Summary
Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied ...as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age‐dependent epilepsy syndrome but are now past the applicable age or who have remained seizure‐free for the last 10 years and off antiseizure medicines for at least the last 5 years. “Resolved” is not necessarily identical to the conventional view of “remission or “cure.” Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use.
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•NMR metabonomics identifies 60 and quantifies 38 metabolites in CSF.•Patients with Parkinson’s disease (PD) are distinguished from control subjects.•Uni- and multivariate statistics identify nine ...significantly changed metabolites.•Subsets of these nine metabolites also separate the PD and control groups.•NMR metabonomics may provide a supporting tool useful for diagnosis of PD.
This study assesses if nuclear magnetic resonance (NMR) metabonomics can discriminate between Parkinson’s disease (PD) patients and control subjects, and consequently identify metabolic markers for the disease. One-dimensional 1H NMR spectroscopy was used for quantitative analysis of metabolites in the cerebrospinal fluid (CSF) from 10 PD patients and 10 control individuals, together with uni- and multivariate statistical analysis to discriminate between the groups and to identify significantly altered metabolite concentrations. In total 60 metabolites were identified and of those 38 were quantified in all CSF samples. An overall lowering of metabolite content was observed in PD patients compared to control subjects (fold change of 0.85±0.30). Multivariate statistics reveal significant changes (ǀw*ǀ>0.2) among nine metabolites (alanine, creatinine, dimethylamine, glucose, lactate, mannose, phenylalanine, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid). Three of these (alanine, creatinine and mannose) are identified as significantly changed also by univariate statistics (p<0.00132, Bonferroni corrected). Panels with all or a selected set of these metabolites were successfully used for discriminating between the two groups. In conclusion, NMR metabonomics can readily determine metabolite concentrations in CSF, identify putative biomarkers that distinguish between the PD patients and control subjects, and thus potentially become a tool for diagnostic purposes.
Summary
Purpose: To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for ...specific etiologies.
Methods: Systematic review of the literature and of epidemiologic studies.
Results: An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well‐defined epileptogenic drugs.
Discussion: Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
Summary Background Many patients with Parkinson's disease have mild cognitive impairment (MCI). Deficits in executive functions and working memory suggest dysfunctional frontostriatal brain ...circuitry. We aimed to assess brain responses during a working memory task in a cohort of newly diagnosed drug-naive patients with Parkinson's disease with and without MCI. Methods Participants were recruited within a prospective cohort study of incident patients with idiopathic parkinsonism, including Parkinson's disease. Between Jan 1, 2004, and April 30, 2009, all physicians in the Umeå catchment area were requested to refer all individuals with suspected parkinsonism to the Department of Neurology at Umeå University. Included patients fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease. Control individuals were matched on the basis of age and sex with the first 50 patients included in the study. Participants who scored 1·5 SDs or more below the population mean on at least two cognitive measures were diagnosed with MCI. The primary outcome measures were functional MRI blood-oxygen-level-dependent signal and SPECT presynaptic uptake. Functional MRI was done during a verbal two-back working memory task. Presynaptic dopamine SPECT was done to assess presynaptic striatal dopaminergic system integrity. Event-related transient analyses of functional MRI data were done for the whole brain and for frontostriatal regions of interest, and semi-quantitative SPECT analyses were done for striatal regions of interest. Findings Compared with controls (n=24), patients with Parkinson's disease (n=77) had under-recruitment in an extensive brain network including bilateral striatal and frontal regions (p<0·001). Within the Parkinson's disease group, patients with Parkinson's disease and MCI (n=30) had additional under-recruitment in the right dorsal caudate nucleus (p=0·005) and the bilateral anterior cingulate cortex (p<0·001) compared with patients with Parkinson's disease without MCI (n=26). In patients with Parkinson's disease and MCI, SPECT uptake in the right caudate was lower than in patients with Parkinson's disease without MCI (p=0·008) and correlated with striatal functional MRI blood-oxygen-level-dependent signal ( r =0·32, p=0·031). Interpretation These altered brain responses in patients with Parkinson's disease and MCI suggest that cognitive impairment is linked to frontostriatal dysfunction. Funding Swedish Medical Research Council, Swedish Parkinson Foundation, Swedish Parkinson's Disease Association, Umeå University, Kempe Foundation, Foundation for Clinical Neuroscience at Umeå University Hospital, Västerbotten County Council (ALF), King Gustaf V's and Queen Victoria's Freemason Foundation, Knut and Alice Wallenberg Foundation, and Swedish Brain Power.
