First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

Impact of HIV impact on outcomes of deep-brain stimulation of the subthalamic nucleus for Parkinson's disease.

BACKGROUND AND PURPOSE: Middle-aged persons living with HIV (PLHIV) have a heightened risk of more concomitant age-related comorbidities that are acknowledged as signs of poorer prognosis after deep-brain stimulation of the subthalamic nucleus (STN-DBS) at younger-than-expected ages. To assess the beneficial and adverse effects of STN-DBS in PLHIV with Parkinson's disease (PD). METHODS: We retrospectively included nine PLHIV with PD who had sustained virological control. Patients were followed up for 7 ± 4 years. RESULTS: Patients' mean ages at PD onset and STN-DBS were 45 ± 15 and 53 ± 16 years, respectively. At STN-DBS, mean HIV infection and PD durations were 15 ± 12 and 8 ± 4 years, respectively. STN-DBS significantly improved 1-year Unified Parkinson's Disease Rating Scale (UPDRS)-III scores (71%), daily off-time (63%), motor fluctuations (75%) and daily levodopa-equivalent dose (68%); mean 5-year UPDRS-III score and motor fluctuation improvements remained ~45%. Impulse control disorders (affecting 6/9 patients) fully resolved after STN-DBS. Postoperative course was uneventful. No serious adverse events occurred during follow-up. CONCLUSION: Our findings indicate that STN-DBS is a safe and effective treatment for PLHIV with PD.

Metabolic Syndrome and Cardiovascular Disease Impacts on the Pathophysiology and Phenotype of HIV-Associated Neurocognitive Disorders.

Evidence from epidemiological studies on the general population suggests that midlife cardiovascular disease (CVD) and/or metabolic syndrome (MetS) are associated with an increased risk of cognitive impairment and dementia later in life. In the modern combined antiretroviral therapy (cART) era, as in the general population, CVD and MetS were strongly and independently associated with poorer cognitive performances of sustained immunovirologically controlled persons living with human immunodeficiency viruses (PLHIVs). Those findings suggest that CV/metabolic comorbidities could be implicated in the pathogenesis of HIV-associated neurocognitive disorders (HAND) and might be more important than factors related to HIV infection or its treatment, markers of immunocompetence, or virus replication. The association between CVD/MetS and cognition decline is driven by still not well-understood mechanisms, but risk might well be the consequence of increased brain inflammation and vascular changes, notably cerebral small-vessel disease. In this review, we highlight the correspondences observed between the findings concerning CVD and MetS in the general population and virus-suppressed cART-treated PLHIVs to evaluate the real brain-aging processes. Indeed, incomplete HIV control mainly reflects HIV-induced brain damage described during the first decades of the pandemic. Given the growing support that CVD and MetS are associated with HAND, it is crucial to improve early detection and assure appropriate management of these conditions.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Correction: Absence of peripapillary retinal nerve-fiber-layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV.

[This corrects the article DOI: 10.1371/journal.pone.0229977.].

Absence of peripapillary retinal nerve-fiber-layer thinning in combined antiretroviral therapy-treated, well-sustained aviremic persons living with HIV.

PURPOSE: To compare peripapillary retinal nerve-fiber-layer (pRNFL) thickness, total retina macular volume, and ganglion-cell-layer (GCL) macular volume and thickness between persons living with HIV (PLHIVs) with well-controlled infections and good immune recovery, and sex- and age-matched HIV-uninfected controls (HUCs). METHODS: This prospective cross-sectional study (www.clinicaltrials.gov identifier: NCT02003989) included 56 PLHIVs, infected for ≥10 [median 20.2] years and with sustained plasma HIV-load suppression on combined antiretroviral therapy (cART) for ≥5 years, and 56 matched HUCs. Participants underwent spectral-domain optical coherence tomography (SD-OCT) with thorough ophthalmological examinations and brain magnetic resonance imaging (MRI). Their overall and quadrant pRNFL thicknesses, total macular volumes, and GCL macular volumes and thicknesses were compared. Cerebral small-vessel diseases (CSVD) complied with STRIVE criteria. RESULTS: Median [interquartile range, IQR] ages of PLHIVs and HUCs, respectively, were 52 [46-60] and 52 [44-60] years. Median [IQR] PLHIVs' nadir CD4+ T-cell count and current CD4/CD8 T-cell ratio were 249/µL [158-350] and 0.95 [0.67-1.10], respectively; HIV-seropositivity duration was 20.2 [15.9-24.5] years; cART duration was 16.8 [12.6-18.6] years; and aviremia duration was 11.4 [7.8-13.6] years. No significant between-group pRNFL thickness, total macular volume, macular GCL-volume and -thickness differences were found. MRI-detected CSVD in 21 (38%) PLHIVs and 14 (25%) HUCs was associated with overall thinner pRNFLs, and smaller total retina and GCL macular volumes, independently of HIV status. CONCLUSIONS: SD-OCT could not detect pRNFL thinning or macular GCL-volume reduction in well-sustained, aviremic, cART-treated PLHIVs who achieved good immune recovery. However, CSVD was associated with thinner pRNFLs and GCLs, independently of HIV status.

