Cortical blindness as a sign of delayed post-hypoxic encephalopathy: a case report.

We present a case of a 67-year-old female patient, who presented with acute cortical blindness five days after a successful resuscitation from cardiac arrest. The magnetic resonance tomography revealed a mild FLAIR signal increase of the bilateral occipital cortex. A lumbar puncture revealed considerably elevated tau protein levels, in the presence of normal phospho-tau, as a marker of brain injury, whilst neuron-specific enolase levels were normal. The diagnosis of delayed post-hypoxic encephalopathy was set. We hereby describe a rare clinical manifestation after initially successful resuscitation and encourage the studying of tau protein as a potential marker of this disease entity.

Course of neuropsychological impairment during natalizumab-associated progressive multifocal leukoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML), an opportunistic infection of the central nervous system from the John Cunningham virus (JCV), is a side effect of natalizumab (NTZ) treatment for relapsing-remitting multiple sclerosis (RRMS), potentially leading to a substantial increase of physical and mental disability. Nevertheless, data of neuropsychological impairment during the NTZ-PML disease course are missing. Our objective was to evaluate the neuropsychological disease course of NTZ-PML patients and to compare neuropsychological deficits of NTZ-PML patients with two different non-PML multiple sclerosis (MS) cohorts. METHODS: Neuropsychological examinations of 28 NTZ-PML patients performed during different phases of the disease ([i] at PML diagnosis, [ii] during immune reconstitution inflammatory syndrome [IRIS], and [iii] post-IRIS/PML) were retrospectively analyzed and compared to those of NTZ-treated RRMS or secondary progressive MS patients with and without immunotherapy. RESULTS: Compared to controls, NTZ-PML patients performed worse in neuropsychological examinations during all stages of disease, mainly affecting visuospatial ability and working memory. Furthermore, failure to eliminate the JCV from the central nervous system was associated with a progredient decline of cognition, especially working memory. CONCLUSIONS: Working memory and visuospatial abilities are the core neuropsychological deficits of NTZ-PML patients in long-term follow-up. Our findings should be implemented in neurorehabilitation strategies.

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis.

OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.

Clinical Outcomes and Neuroimaging Profiles in Nondisabled Patients With Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- The aim of this study was to prospectively validate our prior findings of smaller hematoma volume and lesser neurological deficit in nonvitamin K oral anticoagulant (NOAC) compared with Vitamin K antagonist (VKA)-related intracerebral hemorrhage (ICH). Methods- Prospective 12-month observational study in 15 tertiary stroke centers in the United States, Europe, and Asia. Consecutive patients with premorbid modified Rankin Scale score of <2 with acute nontraumatic anticoagulant-related ICH divided into 2 groups according to the type of anticoagulant: NOAC versus VKA. We recorded baseline ICH volume, significant hematoma expansion (absolute [12.5 mL] or relative [>33%] increase), neurological severity measured by National Institutes of Health Stroke Scale score, 90-day mortality, and functional status (modified Rankin Scale score). Results- Our cohort comprised 196 patients, 62 NOAC related (mean age, 75.0±11.4 years; 54.8% men) and 134 VKA related (mean age, 72.3±10.5; 73.1% men). There were no differences in vascular comorbidities, antiplatelet, and statin use; NOAC-related ICH patients had lower median baseline hematoma volume (13.8 [2.5-37.6] versus 19.5 [6.6-52.0] mL; P=0.026) and were less likely to have severe neurological deficits (National Institutes of Health Stroke Scale score of >10 points) on admission (37% versus 55.3%, P=0.025). VKA-ICH were more likely to have significant hematoma expansion (37.4% versus 17%, P=0.008). NOAC pretreatment was independently associated with smaller baseline hematoma volume (standardized linear regression coefficient:-0.415 [95% CI, -0.780 to -0.051]) resulting in lower likelihood of severe neurological deficit (odds ratio, 0.44; 95% CI, 0.22-0.85) in multivariable-adjusted models. Conclusions- Patients with NOAC-related ICH have smaller baseline hematoma volumes and lower odds of severe neurological deficit compared with VKA-related ICH. These findings are important for practicing clinicians making anticoagulation choices.

Proteomic profiling of tracheal fluid in an ovine model of congenital diaphragmatic hernia and fetal tracheal occlusion.

