RISK FACTORS AND OUTCOMES OF HIV-ASSOCIATED STROKE IN ZAMBIA

ObjectiveTo compare risk factors and clinical outcomes between people living with HIV (PLWH) and HIV-uninfected (HIV-) adults with stroke hospitalized in Zambia.MethodsWeretrospectively reviewed charts of all adults admitted to the University Teaching Hospital in Lusaka, Zambia with a clinical diagnosis of stroke between October 2018 and March 2019. Standardized data collection instruments were used to collect demographic, clinical, laboratory and imaging results. Comparison between individuals with and without HIV infection was made using t-tests for continuous parametric variables, Wilcoxon rank-sum tests for continuous non-parametric variables, and chi-square analyses for categorical variables.Results272adults with stroke were admitted of whom 58 (21%) were PLWH. Compared to HIV- participants, PLWH were younger (48 ± 14) years versus 62 ± 18) years, p<0.001). PLWH were less likely to have hypertension (65% vs 83%, p=0.003) and more likely to have no traditional cerebrovascular risk factors (34% vs 15%, p=0.01). Deep vein thrombosis (DVT) (4% vs 1%, p=0.04) was more common during hospitalization amongst PLWH, but there was no difference in in-hospital mortality (21% vs 23%, p=0.65). Among PLWH with stroke, factors associated with in-hospital mortality were Glasgow Coma Scale (GCS) on admission (7 vs 10, p=0.046), hypertension (92% vs 59%, p=0.04) and fever (58% vs 13%, p=0.003).ConclusionThis Zambian cohort of PLWH and stroke is notable for being significantly younger with fewer traditional stroke risk factors but higher rates of DVT than their HIV-uninfected counterparts. GCS on admission, hypertension and fever were associated with in-hospital mortality.     

An Analysis of Stroke Risk Factors by HIV Serostatus in Uganda: Implications for Stroke Prevention in Sub-Saharan Africa

ObjectiveHIV infection is an important stroke risk factor in sub-Saharan Africa.  However, data on stroke risk factors in the era of antiretroviral therapy (ART) are sparse. We aimed to determine if stroke risk factors differed by HIV serostatus in Uganda.MethodsWe conducted a matched cohort study, enrolling persons living with HIV (PWH) with acute stroke, matched by sex and stroke type to HIV uninfected (HIV-) individuals. We collected data on stroke risk factors and fitted logistic regression models for analysis.ResultsWe enrolled 262 participants:105 PWH and 157 HIV-. The median ART duration was 5 years, and the median CD4 cell count was 214 cells/uL. PWH with ischemic stroke had higher odds of hypertriglyceridemia (AOR 1.63; 95% CI 1.04, 2.55, p=0.03), alcohol consumption (AOR 2.84; 95% CI 1.32, 6.14, p=0.008), and depression (AOR 5.64; 95%CI 1.32, 24.02, p=0.02) while HIV- persons with ischemic stroke were more likely to be > 55 years of age (AOR 0.43; 95%CI 0.20-0.95, p=0.037), have an irregular heart rhythm (AOR 0.31; 95%CI 0.10-0.98, p=0.047) and report low fruit consumption (AOR 0.39; 95%CI 0.18-0.83, p=0.014).  Among all participants with hemorrhagic stroke (n=78) we found no differences in the prevalence of risk factors between PWH and HIV-.ConclusionsPWH with ischemic stroke in Uganda present at a younger age, and with a combination of traditional and psychosocial risk factors. By contrast, HIV- persons more commonly present with arrhythmia. A differential approach to stroke prevention might be needed in these populations.     

Stroke in Sierra Leone. the stroke risk factors for people with HIV: A prospective case-control study

BackgroundHIV infection rates are relatively low in Sierra Leone and in West Africa but the contribution of HIV to the risk factors for stroke and outcomes is unknown. In this study, we examined stroke types, presentation, risk factors and outcome in HIV stroke patients compared with controls.MethodsWe used data from the Stroke in Sierra Leone Study at 2 tertiary hospitals in Freetown, Sierra Leone. A case control design was used to compare stroke type, presentation, risk factors and outcome in sero-positive HIV patients with HIV negative stroke controls. Controls were matched for age and gender and a 1:4 ratio cases to controls was used to optimize power. Analysis was performed using the Pearson x² for categorical variable, Paired-T test and Mann-Whitney U test for continuous variables. A p-value of less than 0.05 was taken as the level of statistical significance.ResultsOf 511 (51.8%) stroke patients tested for HIV, 36 (7.1%) were positive. Univariate unmatched analysis showed a stroke mean age of 49 years in HIV-positive versus 58 years in HIV-negative population (p = <0.001). In the case-control group, ischaemic stroke is the major type reported in both populations, HIV-negative population: 77 (53.5%) versus HIV-positive: 25 (69.4%) (p = 0.084). Hypertension is the most prevalent risk factor in both groups, HIV-positive: 23 (63.9%) versus HIV-negative: 409 (86.1%) (p = 0.001). Lower CD4+ count is associated in-hospital mortality (p = <0.001).ConclusionThese findings support the current call for timely management of stroke and HIV through integrated care.     

