Chronic Neurological Disability Research Articles

Proinflammatory factors inhibition and fish oil treatment: A promising therapy for neonatal seizures

Brain injury is one of the most important causes of infant mortality and chronic neurological disabilities. Hypoxia is an acute brain injury which led to various cognitive, behavioral, and memory disorders throughout life. Previous studies reported neuroprotective possibilities for fish oil (FO) in brain-injured situations. In this study, we evaluated the effect of the FO diet during the lactation period on seizure activity, behavioral performance, histomorphometry, and inflammatory changes in the brains of hypoxia rats. Male Wistar rats were randomly divided in to 4 groups: Sham (intact rats), hypoxia, FO and FO+hypoxia groups. Hypoxia was induced by keeping neonate rats at PND12 in a hypoxic chamber (7 % oxygen and 93 % nitrogen intensity) for 15 minutes. In the FO groups, rats received oral FO (1 ml/day) for 12 days during the lactation period. Seizure activity was assessed by measuring the number of tonic-clonic seizures and seizure thresholds. Novel object recognition tests (NORT), rotarod, and open field tests were used to measure behavioral performances. A Histological study was performed to evaluate histomorphometric changes in the hippocampus and cerebellum. The gene expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was measured using RT-PCR. Findings showed that the number of tonic-clonic seizures, atrophy, and cell death in the hippocampus and cerebellum, the gene expression of TNF-α and IL-1β in the hippocampus, and behavioral disorders were significantly increased in the hypoxia rats compared to the sham group. Administration of FO in the hypoxia groups significantly decreased the gene expression of TNF-α and IL-1β, the number of tonic-clonic seizures, and neuronal cell death in the hippocampus and cerebellum compared to the hypoxia groups. Furthermore, it can improve behavioral tasks and cognitions.

Alterations of Thymus-Derived Tregs in Multiple Sclerosis.

Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear. By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors. Patients with MS showed a reduced frequency of CD4+ T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs. Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.

Dysphagia Intervention in Patient with Diffusion Axon Injury with Bilateral Frontal Lobe Contusion: A Case Report

Introduction: Traumatic brain injury (TBI) is a leading cause of chronic neurologic disability. Damage often affects the frontal lobes, and thus the most frequent cognitive sequelae are deficits in the prefrontal cortex (PFC)-dependent functions, such as attention, working memory, social behavior, mental flexibility, and task switching. Objective: The goal of this case report is to highlight the assessment and intervention of the dysphagia program. Case Report: The patient was diagnosed with diffuse axonal injury with bilateral frontal lobe contusion. The patient is receiving care in the Physical Medicine and Rehabilitation (PMR) unit, where they are undergoing physiotherapy occupational therapy, and speech therapy. Results: Speech Assessment revealed deviated voice and resonance characteristics with Substitution & Distortion of speech sounds. Swallowing assessment revealed Oro-pharyngeal Dysphagia. The patient was also undergoing Chemotherapy and Radiation-therapy. Recommendations for further follow-ups for speech & swallowing therapy and other medical management were made. Conclusion: This study is useful in creating evidence regarding the assessment & rehabilitation of Speech and swallowing in patients undergoing hemi-glossectomy. It also emphasizes the input from other medical professionals as an interdisciplinary team member.

Locus for severity implicates CNS resilience in progression of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults1,2. Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with ashortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriersand with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility3, these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS.

In silico Analysis of Common Autism Spectrum Disorder Genetic Risk Variations

Autism spectrum disorder (ASD) is a chronic neurological and developmental disability characterised by inability to develop social relationships, trouble expressing feelings, and repeated behaviours - clinically defined as stereotyped behaviour - that affect how people interact, learn, and behave. Because of the vast range of types and severity of symptoms, it is classified as a "spectrum" disorder. Over the last two decades, the prevalence of ASD has progressively increased, and one out of every 160 children worldwide is estimated to have an ASD. Over 75 percent of ASD patients show psychiatric disorders like depression, stress, bipolar disorder, Tourette syndrome, attention deficit hyperactivity disorder (ADHD). In the present study, in silico analysis was done to identify different rare mutations in genes implicated in ASD. Single nucleotide polymorphisms in ADNP, ARID1B, ASH1L, CHD2, CHD8, DYRK1A, POGZ, SHANK3, and SYNGAP1 genes were identified to be associated with ASD aetiology. A single mutation in these genes can result in defective chromatin remodeling, altering the function of several genes and potentially causing intellectual impairment and autism spectrum disorder (ASD). Understanding and analyzing these SNPs linked to ASD as risk factors can aid in the early detection and diagnosis of the disorder.

