Clinical predictors of Alzheimer's disease-like brain atrophy in individuals with memory complaints.

OBJECTIVES: The definition and assessment methods for subjective cognitive decline (SCD) vary among studies. We aimed to investigate which features or assessment methods of SCD best predict Alzheimer's disease (AD)-related structural atrophy patterns. METHODS: We assessed 104 individuals aged 55+ with memory complaints but normal cognitive screening. Our research questions were as follows: To improve the prediction of AD related morphological changes, (1) Would the use of a standardized cognitive screening scale be beneficial? (2) Is conducting a thorough neuropsychological evaluation necessary instead of relying solely on cognitive screening tests? (3) Should we apply SCD-plus research criteria, and if so, which criterion would be the most effective? (4) Is it necessary to consider medical and psychiatric comorbidities, vitamin deficiencies, vascular burden on MRI, and family history? We utilized Freesurfer to analyze cortical thickness and regional brain volume meta-scores linked to AD or predicting its development. We employed multiple linear regression models for each variable, with morphology as the dependent variable. RESULTS: AD-like morphology was associated with subjective complaints in males, individuals with advanced age, and higher education. Later age of onset for complaints, complaints specifically related to memory, excessive deep white matter vascular lesions, and using medications that have negative implications for cognitive health (according to the Beers criteria) were predictive of AD-related morphology. The subjective cognitive memory questionnaire scores were found to be a better predictor of reduced volumes than a single-question assessment. It is important to note that not all SCD-plus criteria were evaluated in this study, particularly the APOE genotype, amyloid, and tau status, due to resource limitations. CONCLUSIONS: The detection of AD-related structural changes is impacted by demographics and assessment methods. Standardizing SCD assessment methods can enhance predictive accuracy.

Hybrid PET/MRI with Flutemetamol and FDG in Alzheimer's Disease Clinical Continuum.

AIMS: We aimed to investigate the interaction between ß -amyloid (Aß) accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes in the Alzheimer's disease (AD) clinical continuum. BACKGROUND: Utility of positron emission tomography (PET) / magnetic resonance imaging (MRI) hybrid imaging for diagnostic categorization of the AD clinical continuum including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD) has not been fully crystallized. OBJECTIVE: To evaluate the interaction between Aß accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes such as cortex thickness or cerebral white matter disease burden and to detect the discriminative yields of these imaging modalities in the AD clinical continuum. METHODS: Fifty patients (20 women and 30 men; median age: 64 years) with clinical SCD (n=11), aMCI (n=17) and ADD (n=22) underwent PET/MRI with [18F]-fluoro-D-glucose (FDG) and [18F]- Flutemetamol in addition to cerebral blood flow (CBF) and quantitative structural imaging along with detailed cognitive assessment. RESULTS: High Aß deposition (increased temporal [18F]-Flutemetamol standardized uptake value ratio (SUVr) and centiloid score), low glucose metabolism (decreased temporal lobe and posterior cingulate [18F]-FDG SUVr), low parietal CBF and right hemispheric cortical thickness were independent predictors of low cognitive test performance. CONCLUSION: Integrated use of structural, metabolic, molecular (Aß) and perfusion (CBF) parameters contribute to the discrimination of SCD, aMCI, and ADD.

Perspectives of Family Caregivers of People With Alzheimer's Disease on Caregiving Experience and Needs: A Qualitative Study.

The current study aimed to investigate the perspectives of family caregivers of people with Alzheimer's disease on caregiving experience and needs. A qualitative descriptive method was used with a sample of 23 family caregivers. Data were collected through in-depth, face-to-face interviews using a pilot-tested semi-structured interview guide. Data analysis was performed via content analysis. Three major themes emerged: (1) Stuck in Caregiving, (2) A Life in Metamorphosis, and (3) Needs. Findings revealed that caregivers struggled to manage the care process, adapt to life changes, and fulfill their needs. This study provides rich data to help create interventions to assist family caregivers. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Post-inflammatory administration of N-acetylcysteine reduces inflammation and alters receptor levels in a cellular model of Parkinson's disease.

Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease with a prevalence of 1% over the age of 55. Neuropathological hallmarks of PD include the loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies that contain a variety of proteins and lipids including alpha-synuclein (α-syn). Although the formation of α-syn occurs intracellularly, it can also be found in the extracellular space where it can be taken up by neighboring cells. Toll-like receptor 2 (TLR2) is an immune system receptor that has been shown to recognize extracellular α-syn and modulate its uptake by other cells. Lymphocyte-activation gene 3 (LAG3), an immune checkpoint receptor, has also been proposed to play a role in extracellular α-syn internalization; however, a recent study has disputed this role. Internalized α-syn can trigger expression and secretion of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-2, and IL-6 and induce neuroinflammation, apoptosis, and mitophagy that results in cellular death. In this study, we tested if N-acetylcysteine (NAC), an anti-inflammatory and anti-carcinogenic drug, can circumvent the detrimental effects of neuroinflammation and induce an anti-inflammatory response by modulating transcription and expression of TLR2 and LAG3 receptors. Cells overexpressing wild-type α-syn were treated with TNF-α to induce inflammation followed by NAC to inhibit the deleterious effects of TNF-α-induced inflammation and apoptosis. SNCA gene transcription and α-syn protein expression were validated by q-PCR and Western blot (WB), respectively. Cell viability was measured, and apoptosis was evaluated by WB and terminal deoxynucleotidyl transferase nick end labeling methods. Alterations in LAG3 and TLR2 receptor levels were evaluated by immunofluorescent labeling, WB, and q-PCR. TNF-α not only increased inflammation but also increased endogenous and overexpressed α-syn levels. NAC treatment decreased expression of TLR2 and increased transcription of LAG3 receptor and diminished inflammation-mediated toxicity and cell death. Here, we demonstrate that NAC can reduce neuroinflammation that occurs as a result of alpha-synuclein overexpression, via a TLR2-associated pathway, making it a promising candidate for therapeutic intervention. Further studies are needed to elucidate molecular mechanisms and pathways related to neuroinflammation in PD and to develop possible new therapeutic approaches to slow the clinical progression of PD.

Cerebral vasomotor reactivity across the continuum of subjective cognitive impairment, amnestic mild cognitive impairment and probable Alzheimer's dementia: A transcranial Doppler and PET/MRI study.

Cerebrovascular dysfunction has been suggested as a physiomarker of Alzheimer's disease (AD)-associated neuronal degeneration, but the underlying mechanisms are still debated. Herein cerebral vasomotor reactivity (VMR, breath-hold index: BHI), metabolic activity (lobar SUVs, FDG PET MRI), amyloid load (Centiloid score, Flutemetamol PET MRI), hemispheric cortical thickness, white matter lesion load and cerebral blood flow (ASL) were studied in 43 consecutive subjects (mean age: 64 years, female 13), diagnosed with subjective cognitive impairment (SCI, n = 10), amnestic mild cognitive impairment (aMCI, n = 15), and probable Alzheimer's dementia (AD, n = 18). BHI was significantly reduced in AD and aMCI patients compared to SCI subjects. A highly significant inverse correlation was found between BHI and the centiloid score (r = -0.648, p < 0.001). There was moderate positive correlation between BHI and frontal, temporal and parietal FDG SUV and ASL values, and a borderline negative correlation with age and white matter lesion volume. The link between amyloid burden and VMR was independent and strong in linear regression models where all these parameters were included (ß from -0.580 to -0.476, p < 0.001). In conclusion, our study confirms the negative association of cerebral amyloid accumulation and vasomotor reactivity in Alzheimer's disease with the most direct data to date in humans.

Sleep disorders and polysomnography findings in patients with autoimmune encephalitis.