Characteristics and evolution of cerebral aneurysms among adults living with HIV: A retrospective,longitudinal case series

ObjectivePrevious research indicates an increased risk of cerebral aneurysm formation in adults living with human immunodeficiency virus (ALWH), however there are few longitudinal studies on the risk factors for and outcomes of cerebral aneurysms in this population. We aim to describe the characteristics and evolution of cerebral aneurysms in a large cohort of ALWH.Materials and MethodsA chart review was completed for all adults evaluated at an urban, safety-net U.S. hospital between January 1, 2000, and October 22, 2021, with history of both HIV and at least one cerebral aneurysm.ResultsA total of 82 cerebral aneurysms were identified amongst 50 patients (52% female sex). Forty-six percent of patients with a nadir CD4 count less than 200 cells/mm³ (N=13) and 44% of patients with maximum viral load >10,000 copies/mL (N=18) developed new aneurysms or were found to have aneurysm growth over time compared with 29% of patients with a CD4 nadir above 200 cells/mm³ (N=21) and 22% of patients with maximum viral load </= 75 copies/mL (N=9). New aneurysms were found, or existing aneurysms grew in 67% of those not on antiretroviral therapy (ART) at time of aneurysm diagnosis (N=6), 38% of those with inconsistent ART use (N=8), and 21% of those with consistent ART (N=19).ConclusionsAmong ALWH, lower CD4 nadir, higher zenith viral load, and inconsistent ART use may contribute to aneurysm formation or growth. Further studies are needed to more thoroughly characterize the association between immunologic status and cerebral aneurysm formation.     

Neurological involvement in patients with acute/recent HIV-1 infection. A case-control study

Primary HIV-1 infection is a relevant period for its virological and epidemiological consequences. Most patients present a symptomatic disease that can be potentially serious, but neurological involvement during primary HIV-1 infection has been poorly studied. The aim of this study was to describe the characteristics and outcomes of primary HIV-1 infection patients presenting neurological symptoms and to compare them with primary HIV-1 infection patients without neurological involvement. Retrospective case-control study (1:3) comparing primary HIV-1 infection patients with and without neurological involvement enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016. Matching criteria included age (±10 years), gender, year of diagnosis (±4 years), and Fiebig stage. The conditional logit model was used for comparisons. Fourteen out of 463 patients (3.02%) enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016 presented neurological symptoms. 28.5% of cases presented as meningitis and 71.5% as meningoencephalitis. Cerebrospinal fluid showed non-specific findings, including pleocytosis with lymphocyte predominance and increased protein levels. All cases required hospitalisation, whereas only 19% of the controls did. No other pathogen was identified in any case, but five patients initiated empirically antimicrobial treatment for other aetiologies until diagnosis was confirmed. CD4/CD8 ratio was significantly lower (p = 0.039) and plasmatic viral load significantly higher in the case group, compared to controls (p = 0.028). Risk factors, HIV-1 tropism, subtype distribution, and prescribed ART regimens were comparable between cases and controls. After 6 months on ART, 92% of cases had undetectable viral load, similar to controls, and CD4/CD8 ratio became also comparable between groups. All cases recovered rapidly with ART and were discharged without sequels. Neurological involvement during primary HIV-1 infection is unusual but serious, always requiring hospitalisation. Diagnosis is difficult because of the wide range of symptoms and similarities with other viral aetiologies. Neurological manifestations during primary HIV-1 infection are associated with a lower CD4/CD8 ratio and with a higher viral load than controls. Immediate ART initiation and rapid viral load decrease are required, allowing complete clinical recovery.     

