Evaluation of macrolinguistic aspects of the oral discourse in patients with Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a degenerative syndrome that impairs cognitive functioning, including speech and language. Discourse can be used to analyze language processing, which is organized into microlinguistic and macrolinguistic dimensions. OBJECTIVES: To identify the occurrence of changes in the macrolinguistic dimension of oral discourse in AD patients. Design: This was developed as a cross-sectional study. Setting: Outpatient clinic of the Behavioural Neurology Division of São Paulo Federal University. PARTICIPANTS: 121 elderly patients, with ≥ 4 years of education, divided into AD and comparison groups. MEASUREMENTS: The subjects were asked to create a narrative based on seven figures that made up a story. The macrolinguistic aspects of the narratives were analyzed. RESULTS: The performance of the AD group was inferior to that of the comparison group on content-related, no-content-related complete and incomplete propositions as well as macropropositions, main information units, appropriated local and global coherence, cohesive devices and all subtypes, cohesive errors and some of their subtypes. Global coherence, macropropositions and ellipsis subtype of cohesive devices were the variables that best differentiated the groups. CONCLUSIONS: Changes were observed in most aspects of the macrolinguistic dimension of oral discourse in patients with AD.

Neuropathology of White Matter Lesions, Blood-Brain Barrier Dysfunction, and Dementia.

BACKGROUND AND PURPOSE: We tested whether blood-brain barrier dysfunction in subcortical white matter is associated with white matter abnormalities or risk of clinical dementia in older people (n=126; mean age 86.4, SD: 7.7 years) in the MRC CFAS (Medical Research Council Cognitive Function and Ageing Study). METHODS: Using digital pathology, we quantified blood-brain barrier dysfunction (defined by immunohistochemical labeling for the plasma marker fibrinogen). This was assessed within subcortical white matter tissue samples harvested from postmortem T2 magnetic resonance imaging (MRI)-detected white matter hyperintensities, from normal-appearing white matter (distant from coexistent MRI-defined hyperintensities), and from equivalent areas in MRI normal brains. Histopathologic lesions were defined using a marker for phagocytic microglia (CD68, clone PGM1). RESULTS: Extent of fibrinogen labeling was not significantly associated with white matter abnormalities defined either by MRI (odds ratio, 0.90; 95% confidence interval, 0.79-1.03; P=0.130) or by histopathology (odds ratio, 0.93; 95% confidence interval, 0.77-1.12; P=0.452). Among participants with normal MRI (no detectable white matter hyperintensities), increased fibrinogen was significantly related to decreased risk of clinical dementia (odds ratio, 0.74; 95% confidence interval, 0.58-0.94; P=0.013). Among participants with histological lesions, increased fibrinogen was related to increased risk of dementia (odds ratio, 2.26; 95% confidence interval, 1.25-4.08; P=0.007). CONCLUSIONS: Our data suggest that some degree of blood-brain barrier dysfunction is common in older people and that this may be related to clinical dementia risk, additional to standard MRI biomarkers.

Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND).

Background: vascular cognitive impairment no dementia (VCI-ND) defines a preclinical phase of cognitive decline associated with vascular disorders. The neuropsychological profile of VCI-ND may vary according to different vascular conditions. Objective: to determine the neuropsychological profile of individuals with no dementia and vascular disorders, including hypertension, peripheral vascular disease (PVD), coronary heart disease (CHD), diabetes and stroke. Risk of 2-year incident dementia in individuals with disease and cognitive impairment was also tested. Methods: participants were from the Cognitive Function and Ageing Study. At baseline, 13,004 individuals aged ≥65 years were enrolled into the study. Individuals were grouped by baseline disorder status (present, absent) for each condition. Cognitive performance was assessed using the Mini Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG). Dementia was assessed at 2 years. Results: in the cross-sectional analysis, hypertension, PVD and CHD were not associated with cognitive impairment. Stroke was associated with impaired global (MMSE) and CAMCOG sub-scale (including memory and non-memory) scores. Diabetes was associated with impairments in global cognitive function (MMSE) and abstract thinking. In the longitudinal analysis, cognitive impairments were associated with incident dementia in all groups. Conclusion: the neuropsychological profile in individuals with vascular disorders depends on the specific condition investigated. In all conditions cognitive impairment is a risk factor for dementia. A better understanding of which cognitive domains are affected in different disease groups could help improve operationalisation of the neuropsychological criteria for VCI-ND and could also aid with the development of dementia risk prediction models in persons with vascular disease.

