Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study.

INTRODUCTION: Individuals with dementia are underrepresented in interventional studies for acute ischemic stroke (AIS). This research gap creates a bias against their treatment in clinical practice. Our goal was to compare the safety and efficacy of intravenous-thrombolysis (t-PA) and endovascular treatment (EVT) in individuals with or without pre-AIS dementia. METHOD: A retrospective study of AIS patients receiving t-PA or EVT between 2019 and 2022. Patients were classified as dementia on a case-by-case review of baseline assessment. Additional variables included demographic, vascular risk factors, AIS severity and treatment. Outcomes of interest were intracerebral hemorrhage, mortality in 90-days, and the difference in modified rankin scale (mRS) before AIS and in 90-days follow-up. Outcomes were compared across non-matched groups and following propensity-score matching. RESULTS: Altogether, 628 patients were included, of which 68 had pre-AIS dementia. Compared to non-dementia group, dementia group were older, had a higher rate of vascular risk factors, higher pre-stroke mRS and higher baseline NIHSS. Individuals with dementia had higher rates of mortality (25% vs.11%,p < 0.01) on non-matched comparison. All cohort and restricted t-PA EVT matched analysis showed no difference in any outcome. Regression analysis confirmed that AIS severity at presentation and its treatment, not dementia, were the chief contributors to patients' outcomes. DISCUSSION: Our results indicate that pre-AIS dementia does not impact the efficacy or safety of EVT or t-PA for AIS. We thus call for more inclusive research on stroke therapy with regards to baseline cognitive status. Such studies are urgently required to inform stroke guidelines and enhance care.

Biomedical synthetic biology: an overview for physicians.

Synthetic bioiogy is a ,relatively new fieild of bologlcal research and development that focases on the engineering of genetic molecular machlnes wIth a specific predefined function. Plainly put the newly engineered organism functions as a machine. It can process information. manufature, heal and even diagnose. We just have to engineer It to do so. The famous quote "Biology Is the nanotechnology that works" is currently being put to the test on a worldwide scale. The application of these machines Is theoretically boundless. In laboratories worldwide synthetic biology technologies are being rationally designed to assist in diagnosis or disrupt disease mechnisms. In the not too distant future they are expected to reach the clinical setting. This new field should be distinguished from classic genetic engineering. The latter researches naturalfy found DNA segments via cloning. It is weakly associated with engineering. Synthetic biology focuses on the engineering of molecular biological machines for the benefit of mankind. This is done via synthetic (computer printed) DNA sequences, man-designed or altered in silico. In this article I will briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an independent fast-growing synthetic biology-sharing movement, and report on selected developing applications for medicine.

Elevated lumbar puncture opening pressure in aseptic meningitis.

OBJECTIVES: Elevated lumbar puncture opening pressure (ELPOP) is a reported but understudied phenomenon in aseptic meningitis. This study aimed to characterize the features of ELPOP in aseptic meningitis patients. METHODS: An observational, retrospective, single-center study was conducted. We included all adult patients diagnosed with aseptic meningitis or meningoencephalitis from October 2015 to May 2017, for whom lumbar puncture opening pressure (LP OP) was measured. OP > 25 cm H2O was documented as ELPOP. Patients' demographic characteristics, clinical data, laboratory and cerebrospinal fluid (CSF) results, as well as optic disc appearance were analyzed. RESULTS: Among 116 patients (61 males) included, 16 patients (14 %) had ELPOP (11 males). The average age of those patients was 32.4 years (SD = 9.8), and the mean OP was 31.7 cm H2O (SD = 6.02) as opposed to the mean normal LPOP (NLPOP) of16.13 cm H2O (SD = 4.15). Body mass index (BMI) was significantly higher in the ELPOP group (p = 0.0081). Funduscopic examination was documented in 15/16 patients in the ELPOP group and revealed swollen optic discs in 6 (40 %) patients. Fundus examination was performed in 62 patients in the NLPOP group, of whom 2 (3.2 %) had a swollen disc. There was no difference in CSF content between groups. CONCLUSIONS: This study fills the void of information lacking on the frequency of ELPOP in aseptic meningitis. Its association with increased BMI may be related to the pathogenesis. LP OP should be measured in all patients with aseptic meningitis. Additional research is needed to determine the threshold of tolerated intracranial pressure (ICP).