Acute meningoencephalitis due to human immunodeficiency virus type 1 infection in 13 patients: clinical description and follow-up

The objective of this study is to describe a series of cases of severe meningitis caused by human immunodeficiency virus type 1 (HIV-1) occurring during primary infection or after antiretroviral treatment interruption. In an observational cohort study, 13 patients with clinical diagnosis of meningitis or meningoencephalitis were reviewed. Ten cases occurred during primary HIV-1 infection and 3 after antiretroviral therapy (ART) withdrawal. Demographic parameters, clinical presentation and outcome, and laboratory and cerebrospinal fluid (CSF) parameters were recorded. The risk factor for HIV-1 infection acquisition was sexual transmission in all cases. The most frequent systemic symptoms were fever (12/13) and headeache (9/13). Among neurologic symptoms, focal signs appeared in seven patients (53.8%), confusion in six (46.2%), and agitation in five (38.5%). The median CD4 cell count was 434 cells/mm3. In all cases, CSF was a clear lymphocytaire fluid with normal glucose levels. Cranial computerized tomography was performed in seven patients, with a normal result in all of them; brain magnetic resonance in eight patients was normal in five cases and showing cortical atrophy, limbic encephalitis, and leptomeningeal enhancement in one patient each. The electroencephalographs (EEG) just showed diffuse dysfunction in three cases. ART was started in 11 patients. HIV RNA load at 12 months was <50 copies/ ml in all treated patients. The 13 patients recovered without neurologic sequela. Meningitis or meningoencephalitis during primary HIV-1 infection or after ART cessation are unusual but sometimes a life-threatening manifestation. Although all patients tend to recover and the necessity of ART is not well established, some data suggest its potential benefit in these patients.     

Risk Factors for Stroke in HIV-Positive and-Negative Patients in Pretoria,South Africa

ObjectivesLow- to middle-income countries experience a marked rise in cardiovascular diseases, and have the highest incidence of HIV infection. Stroke data in HIV-positive patients is still scarce. This study compares risk factors and types of stroke between HIV-positive and –negative patients in South Africa.Materials and MethodsWe conducted a cross-sectional study at Kalafong Provincial Tertiary Hospital in Pretoria over a 10-month period. All adult patients presenting with an acute stroke were included.ResultsOne hundred and forty consecutive patients with stroke were included, 23% were HIV-positive. The average age in the HIV-positive group was 41 years, compared to 61 years in the HIV-negative group (p < 0.01). Ischemic infarcts occurred in 80.7 and 19.3% were hemorrhagic, with no significant difference between the HIV-positive and -negative group (ischemic: 81% vs 80%; hemorrhagic: 19% vs 20%; p = 0.55). Small vessel infarcts occurred more frequently in HIV-positive patients (25% vs 9.3%; p < 0.02). While 78% of HIV-positive patients presented with concomitant infections, these were found in only 23% of HIV-negative patients (P < 0.001). Hypertension (81% vs 37.5%; p = 0.01) and dyslipidemia (62% vs 38%; p = 0.01) were more prevalent in the HIV-negative patients. Confounding variables were gender and age. Although more than half of the HIV-positive patients were on antiretroviral therapy, the majority (62.5%) showed virological non-suppression.ConclusionsHIV infection occurred in almost one-quarter of stroke patients and was seen more in the younger age group. Small vessel ischemic infarcts and underlying infections were more common in HIV-positive patients. The high number of HIV-positive patients with virological non-suppression is concerning and needs to be addressed.     

Meningitis in a community with a high prevalence of tuberculosis and HIV infection

OBJECTIVES: To evaluate the spectrum of aetiologies, and distinguishing clinical and laboratory features, of meningeal infection in a community with a high prevalence of tuberculosis (TB) and HIV infection. SETTING: A hospital serving mineworkers, originating from rural areas of Southern Africa. DESIGN: Prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis. MEASUREMENTS: Clinical history and examination; concurrent cerebrospinal fluid (CSF) and blood samples; mortality status six months after entry to study. RESULTS: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis (TBM) and two had tuberculomas; four developed disease while on TB therapy. There was one case of multidrug, and two of isoniazid-resistant TBM. There were nine episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis, two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were significantly younger (p=0.004). All patients with tuberculous, cryptococcal (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive. Within six months, 19 patients had died. Death was associated with HIV positivity (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis, CNS TB or ADC. CONCLUSION: HIV has a major impact on the burden of disease and mortality, with a predominance of opportunistic chronic meningitides, despite a meningococcal outbreak, in this community. Of concern is the development of TBM despite therapy, and the emergence of drug-resistant strains.     

