Leukoencephalopathy with transient splenial lesions related to 5-fluorouracil or capecitabine.

BACKGROUND: 5-Fluorouracil (5-FU) and its oral prodrug capecitabine have been rarely but consistently associated with acute central nervous system toxicity, including transient leukoencephalopathies involving the splenium of the corpus callosum. METHODS: We performed a retrospective search in the French Pharmacovigilance database (FPDB) (January 1985-July 2020) for adult patients affected by solid cancers who developed acute toxic leukoencephalopathies with splenial lesions following treatment with 5-FU or capecitabine. A comprehensive review of the literature helped to circumstantiate our findings. RESULTS: Our research in the FPDB identified six patients who, within 3 days from their first cycle of 5-FU or capecitabine, developed acute neurological symptoms, including gait ataxia (n = 4), dysarthria (n = 3), dysmetria (n = 2), headache (n = 2), and confusion (n = 2). Brain magnetic resonance imaging (MRI) showed T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities in the corpus callosum, with diffusion restriction and no contrast enhancement, generally accompanied by additional alterations in the bilateral supratentorial white matter (n = 5). All patients discontinued the agent supposedly responsible for the toxicity and experienced full recovery after a median of 8.5 days from symptom onset. Control MRI showed a progressive normalization of acute MRI abnormalities. Literature review identified 26 cases with similar clinical and paraclinical characteristics. A single patient from the literature resumed 5-FU at a lower dose, with no recurrent toxicity. CONCLUSIONS: 5-FU and capecitabine might be responsible for acute leukoencephalopathies with transient splenial lesions that are generally reversible upon drug discontinuation. Resuming the agent responsible for toxicity might be feasible in selected cases, after having excluded dihydropyrimidine dehydrogenase deficiency, if expected benefits outweigh the risks.

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma.

INTRODUCTION: Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) have been used to assess cognition in these patients. Here we assessed the sensitivity of the MoCA in screening for cognitive impairment in a cohort of 156 patients with newly-diagnosed high-grade glioma, after surgery and before radiochemotherapy. METHODS: We assessed cognitive performance with the MoCA and a neuropsychological battery. Cognitive scores were analyzed in terms of a previously validated framework designed to control false positives and data for 1003 control participants from the GRECOGVASC study. After comparison of performance on the tests, we used stepwise logistic regression to produce a cognitive summary score from the neuropsychological battery. Then we analyzed sensitivity and specificity of the MoCA with receiver operator characteristic (ROC) curve analysis. RESULTS: Both raw and adjusted MoCA scores showed only moderate sensitivity. The area under the ROC curve was 0.759 (95% CI 0.703-0.815) for the raw score and 0.788 (95% CI 0.734-0.842) for the adjusted score. Optimal discrimination was obtained with a raw score ≤ 25 (sensitivity: 0.526; specificity: 0.832; positive predictive value: 0.2; negative predictive value: 0.96) and an adjusted score - 0.603 (sensitivity: 0.716; specificity: 0.768; positive predictive value: 0.24; negative predictive value: 0.96). CONCLUSION: The moderate sensitivity of MoCA indicates that it is not a suitable screening tool for detecting cognitive impairment in patients with newly-diagnosed high-grade glioma.

Prevalence of Poststroke Neurocognitive Disorders Using National Institute of Neurological Disorders and Stroke-Canadian Stroke Network, VASCOG Criteria (Vascular Behavioral and Cognitive Disorders), and Optimized Criteria of Cognitive Deficit.