Microalbuminuria: a sentinel of neurocognitive impairment in HIV-infected individuals?

BACKGROUND: According to population-based studies, microalbuminuria is associated with subsequent cognitive decline over a 4-6-year period, because of cerebral small-vessel disease (CSVD). This prospective cross-sectional study (NCT02852772) was designed to evaluate whether a history of microalbuminuria is associated with subsequent cognitive decline in combined antiretroviral therapy (cART)-treated persons living with human immunodeficiency virus (PLHIVs). METHODS: From our computerized medical database, we identified 30 PLHIVs (median age 52 years), immunovirologically controlled on cART, who had microalbuminuria in 2008 and had undergone, between 2013 and 2015, a comprehensive neuropsychological assessment (NPA) including seven domains (cases): information-processing speed, motor skills, executive functions, attention/working memory, learning/memory, reasoning and verbal fluency. Forty-nine PLHIVs matched for age (median age 48 years; p = 0.19), sex, and year of first HIV-seropositivity without microalbuminuria in 2008 were identified and underwent the same NPA between 2013 and 2015 (controls). RESULTS: Cases performed less well than controls for information-processing speed (p = 0.01) and motor skills (p = 0.02), but no differences were found for the other cognitive domains and global z-scores. A multivariable linear-regression model adjusted for confounding factors confirmed the microalbuminuria effect for the information-processing-speed z score. CONCLUSION: cART-treated PLHIVs with a history of microalbuminuria subsequently had worse cognitive performances for the information-processing-speed domain, possibly because of CSVD. Our observations should be considered preliminary findings of a temporal link between microalbuminuria, CSVD, and subsequent cognitive impairment.

Brief Report: Impact of ART Classes on the Increasing Risk of Cerebral Small-Vessel Disease in Middle-Aged, Well-Controlled, cART-Treated, HIV-Infected Individuals.

BACKGROUND: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD. METHODS: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group. RESULTS: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class. CONCLUSION: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

Five-year outcome in the copaxone observatory: a nationwide cohort of patients with multiple sclerosis starting treatment with glatiramer acetate in France.

The benefits provided by disease-modifying treatments in multiple sclerosis have been demonstrated in clinical trials, but the extent to which they can be extrapolated to everyday care is less clear, as are the long-term benefits of treatment. The objective of this prospective observational cohort study performed in France was to evaluate the effectiveness and safety of glatiramer acetate in patients with relapsing-remitting multiple sclerosis over a 5-year period. All neurologists in France were invited to participate and enroll adult patients starting a first treatment with brand glatiramer acetate 20 mg. Given the observational nature of the study, no fixed study visits were imposed; consultations took place according to the investigator's normal practice. Occurrence of disease exacerbations and adverse events was documented and neurological disability evaluated with the EDSS at each consultation. Overall, 852 patients were analysable and 269 took glatiramer acetate continuously for 5 years. Median treatment duration was 3.4 years. Principal reasons for discontinuation were inadequate efficacy (38.9%), local tolerability (22.6%) and personal convenience (21.3%). Age, employment status, baseline EDSS score and number of previous exacerbations were variables associated with treatment persistence. The annualised exacerbation rate (5 years) was 0.41 [95% CI 0.39-0.44]; 316 patients (37.2%) remained exacerbation-free throughout. The risk of confirmed disability worsening (5 years) was 43.8% [95% CI 39.9-47.9%]. The most frequent adverse drug reactions were local injection site reactions (584 patients; 68.5%) and systemic immediate post-injection reactions (168 patients; 19.7%). Overall, these findings are consistent with those of previous clinical trials.