Microglial immunophenotype in dementia with Alzheimer's pathology.

BACKGROUND: Genetic risk factors for Alzheimer's disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes. METHODS: Using the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer's pathology. Cerebral cortex obtained at post-mortem from 299 participants was analysed by immunohistochemistry for cluster of differentiation (CD)68 (phagocytosis), human leukocyte antigen (HLA)-DR (antigen-presenting function), ionized calcium-binding adaptor molecule (Iba1) (microglial motility), macrophage scavenger receptor (MSR)-A (plaque-related phagocytosis) and CD64 (immunoglobulin Fcγ receptor I). RESULTS: The presence of dementia was associated positively with CD68 (P < 0.001), MSR-A (P = 0.010) and CD64 (P = 0.007) and negatively with Iba1 (P < 0.001). Among participants without dementia, the cognitive function according to the Mini-Mental State Examination was associated positively with Iba1 (P < 0.001) and negatively with CD68 (P = 0.033), and in participants with dementia and Alzheimer's pathology, positively with all microglial markers except Iba1. Overall, in participants without dementia, the relationship with Alzheimer's pathology was negative or not significant, and positive in participants with dementia and Alzheimer's pathology. Apolipoprotein E (APOE) ε2 allele was associated with expression of Iba1 (P = 0.001) and MSR-A (P < 0.001) and APOE ε4 with CD68, HLA-DR and CD64 (P < 0.001). CONCLUSIONS: Our findings raise the possibility that in dementia with Alzheimer's pathology, microglia lose motility (Iba-1) necessary to support neurons. Conversely, other microglial proteins (CD68, MSR-A), the role of which is clearance of damaged cellular material, are positively associated with Alzheimer's pathology and impaired cognitive function. In addition, our data imply that microglia may respond differently to Aß and tau in participants with and without dementia so that the microglial activity could potentially influence the likelihood of developing dementia, as supported by genetic studies, highlighting the complexity and diversity of microglial responses.

Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.

AIMS: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS: Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis. RESULTS: Two thousand three hundred seventy-eight genes were significantly differentially expressed (1690 up-regulated, 688 down-regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up-regulation of glycogen synthase kinase 3ß. Candidate genes were validated by quantitative real-time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)-hydroxycholesterol associated with neuronal DDR across all Braak stages (rs = 0.30, P = 0.03). CONCLUSIONS: A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3ß, thereby contributing to neuronal dysfunction independent of Alzheimer-type pathology in the ageing brain.

Dementia prediction for people with stroke in populations: is mild cognitive impairment a useful concept?

BACKGROUND: criteria for mild cognitive impairment (MCI) capture an intermediate cognitive state between normal ageing and dementia, associated with increased dementia risk. Whether criteria for MCI are applicable in the context of stroke and can be used to predict dementia in stroke cases is not known. OBJECTIVES: to determine the prevalence of MCI in individuals with stroke and identify predictors of 2-year incident dementia in stroke cases. METHODS: individuals were from the Medical Research Council Cognitive Function and Ageing Study. MCI prevalence in individuals with stroke was determined. Logistic regression, with receiver operating characteristic curve analysis, was used to identify variables associated with risk of dementia in stroke cases including MCI criteria, demographic, health and lifestyle variables. FINDINGS: of 2,640 individuals seen at the first assessment, 199 reported stroke with no dementia. In individuals with stroke, criteria for MCI are not appropriate, with less than 1% of stroke cases being classified as having MCI. However, in individuals with stroke two components of the MCI definition, subjective memory complaint and cognitive function (memory and praxis scores) predicted 2-year incident dementia (area under the curve = 0.85, 95% CI: 0.77-0.94, n = 113). CONCLUSION: criteria for MCI do not appear to capture risk of dementia in the context of stroke in the population. In stroke cases, subjective and objective cognitive performance predicts dementia and these variables could possibly be incorporated into dementia risk models for stroke cases. Identifying individuals with stroke at greatest risk of dementia has important implications for treatment and intervention.

Education associated with a delayed onset of terminal decline.