Organizational ethics in urgent transfers of severely disabled people to intensive care units – a qualitative study

Purpose Urgent transfers of severely impaired patients with chronic neurological disability (PwND) from a neurological physical and rehabilitation medicine (nPRM) to an intensive care unit (ICU) or an emergency room (ER) served as the basis for this study. We hypothesized that human and structural factors interfered with but were not directly related to the acute context. Methods We decided to use a qualitative methodology, based on in-depth interviews with 16 ICU/ER physicians. We used mixed bottom-up and top-down methods. We interpreted our data using a thematic approach based on the key principles of grounded theory, which were modified with consideration of the literature. Results Three main domains emerged. The impact of the clinical setting notably implied the patient’s clinical typology between the acute event and the chronic background, but also bed availability. Key elements of the telephone negotiation were confidence and perceived usefulness of the transfer. Finally, the otherness of some categories of patients, transferred with more difficulty, involved those with cognitive impairment. Conclusions The existence of healthcare pathways for many years has created an organizational culture between departments of nPRM and ICUs. But urgent transfers also imply organizational ethics, as a balance should be struck between utility and equity. IMPLICATIONS FOR REHABILITATION Structural and human factors interfere in urgent transfers, involving the settings within health pathways, the key elements of negotiation to get confidence and a perceived utility of transfer, and certain categories of people, especially those with cognitive impairment. Transfers that imply negotiation between practitioners from physical and rehabilitation medicine and intensive care unit departments, lead to a need of organizational ethics, as a balance should be struck between the principles of utility and equity. The development of facilitating tools such as a commitment charter is of paramount importance as it can support ethical decision-making.

Predictors of unemployment status in people with relapsing multiple sclerosis: a single center experience

BackgroundMultiple sclerosis (MS) is the most common cause of nontraumatic chronic neurological disability affecting young adults during their crucial employment years.ObjectivesTo evaluate patients and disease related factors associated to unemployment in a cohort of relapsing–remitting (RR) MS patients.MethodsWe included RRMS patients with a follow-up of at least 1 year. We collected data about years of school education and employment status. Patients underwent a neuropsychological evaluation using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Demographic and clinical predictors of unemployment were assessed through a multivariable stepwise logistic regression model.ResultsWe evaluated 260 consecutive RRMS patients. Employed patients were less frequently female (68.4% vs 83.3%, p = 0.006), less disabled (median Expanded Disability Status Scale (EDSS) score: 2.0 (0–7.0) vs 2.5 (0–7.5), p < 0.001), with more years of school education (mean ± standard deviation (SD), years: 13.74 ± 0.30 vs 10.86 ± 3.47, p < 0.001). Female sex and a higher EDSS score resulted associated with a greater risk of unemployment (OR 3.510, 95% CI 1.654–7.448, p = 0.001; OR 1.366, 95% CI 1.074–1.737, p = 0.011, respectively), whereas a greater number of years of schooling and current disease-modifying therapy exposure resulted protective factors (OR 0.788, 95% CI 0.723–0.858, p < 0,001; OR 0.414, 95% CI 0.217–0.790, p = 0.008, respectively).ConclusionsUnderstanding work is pervasively influenced by consequences of MS, we confirmed the impact of demographic, physical, and cognitive factors on employment status in RRMS patients.

Evaluation of micronutrient levels in children with cerebral palsy.