A novel method of inducing endogenous pupil oscillations to detect patients with unilateral optic neuritis.

PURPOSE: To use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants. METHOD: Pupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs. RESULTS: On average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients' affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%). CONCLUSIONS: The new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc).

Efficacy of Exome-Targeted Capture Sequencing to Detect Mutations in Known Cerebellar Ataxia Genes.

Importance: Molecular diagnosis is difficult to achieve in disease groups with a highly heterogeneous genetic background, such as cerebellar ataxia (CA). In many patients, candidate gene sequencing or focused resequencing arrays do not allow investigators to reach a genetic conclusion. Objectives: To assess the efficacy of exome-targeted capture sequencing to detect mutations in genes broadly linked to CA in a large cohort of undiagnosed patients and to investigate their prevalence. Design, Setting, and Participants: Three hundred nineteen index patients with CA and without a history of dominant transmission were included in the this cohort study by the Spastic Paraplegia and Ataxia Network. Centralized storage was in the DNA and cell bank of the Brain and Spine Institute, Salpetriere Hospital, Paris, France. Patients were classified into 6 clinical groups, with the largest being those with spastic ataxia (ie, CA with pyramidal signs [n = 100]). Sequencing was performed from January 1, 2014, through December 31, 2016. Detected variants were classified as very probably or definitely causative, possibly causative, or of unknown significance based on genetic evidence and genotype-phenotype considerations. Main Outcomes and Measures: Identification of variants in genes broadly linked to CA, classified in pathogenicity groups. Results: The 319 included patients had equal sex distribution (160 female [50.2%] and 159 male patients [49.8%]; mean [SD] age at onset, 27.9 [18.6] years). The age at onset was younger than 25 years for 131 of 298 patients (44.0%) with complete clinical information. Consanguinity was present in 101 of 298 (33.9%). Very probable or definite diagnoses were achieved for 72 patients (22.6%), with an additional 19 (6.0%) harboring possibly pathogenic variants. The most frequently mutated genes were SPG7 (n = 14), SACS (n = 8), SETX (n = 7), SYNE1 (n = 6), and CACNA1A (n = 6). The highest diagnostic rate was obtained for patients with an autosomal recessive CA with oculomotor apraxia-like phenotype (6 of 17 [35.3%]) or spastic ataxia (35 of 100 [35.0%]) and patients with onset before 25 years of age (41 of 131 [31.3%]). Peculiar phenotypes were reported for patients carrying KCND3 or ERCC5 variants. Conclusions and Relevance: Exome capture followed by targeted analysis allows the molecular diagnosis in patients with highly heterogeneous mendelian disorders, such as CA, without prior assumption of the inheritance mode or causative gene. Being commonly available without specific design need, this procedure allows testing of a broader range of genes, consequently describing less classic phenotype-genotype correlations, and post hoc reanalysis of data as new genes are implicated in the disease.

Silent Cerebral Small-Vessel Disease Is Twice as Prevalent in Middle-Aged Individuals With Well-Controlled, Combination Antiretroviral Therapy-Treated Human Immunodeficiency Virus (HIV) Than in HIV-Uninfected Individuals.

Background: Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results: Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54-60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions: HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs. Clinical Trials Registration: NCT02082574.

Long-term AIDS-related PCNSL outcomes with HD-MTX and combined antiretroviral therapy.