BACKGROUND: Sleep disorders in patients with autoimmune encephalitis (AE) are increasingly reported. Early recognition and treatment have significant importance regarding the potential of sleep disorders' effect on morbidity and even mortality. There are a limited number of studies related to polysomnography (PSG) in these patients. Here, we report the clinical and PSG data of patients with AE and sleep disorders, with a particular interest in sleep-related breathing disorders (SRBD). METHODS: Seventeen patients with diagnosed AE and acute or subacute onset sleep complaints who underwent video-electroencephalography-PSG recordings in our tertiary center were investigated. RESULTS: The mean age was 50, with eight females and nine males. The detected antibodies were against leucine-rich glioma-inactivated 1(LGI-1) in 6, anti-contactin-associated protein-2(CASPR2) in 3, voltage-gated potassium channel complex antigens(VGKC) in 1, anti-glycine in 1, dipeptidyl-peptidase-like protein-6(DPPX) in 1, anti-Hu in 1, and anti-amphiphysin in 1. All commercially available and known autoimmune encephalitis-related antibodies were negative in 3 of the patients. Final diagnosis after PSG was circadian rhythm sleep disorder (n = 3), periodic limb movement disorder (n = 3), insomnia (n = 5), central apnea with or without Cheyne-Stokes breathing (CSB) (n = 4), obstructive sleep apnea (OSA) (n = 4), non-rapid eye movement (NREM) and REM parasomnia (n = 8), faciobrachial dystonic seizures (n = 2), and subclinical seizures (n = 1). Sleep microstructure was disrupted in 9, REM periods without atonia occurred in 4, and brief sleep fragments consisting of theta activity interspersed with faster rhythms existed in 7 patients. Nearly half of our patients (47%) had SRBD, and the mean apnea-hypopnea index (AHI) was 14. CONCLUSIONS: Sleep disorders are frequent and essential components of AEs. Systematic clinical questionnaires and routine PSG assessments would significantly impact the correct diagnosis and proper treatment of SRBD and the overall prognosis of AE.

Two cases with mitochondrial membrane protein-associated neurodegeneration: genetic features and long-term clinical follow-up.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological disease with childhood or adult onset. It is a subtype of clinically and genetically heterogeneous group of disorders, collectively known as neurodegeneration with brain iron accumulation . MPAN is generally associated with biallelic pathogenic variants in C19orf12. Herein, we describe genetic and clinical findings of two MPAN cases from Turkey. In the first case, we have identified the relatively common pathogenic variant of C19orf12 in the homozygous state, which causes late-onset MPAN. The second case was homozygous for an essential splice-site variation.

Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease.

In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.

Modelling cognitive deficits in Parkinson's disease: Is CA2 a gateway for hippocampal synucleinopathy?

BACKGROUND: Cognitive dysfunction is one of the most disabling non-motor symptoms of Parkinson's disease (PD), though its pathological correlates still remain elusive. Hippocampal Lewy pathology has recently been correlated by compelling evidence from post-mortem and imaging studies. Animal models recapitulating cognitive impairment in PD are essential to better understand the underlying pathophysiology. To investigate the hippocampal involvement in cognitive dysfunction of PD, we generated an experimental model by inducing midbrain and hippocampal α-synuclein pathology simultaneously. METHODS: Rats were injected either with human α-synuclein or green fluorescent protein (GFP) expressing adeno-associated viral vectors (AAV), or saline bilaterally into substantia nigra (SN) and dentate gyrus (DG). A group of untreated animals were used as naïve controls. Cognitive and behavioral changes were evaluated with tests probing for spatial learning, short-term memory, anxiety and hedonistic behavior. Immunohistochemical staining, immunoblotting and stereological analysis were performed for pathological characterization. RESULTS: Bilateral α-synuclein overexpression in SN and DG led to mild but significant motor impairment as well as dysfunctions in short-term memory and spatial learning. There was no hedonistic deficit, whereas a hypo-anxious state was induced. While stereological analysis revealed no significant neuronal loss in any sectors of cornu ammonis, there was considerable decrease (43%) in TH+-neurons in SN pars compacta supporting the well-known vulnerability of nigral dopaminergic neurons to α-synuclein mediated neurodegeneration. On the other hand, synaptophysin levels decreased in similar amounts both in striatum and hippocampus, suggesting comparable synaptic loss in target areas. Interestingly, phosphorylated-S129-α-synuclein staining revealed significant expression in CA2 characterized by more mature and dense cellular accumulations compared to CA1-CA3 sub-regions displaying more diffuse grain-like aggregates, suggesting preferential susceptibility of CA2 to produce α-synuclein induced pathology. CONCLUSION: Bilateral α-synuclein overexpression in DG and SN reproduced partial motor and hippocampus related cognitive deficits. Using this model, we showed a predisposition of CA2 for pathological α-synuclein accumulation, which may provide further insights for future experimental and clinical studies.

The Sole Initial Imaging Finding in Creutzfeldt-Jacob Disease: Focal FDG-PET Hypometabolism.