Inflammatory Bowel Disease as a Precondition for Stroke or TIA: A Matter of Crohn's Disease Rather than Ulcerative Colitis

BackgroundAs a chronic systemic inflammation may be associated with an increased risk of vascular events, the aim of the present study was to assess the incidence of stroke and transient ischemic attack (TIA) in patients with inflammatory bowel disease over a period of 15 years.MethodsThis cohort study included patients for whom the initial diagnosis of an inflammatory bowel disease (IBD) (Crohn's disease: CD and ulcerative colitis: UC) was documented anonymously between 2000 and 2015 in 1,262 general practices in Germany. IBD patients were matched to patients without IBD using propensity scores based on age, sex, physician, co-diagnoses and co-therapies. Cox regression models were used to study the incidence of stroke and TIA as a function of CD and UC.ResultsEach of the matched groups included 11,947 participants. In the IBD group, 43.5% had CD and 56.5% UC respectively. Higher incidences of both stroke and TIA were detected for IBD (stroke: 279.0 versus 222.6 cases per 100,000 patient years, HR 1.30, p=0.011; TIA: 203.1 versus 141.1 cases per 100,000 patient years, HR 1.42, p=0.006). Stroke and TIA incidences (cases per 100,000 patient years) were higher than in controls (stroke: 314.7 versus 204.5, HR: 1.50, p=0.013; TIA: 183.8 versus 95.3, HR: 1.93, p=0.004) in CD patients only. No relevant differences in incidences were found for patients with UC.ConclusionWhile CD turned out to be a relevant precondition for stroke or TIA, this was not the case for UC.     

Increased stroke severity and mortality in patients with SARS-CoV-2 infection: An analysis from the N3C database

BackgroundStudies from early in the COVID-19 pandemic showed that patients with ischemic stroke and concurrent SARS-CoV-2 infection had increased stroke severity. We aimed to test the hypothesis that this association persisted throughout the first year of the pandemic and that a similar increase in stroke severity was present in patients with hemorrhagic stroke.MethodsUsing the National Institute of Health National COVID Cohort Collaborative (N3C) database, we identified a cohort of patients with stroke hospitalized in the United States between March 1, 2020 and February 28, 2021. We propensity score matched patients with concurrent stroke and SARS-COV-2 infection and available NIH Stroke Scale (NIHSS) scores to all other patients with stroke in a 1:3 ratio. Nearest neighbor matching with a caliper of 0.25 was used for most factors and exact matching was used for race/ethnicity and site. We modeled stroke severity as measured by admission NIHSS and the outcomes of death and length of stay. We also explored the temporal relationship between time of SARS-COV-2 diagnosis and incidence of stroke.ResultsOur query identified 43,295 patients hospitalized with ischemic stroke (5765 with SARS-COV-2, 37,530 without) and 18,107 patients hospitalized with hemorrhagic stroke (2114 with SARS-COV-2, 15,993 without). Analysis of our propensity matched cohort revealed that stroke patients with concurrent SARS-COV-2 had increased NIHSS (Ischemic stroke: IRR=1.43, 95% CI:1.33–1.52, p<0.001; hemorrhagic stroke: IRR=1.20, 95% CI:1.08–1.33, p<0.001), length of stay (Ischemic stroke: estimate = 1.48, 95% CI: 1.37, 1.61, p<0.001; hemorrhagic stroke: estimate = 1.25, 95% CI: 1.06, 1.47, p=0.007) and higher odds of death (Ischemic stroke: OR 2.19, 95% CI: 1.79–2.68, p<0.001; hemorrhagic stroke: OR 2.19, 95% CI: 1.79–2.68, p<0.001). We observed the highest incidence of stroke diagnosis on the same day as SARS-COV-2 diagnosis with a logarithmic decline in counts.ConclusionThis retrospective observational analysis suggests that stroke severity in patients with concurrent SARS-COV-2 was increased throughout the first year of the pandemic.     

EEG in early HIV-1 infection is characterized by anterior dysrhythmicity of low maximal amplitude

We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1.     

Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection

Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1—infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI. NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because “practice effects” are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.     

