficients assessed associations between serum NfL and (1) estimated years to/from symptom onset (EYO), (2) cognitive measures, and (3) MRI measures of atrophy.
Results: Nineteen of the asymptomatic participants were mutation carriers (mean EYO −9.6); 11 were noncarriers. Compared with noncarriers, serum NfL concentration was higher in both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007). Across all mutation carriers, serum NfL correlated with EYO (ρ = 0.81, p< 0.0001) and multiple cognitive and imaging measures, including Mini-Mental State Examination (ρ = −0.62, p = 0.0001), Clinical Dementia Rating Scale sum of boxes (ρ = 0.79, p < 0.0001), baseline brain volume (ρ = −0.62, p = 0.0002), and whole-brain atrophy rate (ρ = 0.53, p = 0.01).
Conclusions: Serum NfL concentration is increased in FAD prior to symptom onset and correlates with measures of disease stage and severity. Serum NfL may thus be a feasible biomarker of early AD-related neurodegeneration.

Neurology 2017

NEWS FROM THE WORLD- Monitoring disease activity in multiple sclerosis using serum neurofilament light protein

ABSTRACT

Objective: To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).
Methods: NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.
Results: In MS, the correlation between serum and CSF NFL was r = 0.62 (p < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, p < 0.001 and p < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6–32.7) ng/L to 15.7 (IQR 9.6–22.7) ng/L (p < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission (p < 0.001) or those without new lesions on MRI (p < 0.001).
Conclusions: Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.
Neurology 2017

NEWS FROM THE WORLD- Early weight loss in parkinsonism predicts poor outcomes Evidence from an incident cohort study

ABSTRACT

Objective: To compare weight change over time in patients with Parkinson disease (PD), those with atypical parkinsonism, and matched controls; to identify baseline factors that influence weight loss in parkinsonism; and to examine whether it predicts poor outcome.
Methods: We analyzed data from the Parkinsonism Incidence in North-East Scotland (PINE) study, an incident, population-based prospective cohort of parkinsonian patients and age- and sex-matched controls with annual follow-up. Mixed-model analysis described weight change in patients with PD, those with atypical parkinsonism, and controls. Baseline determinants of sustained clinically significant weight loss (>5% loss from baseline) and associations between early sustained weight loss and death, dementia, and dependency in parkinsonism were studied with Cox regression.
Results: A total of 515 participants (240 controls, 187 with PD, 88 with atypical parkinsonism) were followed up for a median of 5 years. At diagnosis, atypical parkinsonian patients had lower body weights than patients with PD, who were lighter than controls. Patients with PD lost weight more rapidly than controls, and weight loss was most rapid in atypical parkinsonism. After multivariable adjustment for potential confounders, only age was independently associated with sustained clinically significant weight loss (hazard ratio [HR] for 10-year age increase 1.83, 95% confidence interval [CI] 1.44–2.32). Weight loss occurring within 1 year of diagnosis was independently associated with increased risk of dependency (HR 2.11, 95% CI 1.00–4.42), dementia (HR 3.23, 95% CI 1.40–7.44), and death (HR 2.23, 95% CI 1.46–3.41).
Conclusion: Weight loss occurs in early parkinsonism and is greater in atypical parkinsonism than in PD. Early weight loss in parkinsonism has prognostic significance, and targeted dietary interventions to prevent it may improve long-term outcomes.
Neurology 2017

sabato 21 ottobre 2017

NEWS FROM THE WORLD- Effect of sensory and motor connectivity on hand function in pediatric hemiplegia

Abstract

Objective: We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development: while the motor system can maintain connections to the impaired hand from the uninjured hemisphere, this doesn't occur in the somatosensory system. As a corollary, cortical injury strongly impairs sensory function, so we hypothesized that cortical lesions would impair hand function more than subcortical lesions.
Methods: Twenty-four children with unilateral CP had physiological and anatomical measures of the motor and somatosensory systems and lesion classification. Motor physiology was performed with transcranial magnetic stimulation and somatosensory physiology with vibration-evoked EEG potentials. Tractography of the corticospinal tract and the medial lemniscus were performed with diffusion tensor imaging, and lesions were classified by MRI. Anatomical and physiological results were correlated with measures of hand function using two independent statistical methods.
Results: Children with disruptions in the somatosensory connectivity, and cortical lesions had the most severe upper extremity impairments, particularly somatosensory function. Motor system connectivity was significantly correlated with bimanual function, but not unimanual function or somatosensory function.
Interpretation: Both sensory and motor connectivity impact hand function in children with USCP. Somatosensory connectivity could be an important target for recovery of hand function in children with USCP. This article is protected by copyright.


Annals of Neurology 2017