Congenital diaphragmatic hernia (CDH) occurs in ~1:2,000 pregnancies and is associated with substantial morbidity and mortality. Fetal tracheal occlusion (TO) is an emerging therapy that improves lung growth and reduces mortality, although substantial respiratory compromise persists in survivors. In this study, we used tracheal fluid in a fetal sheep model of CDH with TO for proteomic analysis with subsequent validation of findings in sheep lung tissue. We found that the proteomic profiles of CDH tracheal fluid was most similar to control lung and CDH/TO lung most similar to TO lung. Among 118 proteins altered in CDH, only 11 were reciprocally regulated in CDH/TO. The most significantly altered pathways and processes were cell proliferation, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling, inflammation, and microtubule dynamics. CDH suppressed and TO promoted cell proliferation and AKT-related signaling cascades. By Western blot analysis and immunohistochemistry, epithelial PCNA and phosphorylated AKT were decreased in CDH and increased in TO and CDH/TO lungs. The Wnt target Axin2 was decreased threefold in CDH lung compared with control without a significant increase in CDH/TO lung. Cilia-related pathways were among the most dysregulated with CDH lung having a nearly twofold increase in acetylated α-tubulin and a relative increase in the number of ciliated cells. While TO improves lung growth and patient survival in CDH, the procedure substantially alters many processes important in lung development and cell differentiation. Further elucidation of these changes will be critical to improving lung health in infants with CDH treated with TO.

Orthostatic tolerance is difficult to predict in recurrent syncope patients.

OBJECTIVES: We tested the hypothesis that detailed anthropometric and hemodynamic measurements predict orthostatic tolerance in neurally mediated syncope patients. In addition, we tested whether orthostatic tolerance is related to syncope frequency in real life. BACKGROUND: Earlier studies in patients with neurally mediated syncope suggested that orthostatic heart rate and blood pressure responses predict the tilt table responses with high sensitivity and specificity. METHODS: We analyzed data from 157 consecutive patients (n = 100 exploratory cohort, n = 57 confirmatory cohort) with recurrent syncope in whom orthostatic tolerance was quantified as the time to (pre)syncope during head-up tilt testing combined with lower body negative pressure. We measured heart rate, brachial blood pressure, cardiac stroke volume, heart rate and blood pressure variability, and spontaneous baroreflex sensitivity supine and early during head-up tilt. RESULTS: The orthostatic heart rate increase showed the strongest correlation with orthostatic tolerance. The best multivariate model including age, supine diastolic blood pressure, supine blood pressure variability, as well as tilt-induced changes in diastolic blood pressure and heart rate explained no more that 40% of the variability in orthostatic tolerance. The model failed to predict orthostatic tolerance in the confirmatory cohort. Frequency or number of free-living syncopal episodes were only weakly related to orthostatic tolerance. CONCLUSIONS: In patients with neurally mediated syncope, orthostatic tolerance in the clinical laboratory is difficult to predict with a wide range of anthropometric and cardiovascular measurements and correlates poorly with syncope occurrence in real life.

Changes in protein expression due to metformin treatment and hyperinsulinemia in a human endometrial cancer cell line.

The incidence of endometrial cancer (EC) has increased over the past years and mainly affects women above the age of 45 years. Metabolic diseases such as obesity and type II diabetes mellitus as well as associated conditions like polycystic ovary syndrome (PCOS), insulin resistance and hyperinsulinemia lead to elevated levels of circulating estrogens. Increased estrogen concentrations, in turn, further trigger the proliferation of endometrial cells and thus promote EC development and progression, especially in the absence of progesterone as seen in postmenopausal women. Elevated blood glucose levels in diabetic patients further contribute to the risk of EC development. Metformin is an insulin-sensitizing biguanide drug, commonly used in the treatment of type II diabetes mellitus, especially in obese patients. Besides its effects on glucose metabolism, metformin displayed anti-cancer effects in various cancer types, including EC. Direct anti-cancer effects of metformin target signaling pathways that are involved in cellular growth and proliferation, e.g. the AKT/PKB/mTOR pathway. Further proteins and pathways have been suggested as potential targets, but the underlying mechanism of action of metformin's anti-cancer activity is still not completely understood. In the present study, the effects of metformin on protein expression were investigated in the human EC cell line HEC-1A using an affinity proteomic approach. Cells were treated with 0.5 mmol/L metformin over a period of 7 days and changes in the expression pattern of 1,300 different proteins were compared to the expression in untreated control cells as well as insulin-treated cells. Insulin treatment (100 ng/mL) was incorporated into the study in order to implement a model for insulin resistance and associated hyperinsulinemia, conditions that are often observed in obese and diabetic patients. Furthermore, the culture medium was supplemented with 10 nmol/L ß-estradiol (E2) during treatments to mimic increased estrogen levels, a common risk factor for EC development. Based on the most prominent and significant changes in expression, a set of 80 proteins was selected and subjected to a more detailed analysis. The data revealed that metformin and insulin targeted similar pathways in the present study and mostly acted on proteins related to proliferation, migration and tumor immune response. These pathways may be affected in a tumor-promoting as well as a tumor-suppressing way by either metformin treatment or insulin supplementation. The consequences for the cells resulting from the detected expression changes were discussed in detail for several proteins. The presented data helps identify potential targets affected by metformin treatment in EC and allows for a better understanding of the mechanism of action of the biguanide drug's anti-cancer activity. However, further investigations are necessary to confirm the observations and conclusions drawn from the presented data after metformin administration, especially for proteins that were regulated in a favorable way, i.e. AKT3, CCND2, CD63, CD81, GFAP, IL5, IL17A, IRF4, PI3, and VTCN1. Further proteins might be of interest, where metformin counteracted unfavorable effects that have been induced by hyperinsulinemia.