IMPORTANCE: Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo ...biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE: To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS: Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by a movement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid–binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS: Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid–binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE: The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid–binding protein were related to future PDD, providing new insights into the etiology of PDD.
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are protein-aggregation diseases that lack clear molecular etiologies. Biomarkers could aid in diagnosis, prognosis, planning of care, ...drug target identification and stratification of patients into clinical trials. We sought to characterize shared and unique metabolite perturbations between ALS and PD and matched controls selected from patients with other diagnoses, including differential diagnoses to ALS or PD that visited our clinic for a lumbar puncture. Cerebrospinal fluid (CSF) and plasma from rigorously age-, sex- and sampling-date matched patients were analyzed on multiple platforms using gas chromatography (GC) and liquid chromatography (LC)-mass spectrometry (MS). We applied constrained randomization of run orders and orthogonal partial least squares projection to latent structure-effect projections (OPLS-EP) to capitalize upon the study design. The combined platforms identified 144 CSF and 196 plasma metabolites with diverse molecular properties. Creatine was found to be increased and creatinine decreased in CSF of ALS patients compared to matched controls. Glucose was increased in CSF of ALS patients and α-hydroxybutyrate was increased in CSF and plasma of ALS patients compared to matched controls. Leucine, isoleucine and ketoleucine were increased in CSF of both ALS and PD. Together, these studies, in conjunction with earlier studies, suggest alterations in energy utilization pathways and have identified and further validated perturbed metabolites to be used in panels of biomarkers for the diagnosis of ALS and PD.
Objective
The objectives of this study were to explore the changes in the activities of daily living (ADL) in persons with Parkinson's disease (pwPD) over time and to investigate possible differences ...in ADL performance between men and women with PD.
Materials & Methods
One hundred twenty‐nine persons (76 men) with a clinically established PD self‐assessed their ADL performance from the time of diagnosis up to 8 years follow‐up using the ADL taxonomy. Other demographic and clinical data (motor state, cognition, depression) were also collected and subjected to further analysis.
Results
Nine of 12 domains in the ADL taxonomy showed a change over time (Eating and Drinking P = .009, Mobility P < .001, Toilet activities P = .031, Dressing P < .001, Personal hygiene P < .001, Communication P < .001, Cooking P = .001, Shopping P < .001 and Cleaning P < .001). In addition to time, two domains, (Shopping P = .007 and Cleaning P = .027) also showed an effect of gender with worse scores in women. The nine ADL domains showing effect of time, showed temporary improvement at 12 months follow‐up, most probably due to dopaminergic medication. All nine domains deteriorated at later follow‐up.
Conclusions
As expected, there was deterioration in self‐assessed performance in the majority od ADL domains over time. Women assessed their ADLs worse in two domains (Shopping and Cleaning) probably reflecting a general gender‐related activity pattern rather than being a PD‐specific finding.
Abstract Introduction Studies report that up to 90% of patients with idiopathic Parkinson's disease (PD) have olfactory dysfunction (hyposmia). Hyposmia has also been connected to cognitive ...impairment and dementia in PD, but no studies of newly diagnosed patients followed longer than three years exists. The present study investigates the prevalence of olfactory dysfunction at PD diagnosis, how it evolves over time and whether hyposmia increases the risk of dementia in Parkinson's disease. Methods Olfactory function was assessed with Brief Smell Identification Test (B-SIT) in 125 newly diagnosed patients with PD. They were followed for a maximum of 10 years (median six years) with extensive investigations at baseline, 12, 36, 60 and 96 months. Patients with B-SIT<9 were considered hyposmic. Results Hyposmia was found in 73% of the patients at diagnosis. During the follow up period of ten years 42 (46%) patients with hyposmia at baseline developed dementia compared to seven (21%) of the normosmic patients. Cox proportional hazards model showed that hyposmia at baseline (controlled for age, gender, UPDRS III and Mild Cognitive Impairment) increased the risk of developing dementia (hazard ratio (95%CI): 3.29 (1.44–7.52), p = 0.005). Only one of 22 patients with normal cognition and normal olfaction at baseline developed dementia. Conclusions Olfactory dysfunction was common at the time of PD diagnosis and increased the risk of dementia up to ten years after PD diagnosis regardless of baseline cognitive function. Normal olfaction together with normal cognition at baseline predicted a benign cognitive course up to ten years after diagnosis.
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