BACKGROUND: the terminal decline hypothesis suggests an acceleration in the rate of loss of cognitive function before death. Evidence about the association of educational attainment and the onset of terminal decline is scarce. OBJECTIVE: to investigate the association of education with the onset of terminal decline in global cognitive function measured by Mini Mental State Exam (MMSE) scores. SUBJECTS: deceased participants of the Cambridge City over 75 Cohort Study who were interviewed at about 2, 7, 9, 13, 17 and 21 years after baseline. METHODS: regular and Tobit random change point growth models were fitted to MMSE scores to identify the onset of terminal decline and assess the effect of education on this onset. RESULTS: people who left school at an older age had a delayed onset of terminal decline. Thus better educated individuals experience a slightly shorter period of faster decline before death. CONCLUSION: an important finding emerging from our work is that education does appear to delay the onset of terminal decline, although only by a limited amount.

C-reactive protein, APOE genotype and longitudinal cognitive change in an older population.

BACKGROUND: circulating measures of inflammatory markers, such as C-reactive protein (CRP) have been associated with an increased risk of future cognitive decline. However, the nature of the relationship among the very old (>75 years) is unclear. Cross-sectional evidence suggests that elevated CRP may even be protective in this age group. This study examines these associations longitudinally. METHODS: logistic regression was used to investigate the association between CRP and drop in cognitive performance (≥3 point change on the Mini-Mental State Examination) over a 4-year period in a population of 266 people, mean age 77 years. RESULTS: increased levels of CRP were associated with a decreased risk of a drop in cognitive performance; however, this association was only seen in those without an APOE e4 allele [odds ratio of decline per unit increase in ln(CRP) 0.57, P = 0.04]. The magnitude of the finding remained consistent after adjustment for cardiovascular confounders (smoking, drinking, MI, stroke, diabetes, education, medication and blood pressure). For those with an e4 allele, the relationship with longitudinal cognitive decline was neither statistically significant nor in a consistent direction after controlling for acute inflammation. CONCLUSIONS: this study strengthens previous cross-sectional findings and shows elevated levels of CRP to be linked to a decreased risk of longitudinal cognitive decline in the very old. However, as with prior analyses, this was only observed in those not carrying an APOE e4 allele. Future work on larger APOE e4 allele carrying samples is required to determine the nature of the association in this population.

Assessing environmental features related to mental health: a reliability study of visual streetscape images.

BACKGROUND: An association between depressive symptoms and features of built environment has been reported in the literature. A remaining research challenge is the development of methods to efficiently capture pertinent environmental features in relevant study settings. Visual streetscape images have been used to replace traditional physical audits and directly observe the built environment of communities. The aim of this work is to examine the inter-method reliability of the two audit methods for assessing community environments with a specific focus on physical features related to mental health. METHODS: Forty-eight postcodes in urban and rural areas of Cambridgeshire, England were randomly selected from an alphabetical list of streets hosted on a UK property website. The assessment was conducted in July and August 2012 by both physical and visual image audits based on the items in Residential Environment Assessment Tool (REAT), an observational instrument targeting the micro-scale environmental features related to mental health in UK postcodes. The assessor used the images of Google Street View and virtually "walked through" the streets to conduct the property and street level assessments. Gwet's AC1 coefficients and Bland-Altman plots were used to compare the concordance of two audits. RESULTS: The results of conducting the REAT by visual image audits generally correspond to direct observations. More variations were found in property level items regarding physical incivilities, with broad limits of agreement which importantly lead to most of the variation in the overall REAT score. Postcodes in urban areas had lower consistency between the two methods than rural areas. CONCLUSIONS: Google Street View has the potential to assess environmental features related to mental health with fair reliability and provide a less resource intense method of assessing community environments than physical audits.

Migraine is frequent in children and adolescents with neurofibromatosis type 1.

BACKGROUND: Despite the high prevalence of headache in patients with neurofibromatosis type 1 (NF1), little data exist regarding the classification and characterization of headaches experienced by these patients. This paper describes a study of headache in patients with NF1 compared with healthy controls. METHODS: In this transversal study, participants (aged 4-19 years) were classified into two groups: NF1 patients or control subjects. The diagnosis of NF1 was performed according to the diagnostic criteria of the National Institutes of Health Consensus Conference, and the headache diagnosis was performed according to the diagnostic criteria of the International Classification of Headache Disorders, Second Edition. All participants underwent physical and neurologic evaluation and completed a detailed headache questionnaire. RESULTS: The comparison of 50 patients with NF1 and 50 age-matched controls revealed that the complaint of headache was significantly more frequent in the NF1 group than in the control group (CG) (62% vs 14%, χ(2)(1) = 22.4; P < 0.001). Migraine was significantly more frequent in patients with NF1 than in the CG (54% vs 14%, χ(2)(1) = 17.82; P < 0.001). No differences were found between the two groups regarding the use of simple analgesics (NF1: 14% vs CG: 5%, χ(2)(1) = 1.18; P = 0.276). CONCLUSIONS: Children and adolescents with NF1 are prone to migraines. Complaints of headache are very frequent in this population.