Laboratory studies such as electroencephalography, cerebrospinal fluid examination and diffusion-weighted magnetic resonance imaging (DWI-MRI) are valuable in the diagnosis of Creutzfeldt-Jacob disease (CJD),. However, these laboratory studies may not show the characteristic findings in the very early stage of the disease. Here, we present a case of CJD who had atypical neurologic presentation initially and had only a focal parietal 2-(18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) hypometabolism as the sole imaging abnormality at the beginning. The patient progressed rapidly, and showed typical neurological findings for CJD. The brain MRI was performed two weeks after the FDG-PET study, finally demonstrated increased signal intensity in DWI in caudat nucleus, putamen, and cerebral cortex, especially on left parietal region. Imaging methods demonstrating functional alterations in the brain should be obtained in the early period in patients with normal MRI suspected having CJD. Repeating DWI could also be an effective diagnostic approach.

Adaptation of the Modified Mini-Mental State Examination (3MS) and Determination of Its Normative Values in Turkey.

BACKGROUND/AIMS: This study aimed to adapt the Modified Mini-Mental State Examination (3MS) and determine its normative values in Turkey. METHODS: After translation and cultural adaptation processes, a population-based study was conducted between February and June 2016 in Ankara with individuals over the age of 55 years. Subjects with a previous diagnosis of dementia along with neuropsychiatric disorders that might affect cognition were excluded. Data analyses were performed to assess the association of sociodemographic variables with 3MS scores. RESULTS: Two versions of the Turkish 3MS (for educated and minimally educated individuals) were developed. A total of 2,235 participants were included in the field study. After exclusion, the data on the final sample of 1,909 individuals were analyzed, where age, gender, and education accounted for variance in 3MS scores. Younger age and higher educational attainment were associated with better 3MS performance. CONCLUSIONS: A widely applicable dementia screening test was adapted to Turkish and its normative values were determined. The test will make it possible to evaluate the cognitive performance of both educated and minimally educated elderly individuals based on their age, gender, and educational level.

Turkish Standardization of Movement Disorders Society Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale.

BACKGROUND: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) were developed as standard tools to rate Parkinson's disease (PD) and drug-induced dyskinesias of PD. As these scales have become widely used, there is a need for translation to non-English languages. Here we present the standardization for the Turkish translations. METHODS: The scales were translated into Turkish and then back-translated to English. These back-translations were reviewed by the MDS team. After cognitive pretesting, movement disorder specialists from nine centers tested 352 patients for MDS-UPDRS, and 250 patients for UDysRS. Confirmatory factor analyses (CFAs) were used to determine if the factor structures for the reference standards could be confirmed in the Turkish data. The comparative fit indexes (CFIs) for the scales were required to be 0.90 or higher. Exploratory factor analyses (EFAs) were conducted to explore the underlying factor structure without the constraint of a pre-specified factor structure. RESULTS: For both scales, the CFIs were 0.94 or greater as compared to the reference standard factor structures. The factor structures were consistent with that of reference standards, although there were some differences in some areas as compared to the EFA of the reference standard dataset. This may be due to the inclusion of patients with different stages of PD and different cultural properties of raters and patients. CONCLUSIONS: These results demonstrate that the Turkish translations of MDS-UPDRS and UDysRS have adequate clinimetric properties. They are established as the official translations and can be reliably used in Turkish speaking populations.

Striatal Neurotransmitter Release-related Presynaptic Proteins in L-dopa Induced Dyskinesia in a Model of Parkinsonism.

INTRODUCTION: In Parkinson's disease, L-dopa-induced dyskinesia (LID) and motor fluctuations incapacitate patients as much as the disease itself. Many studies demonstrated that postsynaptic alterations and striatal synaptic plasticity changes play a role in LID development. Here, we aimed to study the role of striatal presynaptic proteins in LID pathogenesis. METHODS: For this purpose, 6-hydroxydopamine model of parkinsonism was used. To induce LID, these rats were treated with intraperitoneal injections of L-dopa 25 mg/kg with benserazide 6.25 mg/kg b.i.d for 21 days. Rats with parkinsonism treated with saline and control rats treated with saline or L-dopa/ benserazide were also included. Behaviors of rats were videotaped and scored according to dyskinesia scale. Striatal tissue was analysed with immunofluorescence staining and immunoblotting to confirm loss of tyrosine hydroxylase (TH) expression due to dopaminergic denervation and to explore the alterations in the expression of presynaptic proteins, secretogranin 2 (SG2), synaptophysin (Syp) and synaptotagmin 7 (Syt7). RESULT: LID developed only in rats with parkinsonism treated with chronic L-dopa. Immunofluorescence and immunoblotting studies for TH confirmed depletion of dopaminergic neurons, which was also strongly and negatively correlated with severity of LID. Striatal SG2 and Syp levels were found increased in parkinsonian rats. Chronic L-dopa treatment further increased SG2 levels in denervated striatum. Striatal SG 2 level showed a significant moderate, positive correlation with LID severity. Immunofluorescence studies also demonstrated increased expression of these presynaptic proteins in the denervated striatum. CONCLUSION: As, severity of LID was clearly correlated with striatal SG2 expression; there is supposedly a functional relationship between striatal SG2 and LID. Further studies are needed to find out molecular mechanisms linking increased SG2 expression and LID.