Many studies evaluating the nutritional status of children with cerebral palsy (CP) have focused on energy requirements and protein intake. The present work aimed to assess nutritional status and micronutrient levels of children with (CP). This multicenter, cross-sectional and observational study was conducted in 10 different cities in Turkey. Data were available for 398 participants. Anthropometric measurements, feeding mode, nutritional status, and micronutrient levels were evaluated. The study was conducted with 398 participants (303 patients and 95 healthy controls). Statistical analysis showed that according to the Gomez Classification, weight-for-age (WFA) revealed malnutrition in 92.6% of children with CP, based on Centers for Disease Control and Prevention percentiles. Measurements of micronutrient levels showed that zinc levels were low in patients, whereas vitamin A levels were low in controls. Phosphorous and manganese levels were significantly lower in malnourished children than in typical children. The results revealed that children consuming enteral nutrition solutions had higher selenium and lower zinc levels than non-consumers. Malnutrition is not only a protein- or calorie-based problem; micronutrient deficiencies might cause severe health problems. Children with chronic neurological disabilities must be carefully evaluated for these issues. Therefore, nutritional interventions should be adapted to nutrition.

Evaluating the Correlation between Brain Ultra Sonographic, Brain MRI, and Electroencephalography Findings and the Severity of Asphyxia and Neurodevelopment in Infants with Hypoxic-ischemic Injury.

ObjectiveHypoxia-ischemia-induced brain injury is a major cause of acute mortality and chronic neurological disability in infants and children. Imaging plays a vital role in diagnosing and treating hypoxic-ischemic encephalopathy (HIE) and as an adjunct to acute conditions and provides valuable information on long-term prognosis. Materials & Methods Our study was prospective with 50 neonates aged 34 weeks and older with HIE. Cerebral ultrasound and MRI were performed on the infants, and the pattern of lesions was recorded. A pediatric neurologist examined the infants, and their developmental status was assessed and recorded with electroencephalography (EEG) findings. The data were analyzed.Results The sonography pattern was normal in 26 (76.5%) term neonates, and also, the PVL pattern was observed in 10 term neonates. The incidence of observing an edema pattern (17.6%) was significantly different between the term and pre-term infants (P-value = 0.001). MRI findings were normal in 20 (58.8%) term neonates and 11 premature neonates. However, the PVL pattern was observed in MRI performed in six term neonates (6.6%). The watershed pattern (17%) showed that these differences were significant between the term and pre-term infants (P-value = 0/001).Conclusion Normal sonography was significantly higher in neonates with normal neurodevelopment than in patients with normal MRI and EEG findings but with poor neurodevelopment. Also, the probability of having normal MRI results was lower in neonates with moderate to severe asphyxia compared to ultrasound and EEG.

SAFETY AND QUALITY OF INTRAVENOUS LIPIDS FOR NEWBORNS: EFFECTS ON CRITICAL DISEASES AND METABOLIC DISORDERS (PART II)

Premature birth and its complications cause stress in newborns, which restrains their physical growth for several weeks after birth and is associated with chronic morbidity and neurological disability in the future. Preterm infants face such difficulties as respiratory distress, cardiovascular disease, gastrointestinal dysfunction and very low birth weight. Most complications in newborns are associated with oxidative stress that develops during the early period of growth. The formation of free radicals entails oxidative damage to many organs and systems of the body and is the main factor responsible for the development of typical diseases of preterm infants, such as bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage, and respiratory distress syndrome.&#x0D; Premature infants depend on adequate early parenteral nutrition, which not only guarantees they will survive but also ensures positive health outcomes later in life. Early use of intravenous lipids helps to prevent essential fatty acid deficiencies, provides energy and substrates for cell membrane synthesis, which are important for the growth and development of infants with very low and extremely low birth weight. This publication represents data on the effect of intravenous lipids on critical conditions and metabolic disorders in newborns. Literature sources are analyzed and the existing evidence of the possible influence of lipid emulsions on critical diseases in newborns is presented: intraventricular hemorrhage; necrotizing enterocolitis, patent ductus arteriosus and thrombocytopenia; glucose metabolism (hypo- and hyperglycemia); hyperbilirubinemia and chronic liver damage. The literature review is aimed at finding optimal strategies for the use of lipid emulsions in intensive care of newborns to improve the quality of care for premature infants. The purpose of this work is to analyze the results of published studies and systematize data on the feasibility and safety of lipid emulsions used in newborns with critical diseases of the perinatal period.