BACKGROUND AND PURPOSE: The prevalence of poststroke neurocognitive disorder (NCD) has yet to be accurately determined. The primary objective of the present study was to optimize operationalization of the criterion for NCD by using an external validity criterion. METHODS: The GRECOG-VASC cohort (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) of 404 stroke patients with cerebral infarct (91.3%) or hemorrhage (18.7%) was assessed 6 months poststroke and 1003 healthy controls, with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network standardized battery. Three dimensions of the criterion for cognitive impairment were systematically examined by using the false-positive rate as an external validity criterion. Diagnosis of mild and major NCD was based on the VASCOG criteria (Vascular Behavioral and Cognitive Disorders). The mechanisms of functional decline were systematically assessed. RESULTS: The optimal criterion for cognitive impairment was the shortened summary score (ie, averaged performance for action speed, executive functions, and language) because it was associated with the highest (P=0.0001) corrected true-positive rate (43.5%) and a false-positive rate ≤5%. Using this criterion, the mean (95% confidence interval) prevalence of poststroke NCD was 49.5% (44.6-54.4), most of which corresponded to mild NCD (39.1%; 95% confidence interval, 34.4-43.9) rather than dementia (10.4%; 95% confidence interval, 7.4-13.4). CONCLUSIONS: This study is the first to have optimized the operationalization of the criterion for poststroke cognitive impairment. It documented the prevalence of poststroke NCD in the GRECOG-VASC cohort and showed that mild cognitive impairment accounts for 80% of the affected patients. Finally, the method developed in the present study offers a means of harmonizing the diagnosis of NCD. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01339195.

New insights in radiation-induced leukoencephalopathy: a prospective cross-sectional study.

BACKGROUND: Radiation-induced leukoencephalopathy (RIL) is the most threatening delayed complication of cerebral radiotherapy (RT) and remains roughly defined by cognitive dysfunction associated with diffuse FLAIR MRI white matter hyperintensities after brain irradiation. We documented clinical, neuropsychological, and radiological aspects of RI in order to refine diagnostic criteria. METHODS: Patients referred to our center for deterioration in cognitive complaint at least 6 months after completing a focal or whole brain RT underwent a systematic cross-sectional assessment including clinical examination, neuropsychological tests, and a standardized MRI protocol. Patients with progressive tumor were excluded. RESULTS: Forty patients were prospectively enrolled. Of these, 26 had received a focal RT, median dose of 53 Gy (range 50 to 60), and 14 had received a whole brain RT, median dose of 30 Gy. Cognitive complaints, gait apraxia, and urinary troubles were reported in 100, 67, and 38% of cases, respectively. On neuropsychological examination, patients displayed a global and severe cognitive decline through a subcortical frontal mode. The cognitive changes observed were not hippocampic, but related to executive dysfunction. On MRI, 68% of the patients had extensive FLAIR hyperintensities with anterior predominance, 87% had brain atrophy, and 21% had intraparenchymal cysts. T2*-weighted MRI showed small asignal areas in 53% of the patients. These abnormalities are evocative of cerebral small vessel disease. Fractional anisotropy in the corpus callosum correlated with the cognitive evaluation. No differentiation in terms of cognitive and MRI features could be made between patients treated with focal brain RT (glioma) and patients treated with WBRT (for brain metastases or PCNSL). CONCLUSIONS: RIL can be defined by clinical symptoms (subcortical frontal decline, gait apraxia, urinary incontinence) and MRI criteria (cortico-subcortical atrophy, spread FLAIR HI, T2* asignals). This condition mimics a diffuse progressive cerebral small vessel disease triggered by RT, independent of RT protocol.

Ebola Virus-Related Encephalitis.

Ebola patients frequently exhibit behavioral modifications with ideation slowing and aggressiveness, sometimes contrasting with mild severity of Ebola disease. We performed lumbar punctures in 3 patients with this presentation and found Ebola virus in all cerebrospinal fluid samples. This discovery helps to discuss the concept of a specific Ebola virus encephalitis.

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

Late-onset vascular complications of radiotherapy for primary brain tumors: a case-control and cross-sectional analysis.