Cognitive Dysfunction in Relation to Topography and Burden of Cerebral Microbleeds.

INTRODUCTION: Contribution of cerebral microbleeds (CMBs) on cognitive dysfunctions in elderly patients with otherwise asymptomatic white matter lesions (WMLs) is not well-documented. METHODS: MRI parameters of cerebral atrophy, CMBs and WMLs were herein analyzed in relation to global and main domains (attention, executive, memory, visuospatial, language) of cognitive function. Eighty-five patients older than 50, without neurodegenerative/cerebrovascular disease, but had CMBs were recruited from 2562 with T2*-gradient-echo MR imaging during one-year period. RESULTS: Global cognition, evaluated by mini-mental status examination (MMSE), was impaired (score ≤24) in 42%. In contrast to CMBs load, WML burden and temporal atrophy were significantly higher in cases with MMSE≤24. Cholinergic Pathways HyperIntensities Scale (CHIPS) was positively correlated with global cognitive dysfunction but its CMB counterpart, Cholinergic Pathways Bleeding Scale described herein, was not. However, burden of CMBs in thalamic/cortical regions predicted language dysfunction. CONCLUSION: Cognitive dysfunction associated with CMBs may be dependent on their distribution rather than their absolute number.

[A Population-Based Study for the Standardization of the Turkish Version of the Modified Mini Mental State Examination (3MS) and Assessment of Certain Environmental Risk Factors for Dementia: Methodology and Sample Characteristics]. / Modifiye-Mini-Mental Test (3MS) Türkçe Formu’nun Standardizasyonu ve Demansla Iliskili Bazi Çevresel Risk Etmenlerinin Tespiti için Toplum Temelli bir Çalisma: Metodoloji ve Örneklem Özellikleri.

OBJECTIVE: Objective assessment of the cognitive status and activities of daily living are required for the diagnosis of neurocognitive disorders. No cognitive screening test with normative values exist in Turkey. This study aims to standardize a widely applicable cognitive screening test, determine the activities of daily living in a population-based sample as well as identifying certain individual and environmental risk factors for cognitive disorders. METHOD: Since Mini-Mental-State-Examination (MMSE) is widely used in primary and secondary care and a version for the uneducated exists, an expanded and modified version of MMSE, Modified Mini Mental Test (3MS) was selected for standardization. After the adaptation and pre-testing processes, a population-based study including the individuals over the age of 55 was planned to determine the normative values using the primary health care system in Ankara, Turkey, An age-based stratification procedure was applied. Data were collected through a survey form that was developed to identify certain healthrelated, occupational and environmental risk factors associated with cognitive disorders among with the cognitive evaluation. The study was funded by the Scientific and Technological Research Council of Turkey, Grant No: 214S048. RESULTS: The population-based study was conducted between January and June 2016. The data of a total of 2158 participants were analyzed. The geographic distribution of the final sample was representative of the total population in Ankara. Of the study sample, 51,3%were female, and 60% had over 5 years of education. Approximately 25% of all participants were 'screening-positive' for neurocognitive impairment and age was inversely related with daily functioning. CONCLUSION: We were able to reach a population-based sample to determine the normative values of a widely applicable cognitive screening test and the activities of daily living as well as evaluate dementia-related risk factors in Turkey. The findings of the study indicated that 3MS-Turkish form is a cognitive secreening test, which can be widely used in Turkey.