A case series of serious and unexpected adverse drug reactions under treatment with cariprazine.

Reporting of new or unexpected adverse drug reactions of medicines that are subject to additional monitoring ("black triangle" label), such as the antipsychotic drug cariprazine, is of paramount importance to improve pharmacotherapy safety.

Heritage Speakers as Part of the Native Language Continuum.

We argue for a perspective on bilingual heritage speakers as native speakers of both their languages and present results from a large-scale, cross-linguistic study that took such a perspective and approached bilinguals and monolinguals on equal grounds. We targeted comparable language use in bilingual and monolingual speakers, crucially covering broader repertoires than just formal language. A main database was the open-access RUEG corpus, which covers comparable informal vs. formal and spoken vs. written productions by adolescent and adult bilinguals with heritage-Greek, -Russian, and -Turkish in Germany and the United States and with heritage-German in the United States, and matching data from monolinguals in Germany, the United States, Greece, Russia, and Turkey. Our main results lie in three areas. (1) We found non-canonical patterns not only in bilingual, but also in monolingual speakers, including patterns that have so far been considered absent from native grammars, in domains of morphology, syntax, intonation, and pragmatics. (2) We found a degree of lexical and morphosyntactic inter-speaker variability in monolinguals that was sometimes higher than that of bilinguals, further challenging the model of the streamlined native speaker. (3) In majority language use, non-canonical patterns were dominant in spoken and/or informal registers, and this was true for monolinguals and bilinguals. In some cases, bilingual speakers were leading quantitatively. In heritage settings where the language was not part of formal schooling, we found tendencies of register leveling, presumably due to the fact that speakers had limited access to formal registers of the heritage language. Our findings thus indicate possible quantitative differences and different register distributions rather than distinct grammatical patterns in bilingual and monolingual speakers. This supports the integration of heritage speakers into the native-speaker continuum. Approaching heritage speakers from this perspective helps us to better understand the empirical data and can shed light on language variation and change in native grammars. Furthermore, our findings for monolinguals lead us to reconsider the state-of-the art on majority languages, given recurring evidence for non-canonical patterns that deviate from what has been assumed in the literature so far, and might have been attributed to bilingualism had we not included informal and spoken registers in monolinguals and bilinguals alike.

Autonomic failure in a HIV-infected patient.

We present a case report of severe autonomic failure in a 43-year-old well-controlled HIV patient. Clinical and pharmacological autonomic function testing supported the diagnosis of peripheral autonomic failure. Simple physiological manoeuvres substantially improved symptoms.

Quantification of Optic Nerve and Sheath Diameter by Transorbital Sonography: A Systematic Review and Metanalysis.

