Major Disability Research Articles

Pan-neurofascin autoimmune nodoparanodopathy: A case report and literature review.

Locked-in syndrome (and its variant, completely locked-in state) generally has a high mortality rate in the acute setting; however, when induced by conditions such as acute inflammatory polyradiculoneuropathy, it may well be curable such that an attempt at cure should be systematically sought by clinicians. A 52-year-old man presented with acute tetraparesia and areflexia, initially diagnosed as Guillain-Barré syndrome. Despite appropriate treatment, his condition deteriorated, evolving into a completely locked-in state. The detection of anti-pan-neurofascin antibodies led to the correct diagnosis, acute pan-neurofascin autoimmune nodoparanodopathy. Immunosuppressive treatment (rituximab) and plasma exchanges were performed. After several months, the patient's neurological symptoms almost completely subsided, without any major sequelae. In patients with locked-in syndrome (or its variant), neurologists and intensive care physicians must be aware of, and look for, the main etiologies (including pan-neurofascin autoimmune nodoparanodopathy), to allow the prompt initiation of treatment and thus a rapid recovery for these ultimately curable conditions. Despite causing major disability, pan-neurofascin autoimmune nodoparanodopathy is curable if the appropriate treatment is given.

Wealth is health: High economic status in Cameroon correlates with protective gear use in traffic injuries and improved clinical outcomes.

Africa is the least motorized populated continent, yet it experiences the highest traffic fatality rate. Despite laws mandating helmet and seatbelt use, data on protective gear use among Cameroonian road traffic injury (RTI) patients remains sparse. We extracted Cameroon Trauma Registry data prospectively collected from 10 hospitals during July 2022 to December 2023. Protective gear users wore helmets in motorcycle and seatbelts/car seats in vehicle crashes. We categorized patients into five economic clusters based on ownership of durable goods using parallel distance matrix computation. We analyzed associations between continuous variables with Wilcoxon rank-sum and categorical variables with χ2 and multivariate logistic regression. Our primary outcome was in-hospital death or major disability at discharge. Among 3,554 RTI patients, 303 (9%) used protective gear. A larger proportion of patients who did not use protective gear were designated as majorly disabled or dead (20% vs. 16%, p < 0.001). The greatest percentage of protective gear users belonged to the richest cluster, while the poorest cluster patients comprised the smallest proportion of protective gear users (13% vs. 3%, p < 0.001). The richest cluster demonstrated the smallest percentage of major disability or death (13%), while the poorest cluster had the greatest percentage (28%, p < 0.001). When controlling for age, protective gear use, and injury severity, the three poorest clusters showed the greatest odds of major disability or death (cluster 3: adjusted odds ratio [AOR], 2.34; 95% confidence interval [CI], 1.58-3.46; cluster 4: AOR, 2.09; 95% CI, 1.59-2.74; cluster 5: AOR, 2.38; 95% CI, 1.24-4.58). Greater economic status is associated with increased protective gear use during RTIs in Cameroon. Despite suffering the most severe outcomes, the poorest patients remain less likely to use protective gear. Enforcement of protective gear laws and economic incentives such as price subsidies for helmets and seatbelts would particularly benefit the most vulnerable population. Retrospective Comparative Study; Level IV.

Schmid metaphyseal chondrodysplasia: consideration in differential diagnosis of rickets

Schmid metaphyseal chondrodysplasia is a rare inherited cause of skeletal dysplasia caused by COL10A1 gene mutation, characterized by skeletal abnormalities and progressive short stature not usually associated with any other major anomalies or cognitive disability. We report a case of a 3-year-old girl with short stature, genu varum, and motor developmental delay, who was initially misdiagnosed and treated as rickets. Blood investigations and radiographic findings were crucial to guide the diagnosis. Genetic testing allows definitive molecular diagnosis leading to proper treatment and counselling.

Effects of statins on kidney function in older adults.