Modulation of Cerebellar-Cortical Connections in Multiple System Atrophy Type C by Cerebellar Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: This study aims at modulating the altered cerebellar-cortical interactions in patients with multiple system atrophy-cerebellar subtype (MSA-C) by using cerebellar repetitive transcranial magnetic stimulation (rTMS). We hypothesized that cerebellar modulation by low-frequency rTMS can resolve the abnormal cortical excitability in multiple system atrophy cerebellar subtype. MATERIALS AND METHODS: We studied detailed effects of rTMS of the cerebellum on reaction time (RT) and short-latency afferent inhibition (SAI) response in MSA-C group, Alzheimer Disease (AD) group, and a control group of healthy individuals. The RT and SAI responses were measured before and after 1 Hz cerebellar rTMS in all groups. The study was conducted in the neurophysiology laboratory in Hacettepe University Hospital. RESULTS: Our results indicated that motor cortex disinhibition was predominant in patients with AD and MSA-C. In AD and control groups, there were no changes in SAI after rTMS. However, after application of rTMS over the cerebellum in MSA-C patients, the pathological disinhibition and RT results showed an improvement compared to their previous results. CONCLUSION: Our study highlights that cerebellar rTMS impairs abnormal cerebellar-cortical inhibitory connections in case of MSA-C.

Recrudescence of Deficits After Stroke: Clinical and Imaging Phenotype, Triggers, and Risk Factors.

Importance: Reemergence of previous stroke-related deficits (or poststroke recrudescence [PSR]) is an underrecognized and inadequately characterized phenomenon. Objective: To investigate the clinical features, triggers, and risk factors for PSR. Design, Setting, and Participants: This retrospective study incorporated a crossover cohort study to identify triggers and a case-control study to identify risk factors. The study used the Massachusetts General Hospital Research Patient Data Repository to identify patients for the period January 1, 2000, to November 30, 2015, who had a primary or secondary diagnosis of cerebrovascular disease, who underwent magnetic resonance imaging of the brain at least once, and whose inpatient or outpatient clinician note or discharge summary stated the term recrudescence. In all, 153 patients met the preliminary diagnostic criteria for PSR: transient worsening of residual poststroke focal neurologic deficits or transient recurrence of prior stroke-related focal deficits, admission magnetic resonance imaging showing a chronic stroke but no acute infarct or hemorrhage, no evidence of transient ischemic attack or seizure, no acute lesion on diffusion-weighted imaging, and no clinical or electroencephalographic evidence of seizure around the time of the event. Main Outcomes and Measures: Clinical and imaging features of PSR; triggers (identified by comparing PSR admissions with adjacent admissions without PSR); and risk factors (identified by comparing PSR cases with control cases from the Massachusetts General Hospital Stroke Registry). Results: Of the 153 patients, 145 had prior infarct, 8 had hypertensive brain hemorrhage, and 164 admissions for PSR were identified. The patients' mean (SD) age was 67 (16) years, and 92 (60%) were women. Recrudescence occurred a mean (SD) of 3.9 (0.6) years after the stroke, lasted 18.4 (20.4) hours, and was resolved on day 1 for 91 of the 131 episodes with documented resolution time (69%). Deficits were typically abrupt and mild and affected motor-sensory or language function. No patient had isolated gaze paresis, hemianopia, or neglect. During PSR, the National Institutes of Health Stroke Scale (NIHSS) score worsened by a mean (SD) 2.5 (1.9) points, and deficits were limited to a single NIHSS item in 62 episodes (38%). The underlying chronic strokes were variably sized, predominantly affected white matter tracts, and involved the middle cerebral artery territory for 112 patients (73%). Infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use were higher during PSR admissions. Compared with the control group (patients who did not experience recrudescence), the PSR group (patients who were hospitalized for recrudescence) had more women, African American individuals, and those who self-identified as being from "other" race. The PSR group also had more diabetes, dyslipidemia, smoking, infarcts from small-vessel disease, and "other definite" causes and worse onset NIHSS scores. Six patients (4%) received intravenous tissue plasminogen activator without complications. Conclusions and Relevance: The PSR features identified in the study should enable prompt diagnosis and distinguish recrudescence from mimics, such as transient ischemic attacks, migraine, Todd paralysis, and Uhthoff phenomenon. Prospective studies are required to validate the proposed diagnostic criteria and to decipher underlying mechanisms.

Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions.

Background and aim The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.