PURPOSE: Radiotherapy (RT) is a recognized risk factor for cerebrovascular (CV) disease in children and in adults with head and neck cancer. We aimed to investigate whether cerebral RT increases the risk of CV disease in adults with primary brain tumors (PBT). METHODS: We retrospectively identified adults with a supratentorial PBT diagnosed between 1975 and 2006 and with at least 10 years follow-up after treatment. We analyzed demographic, clinical, and radiological features with special attention to CV events. We also described CV events, vascular risk factors, and intracranial artery modifications in a cross-sectional study of irradiated patients alive at the time of the study. RESULTS: A total of 116 patients, treated with RT (exposed group), and 85 non-irradiated patients (unexposed group) were enrolled. Stroke was more frequent in irradiated PBT patients than in the unexposed group (42/116 (36%) vs 7/85 (8%); p < 0.001), with higher prevalence of both ischemic (27/116 (23%) vs 6/85 (7%); p = 0.004) and hemorrhagic (12/116 (10%) vs 1/85 (1%); p = 0.02) stroke. In the irradiated group, patients with tumors near the Willis Polygon were more likely to experience stroke (p < 0.016). Fourty-four alive irradiated patients were included in the cross-sectional study. In this subgroup, intracranial arterial stenosis was more prevalent (11/45, 24%) compared to general population (9%). CONCLUSIONS: Stroke prevalence is increased in long-surviving PBT patients treated with cranial RT. IMPLICATIONS FOR CANCER SURVIVORS: CV events are frequent in long survivors of PBT treated with cerebral RT. We propose a check list to guide management of late CV complications in adults treated with RT for PBT.

Innovative multidimensional gait evaluation using IMU in multiple sclerosis: introducing the semiogram.

Background: Quantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group. Methods: Twenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram. Results: For both cohorts, all criteria showed moderate to very high test-retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria. Conclusions: The proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS.

Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort.

INTRODUCTION: Natalizumab, a therapy for relapsing-remitting multiple sclerosis (RRMS), is associated with a risk of progressive multifocal leukoencephalopathy (PML). Over the last several years, practitioners have used off-label extended interval dosing (EID) of natalizumab to reduce PML risk, despite the absence of a large-scale efficacy evaluation. METHODS: We conducted a retrospective, multicenter cohort study among adults with RRMS receiving stable standard interval dosing (SID), defined as a ≥ 12-month consecutive period of ≥ 11 natalizumab infusions/year in France. We compared the 12-month risk difference of remaining relapse-free (primary endpoint) between patients who switched to EID (≤ 9 natalizumab infusions) and those who remained on SID, with a noninferiority margin of - 11%. We used propensity score methods such as inverse probability treatment weighting (IPTW) and 1:1 propensity score matching (PSM). Secondary endpoints were annualized relapse rate, disease progression, and safety. RESULTS: Baseline characteristics were similar between patients receiving EID (n = 147) and SID (n = 156). The proportion of relapse-free patients 12 months postbaseline was 142/147 in the EID (96.6%) and 144/156 in the SID group (92.3%); risk difference (95% CI) 4.3% (- 1.3 to 9.8%); p < 0.001 for non-inferiority. There were no significant differences between relapse rates (0.043 vs. 0.083 per year, respectively; p = 0.14) or Expanded Disability Status Scale mean scores (2.43 vs. 2.72, respectively; p = 0.18); anti-JC virus index values were similar (p = 0.23); and no instances of PML were reported. The comparisons using IPTW (n = 306) and PSM (n = 204) were consistent. CONCLUSION: These results support the pertinence of using an EID strategy for RRMS patients treated with natalizumab. CLINICAL TRIALS: gov identifier (NCT04580381).

Severe meningo-radiculo-neuritis associated with ipilimumab.

PURPOSE: Ipilimumab is a T-cell-potentiating monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) to promote antitumoural immunity. In phase III trials, ipilimumab was shown to be the first agent to improve survival in advanced melanoma patients, regardless of previous treatment. We report a case of severe neurologic disease after ipilimumab treatment. PATIENT AND METHODS: Neurologic symptoms including facial diplegia, tetraplegia, areflexia progressed with time a few days after the fourth monthly ipilimumab infusion. Analysis of the cerebro-spinal fluid showed elevated proteinorachy and lymphocytic meningitis. Despite high doses of steroids and symptomatic treatment, the symptoms worsened. RESULTS: Veinoglobulins were then infused and the patient began to improve and recovered almost normal activity two years later. CONCLUSION: The adverse event profile associated with ipilimumab was primarily immune-related. This is the first case in which such a severe event has been reported.