A biocompatible and injectable hydrogel to boost the efficacy of stem cells in neurodegenerative diseases treatment

AimsStem cell therapies emerged as treatment modalities with potential to cure neurodegenerative diseases (NDs). However, despite high expectations, their clinical use is still limited. Critical issues in treatment outcomes may be related to stem cells formulation and administration route. We develop a hydrogel as a cell carrier, consisting of compounds (phospholipids and hyaluronic acid-HA) naturally present in the central nervous system (CNS). The HA-based hydrogel physically crosslinked with liposomes is designed for direct injection into the CNS to significantly increase the bone marrow mesenchymal stem cells (BMSCs) bioavailability. Materials and methodsHydrogel compatibility is confirmed in vitro with BMSCs and in vivo through its intracerebroventricular injection in rats. To assess its efficacy, the main cause of chronic neurologic disability in young adults is selected, namely multiple sclerosis (MS). The efficacy of the developed formulation containing a lower number of cells than previously reported is demonstrated using an experimental autoimmune encephalomyelitis (EAE) rat model. Key findingsThe distribution of the engineered hydrogel into corpus callosum can be ideal for NDs treatment, since damage of this white matter structure is responsible for important neuronal deficits. Moreover, the BMSCs-laden hydrogel significantly decreases disease severity and maximum clinical score and eliminated the relapse. SignificanceThe engineering of advanced therapies using this natural carrier can result in efficacious treatments for MS and related debilitating conditions.

Effectiveness of respiratory physiotherapy combined with postural education in children with chronic neurological diseases

Children with chronic neurological diseases present motor disability and increased respiratory morbidity and mortality. The aim of this study was to assess whether children with chronic neurological impairment benefit from respiratory physiotherapy and postural hygiene. Quasi-experimental study in which six fortnightly respiratory physiotherapy sessions and workshops on postural hygiene were carried out on children aged 0 to 6 years with chronic neurological disease and respiratory impairment. A PedsQL questionnaire assessed respiratory clinical variables, expectorated secretions, respiratory exacerbations and quality of life. Assessments were performed at baseline, post-intervention, and at a 3-month follow-up. After physiotherapy sessions, all participants (n=30) experienced a significant (p<0.001) improvement in average oxygen saturation (94.37 to 98.3%), heart rate (126.03 to 103.6 beats/minute) and respiratory rate (42.13 to 34.27 breaths/minute), as well as a decrease in secretions (from 45.33 to 28.17 mL). This improvement was maintained after a 3-month follow-up. The average respiratory exacerbations decreased (p<0.001) compared to the previous six months: hospitalizations (from 1.6 to 0.5), visits to the emergency department (from 2.59 to 1.53) and to primary care Pediatric consultations (from 7 to 5.03). The mean score on the PedsQL questionnaire demonstrated a significant increase (p<0.001) in the quality of life after the intervention for physical (27%, to 73.4) and mental health (12%, to 70.09%). Respiratory physiotherapy combined with postural hygiene is effective for the clinical status and quality of life in children with chronic neurological diseases, and therefore could be introduced in habitual clinical practice.

Degenerative Cervical Myelopathy: Clinical Presentation, Assessment, and Natural History.

Degenerative cervical myelopathy (DCM) is a leading cause of spinal cord injury and a major contributor to morbidity resulting from narrowing of the spinal canal due to osteoarthritic changes. This narrowing produces chronic spinal cord compression and neurologic disability with a variety of symptoms ranging from mild numbness in the upper extremities to quadriparesis and incontinence. Clinicians from all specialties should be familiar with the early signs and symptoms of this prevalent condition to prevent gradual neurologic compromise through surgical consultation, where appropriate. The purpose of this review is to familiarize medical practitioners with the pathophysiology, common presentations, diagnosis, and management (conservative and surgical) for DCM to develop informed discussions with patients and recognize those in need of early surgical referral to prevent severe neurologic deterioration.