Diagnostic Utility of Measuring Cerebral Atrophy in the Behavioral Variant of Frontotemporal Dementia and Association With Clinical Deterioration.

Importance: The presence of atrophy on magnetic resonance imaging can support the diagnosis of the behavioral variant of frontotemporal dementia (bvFTD), but reproducible measurements are lacking. Objective: To assess the diagnostic and prognostic utility of 6 visual atrophy scales (VAS) and the Magnetic Resonance Parkinsonism Index (MRPI). Design, Setting, and Participants: In this diagnostic/prognostic study, data from 235 patients with bvFTD and 225 age- and magnetic resonance imaging-matched control individuals from 3 centers were collected from December 1, 1998, to September 30, 2019. One hundred twenty-one participants with bvFTD had high confidence of frontotemporal lobar degeneration (FTLD) (bvFTD-HC), and 19 had low confidence of FTLD (bvFTD-LC). Blinded clinicians applied 6 previously validated VAS, and the MRPI was calculated with a fully automated approach. Cortical thickness and subcortical volumes were also measured for comparison. Data were analyzed from February 1 to June 30, 2020. Main Outcomes and Measures: The main outcomes of this study were bvFTD-HC or a neuropathological diagnosis of 4-repeat (4R) tauopathy and the clinical deterioration rate (assessed by longitudinal measurements of Clinical Dementia Rating Sum of Boxes). Measures of cerebral atrophy included VAS scores, the bvFTD atrophy score (sum of VAS scores in orbitofrontal, anterior cingulate, anterior temporal, medial temporal lobe, and frontal insula regions), the MRPI, and other computerized quantifications of cortical and subcortical volumes. The areas under the receiver operating characteristic curve (AUROC) were calculated for the differentiation of participants with bvFTD-HC and bvFTD-LC and controls. Linear mixed models were used to evaluate the ability of atrophy measures to estimate longitudinal clinical deterioration. Results: Of the 460 included participants, 296 (64.3%) were men, and the mean (SD) age was 62.6 (11.4) years. The accuracy of the bvFTD atrophy score for the differentiation of bvFTD-HC from controls (AUROC, 0.930; 95% CI, 0.903-0.957) and bvFTD-HC from bvFTD-LC (AUROC, 0.880; 95% CI, 0.787-0.972) was comparable to computerized measures (AUROC, 0.973 [95% CI, 0.954-0.993] and 0.898 [95% CI, 0.834-0.962], respectively). The MRPI was increased in patients with bvFTD and underlying 4R tauopathies compared with other FTLD subtypes (14.1 [2.0] vs 11.2 [2.6] points; P < .001). Higher bvFTD atrophy scores were associated with faster clinical deterioration in bvFTD (1.86-point change in Clinical Dementia Rating Sum of Boxes score per bvFTD atrophy score increase per year; 95% CI, 0.99-2.73; P < .001). Conclusions and Relevance: Based on these study findings, in bvFTD, VAS increased the diagnostic certainty of underlying FTLD, and the MRPI showed potential for the detection of participants with underlying 4R tauopathies. These widely available measures of atrophy can also be useful to estimate longitudinal clinical deterioration.

Pattern and degree of individual brain atrophy predicts dementia onset in dominantly inherited Alzheimer's disease.