The effect of statin therapy on kidney function among older adults is unclear. To examine the association between statin use and changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), positive or negative, in an older adult cohort with versus without chronic kidney disease (CKD) at baseline. This analysis included 18,056 participants aged ≥65 years with versus without CKD at baseline in a randomized trial of low-dose aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially. Outcome measures included eGFR and UACR. Linear mixed-effects models were used to estimate the associations of baseline statin use versus no use with eGFR and UACR changes over time. The inverse-probability of treatment-weighting technique was used for all analyses to address confounding by indication due to the lack of randomization in treatment assignment. Statin use was not associated with change in eGFR, UACR, or incident CKD in participants with or without CKD at baseline (p > 0.05 for all associations). Subgroup analyses found no significant interactions between statin and age, sex, diabetes, country, and frailty status on any of the study outcomes. Among adults ≥65 years of age, with and without CKD, statin therapy was not associated with improved or worsened kidney function. This data suggests that the decision to use versus not use statins in this population may be ideally guided by factors other than kidney health.

Acupuncture for hypoxic ischemic encephalopathy in neonates.

Peripartum asphyxia affects three to five per 1000 live births, with moderate or severe hypoxic ischemic encephalopathy (HIE) occurring in 0.5 to 1 per 1000 live births, and is associated with high mortality and morbidity. Therapeutic hypothermia is an effective treatment, but alternative therapies such as acupuncture are also used. To determine the benefits and harms of acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure) on mortality and morbidity in neonates with HIE, compared with 1) no treatment, 2) placebo or sham treatment, 3) any pharmacologic treatment, or 4) different types of acupuncture. We searched CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the WHO ICTRP in March 2023. We conducted a search of the grey literature to identify reports of trials conducted by or referenced in research by CORDIS EU, National Institute for Health and Care Excellence (NICE), and NHSGGC Paediatrics for Health Professionals. We also checked the reference lists of relevant articles to identify additional studies. We included randomized controlled trials (RCTs) or quasi-RCTs and cluster-randomized trials. We included studies where participants were term infants (37 weeks or greater) and late preterm infants (34 + 0 to 36 + 6 weeks' gestation) 10 days of age or less, with evidence of peripartum asphyxia. We included studies on acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure). We included studies where acupuncture was compared with: 1) no treatment; 2) placebo or sham treatment; 3) any pharmacologic treatment; or 4) different types of acupuncture. We used standard Cochrane methods. Our primary outcomes were all-cause mortality at the latest follow-up, major neurodevelopmental disability in children aged 18 to 24 months and aged 3 to 5 years, adverse events until hospital discharge, and length of hospital stay. We included four studies (enrolling 464 infants) that compared acupuncture with no treatment. The studies ranged in size from 60 to 200 infants. Three studies were conducted in China and one in Russia. None of the four studies reported on any of the prespecified outcomes of our review. We did not identify any ongoing studies. There is limited availability of studies addressing this specific population. The included studies did not assess mortality, long-term neurodevelopmental outcomes, or adverse effects of acupuncture. We are unable to draw any conclusions about the benefits and harms of acupuncture for HIE in neonates. In light of the current limitations, clinicians are urged to approach the use of acupuncture in neonates with HIE cautiously, as there is no evidence to support its routine application. The available trials assessed surrogate outcomes that have a relatively small impact on newborns, and failed to report important outcomes such as mortality and long-term neurodevelopmental outcomes. Other available trials were performed on older infants who had experienced neonatal HIE. Given the lack of available evidence, well-designed randomized controlled trials with relevant outcomes such as mortality and neurodevelopmental outcomes are essential to evaluate the efficacy and safety of acupuncture for HIE in neonates.

Patterns and Clinical Implications of Hemorrhagic Transformation After Thrombolysis in Acute Ischemic Stroke: Results From the ENCHANTED Study.