BACKGROUND AND PURPOSE: To date, normal values for optic nerve diameter (OND) and optic nerve sheath diameter (ONSD) for transorbital sonography (TOS) have only been reported by individual small-scale studies, exposing a great variability in the measurement of the OND and ONSD. METHODS: We performed a systematic review and metanalysis of available to date studies on TOS evaluation of adults without elevated intracranial pressure to provide an overview of the published literature, measuring methods and further specify normal values for OND and ONSD. RESULTS: In total, we included 39 studies with 2,927 healthy volunteers (mean age 36.1 years, 44.4% female), so that a total of 5,854 eyes were examined. All pooled analyses were based on random effect models. Mean values for OND were provided in 13 studies. Calculated mean pooled OND value was 3.08 mm (95% confidence interval [CI], 2.9-3.25), with low heterogeneity across studies (I2 = 12.7%). Thirty-four studies provided mean values for ONSD measurement. The pool of mean ONSD measurements was 4.78 mm (95% CI, 4.63-4.94), with evidence of substantial heterogeneity between estimates ONSD (I2 = 50.6%). There were no significant differences (P = .139) in the subsequent subgroup analysis for the different geographic continents. Also, no significant differences could be recorded for the effect of age (P = .824) or gender (P = .093). CONCLUSIONS: TOS is a frequently described and widely used method. We provide reference values of OND and ONSD that are based on metanalytical analysis. Different measuring methods of ONSD result in higher heterogeneity. Subgroup analysis revealed no significant correlation between ONSD and age, gender, or geographic origin.

Optimization of risk stratification for anticoagulation-associated intracerebral hemorrhage: net risk estimation.

BACKGROUND: Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether combining ischemic and hemorrhagic stroke risk in individual patients might provide a meaningful paradigm for risk stratification. METHODS: We enrolled consecutive patients with anticoagulation-associated ICH in 15 tertiary centers in the USA, Europe and Asia between 2015 and 2017. Each patient was assigned baseline ischemic stroke and hemorrhage risk based on their CHA2DS2-VASc and HAS-BLED scores. We computed a net risk by subtracting hemorrhagic from ischemic risk. If the sum was positive the patient was assigned a "Favorable" indication for anticoagulation; if negative, "Unfavorable". RESULTS: We enrolled 357 patients [59% men, median age 76 (68-82) years]. 31% used non-vitamin K antagonist (NOAC). 191 (53.5%) patients had a favorable indication for anticoagulation prior to their ICH; 166 (46.5%) unfavorable. Those with unfavorable indication were younger [72 (66-80) vs 78 (73-84) years, p = 0.001], with lower CHA2DS2-VASc score [3(3-4) vs 5(4-6), p < 0.001]. Those with favorable indication had a significantly higher prevalence of most cardiovascular risk factors and were more likely to use a NOAC (35% vs 25%, p = 0.045). Both groups had similar prevalence of hypertension and chronic kidney disease. CONCLUSIONS: In this anticoagulation-associated ICH cohort, baseline hemorrhagic risk exceeded ischemic risk in approximately 50%, highlighting the importance of careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining 50% suffered an ICH despite excess baseline ischemic risk, stressing the need for biomarkers to allow more precise estimation of hemorrhagic complication risk.

Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders.

OBJECTIVE: To investigate if patients with neuromyelitis optica spectrum disorder (NMOSD) develop subclinical visual pathway impairment independent of acute attacks. METHODS: A total of 548 longitudinally assessed full-field visual evoked potentials (VEP) of 167 patients with NMOSD from 16 centers were retrospectively evaluated for changes of P100 latencies and P100-N140 amplitudes. Rates of change in latencies (RCL) and amplitudes (RCA) over time were analyzed for each individual eye using linear regression and compared using generalized estimating equation models. RESULTS: The rates of change in the absence of optic neuritis (ON) for minimal VEP intervals of ≥3 months between baseline and last follow-up were +1.951 ms/y (n = 101 eyes; SD = 6.274; p = 0.012) for the P100 latencies and -2.149 µV/y (n = 64 eyes; SD = 5.013; p = 0.005) for the P100-N140 amplitudes. For minimal VEP intervals of ≥12 months, the RCL was +1.768 ms/y (n = 59 eyes; SD = 4.558; p = 0.024) and the RCA was -0.527 µV/y (n = 44 eyes; SD = 2.123; p = 0.111). The history of a previous ON >6 months before baseline VEP had no influence on RCL and RCA. ONs during the observational period led to mean RCL and RCA of +11.689 ms/y (n = 16 eyes; SD = 17.593; p = 0.003) and -1.238 µV/y (n = 11 eyes; SD = 3.708; p = 0.308), respectively. CONCLUSION: This first longitudinal VEP study of patients with NMOSD provides evidence of progressive VEP latency delay occurring independently of acute ON. Prospective longitudinal studies are needed to corroborate these findings and help to interpret the clinical relevance.