Prevalence of sleep disorders in a large French cohort of aircrew members and risk of in-flight sleepiness.

BACKGROUND: /objectives: Sleep disorders are a critical issue for flight safety. Previous studies have shown a high prevalence of sleep disorders and excessive sleepiness in the general population and some aircrews. The objectives of this study are to measure the prevalence of excessive daytime sleepiness and sleep disorders in aircrews, and to determine the risk factors of falling asleep during a flight. METHODS: this is a monocentric study based on questionnaires, including all professional civilian and military aircrews examined in an aeromedical center between January and May 2021. The questionnaire, created for this study, included information about socio-demographic characteristics, aeronautical experience, lifestyle, sleep habits, an Epworth sleepiness scale, and screening tests for chronic insomnia, sleep apnea syndrome and restless legs syndrome. RESULTS: 749 aircrew members were included (86.2% male, 58.9% civilian, 74.1% pilot, mean age 43.4 ± 9.6 years), 45.9% of the population had at least one sleep disorder (chronic insomnia 39.5%, sleep apnea syndrome 10.5%, restless legs syndrome 4.1%), 15.5% had an excessive daytime sleepiness, and 24.6% reported in-flight sleep while on duty. Chronic insomnia, screen use before bedtime, use of sleeping pills, inadequate recovery time after a flight, female gender and civilian status were found as risk factors of in-flight sleep in the multivariate analysis. CONCLUSION: this study emphasizes the need to improve the screening and prevention of sleep disorders in this particular population.

Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors.

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18-69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

Longitudinally Extensive Myelitis Associated With Immune Checkpoint Inhibitors.

OBJECTIVE: To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs). METHODS: We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011-2020). A systematic review of the literature was performed to identify similar cases. RESULTS: We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients. CONCLUSION: Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.

Episodic Memory Impairments in Primary Brain Tumor Patients.

OBJECTIVE: Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. METHOD: We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. RESULTS: Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. CONCLUSION: Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors.

Balance Impairment in Radiation Induced Leukoencephalopathy Patients Is Coupled With Altered Visual Attention in Natural Tasks.

Background: Recent studies have shown that alterations in executive function and attention lead to balance control disturbances. One way of exploring the allocation of attention is to record eye movements. Most experimental data come from a free viewing of static scenes but additional information can be leveraged by recording eye movements during natural tasks. Here, we aimed to provide evidence of a correlation between impaired visual alteration in natural tasks and postural control in patients suffering from Radiation-Induced Leukoencephalopathy (RIL). Methods: The study subjects were nine healthy controls and 10 patients who were diagnosed with RIL at an early stage, with isolated dysexecutive syndrome without clinically detectable gait or posture impairment. We performed a balance evaluation and eye movement recording during an ecological task (reading a recipe while cooking). We calculated a postural score and oculomotor parameters already proposed in the literature. We performed a variable selection using an out-of-bag random permutation and a random forest regression algorithm to find: (i) if visual parameters can predict postural deficit and, (ii) which are the most important of them in this prediction. Results were validated using the leave-one-out cross-validation procedure. Results: Postural scores indeed were found significantly lower in patients with RIL than in healthy controls. Visual parameters were found able to predict the postural score of RIL patients with normalized root mean square error (RMSE) of 0.16. The present analysis showed that horizontal and vertical eye movements, as well as the average duration of the saccades and fixations influenced significantly the prediction of the postural score in RIL patients. While two patients with very low MATTIS-Attention sub score showed the lowest postural scores, no statistically significant relationship was found between the two outcomes. Conclusion: These results highlight the significant relationship between the severity of balance deficits and the visual characteristics in RIL patients. It seems that increased balance impairment is coupled with a reduced focusing capacity in ecological tasks. Balance and eye movement recordings during a natural task could be a useful aspect of multidimensional scoring of the dysexecutive syndrome.

Who should undergo a comprehensive cognitive assessment after a stroke? A cognitive risk score.