Hemorrhagic transformation may be a potentially devastating complication of IV thrombolysis (IVT) in acute ischemic stroke, but what degree of hemorrhage indicates the greatest negative effect is not known. We aimed to define the associations between hemorrhagic transformation patterns, classified according to clinical and imaging categories, and clinical outcomes after IVT. We conducted a post hoc analysis from the international Enhanced Control of Hypertension and Thrombolysis Stroke Study. Symptomatic intracerebral hemorrhage (sICH) was defined based on established criteria, such as the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) criteria. Asymptomatic intracerebral hemorrhage (aICH) was defined as any intracerebral hemorrhage that did not meet the criteria for sICH. Imaging subtypes of hemorrhagic transformation were assessed using the Heidelberg Bleeding Classification system. The primary outcome was death or major disability, defined by modified Rankin scale (mRS) scores 3-6 at 90 days. Secondary outcomes included death, death or disability (mRS 2-6), and poor health-related quality of life (HRQoL), defined as an overall heath utility score ≤0.7 (mean). Of the 4,370 participants, 779 (17.8%) developed any intracranial hemorrhage (ICH), with a median time from randomization to hemorrhage of 23.5 hours (interquartile range 18.92-26.07). According to the SITS-MOST criteria, 62 patients (1.4% of 4,370) were classified as sICH, and 717 patients (16.4% of 4,370) were classified as aICH. sICH per SITS-MOST criteria was associated with death or major disability (odds ratio [OR] 23.05, 95% CI 8.97-59.23), death (OR 20.14, 95% CI 11.32-35.84), death or disability (OR 61.36, 95% CI 8.40-448.01), and poor HRQoL (OR 17.87, 95% CI 7.47-42.71). Similarly, aICH per SITS-MOST criteria was also associated with death or major disability (OR 2.23, 95% CI 1.84-2.70), death (OR 1.82, 95% CI 1.39-2.38), death or disability (OR 2.29, 95% CI 1.87-2.80), and poor HRQoL (OR 1.81, 95% CI 1.50-2.18). Comparable associations were observed for sICH and aICH defined by other criteria, as well as for imaging subtypes based on Heidelberg Bleeding Classification system. All forms of post-IVT hemorrhagic transformation in acute ischemic stroke are associated with increased odds of poor clinical outcomes. Of note, aICH after IVT should not be considered clinically innocuous. ClinicalTrials.gov (NCT01422616).

Influence of renal function on blood pressure control and outcome in thrombolyzed patients after acute ischemic stroke: post-hoc analysis of the ENCHANTED trial.

The effect of renal impairment in patients who receive intravenous thrombolysis for acute ischemic stroke (AIS) is unclear. We aimed to determine the associations of renal impairment and clinical outcomes and any modification of the effect of intensive versus guideline-recommended blood pressure (BP) control in the BP arm of the International Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). We conducted a post-hoc analysis of the ENCHANTED BP arm, which involved 2,196 thrombolyzed AIS patients. Logistic regression models were used to define the association between eGFR and clinical outcomes of death, death or major disability [modified Rankin scale (mRS) scores 3-6], and major disability (mRS 3-5) at 90 days. Of the 2,151 patients with available baseline renal function data (mean age 66.9 years; 38% women), 993 (46.2%), 822 (38.2%), and 336 (15.6%) had normal (eGFR ≥ 90 mL/min/1.73 m2), mildly (60-89), and moderate-to-severely impaired (<60) renal function, respectively. Compared with patients with normal eGFR, mortality was higher in those with moderate-to-severe renal impairment (adjusted odds ratio 1.77, 95% confidence interval 1.05-2.99; p = 0.031 for trend). However, the difference in death or major disability (mRS 3-6) was not significant between groups. There was no heterogeneity in the effect of intensive versus guideline-recommended BP-lowering treatment on death by grades of renal function (p for interaction = 0.545). The presence of moderate-to-severe renal impairment is associated with increased mortality in thrombolyzed patients with AIS. Renal function does not modify the effect of early intensive BP-lowering treatment on death in this patient group.

Gut Microbiota, Bacterial Translocation, and Stroke: Current Knowledge and Future Directions.

Stroke is one of the most devastating pathologies in terms of mortality, cause of dementia, major adult disability, and socioeconomic burden worldwide. Despite its severity, treatment options remain limited, with no pharmacological therapies available for hemorrhagic stroke (HS) and only fibrinolytic therapy or mechanical thrombectomy for ischemic stroke (IS). In the pathophysiology of stroke, after the acute phase, many patients develop systemic immunosuppression, which, combined with neurological dysfunction and hospital management, leads to the onset of stroke-associated infections (SAIs). These infections worsen prognosis and increase mortality. Recent evidence, particularly from experimental studies, has highlighted alterations in the microbiota-gut-brain axis (MGBA) following stroke, which ultimately disrupts the gut flora and increases intestinal permeability. These changes can result in bacterial translocation (BT) from the gut to sterile organs, further contributing to the development of SAIs. Given the novelty and significance of these processes, especially the role of BT in the development of SAIs, this review summarizes the latest advances in understanding these phenomena and discusses potential therapeutic strategies to mitigate them, ultimately reducing post-stroke complications and improving treatment outcomes.