Music-based therapy in rehabilitation of people with multiple sclerosis: a systematic review of clinical trials.

Multiple sclerosis (MS) is a major cause of chronic neurological disability in young adults. An increasing number of controlled studies have assessed the potential rehabilitative effects of new drug-free treatments, complementary to the standard care, including music-based therapy (MBT). To analyze the evidence for the effectiveness of MBT within the therapeutic approaches to individuals diagnosed with MS. A systematic review of clinical trials was performed with searches in the following databases: BIOSIS, CINAHL, Cochrane, EBSCO, ERIC, Google Scholar, IBECS, LILACS, LISA (ProQuest), Medline, PEDro, PsycINFO (APA), Psychological & Behavioral, PubMed, SciELO, Scopus, SPORTDiscus and Web of Science. Clinical trials comparing MBT versus conventional therapy/no intervention were included. From the 282 studies identified, 10 trials were selected. Among these, the total sample consisted of 429 individuals: 253 were allocated to the experimental group (MBT) and 176 to the control group (conventional therapies or no intervention). All the studies presented high methodological quality. Modalities of MBT were clustered into four groups: (1) Rhythmic auditory; (2) Playing musical instruments; (3) Dance strategy; and (4) Neurological music therapy. Overall, the studies consistently showed that MBT was better than conventional therapy or no intervention, with regard to gait parameters (double support time and walking speed), fatigue level, fatigability, coordination, dexterity, balance, walking endurance, lower extremity functional strength, emotional status and pain. Regarding mental fatigability and memory, the data were conflicting and the evidence was unclear. MBT is a safe and effective approach for clinical rehabilitation of MS patients that leads to positive results regarding both motor and non-motor functions.

Ozanimod for the treatment of relapsing forms of multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease that causes chronic neurological disability in young adults. Modulation of sphingosine 1-phosphate (S1P) receptors, a group of receptors that, among other things, regulate egression of lymphocytes from lymph nodes, has proven to be effective in treating relapsing MS. Fingolimod, the first oral S1P receptor modulator, has demonstrated potent efficacy and tolerability, but can cause undesirable side effects due to its interaction with a wide range of S1P receptor subtypes. This review will focus on ozanimod, a moreselective S1P receptor modulator, which has recently received approval for relapsing MS. We summarize ozanimod's mechanism of action, and efficacy and safety from clinical trials that demonstrate its utility as another treatment option for relapsing MS.

The Time Burden of Specialty Clinic Visits in Persons With Neurologic Disease: A Case for Universal Telemedicine Coverage.

Objective: Those with chronic neurologic disorders are often burdened not only by the condition itself but also an increased need for subspecialty medical care. This may require long distance travel, while even small distances can be a hardship secondary to impaired mobility and transportation. We sought to examine the burden of time associated with clinical visits for those with chronic neurologic disorders and their family/caregivers. These topics are discussed as an argument to support universal coverage for telemedicine in this population.Design: Cohort Study.Setting: Specialty clinic at community hospital.Participants: 208 unique patients with chronic neurologic disability at physical medicine and rehabilitation or neurourology clinic over a 3-month period.Main Outcome Measures: Patient survey on commute distance, time, difficulties, and need for caregiver assistance to attend visits.Results: Approximately 40% of patients were covered by Medicare. Many patients (42%) perceived it difficult to attend their clinic visit with transportation difficulties, commute time, and changes to their daily schedule being the most commonly cited reasons. Most patients (75%) lived within 25 miles of our clinics and experienced an average commute time of 79.4 min, though 10% required 3 h or more. Additional family/caregiver assistance was required for 76% of patients, which resulted in an inclusive average commute time of 138.2 min per patient.Conclusion: Chronically neurologically-disabled patients and their caregivers may be burdened by the commute to outpatient appointments. To minimize this burden, increased emphasis on telemedicine coverage for those with chronic neurologic disability should be considered by all payors.

Cognitive Capacity Assessment: The Fundamental Element of Neurological Disability Guidelines in India.