OBJECTIVE: To validate the ability of a specifically developed cognitive risk score to identify patients at risk of poststroke neurocognitive disorders (NCDs) who are eligible for a comprehensive cognitive assessment. METHODS: After assessing 404 patients (infarct 91.3%) in the Groupe de Réflexion pour l'Evaluation Cognitive VASCulaire (GRECogVASC) cross-sectional study with the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network battery 6 months after stroke, we used multivariable logistic regression and bootstrap analyses to determine factors associated with NCDs. Independent, internally validated factors were included in a cognitive risk score. RESULTS: Cognitive impairment was present in 170 of the 320 patients with a Rankin Scale score ≥1. The backward logistic regression selected 4 factors (≥73% of the permutations): NIH Stroke Scale score on admission ≥7 (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.29-4.3, p = 0.005), multiple strokes (OR 3.78, 95% CI 1.6-8, p = 0.002), adjusted Mini-Mental State Examination (MMSEadj) score ≤27 (OR 6.69, 95% CI 3.9-11.6, p = 0.0001), and Fazekas score ≥2 (OR 2.34, 95% CI 1.3-4.2, p = 0.004). The cognitive risk score computed with these 4 factors provided good calibration, discrimination (overoptimism-corrected C = 0.793), and goodness of fit (Hosmer-Lemeshow test p = 0.99). A combination of Rankin Scale score ≥1, cognitive risk score ≥1, and MMSEadj score ≥21 selected 230 (56.9%) of the 404 patients for a comprehensive assessment. This procedure yielded good sensitivity (96.5%) and moderate specificity (43%; positive predictive value 0.66, negative predictive value 0.91) and was more accurate (p ≤ 0.03 for all) than the sole use of screening tests (MMSE or Montréal Cognitive Assessment). CONCLUSION: The GRECogVASC cognitive risk score comprises 4 easily documented factors; this procedure helps to identify patients at risk of poststroke NCDs who must therefore undergo a comprehensive assessment. CLINICALTRIALSGOV IDENTIFIER: NCT01339195.

Chemotherapy-related cognitive impairment or « chemobrain ¼: concept and state of art.

Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as « chemobrain ¼. However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.

Refsum Disease Presenting with a Late-Onset Leukodystrophy.

Adult Refsum disease is an autosomal recessive peroxisomal disorder characterized by phytanic acid storage. Clinical symptoms usually begin in late childhood before the age of 20. Typical clinical presentation includes nyctalopia caused by retinitis pigmentosa, and anosmia. After 10-15 years, deafness, cerebellar ataxia, polyneuropathy, ichthyosis, and cardiac arrhythmia can occur.We report the case of a very late-onset adult Refsum disease presenting with marked cognitive decline and severe leukoencephalopathy, without peripheral nervous system involvement. Brain MRI showed a leukoencephalopathy involving the periventricular white matter, subcortical area, and the brainstem with relative sparing of juxtacortical U fibers. This was associated with severe cortical and subcortical atrophy with ventricle dilatation. MR spectroscopy showed a marked increase in the choline/NAA ratio. Elevated plasma phytanic acid level was found, whereas plasma levels of pristanic and very long chain fatty acids were normal. The patient is homozygous for a previously undescribed PHYH frameshift mutation. Whether the very unusual phenotype is related to this peculiar mutation remains unclear.

[Central nervous system complications in patients undergoing cytotoxic chemotherapy and targeted therapies]. / Complications neurologiques centrales des chimiothérapies cytotoxiques et des thérapies ciblées.

Anti-cancer treatments (cytotoxic chemotherapies, targeted therapies and hormonotherapies) are known to induce early and delayed neurological toxicities. Acute encephalopathies and posterior reversible encephalopathies are better known and described, physiopathological hypotheses are emerging. It is difficult to discriminate what drug is causing the symptoms in patients treated with multiple cytotoxic drugs. Methotrexate and ifosfamide are responsible for acute encephalopathies. L-asparaginase and methotrexate or targeted therapies may induce cerebrovascular complications. As life expectancy increases and more complex regimen including innovative targeted therapies are developed, new toxicity profiles can be expected. To be able to provide an early diagnosis, prevention, and treatment (when existing) of these pathologies remains a tremendous challenge that would allow a good quality of life with social and professional life after their cancer is cured.