INTRODUCTION: Asymptomatic and mildly symptomatic dominantly inherited Alzheimer's disease mutation carriers (DIAD-MC) are ideal candidates for preventative treatment trials aimed at delaying or preventing dementia onset. Brain atrophy is an early feature of DIAD-MC and could help predict risk for dementia during trial enrollment. METHODS: We created a dementia risk score by entering standardized gray-matter volumes from 231 DIAD-MC into a logistic regression to classify participants with and without dementia. The score's predictive utility was assessed using Cox models and receiver operating curves on a separate group of 65 DIAD-MC followed longitudinally. RESULTS: Our risk score separated asymptomatic versus demented DIAD-MC with 96.4% (standard error = 0.02) and predicted conversion to dementia at next visit (hazard ratio = 1.32, 95% confidence interval [CI: 1.15, 1.49]) and within 2 years (area under the curve = 90.3%, 95% CI [82.3%-98.2%]) and improved prediction beyond established methods based on familial age of onset. DISCUSSION: Individualized risk scores based on brain atrophy could be useful for establishing enrollment criteria and stratifying DIAD-MC participants for prevention trials.

Meningitis without meningeal irritation signs: What are the alerting clinical markers?

OBJECTIVE: To identify parameters that may increase the likelihood of meningitis, and suggest a need for lumbar puncture (LP), in patients without meningeal irritation signs (MIS). METHODS: We included consecutive adult patients who underwent LP in the emergency department (ED) of Rabin Medical Center between October 2015 and May 2017. Those hospitalized during this period, who did not undergo LP in the ED, but subsequently underwent LP during their hospitalization to rule out central nervous system infection, were also included. Each patient was evaluated prior to LP by a neurologist according to predefined parameters concerning the current disease history and the neurological examination. Patients' medical records were reviewed to obtain additional data. Patients evaluated while in coma or under sedation were excluded. RESULTS: Three hundred and thirty eight patients were included in the final analysis: 96 (28.4%) with meningitis without MIS, 149 (44.1%) without MIS or meningitis, 57 (16.9%) with meningitis and MIS, and 36 (10.6%) with MIS without meningitis. In the absence of MIS, younger age (p = .005), headache (p < .001), nausea (p < .001), vomiting (p = .001), painful eye movements (p < .001) and phonophobia (p = .04) increased the likelihood of meningitis, while fever, laboratory results (leukocytosis; lymphopenia; CRP) and immunosuppression were of no value in this prediction. Photophobia and lymphopenia were more common in meningitis with MIS. Headache was suggestive of meningitis when MIS were present. CONCLUSION: Our study identified several parameters that increase the likelihood of meningitis in patients without MIS. These should be taken into evaluation when LP is considered.

Association of Late-Onset Unprovoked Seizures of Unknown Etiology With the Risk of Developing Dementia in Older Veterans.

Importance: The incidence of unprovoked seizures and epilepsy increases considerably in late life, with approximately one-third of seizures being of unknown etiology. While individuals with dementia have a high risk of developing unprovoked seizures, it is unknown whether older adults with late-onset unprovoked seizures of unknown etiology (LOSU) are at risk of developing dementia. Objective: To determine whether incident LOSU is associated with a higher risk of dementia among older US veterans. Design, Setting, and Participants: This retrospective multicenter cohort study was conducted using data from US Veterans Health Administration medical centers from October 2001 to September 2015. Data were generated from all veteran inpatient and outpatient encounters that occurred within Veterans Health Administration facilities. A random sample of 941 524 veterans 55 years and older was generated. A total of 649 262 veterans previously diagnosed (using International Classification of Diseases, Ninth Revision, Clinical Modification codes) with dementia, unprovoked seizures, epilepsy, and conditions that could lead to seizures (brain tumors, trauma, infections, stroke, and neurotoxin exposure) as well as veterans without follow-up data were excluded. Data were analyzed from October 2018 to July 2019. Exposures: Late-onset unprovoked seizures of unknown etiology were defined as a new diagnosis of epilepsy or unprovoked seizures without a diagnosis of a secondary cause for seizures. Incident LOSU was assessed during a 5-year baseline period. Main Outcomes and Measures: Veterans were assessed for incident dementia diagnosis during an outcome period. Fine-Gray proportional hazards models were used to determine whether LOSU was associated with greater risk of incident dementia. Models were adjusted for demographic variables, cardiovascular risk factors, depression, and traumatic brain injury. Results: Of the 292 262 included veterans, 282 628 (96.7%) were male, and the mean (SD) age was 73.0 [8.8] years. During the baseline period, 2166 veterans developed LOSU. The mean (SD) follow-up after LOSU was 6.1 (2.9) years. After multivariable adjustment, veterans with LOSU had greater risk of dementia compared with veterans without seizures (hazard ratio, 1.89; 95% CI, 1.62-2.20). A sensitivity analysis imposing a 2-year lag between incident LOSU and dementia diagnosis led to similar results. Conclusions and Relevance: These findings suggest LOSU in older veterans is associated with a 2-fold risk of developing dementia. While seizures are commonly thought to occur in late stages of dementia, these findings suggest unexplained seizures in older adults may be a first sign of neurodegenerative disease.