Language impairments in Alzheimer´s disease: What changes can be found between mild and moderate stages of the disease?

OBJECTIVE: To investigate how language deteriorates over the Alzheimer's Disease course. METHODS: A cross-sectional, observational study was carried out. 35 patients diagnosed with dementia due to AD using the NINCDS-ARDRA criteria and undergoing treatment for AD with a therapeutic dose of acetylcholinesterase inhibitors were assessed by the Boston Diagnostic Aphasia Examination (BDAE). The sample comprised 15 patients with mild AD (MMSE > 23, CDR = 0 or 0.5‒1.0) and 20 patients with moderate AD (MMSE = 13‒23, CDR = 2). The results for the 2 groups on all language tasks were compared. RESULTS: A statistically significant difference was found between the mild and moderate AD groups for total score on the BDAE (95% CI 47.10‒114.08, t = 5.0, DF = 21, p = 0.000*), as well as on several tasks involving oral and writing comprehension, language oral expression and writing. CONCLUSION: The study results showed major changes in the moderate stage. Also, the decline in language performance correlated with the worsening of dementia syndrome, independently of sociodemographic variables.

Predicting risk of 2-year incident dementia using the CAMCOG total and subscale scores.

BACKGROUND: being able to identify individuals at high risk of dementia is important for diagnostics and intervention. Currently, there is no standard approach to assessing cognitive function in older aged individuals to best predict incident dementia. OBJECTIVE: to identify cognitive changes associated with an increased risk of 2-year incident dementia using the Cambridge Cognitive Examination (CAMCOG). DESIGN: longitudinal population representative sample aged 65+ years. METHODS: individuals were from the Medical Research Council Cognitive Function and Ageing Study. Classification and Regression Tree analysis was used to detect the optimal cut-off value for the CAMCOG total, subscales and composite memory and non-memory scores, for predicting dementia. Sensitivity and specificity of each cut-off score were assessed. RESULTS: from the 2,053 individuals without dementia at the first assessment, 137 developed dementia at the 2-year follow-up. The results indicate similar discriminative accuracy for incident dementia based on the CAMCOG total, memory subscale and composite scores. However, sensitivity and specificity of cut-off values were generally moderate. Scores on the non-memory subscales generally had high sensitivity but low specificity. Compared with the CAMCOG total score they had significantly lower discriminative accuracy. CONCLUSION: in a population setting, cut-off scores from the CAMCOG memory subscales predicted dementia with reasonable accuracy. Scores on the non-memory scales have lower accuracy and are not recommend for predicting high-risk cases unless all non-memory subdomain scores are combined. The added value of cognition when assessed using the CAMCOG to other risk factors (e.g. health and genetics) should be tested within a risk prediction framework.

Speech and orofacial apraxias in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) affects not only memory but also other cognitive functions, such as orientation, language, praxis, attention, visual perception, or executive function. Most studies on oral communication in AD focus on aphasia; however, speech and orofacial apraxias are also present in these patients. The aim of this study was to investigate the presence of speech and orofacial apraxias in patients with AD with the hypothesis that apraxia severity is strongly correlated with disease severity. METHODS: Ninety participants in different stages of AD (mild, moderate, and severe) underwent the following assessments: Clinical Dementia Rating, Mini-Mental State Examination, Lawton Instrumental Activities of Daily Living, a specific speech and orofacial praxis assessment, and the oral agility subtest of the Boston diagnostic aphasia examination. RESULTS: The mean age was 80.2 ± 7.2 years and 73% were women. Patients with AD had significantly lower scores than normal controls for speech praxis (mean difference=-2.9, 95% confidence interval (CI)=-3.3 to -2.4) and orofacial praxis (mean difference=-4.9, 95% CI=-5.4 to -4.3). Dementia severity was significantly associated with orofacial apraxia severity (moderate AD: ß =-19.63, p= 0.011; and severe AD: ß =-51.68, p < 0.001) and speech apraxia severity (moderate AD: ß = 7.07, p = 0.001; and severe AD: ß =8.16, p < 0.001). CONCLUSION: Speech and orofacial apraxias were evident in patients with AD and became more pronounced with disease progression.