Targeting Remyelination in Spinal Cord Injury: Insights and Emerging Therapeutic Strategies.

Spinal cord injury (SCI) is a severe neurological disease characterized by significant motor, sensory, and autonomic dysfunctions. SCI is a major global disability cause, often resulting in long-term neurological impairments due to the impeded regeneration and remyelination of axons. A SCI interferes with communication between the brain and the spinal cord networks that control neurological functions. Recent advancements in understanding the molecular and cellular mechanisms of remyelination have opened novel therapeutic interventions. This review systematically sourced articles related to spinal chord injury, remyelination, regeneration and pathophysiology from major medical databases, including Scopus, PubMed, and Web of Science. This review discusses the efficacy of targeted therapy in enhancing myelin repair after SCI by identifying key molecules and signaling pathways. This explores the effectiveness of specific pharmacological agents and biological factors in promoting oligodendrocyte precursor cell proliferation, differentiation, and myelin sheath formation using invitro and invivo models. Targeted therapies have shown promising results in improving remyelination, providing hope for functional recovery in SCI patients. This review demonstrates challenges and future perspectives in translating findings into clinical practice, emphasizing safety profiles, delivery method optimization, and combinatory therapy potential. This review also supports the possibility of targeted remyelination therapies as a promising strategy for SCI treatment, paving the way for future clinical applications.

Degloving soft tissue injuries of upper limbs and their management in Khartoum - Sudan: a cross-sectional study.

Degloving soft-tissue injuries are underreported in Sudan and are potentially devastating. They require early recognition and diagnosis with early and systemic management to reduce the complications that may arise, and to minimize delay for proper intervention by a multidisciplinary team that is usually needed to ensure the effective rehabilitation of these patients and a better outcome. To assess the degloving soft tissue injuries of the upper limb and their management in Khartoum. A cross-sectional hospital-based study is multicentric (Khartoum North Teaching Hospital, Association Specialized Hospital, East Nile Hospital) in Khartoum - Sudan. A study was conducted on 82 patients with degloving soft tissue injuries of the upper limbs during the period from 2021 to 2022. Patients with different age groups were included whereas patients with close degloving injuries and degloving injuries of fingers were excluded. Eighty-two patients were studied. The male-to-female ratio was 4.8:1, with a mean age of 31.5. The common (59.8%) injury site was the dominant upper limb, with 58.5% distal UL injuries. The main etiology of injury was road traffic accidents (52.4%), followed by occupational injuries (20.7%). 51.2% of the injury was a noncircumferential single-plane degloving soft tissue injury. Degloving soft tissue injuries of the upper limbs are associated with deep structure injuries in 61% of patients (bone fracture in 43.9%). Serial debridement before reconstruction as a staged procedure was done in 61% of patients. The most common reconstruction method performed was skin grafts (57.3%), followed by flaps (32.9%). Half (52.4%) of the patients developed complications postoperatively, and the most frequent complication was wound infection (23.1%). Upper limb degloving soft tissue injuries are complex life-threatening injuries that, if present late or poorly managed, lead to devastating complications ranging from local infection to major disabilities, amputation, and death.

Plasma neuropeptide Y levels and adverse clinical outcomes after acute ischaemic stroke.

Neuropeptide Y (NPY) has been reported to be involved in the pathophysiology of several cardiovascular disease processes and might contribute to the incidence of stroke, but the prognostic utility of circulating NPY after acute ischaemic stroke is unclear. This study aimed to prospectively examine the association between plasma NPY levels and adverse clinical outcomes after acute ischaemic stroke. Plasma NPY levels were measured in 3250 patients (2066 men and 1184 women) from the China Antihypertensive Trial in Acute Ischaemic Stroke. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 12 months after stroke onset, and secondary outcomes included major disability, death and cardiovascular events. During the 12-month follow-up, 702 participants (21.6%) experienced major disability or died. After multivariable adjustment, odds ratio (95% confidence interval) for the highest quartile of NPY was 1.56 (1.19-2.04) for the primary outcome, compared to the lowest quartile. Each standard deviation (0.27 ng/mL) higher log-transformed NPY was associated with an odds ratio (95% confidence interval) of 1.18 (1.07-1.30) for the primary outcome, 1.28 (1.15-1.42) for major disability. The addition of NPY to a conventional risk factors model improved risk prediction of the composite outcome of death and major disability (category-free net reclassification index 8.82%, p = 0.040; integrated discrimination improvement 0.38%, p = 0.011). Elevated plasma NPY levels in the acute phase of ischaemic stroke were associated with increased risk of poor clinical outcomes after ischaemic stroke, suggesting that plasma NPY may be a potential prognostic biomarker for ischaemic stroke.