The Valsalva maneuver: screening for drug-induced baroreflex dysfunction.

OBJECTIVE: Many drugs can interfere with baroreflex mechanisms thereby impairing blood pressure control, but few have undergone sufficient testing. The state of affairs may be explained by the lack of simple and inexpensive screening tests. METHODS: In eleven healthy men, we tested the hypothesis that a simple Valsalva maneuver could detect drug-induced changes in baroreflex function that have previously been described using more elaborate and invasive methodologies. They performed Valsalva maneuvers after selective pharmacological inhibition of the norepinephrine transporter (NET) in a placebo-controlled, double-blind, randomized, crossover fashion. Patients with severe autonomic failure served as positive controls. RESULTS: NET inhibition profoundly augmented the blood pressure decrease during phase II and attenuated the blood pressure overshoot in phase IV compared with placebo. Furthermore, NET inhibition increased the heart rate response during the Valsalva maneuver. INTERPRETATION: The Valsalva maneuver recapitulated complex alterations in baroreflex regulation during NET inhibition. Thus, this simple and inexpensive test could be employed as a screening tool for drug-induced baroreflex dysfunction.

Circulating endocannabinoid concentrations during orthostatic stress.

BACKGROUND: In animals, the endocannabinoid system is activated during hemodynamic insults and restrains blood pressure in part through sympathetic inhibition. MATERIALS AND METHODS: We tested the hypothesis that hemodynamic stress elicited by head-up tilt testing increases systemic endocannabinoid concentrations in humans and that excessive endocannabinoid availability predisposes to presyncope. RESULTS: With head-up tilt, 2-arachidonoylglycerol increased, whereas anandamide remained unchanged. CONCLUSIONS: In contrast to our expectations, anandamide plasma concentration at rest was directly correlated with orthostatic tolerance, rather than intolerance.

Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer-Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control. METHODS AND MATERIALS: Combined pelvis-external beam radiation/HDR-BT boost to EQD2 >100 Gy (α/ß = 3) was performed in 459 consecutively treated patients. These patients with an FU ≥ 24 months were analyzed and stratified in PSA nadir (nPSA)-groups by PSA nadir within 18 months after radiotherapy (nPSA18). Kaplan-Meier/log-rank tests and Cox-regression models were used to compare the study endpoints. RESULTS: The mean FU was 77 months. A PSA nadir within 18 months (nPSA18) <0.5 ng/mL was achieved in 222 patients with median time to reach nPSA18 of 7 months. The 5-year American Society of Therapeutic Radiology and Oncology (ASTRO) biochemical control (prostate-specific antigen disease-free survival) for the nPSA18 group <0.5 ng/mL was 89% and for the group ≥ 0.5 ng/mL, it was 78.6% (p = 0.011). nPSA18 was an independent predictor of cancer-specific survival, distant metastasis-free survival, and biochemical control (ASTRO) (p = 0.026, p = 0.020, and p = 0.01, respectively). CONCLUSIONS: The present results suggest that the PSA nadir level within 18 months after radiotherapy may serve as an early parameter for long-term biochemical control according to ASTRO definitions following radical dose escalation by HDR-BT for prostate cancer. Excellent outcomes were associated with nPSA18 < 0.5 ng/mL.

Brainstem Encephalitis With Low-Titer Acetylcholine Receptor Antibodies Mimicking Myasthenia Gravis.

Objective: To report a rare case of brainstem encephalitis with low-titer acetylcholine receptor antibodies mimicking myasthenia gravis. Methods: The patient was investigated with repeated brain MRI, CSF examination, repetitive nerve stimulation, thoracic CT, and serologic screening. Our patient passed away and finally autopsy revealed a definitive diagnosis. Written informed consent was obtained from the relatives of the patient for access to clinical files for research purposes and publication. Results: We present a young woman with a subacute bulbar syndrome, who was initially diagnosed with myasthenia gravis based on clinical finding and elevated acetylcholine receptor antibodies. Episodes of numbness in the pharynx and tongue and moderate saccadic horizontal and vertical pursuits were atypical. Despite initial stabilization with intravenous immunoglobulins she developed acute asphyxia after regurgitation of food and had to be resuscitated with ultimately lethal outcome. Autopsy revealed an autoimmune T-cell mediated brainstem encephalitis. Serological screening revealed positive GAD and Ma2 autoantibodies, indicating its probable paraneoplastic nature. Conclusions: Brainstem encephalitis is an important differential diagnosis even in seropositive bulbar myasthenia gravis, as several autoimmune processes often co-occur. Sudden unexpected death must be taken into account in brainstem encephalitis, requiring prolonged monitoring of the patients.