OBJECTIVE: To assess the characteristics and outcomes of patients with AIDS-related primary CNS lymphoma (AR-PCNSL) in the combined antiretroviral therapy (cART) era systematically treated with high-dose methotrexate (HD-MTX). METHODS: We retrospectively analyzed (intention-to-treat analysis) 51 consecutive patients with AR-PCNSL (median age 39 years) who were diagnosed from 1996 to 2014 and treated with a median of 6 (range 1-15) infusions of HD-MTX (3 g/m2) combined with cART. RESULTS: Median all-patients' and survivors' follow-up lasted 23 (range 0-186) and 76 (range 23-186) months, respectively. At PCNSL diagnosis, 83% of the patients were on cART, median plasma HIV load was 175,600 copies/mL, and median CD4+ T-cell count was 24/µL. Median Eastern Cooperative Oncology Group performance status was 2 (range 1-4). Median overall survival (OS) was 5.7 years, with 5- and 10-year rates of 48% and 41%. Median time to progression was not reached (69% at 10 months). PCNSL was the direct cause of 14 deaths, all observed within the 10 months after its diagnosis: 6 patients died before HD-MTX could be administered, 4 had refractory disease, and 4 relapsed. Multivariate analyses retained time interval between AIDS diagnosis and PCNSL diagnosis, age at AR-PCNSL diagnosis, and deep brain structure involvement as independent OS-predictive factors. To restore effective immune function, cART tailored to HIV genotypes was started and combined with HD-MTX; no interactions and no immune reconstitution inflammatory syndrome occurred. No patient died of acute treatment-related toxicity, and 21 of 51 (41%) patients experienced grade 3/4 toxicity. CONCLUSIONS: Combined short-term HD-MTX monochemotherapy and optimal cART simply and effectively treat AR-PCNSL, achieving long-term survival with few relapses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that short-term HD-MTX monochemotherapy improves long-term survival of patients with AIDS with primary CNS lymphoma receiving cARTs.

Progressive multifocal leukoencephalopathy and rheumatoid arthritis treatments.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system due to reactivation of the JC virus (JCV). PML is extremely uncommon despite the high prevalence of the virus in the general population. No specific treatment is available, and the prognosis is bleak. The diagnosis is based on brain imaging findings, detection of the JCV genome in cerebrospinal fluid samples and, in some cases, histological studies of the brain lesions. The pathophysiological mechanisms that drive the development of PML are incompletely understood. However, a consistent feature is the presence of a predisposing factor, most notably immunosuppression. The risk of developing PML varies with the underlying disease (e.g., HIV infection or autoimmune disease) and with the drugs used to treat them. Biologics have been ranked according to the risk of PML during their use. Natalizumab, a monoclonal antibody given to treat multiple sclerosis, is among the drugs associated with a high risk of PML. Patients given natalizumab are now closely monitored based on anti-JCV antibody titers and index values. In rheumatology, the expanding use of biologics has led to an increase in cases of PML, with rituximab being associated with the highest risk. Given the absence of specific recommendations, exhaustive registries and postmarketing observational studies are urgently needed to gauge the risk of PML according to the underlying disease and drug treatments, with the goal of defining optimal monitoring protocols.

[Progressive multifocal leukoencephalopathy]. / Leucoencéphalopathie multifocale progressive.

Progressive multifocal leukoencephalopathy. Progressive multifocal leukoencephalopathy (PML) is a lethal central nervous system (CNS) demyelinating disease caused by the human polyomavirus JC. Primary infection is asymptomatic and occurs in late childhood. JC virus persists in a latent state in different organs, notably kidney. Immunosuppression (including persons with HIV infection, receiving therapeutic immunomodulatory monoclonal antibodies to treat conditions such as multiple sclerosis, and transplant recipients) plays a key role in the viral reactivation leading to PML but also to other more recently described CNS complications. Clinical presentation depends on the localization of the lesions. Diagnosis is based on magnetic resonance imaging, the identification of JC virus in the cerebrospinal fluid, and when necessary on brain pathology. PML natural evolution is lethal. As no specific treatment with clinically relevant efficacy is available, the treatment goal is to restore host immune response to JC virus.

Leucoencéphalopathie multifocale progressive. La leucoencéphalopathie multifocale progressive (LEMP) est une affection démyélinisante du système nerveux central due au polyomavirus JC. Ce virus infecte l'homme de façon asymptomatique au cours de l'enfance et persiste dans l'organisme, au moins dans le tissu rénal. À l'occasion d'un déficit de l'immunité cellulaire principalement (infection par le VIH ou traitements immunosuppresseurs comme certains anticorps monoclonaux utilisés dans la sclérose en plaques, greffe d'organe par exemple), la réactivation du virus est responsable de la LEMP mais aussi d'autres atteintes du système nerveux central plus récemment décrites. Le tableau clinique de ces différentes encéphalopathies varie selon le siège des lésions. Le diagnostic repose sur l'imagerie par résonance magnétique, la présence du génome viral dans le liquide cérébrospinal et quand elle est nécessaire sur l'analyse anatomopathologique du tissu cérébral. Son évolution naturelle est le plus souvent mortelle, et aucun traitement spécifique n'est encore disponible. En revanche, la restauration du système immunitaire peut enrayer la progression des lésions et conduire à des survies prolongées.