Associations Between Gene Variants of Lipid-Lowering Drug Targets and Adverse Outcomes After Ischemic Stroke.

The association of lipid-lowering drug targets and their gene variants with cardiovascular diseases has been previously clarified. However, the relationship between gene variants of lipid-lowering drug targets and the adverse prognosis of ischemic stroke patients remains unclear. Multiple single-nucleotide polymorphisms associated with 6 lipid-lowering drug targets were genotyped for patients with ischemic stroke. The primary outcome was death or major disability within 2 years after ischemic stroke. Genetic risk scorewas constructed from significant single-nucleotide polymorphismsidentified via additive models, which was calculated by multiplying the number of risk alleles at each locus by the corresponding beta coefficient and then summing the products. The rs2006760-C of the HMGCR, rs11206510-T of PCSK9, and rs1864163-G and rs9929488-G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Each additional risk allele was associated with higher odds of adverse outcomes. Genetic risk scorewas positively associated with the odds of primary outcome (odds ratio [OR], 1.48 [95% CI, 1.15-1.90]; Ptrend = 0.001), major disability (OR, 1.56[95% CI, 1.16-2.08]; Ptrend = 0.002), death (hazard ratio [HR], 1.58[95% CI, 1.12-2.25]; Ptrend = 0.011), and the composite outcome of death or cardiovascular events (HR, 1.41[95% CI, 1.08-1.85]; Ptrend = 0.010) when 2 extreme quartiles were compared. rs2006760-C of HMGCR, rs11206510-T of PCSK9, and rs1864163-G and rs9929488-G of CETP were associated with increased odds of adverse outcomes within 2 years after ischemic stroke. Furthermore, higher GRS was positively related to the odds of poor outcomes in patients with ischemic stroke. Registration: URL: https://www.clinicaltrials.gov; Identifier: NCT01840072.

Bone features reinforce differential diagnosis between tuberculous spondylitis and brucellosis spondylitis

BackgroundTuberculous spondylitis (TS) and brucellar spondylitis (BS) both cause major long-term morbidity and disability. Though Spondylodiscitis is sensitive to magnetic resonance images, some are difficult to differentiate. This study aims to identify specific bone changes on computed tomography (CT) images, further to differentiate TS from BS.MethodsWe retrospectively analyzed and enrolled 70 patients with TS and 65 with BS at our hospital from December 2012 to January 2024. Information of bone destruction and formation, vertebral wall integrity, osteosclerosis, and sequestrum on CT images was collected and compared using the chi-square test or t-test. P < 0.01 was considered statistically significant.ResultsBone destruction was greater in the TS group compared to the BS group (519.55 mm2 vs. 316.00 mm2, t = 6.01, P < 0.001), preferentially involving each third of the vertebral body horizontally (41.22% vs. 16.67%, χ2 = 77.76, P < 0.001; positive predictive value [PPV] = 80.6%) and the area under the endplate and equatorial portion of the vertebra longitudinally (80.53% vs. 28.20%, χ2 = 134.19, P < 0.001, PPV = 82.75%). Patients with BS more frequently exhibited fan-shaped osteosclerosis (12.82% vs. 1.15%, χ2 = 71.30, P < 0.001; PPV = 86.96%), longer bone formation surrounding the vertebra (18.06 mm vs. 1.97 mm, t = 14.28, P < 0.001), and longer anterior bone formation (3.86 mm vs. 0.92 mm, t = 6.51, P < 0.001). Anterior and closed bone formation was more common in the BS group than in the TS group (44.87% vs. 7.63%, χ2 = 152.53, P < 0.001; PPV = 77.78%). Fragmented and blocked sequestrum was more common in the TS group than in the BS group and tended to spread in and out of the erosions (22.14% vs. 0.64%, PPV = 98.31% and 22.14% vs. 0.00%, PPV = 100%, χ2 = 102.43, P < 0.001).ConclusionsTS and BS exhibit specific features of bone formation, bone destruction, and sequestrum on CT imaging. Our findings indicate that bone features on CT can help clinicians distinguish between two spinal infections.