Psychiatric symptoms may contribute to poor quality of life in adolescents with migraine.

BACKGROUND: The impact of migraine on quality of life (QOL) can be aggravated by other comorbid factors. The aim of the present study was to assess the differences in the QOL of adolescents with chronic migraine, episodic migraine, and healthy adolescents, and whether the differences in QOL among the diagnostic groups were associated with the presence of self-reported psychiatric symptoms, such as depression and anxiety. METHODS: A total of 157 adolescents (aged 15-19 years old) were included in the study. Fifty patients had episodic migraine, 56 patients suffered from chronic migraine, and 51 healthy adolescents were controls. All of the participants responded to a detailed headache questionnaire, the Medical Outcomes Trust 36-Item Short-form Health Survey, the State-Trait Anxiety Inventory and the Beck Depression Inventory. RESULTS: Chronic migraine patients showed a significantly lower QOL than the control subjects in five dimensions of the Medical Outcomes Trust 36-Item Short-form Health Survey, and lower QOL than the episodic migraine patients in four dimensions. High levels of self-reported depressive symptoms were associated with lower QOL in five dimensions and high levels of self-reported anxiety were associated with lower QOL in four dimensions. CONCLUSIONS: The QOL of adolescent migraine sufferers may be aggravated not only by migraine but also by other factors, such as anxiety and depressive symptoms, which may contribute to the poor QOL in adolescents suffering from migraine.

Community consultation in emergency neurosurgical research: lessons from a proposed trial for patients with chronic subdural haematomas.

INTRODUCTION: Chronic subdural haematoma (CSDH) is one of the most common neurosurgical disorders and is especially prevalent in old age. The subdural evacuating port system (SEPS) has emerged in the last few years as a minimally invasive alternative to the standard procedure of burr-hole evacuation. NHS practice is evidence-driven and evidence from high-quality clinical studies is required prior to implementation of any changes. In the UK, the National Research Ethics Service (NRES) advises community consultation prior to starting a clinical trial, where the patient is unlikely to have capacity to consent to enrolment in the trial. To prepare for a trial comparing minimally invasive (SEPS) versus burr-hole evacuation for evacuation of a CSDH, we have designed and undertaken a pre-protocol community consultation survey to examine potential patient participation. MATERIAL(S) AND METHODS: The study population consisted of patients, family members and carers/friends in neurosurgical clinic waiting rooms and wards at Addenbrooke's Hospital, Cambridge, who individually completed a questionnaire (n = 215). RESULTS: Most respondents were willing to participate in the proposed randomised clinical trial (77%; 165/215). Moreover, 80% (171/215) and 74% (159/215) were willing to allow their next of kin and an independent consultant neurosurgeon to give surrogate consent, respectively. CONCLUSION: The results of our pre-protocol community consultation showed that not only would most respondents be willing to participate in the proposed trial, but also would be happy for either next of kin or an independent consultant neurosurgeon to give surrogate consent if they lacked capacity to consent themselves. The advantages of this type of survey are twofold: they increase patient and public involvement in the research process and allow researchers to design study protocols that are acceptable to the community.

Speech and phonological impairment across Alzheimer's disease severity.

INTRODUCTION: Phonetic-phonological impairments have been described in dementia due to Alzheimer's disease (AD). However, whether the likely phonological-linguistic changes progress with the evolution of the disease or whether phonetic-motor manifestations occur in all three stages of AD (mild, moderate, and severe) has not yet been clarified. Thus, the aim of this study was to verify whether phonological-linguistic and phonetic-motor speech manifestations occur in the mild, moderate, and severe stages of AD. METHODS: Thirty participants in each stage of probable AD (mild, moderate, and severe) and 30 healthy older adults underwent cognitive, instrumental activities of daily living and phonetic-phonological assessments. Phonetic-phonological manifestations were classified into three types: likely phonetic-motor, likely phonological-linguistic, and manifestations that may occur in disorders of both phonetic and phonological origin. RESULTS: The manifestations analyzed in this study occurred rarely. The manifestations that may occur in disorders of both phonetic and phonological origin were the most common in all stages of the disease. The likely phonetic-motor manifestations emerged during the mild stage of the disease (distortions, prolonged intersegment duration, and vowel prolongations), while the likely phonological-linguistic manifestations were present mainly in the moderate (substitutions and attempts at the word level) and severe stages (substitutions, attempts at the word level, self-corrections, and anticipations). The occurrence of phonetic-phonological manifestations increased with disease progression. CONCLUSIONS: The type of phonological and phonetic manifestations in the individuals with AD differed according to the dementia stage and were statistically more frequent as dementia worsened.