Lentiform Nucleus Hyperechogenicity in Parkinsonian Syndromes: A Systematic Review and Meta-Analysis with Consideration of Molecular Pathology.

The hyperechogenicity of the substania nigra (SN) has been established as a valid finding in patients with Parkinson´s disease (PD), probably caused by an increased tissue iron concentration in the SN. The application of transcranial sonography (TCS) has been investigated for further echogenic basal ganglia alterations in patients with extrapyramidal movement disorders. Compared to PD, a hyperechogenic nucleus lentiformis (LN) has been reported to appear more frequently in atypical parkinsonian syndromes (aPS) such as the parkinsonian phenotype of multiple system atrophy (MSA-P) or the progressive supranuclear palsy (PSP). As the evidence providing study sizes are small, we conduct the first meta-analysis of the prevalence of LN hyperechogenicity in PD and aPS. We search for available studies providing prevalence of LN hyperechogenicity in patients with PD and aPS (MSA-P and PSP) detected by TCS in MEDLINE and SCOPUS databases. We calculate the prevalence rates of LN hyperechogenicity detection in patients with clinical diagnosis of PD vs. aPS under the random-effects model. We include a total of 1330 patients, 1091 PD and 239 aPS (MSA-P and PSP). We find a significantly higher prevalence of LN hyperechogenicity in aPS (76%, 95% CI: 0.62-0.88) compared to PD (16%, 95% CI: 0.10-0.23). After proving a higher prevalence of LN hyperechogenicity in aPS compared to PD, its histopathological cause needs to be investigated. Furthermore, its full diagnostic accuracy and the qualification to serve as a risk factor for MSA-P and PSP should also be questioned in future studies.

Functional Neurosonology Reveals Impaired Cerebrovascular Reactivity in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Vascular aspects like global cerebral hypoperfusion are frequently reported in patients with multiple sclerosis (MS). Although mechanistic question remains unanswered, this hemodynamic impairment may be caused by a widespread endothelial dysfunction. Furthermore, impaired cerebrovascular reactivity (CVR) has been described in patients with MS by means of hypercapnic perfusion magnetic resonance imaging (MRI). We sought to further evaluate potential hemodynamic restriction in patients with MS using functional sonographic methods. METHODS: We evaluated consecutive patients with MS and healthy controls with adequate bilateral transtemporal window. CVR was assessed by bilateral transcranial Doppler monitoring of proximal middle cerebral arteries. Mean flow velocities were recorded before and after 30 seconds of breath holding. Vasomotor response was quantified by breath holding index (BHI). RESULTS: A total of 42 patients with MS (mean age 39 ± 12 years; 69% women) were compared to 31 healthy controls (mean age 35 ± 11 years; 71% women). BHI was lower in patients with MS compared to healthy controls (.70 ± .43 vs. .93 ± .55; P = .006), documenting a lower cerebrovascular response to hypercapnia. There was no correlation between patient age (r = .1254; P = .277), expanded disability status scale (r = .1838; P = .109), and disease duration (r = .1882; P = .101) with BHI in patients with MS. CONCLUSIONS: These preliminary sonographic findings appear to independently corroborate the previously reported observation of impaired CVR on brain MRI in patients with MS. However, the underlying pathophysiological mechanisms as well as the clinical impact of this observation remain elusive.

Microbleed prevalence and burden in anticoagulant-associated intracerebral bleed.

Prior studies suggest an association between Vitamin K antagonists (VKA) and cerebral microbleeds (CMBs); less is known about nonvitamin K oral anticoagulants (NOACs). In this observational study we describe CMB profiles in a multicenter cohort of 89 anticoagulation-related intracerebral hemorrhage (ICH) patients. CMB prevalence was 51% (52% in VKA-ICH, 48% in NOAC-ICH). NOAC-ICH patients had lower median CMB count [2(IQR:1-3) vs. 7(4-11); P < 0.001]; ≥5 CMBs were less prevalent in NOAC-ICH (4% vs. 31%, P = 0.006). This inverse association between NOAC exposure and high CMB count persisted in multivariable logistic regression models adjusting for potential confounders (OR 0.10, 95%CI: 0.01-0.83; P = 0.034).