Prevalence, Characteristics and Risk Factors of Migraine Headache Among Students in Horus University-Egypt: A Cross- Sectional Study

Background: Migraine is a common neurological impairment with a significant disease burden. A number of different factors can trigger migraine attacks as anxiety, stress, skipped meals and irregular sleep pattern. Objectives: This study was done to estimate the prevalence of migraine and to determine its characteristics in students of Horus University, Egypt. Methods: A cross-sectional study was done utilizing a self-administered questionnaire. The study included 1339 students. Migraine-related quality of life and disability were evaluated utilizing Migraine Specific Quality of life Questionnaire (MSQ) as well as Migraine Disability Assessment Scale (MIDAS) respectively. Results: Migraine headaches affected 24% of the population. The most frequent migraine triggers were mental stress, exertion, sleep disturbance and prolonged mobile use (74%, 72.7%, 68% and 55.8% respectively). Being a female, in the middle academic years and having low academic degrees were significant predictors of migraine among university students. Regarding migraine students, disability was significantly higher among females and students who don’t live with their families. Besides, their quality of life was significantly low among males, nonmedical students, students with low academic degrees and those with irregular physical exercise. Conclusion: The high prevalence of migraines among college students has a detrimental effect on their quality of life and causes a major disability.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study. Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score, 3-6) at 3 months after ischemic stroke. During 3 months of follow-up, 877 participants experienced the primary outcome. After multivariate adjustment, each 500 ng/mL increase of phenylacetylglutamine was associated with a 7% (P=0.012), 6% (P=0.016), and 6% (P=0.028) increased risk of the primary outcome, major disability, and death, respectively. The odds ratios or hazard ratios in the highest versus the lowest quartile of plasma phenylacetylglutamine were 1.62 ([95% CI, 1.18-2.23]; Ptrend=0.001) for the primary outcome, 1.62 ([95% CI, 1.16-2.24]; Ptrend=0.001) for major disability, and 2.59 ([95% CI, 1.19-5.60]; Ptrend=0.025) for death, respectively. There was a significantly worse shift in the distribution of modified Rankin Scale score at 3 months with higher phenylacetylglutamine quartiles (Ptrend=0.003). Multiple-adjusted spline regression model showed a linear relationship between phenylacetylglutamine and primary outcome (P value for linearity<0.001). The addition of plasma phenylacetylglutamine to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement, 19.34%; P<0.001; integrated discrimination improvement, 0.23%; P=0.019). Elevated plasma phenylacetylglutamine levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that phenylacetylglutamine may be a promising prognostic biomarker for ischemic stroke. Further studies are needed to investigate whether phenylacetylglutamine is a stroke-specific biomarker.

Que peut nous apprendre l’étude du métabolisme cérébral en TEP au 18F-FDG du syndrome de Lance-Adams ?

Lance-Adams syndrome, also known as “chronic post-anoxic myoclonus”, is a rare syndrome characterised by intention and action myoclonus following cerebral anoxia, leading to major disability. The cortical or subcortical origin of the myoclonus is still debated. Answering this question would open up new avenues of translational research to gain a better understanding of the pathophysiology of this syndrome and better guide the therapeutic management of patients. In addition to a neurological examination, the initial diagnostic work-up includes a biological work-up, electrophysiological investigations and brain imaging to rule out diGerential diagnoses. Cerebral MRI is the reference imaging technique. In the literature, more than a third of patients have a normal MRI. MRI is used to rule out a vascular cause and to look for atrophy or neuronal damage. Few data are available in the literature on the role of nuclear medicine. To date, 13 cases have been published using 18F-FDG PET and 4 using cerebral perfusion scintigraphy. Abnormalities of cortical and/or subcortical perfusion or metabolism are reported in 65% of cases; they are limited to the neocortex in 23% and aGect the cerebellum in 12% of cases. In this article, we present three patients who underwent cerebral 18F-FDG PET scans for Lance-Adams syndrome with normal MRI. The results of these examinations are discussed and compared with the data found in the literature.