Punctate and curvilinear gadolinium enhancing lesions in the brain: a practical approach.

INTRODUCTION: Cerebral punctate and curvilinear gadolinium enhancements (PCGE) correspond to opacification of small vessel lumen or its perivascular areas in case of blood-brain barrier (BBB) disruption. We will discuss the possible causes of intra-parenchymal central nervous system PCGE. METHODS: Our review is based on French database including patients presenting with central nervous system PCGE and literature search using PubMed database with the following keywords: punctate enhancement, linear enhancement, and curvilinear enhancement. Disorders which displayed linear leptomeningeal or periventricular enhancements without intra-parenchymal PCGE are excluded of this review. RESULTS: Among our 39 patients with PCGE, 16 different diagnoses were established. After combining our PCGE causes with those described in the literature, we propose a practical approach. Besides physiologic post-contrast enhancement of small vessels, three pathologic conditions may exhibit PCGE: (1) small collateral artery network seen in Moyamoya syndrome, (2) small veins congestions related to developmental or acquired venous outflow disturbance, and (3) disorders causing small vessels BBB disruption indicated by T2 and FLAIR hyperintensities in the corresponding areas of PCGE. Disruption of the BBB could be caused by a direct injury of the endothelial cell, as in posterior reversible encephalopathy syndrome, Susac syndrome, and radiochemotherapy-induced injuries, or by an angiocentric cellular infiltrate, as in inflammatory disorders, demyelinating diseases, host immune responses fighting against infections, prelymphoma states, lymphoma, and in CLIPPERS. CONCLUSION: PCGE may conceal several causes, including physiological and pathological conditions. Nevertheless, a practical approach could improve its management and limit the indications of brain biopsy to very specific situations.

Does HIV Infection Alter Parkinson Disease?

OBJECTIVE: To describe the clinical features, treatment(s), and outcomes of 15 HIV-infected patients with idiopathic Parkinson disease (PD) and sustained virus suppression and immunologic reconstitution, from a reference cohort of 9847 persons living with HIV (PLH). METHODS: This retrospective, single-center matched case-control 1:2 study included PLH-PD patients evaluated over a 12-year period (2002-2013) with mean follow-up of 6.5 years. PD clinical features and dopamine replacement therapy (DRT) were compared, and biologically relevant HIV data were assessed. RESULTS: PD prevalence in PLH was similar to that of the general population. At onset, clinical presentations and therapeutic management were similar for both groups. Rapidly effective DRT was well tolerated without combined antiretroviral therapy interactions or virus escape. At the end of the follow-up, compared with HIV-negative PD, PLH had a significantly lower median Unified Parkinson's Disease Rating Scale motor score (4 vs 14; P < 0.001), median Hoehn and Yahr stage (1 vs 2; P = 0.0005), and median Handipark scale score (2 vs 3; P = 0.0036) under the same daily DRT. One PLH underwent highly successful deep brain stimulation of the subthalamic nucleus. CONCLUSIONS: HIV-associated PD is similar to idiopathic PD with some features suggesting an HIV-induced functional adaptation of dopaminergic neurons that might counterbalance the PD-induced neuronal loss. Concurrent HIV infection does not compromise the outcome of idiopathic PD.

Isolated III cranial nerve palsies may point to primary histiocytic sarcoma.

Primary histiocytic sarcoma (HS) of the central nervous system (CNS) is a rare haematopoietic neoplasm. The inconsistent terminology and diagnostic criteria currently used for CNS HS have complicated the appreciation of the clinical aspects of the disease. The main differential diagnoses are non-Hodgkin's lymphoma, reactive histiocytic proliferation, dendritic cell neoplasm, undifferentiated carcinoma, inflammatory pseudotumour, Rosai-Dorfman disease and abscess. The true diagnosis of CNS HS requires an extensive immunophenotypic workup using specific histiocytic markers, such as CD163, with the exclusion of markers of other cell lineages. This clinicopathological case report describes an improved approach towards the differential diagnosis of CNS HS.