Disability evaluation as per World Health Organization includes assessment of impairments, activity limitations, and participation restriction, which unfortunately is not assessed by the existing guidelines of disability in India. The aim of this study wasto comparea new study criterion with the existing guidelines for assessing cognitive disability for chronic neurological conditions. A cross-sectional pilot study was conducted on 41 participants. They were assessed on an existing guideline (Gazette India 200,1 assessing physical domain and Intelligence Quotient[IQ]) and study criterion assessing three aspects of cognitive capacity: IQ, neurocognitive functioning, and QOL. The existing guideline underestimated 84% of cases for disability. The average percentage of disability measured by the study criterion was 33.2% more as compared to existing guidelines with S.D of 26.6. Cognitive capacity assessment is an important element to be measured in chronic neurological disability certification. However, a large sample is required to make an affirmative claim for the same.

A new neutrophil subset promotes CNS neuron survival and axon regeneration.

Transected axons typically fail to regenerate in the central nervous system (CNS), resulting in chronic neurological disability in individuals with traumatic brain or spinal cord injury, glaucoma and ischemic reperfusion injury of the eye. Although neuroinflammation is often depicted as detrimental, there is growing evidence that alternatively activated, reparative leukocyte subsets and their products can be deployed to improve neurological outcomes. In the current study we identify a unique granulocyte subset, with characteristics of an immature neutrophil, that had neuroprotective properties and drove CNS axon regeneration in vivo, in part via secretion of a cocktail of growth factors. This pro-regenerative neutrophil promoted repair in the optic nerve and spinal cord, demonstrating its relevance across CNS compartments and neuronal populations. Our findings could ultimately lead to the development of novel immunotherapies that reverse CNS damage and restore lost neurological function across a spectrum of diseases.

Sustained Increases in Immune Transcripts and Immune Cell Trafficking During the Recovery of Experimental Brain Ischemia.

Stroke is a major cause of chronic neurological disability. There is considerable interest in understanding how acute transcriptome changes evolve into subacute and chronic patterns that facilitate or limit spontaneous recovery. Here we mapped longitudinal changes in gene expression at multiple time points after stroke in mice out to 6 months. Adult C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Longitudinal transcriptome levels were measured at 10 time points after stroke from acute to recovery phases of ischemic stroke. Localization and the number of mononuclear phagocytes were determined in the postischemic brain. Whole-mount brain imaging was performed in asplenic mice receiving GFP+ (green fluorescent protein)-tagged splenocytes. Sustained stroke-induced mRNA abundance changes were observed in both hemispheres with 2989 ipsilateral and 822 contralateral genes significantly perturbed. In the hemisphere ipsilateral to the infarct, genes associated with immune functions were strongly affected, including temporally overlapping innate and adaptive immunity and macrophage M1 and M2 phenotype-related genes. The strong immune gene activation was accompanied by the sustained infiltration of peripheral immune cells at acute, subacute, and recovery stages of stroke. The infiltrated immune cells were found in the infarcted area but also in remote regions at 2 months after stroke. The study identifies that immune components are the predominant molecular signatures and they may propagate or continuously respond to brain injury in the subacute to chronic phase after central nervous system injury. The study suggests a potential immune-based strategy to modify injury progression and tissue remodeling in ischemic stroke, even months after the initiating event.

Critical Medical Illness and the Nervous System.

Nervous system tissues have high metabolic demands and other unique vulnerabilities that place them at high risk of injury in the context of critical medical illness. This article describes the neurologic complications that are commonly encountered in patients who are critically ill from medical diseases and presents strategies for their diagnosis, prevention, and treatment. Chronic neurologic disability is common after critical medical illness and is a major factor in the quality of life for survivors of critical illness. Studies that carefully assessed groups of patients with general critical illness have identified a substantial rate of covert seizures, brain infarcts, muscle wasting, peripheral nerve injuries, and other neurologic sequelae that are strong predictors of poor neurologic outcomes. As the population ages and intensive care survivorship increases, critical illness-related neurologic impairments represent a large and growing proportion of the overall burden of neurologic disease. Improving critical illness outcomes requires identifying and managing the underlying cause of comorbid neurologic symptoms.