The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global disability and mortality cause, with the gut-brain axis playing a crucial role in its pathophysiology. Neuroinflammation, triggered by microglia and astrocytes, contributes to neuronal damage and cognitive impairment. This paper aims to explore the relationship between the gut-brain axis and neuroinflammation in TBI and its potential implications for therapeutic interventions. A comprehensive review of the literature was conducted using PubMed, MEDLINE, and Google Scholar databases. Studies investigating the gut-brain axis, neuroinflammation, and TBI were included. Evidence suggests that TBI disrupts the gut-brain axis, leading to alterations in gut microbiota composition, intestinal permeability, and immune responses. These gut-related changes promote the activation of microglia and astrocytes in the central nervous system, contributing to neuroinflammation and neuronal damage. Conversely, interventions that modulate gut microbiota or reduce intestinal permeability have been shown to attenuate neuroinflammation and improve cognitive outcomes in TBI models. The gut-brain axis plays a significant role in the pathogenesis of neuroinflammation following TBI. Targeting the gut-brain axis through interventions that restore gut homeostasis and reduce intestinal permeability holds promise as a novel therapeutic strategy for mitigating neuroinflammation and improving cognitive function in TBI patients. Further research is needed to elucidate the specific mechanisms involved and to develop effective therapies based on this understanding.

Nutrition and Physical Activity in Older Adults with CKD: Two Sides of the Same Coin

Introduction: Nutrition and physical activity are two major issues in the management of CKD patients who are often older, have comorbidities, and are prone to malnutrition and physical inactivity, conditions that cause loss of quality of life and increase the risk of death. We performed a multidimensional assessment of nutritional status and of physical performance and activity in CKD patients on conservative therapy in order to assess the prevalence of sedentary behavior and its relationship with body composition. Methods: A total of 115 consecutive stable CKD patients aged 45–80 years were included in the study. They had no major skeletal, muscular, or neurological disabilities. All patients underwent a multidimensional assessment of body composition, physical activity, and exercise capacity. Results: Sedentary patients, as defined by mean daily METs <1.5, were older and differed from non-sedentary patients in terms of body composition, exercise capacity, and nutrient intake, even after adjusting for age. Average daily METs were positively associated with lean body mass, muscle strength, 6MWT performance but negatively associated with fat body mass, body mass index, and waist circumference. In addition, a sedentary lifestyle may have negative effects on free fat mass, muscle strength, and exercise capacity and may increase fat body mass. Conversely, decrease in muscle mass and/or an increase in fat mass may lead to a decrease in physical activity and exercise capacity. Conclusion: There is a clear association and potential interrelationship between nutritional aspects and exercise capacity in older adults with CKD: they are really the two sides of the same coin.

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundCerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.MethodsIn a phase 2–3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.ResultsA total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.ConclusionsAt a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)

Neurology of Aging : adapting neurology provision for an aging population.

Background Over the past few decades, advances in neurology of aging have been considerable and have led to a better understanding of the science of age-related neurological disorders. Likewise, it changed the perception of classical neurology practice, research and the way of looking at age-related conditions. Neurological disorders are the most frequent cause of major disability in the elderly and account for almost half of the incapacitation occurring beyond age 65 and more than 90% of serious dependency. However, a number of neurological changes occur also in the absence of a specific disease, making the assessment and management of neurological complaints and findings a specific expertise. Summary Maximizing success in clinical care of the elderly requires expertise in geriatric neurology, which includes an understanding of current research regarding aging and age-related neurological dysfunctions, and the ability to work with other geriatric health care providers. Although current therapies for neurodegenerative diseases mainly offer symptomatic relief without slowing progression, the landscape is evolving. Biomarkers of pathology and neuroimaging have continued to develop, with a significant impact on diagnosis and treatment. These advances have helped to improve our knowledge of disease pathophysiology but also disease stages, guiding symptomatic monitoring, and possible therapeutic options at a pre-symptomatic stage. Key Messages Neurological disorders are a leading cause of major disability and dependency in the elderly, underscoring the need for expertise in geriatric neurology for effective clinical care of this population. Although current therapies for neurodegenerative diseases primarily provide symptomatic relief without slowing disease progression, advancements in biomarkers and neuroimaging are significantly evolving. These advancements enhance our understanding of disease pathophysiology and stages, guiding symptomatic monitoring and potential therapeutic options at a pre-symptomatic stage. As knowledge about age-associated conditions is steadily rising and geriatric medicine gains further recognition, this article argues for a new focus on the role of neurologists in geriatric medicine, emphasizing the importance of integrating current research and collaborative care approaches in the management of elderly patients.