Early Outcomes of the Pipeline Vantage Flow Diverter : A Multicentre Study.

PURPOSE: The recently introduced Pipeline Vantage Embolization Device with Shield Technology is the fourth generation of Pipeline flow diverter devices. Due to the relatively high rate of intraprocedural technical complications, modifications were subsequently made to the device after a limited release of the device in 2020. This study aimed to evaluate the safety and efficacy of the modified version of this device. METHODS: This was a multicentre retrospective series. The primary efficacy endpoint was aneurysm occlusion in the absence of retreatment. The primary safety endpoint was any neurological morbidity or death. Ruptured and unruptured aneurysms were included in the study. RESULTS: A total of 52 procedures were performed for 60 target aneurysms. Treatment was performed on 5 patients with ruptured aneurysms. The technical success rate was 98%. The mean clinical follow-up time was 5.5 months. In patients presenting with unruptured aneurysms there were no deaths, 3 (6.4%) major complications and 7 (13%) minor complications. In the five patients presenting with subarachnoid haemorrhage there were 2 (40%) major complications with 1 (20%) of these resulting in death, and 1 (20%) minor complication. Of the patients 29 (56%) had undergone 6­monthly postprocedural angiographic imaging with a mean time of 6.6 months demonstrating that 83% of patients had achieved adequate occlusion (RROC1/2) of the aneurysm. CONCLUSIONS: In this non-industry-sponsored study, the occlusion rates and safety outcomes were similar to those seen in previously published studies with flow diverter devices and earlier generation Pipeline devices. Modifications to the device appear to have improved ease of deployment.

Outcome study of the Pipeline Vantage Embolization Device (second version) in unruptured (and ruptured) aneurysms (PEDVU(R) study).

BACKGROUND: The Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate safety and efficacy outcomes. Primary and secondary objectives were to determine outcomes for unruptured and ruptured cohorts, respectively. METHODS: In this multicenter retrospective and prospective study, we analyzed outcome data from eight centers using core laboratory assessments. We determined 30-day and ≥3-month mortality and morbidity rates, and 6- and 18-month radiographic aneurysm occlusion rates for procedures performed during the period July 2021-March 2023. RESULTS: We included 121 consecutive patients with 131 aneurysms. The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90%. Two aneurysms (1.5%) underwent retreatment. When mortality attributed to a palliative case in the unruptured cohort, or subarachnoid hemorrhage in the ruptured cohort, was excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with 0% mortality rates for each. When all event causes were included on an intention-to-treat basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with 0.9% and 22.7% mortality rates. CONCLUSIONS: For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. These are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. Further prospective studies, particularly for ruptured aneurysms, are needed.

Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features.

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado­Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey­Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color­Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color­Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Nocturnal enuresis antecedent is common in adolescents with migraine.

BACKGROUND: Migraine and nocturnal enuresis are highly prevalent disorders with striking similarities. Both have unknown pathophysiology and are considered multifactorial, with neurobiological, genetic, and behavioral aspects involved. Interestingly, the same neurological structures thought to be involved in the pathogenesis of migraine are also thought to be involved in nocturnal enuresis. Few studies, however, have addressed these conditions as related. The aim of this study was to evaluate the antecedent of nocturnal enuresis in a large consecutive series of adolescents with migraine as compared to controls. METHODS: A total of 151 subjects were evaluated; 50 had episodic migraine, 50 had chronic migraine, and 51 were control subjects. All patients were submitted to a detailed questionnaire addressing epidemiological and clinical aspects. RESULTS: There was a strong correlation between the clinical history of nocturnal enuresis and the diagnosis of migraine. CONCLUSION: Our study showed that nocturnal enuresis is a precursor of migraine and a migraine comorbid condition. These results support a pathophysiological linkage between the two conditions.