Non-Ashkenazi Jewish Origin is Associated with Early Onset Alzheimer's Disease.

Early-onset Alzheimer's disease (EOAD) accounts for 1-5% of Alzheimer's disease cases and is associated with specific ethnicities. It has been our impression that non-Ashkenazi Jews have a higher rate of EOAD and we therefore explored this hypothesis. We performed a retrospective case control study of EOAD cases referred to our cognitive neurology clinic between January 1999 and December 2016. Patients (n = 129) were compared to age- and geographically-matched controls generated from the Second Israeli National Health Survey (n = 1,811). Data on country of origin, education, dementia family history, depression, and vascular risk factors were compared between the groups. The association of non-Ashkenazi Jewish heritage and country of origin with EOAD was calculated using a logistic multivariate regression model. The EOAD group's mean age was 59.6±4.1 years, with a female predominance (64.3%). The EOAD group had a higher percentage of individuals of non-Ashkenazi Jewish origin (64.3% versus 51.4%, p = 0.003) and of Yemenite descent in particular (16.28% versus 6.24%, p < 0.001). On multiple logistic regression analysis, Yemenite Jewish origin was an independently associated with EOAD (OR 2.54, 95% CI 1.4-4.8). There were no significant differences in parameters between non-Ashkenazi and Ashkenazi Jews. Only 4.6% of EOAD cases had a positive EOAD family history. In conclusion, EOAD is over-represented among non-Ashkenazi Jews. Yemenite origin is independently associated with EOAD and the majority of patients with EOAD have no family history of Alzheimer's disease. Further evaluation with genetic studies is warranted.

Seasonal Changes in the Incidence of Transient Global Amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is a stereotypic condition characterized by anterograde and retrograde amnesia that typically resolves within 24 hours. The pathophysiology of TGA is still unclear. We noted that patients hospitalized with TGA tend to appear in seasonal clusters, and decided to investigate this phenomenon. METHODS: Every patient with acute presentation of amnesia at our medical center is hospitalized for observation and evaluation. We reviewed the monthly occurrence of TGA in our patient population between 2000 and 2014, and compared this to non-TGA hospitalizations during the same time period. RESULTS: During the analysis period, 154 patients who met the criteria for TGA were hospitalized, as well as 259,007 non-TGA hospitalizations. The annual occurrence of TGA ranged from 5 to 16 hospitalizations. There were 91 TGA events in women and 63 in men, in subjects aged 62.8±10.6 years (mean±SD). The incidence was maximal during December [odds ratio (OR)=2.83, 95% confidence interval (CI)=1.20-6.67] and March (OR=2.77, 95% CI=1.17-6.56), and minimal from April to August. The incidence exhibited an increase followed by a decrease from October to February. A seasonal trend was observed as well, with incidence peaks occurring in winter (OR=1.82, 95% CI=1.12-2.96) and spring (OR=1.80, 95% CI=1.10-2.94). CONCLUSIONS: Our findings suggest that the incidence of TGA exhibits seasonal variations. This observation may help to improve the understanding of the pathophysiology underlying TGA.