Working status is related to post stroke/TIA cognitive decline: data from the TABASCO study

Background and AimsOccupational status may influence physical and mental post-stroke outcomes. We aimed to evaluate the association between occupational status and type, or engagement in social and family activities, neuroimaging measures and cognitive decline (CD) in a prospective cohort of stroke patients.MethodsWe included 273 first-ever stroke survivors at working age. All patients underwent 3T MRI at admission, as well as clinical and cognitive assessments at admission, 6, 12 and 24 months thereafter.ResultsNinty nine (36.3%) of the participants were unemployed prior to the stroke. Age, sex, work type, other comorbidities, stroke severity or location were not associated with return to work. Patients who returned to work (87.4%) had better cognitive results and less depressive symptoms than those who retired after the event.Pre-stroke unemployment was associated with diabetes mellitus, hypertension, dyslipidemia, depression, poorer cognitive scores and brain atrophy. During the follow-up, 11% developed CD. CD was more common among previously unemployed than employed participants (19.2% vs. 6.3%, p = 0.001). Multiple regression adjusted for risk factors, revealed that pre-stroke unemployment was an independent predictor of CD (HR, 3.0; 95% CI: 1.06–8.44). Furthermore, engagement in mentally stimulating jobs decreased the risk for CD.ConclusionsPre-stroke unemployment and post-stroke work disruption were each associated with depression and poorer cognitive performance up to two years post-stroke, as well as with brain atrophy at admission. Retirement after the stroke may increase the risk of developing CD. These results highlight the importance of continued employment in preserving cognitive abilities among stroke survivors.     

Endothelial Progenitor Cells Count after Acute Ischemic Stroke Predicts Functional Outcome in Patients with Carotid Atherosclerosis

ObjectivesCirculating Endothelial Progenitor Cells (EPCs) predict cardiovascular outcomes in patients with coronary disease. However, the predictive value of EPCs after ischemic stroke is not well established. We aimed to study the prognostic role of EPCs in patients with acute ischemic stroke and carotid atherosclerosis, focusing on post-stroke functional outcome and stroke recurrences.Materials and MethodsWe studied consecutive adult patients with an acute (<7 days) anterior circulation ischemic stroke and carotid atherosclerosis. Cardioembolic strokes were excluded. We measured circulating EPCs by flow cytometry (CD34+/CD133+/KDR+) at inclusion (7±1 days after stroke) and at one year of follow-up. At three months and at one year we registered the modified Rankin Scale score, stroke recurrences and coronary syndromes during the follow-up.ResultsWe studied 80 patients with a mean age of 74.3±10.4 years. We divided the population in tertiles according to the EPCs count. At three months we observed a favorable outcome in 25/36 (69.4%) patients in the lowest, 19/22 (86.4%) in the medium and 21/22 (95.5%) in the highest tercile (p=0.037). In the multivariable analysis a higher EPCs count was associated with favorable functional outcome after adjusting for age and baseline NIHSS score (OR=3.61, 95%CI 1.34-9.76; p=0.011). This association persisted at one year of follow-up. We did not find association between counts of EPCs and stroke recurrence.ConclusionsIn patients with acute ischemic stroke and carotid atherosclerosis, a higher count of EPCs was associated with favorable functional outcome in the mid and long-term follow-up. Counts of EPCs did not predict stroke recurrences.     

Premature Atrial Contractions and Their Association with Stroke Features and Outcome

BackgroundFrequent premature atrial contractions (PACs) are associated with atrial fibrillation, stroke, and mortality. However, the cut-off value for PAC counts that could identify patients with different stroke features is unclear, and the association of PACs to outcome is not determined.MethodsThe study retrospectively included patients with acute ischemic stroke who had underwent both a 24 h Holter recording and a brain MRI in Taipei Veterans General Hospital from January 2015 to May 2016. Patients were categorized into four groups according to their PAC frequencies on 24 h Holter recording. We compared the clinical severity, neuroimage features, stroke subtypes, and functional outcome among the four groups of patients.ResultsAmong the 278 patients, the lower, middle, and upper quartiles of the PAC counts were 23, 74, and 459.5, respectively. In contrast to the 1^st quartile of patients, the 3^rd (PAC 75-459/24 h) and the 4^th (PAC ≥460/24 h) quartiles of patients had higher NIH Stroke Scale (NIHSS) at admission (p = 0.014 and p = 0.002, respectively). The frequencies of cryptogenic stroke were not different among the 4 quartiles of the patients, but cryptogenic stroke patients with ≥ 75PACs/24hours had higher stroke severity compared to those with PACs < 75counts/24 h (NIHSS 9.1 vs. 5.2, p = 0.043). There was an increased trend in infarcts of multiple vascular territories and in mortality at 1 year among the four groups of patients with increased PAC frequency (p = 0.045 and p = 0.002, respectively). The 4^th PAC quartile was associated with poor functional outcome (modified Rankin Scale ≥ 4) at 3 months in univariate analysis (OR: 5.66, CI: 2.69–11.91, p < 0.001), but was not an independent predictor after controlling for initial stroke severity.ConclusionsPACs ≥ 75 counts/24 h was associated with higher clinical severity in patients with acute ischemic stroke.     

Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy

ObjectiveHigher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr).MethodsPlasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4⁺ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin.ResultsBefore ART, phe/tyr was mean ± S.D.: 0.99 ± 0.57 μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs = 0.434, and rs = 0.392; both p < 0.001) and less strongly with HIV-RNA levels (rs = 0.173) and CD4⁺ counts (rs = ?0.182, both p < 0.05). After ART, phe/tyr dropped to 0.72 ± 0.16 (=?27%; U = 5.21, p = 0.01) which was due to an average decline of ?14% of phe concentrations from 73.1 ± 34.0 μmol/L at baseline to 62.9 ± 17.8 μmol/L after ART (U = 2.51, p = 0.01) and a concomitant increase of tyr concentrations (+13%, U = 2.46, p = 0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART.ConclusionsIncreased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.     

CNS cryptococcosis with idiopathic CD4+ T lymphocytopenia]

A 33-year-old Japanese man, with a history of recurrent skin cryptococcosis, was admitted complaining of fever and severe headache for 3 weeks. He had no known risk factors for human immunodeficiency virus (HIV) infection. Cerebrospinal fluid examination revealed an elevated opening pressure of 32 cm H2O, cell counts of 884/mm3, a total protein value of 184 mg/dl, a glucose level of 16 mg/dl, and demonstrated a positive India ink stain for fungus. Cultures grew Cryptococcus neoformans. Hematological studies showed a persistently low CD4+ cell count (30/mm3) and a low CD4/CD8 ratio of 0.1. He has been repeatedly seronegative (ELISA and Western blot) for HIV-1 and HIV-2. He responded to fluconazole, and was given itraconazole as secondary prophylaxis because of persistent low CD4 counts. To our knowledge this is the first patient with idiopathic CD4+ T lymphocytopenia associated with CNS cryptococcosis in Japan. CD4 counts should be part of the initial work up for patients with CNS cryptococcosis.     

The diagnostic utility of elevation in cerebrospinal fluid beta 2-microglobulin in HIV-1 dementia. Multicenter AIDS Cohort Study.

We measured serum and CSF beta 2-microglobulin (beta 2M) levels in HIV-1 seropositive individuals with and without dementia to determine the frequency and diagnostic utility of elevation of CSF beta 2M. We compared 34 samples from 27 patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive participants in the Multicenter AIDS Cohort Study, none of whom had progressive dementia. Neurosyphilis and CNS opportunistic processes were excluded in all subjects. We stratified the nondemented subjects by duration of HIV seropositivity and peripheral blood CD4 count. Compared with the nondemented group, demented subjects had significantly higher CSF total protein, IgG%, and CSF albumin/serum albumin ratios. A highly significant association was found between elevated CSF beta 2M and reduced CD4 count (p less than 0.0001). No significant differences were noted between the demented and nondemented groups in CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF beta 2M was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with dementia (p less than 0.0001). We derived a cutoff of 3.8 mg/l from the distribution of CSF beta 2M in the nondemented group. The determination of CSF beta 2M had a sensitivity of 44%, specificity of 90%, and a positive predictive value of 88% for diagnosis of HIV dementia when compared with nondemented subjects with CD4 counts less than 200. In those without dementia, there was a strong correlation between serum and CSF beta 2M (r = 0.50, p less than 0.0001), but in demented subjects CSF beta 2M was elevated independently of serum levels, suggesting that CSF beta 2M is produced within the brain in HIV dementia. In the absence of CNS opportunistic processes, elevated CSF beta 2M greater than 3.8 mg/l is a clinically useful marker for HIV dementia.     

Intracranial artery calcifications: Risk factors and association with cardiovascular disease and cognitive function

Background and aimswe know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function.Methodspatients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination.Results1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p < 0.001), diabetes mellitus (medial iICA, p = 0.004), hypertension (intimal iICA, p < 0.001) and basilar artery, p = 0.019) and smoking (intimal iICA, p = 0.008). iICA calcifications were associated with stroke and intimal calcifications also with myocardial infarction. Intracranial artery calcifications were not associated with cognitive function or type of cognitive disorder.Conclusionthe majority of memory clinic patients had intracranial artery calcifications. Cardiovascular risk factors are differentially related to medial or intimal iICA calcifications. iICA calcifications were associated with myocardial infarction and stroke, but not with cognitive outcomes.