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Introduction Tuberculous meningitis (TBM) results in significant morbidity and mortality among children worldwide. Associated neurocognitive complications are common but not well characterized. The Mullen Scales of Early Learning (MSEL), a well-established measure for assessment of neurodevelopment, has not yet been adapted for use in India. This study’s goal was to adapt the MSEL for local language and culture to assess neurocognition among children in India, and apply the adapted measure for assessment of children with TBM. Methods Administration of MSEL domains was culturally adapted. Robust translation procedures for instructions took place for three local languages: Marathi, Hindi and Tamil. Multilingual staff compared instructions against the original version for accuracy. The MSEL stimuli and instructions were reviewed by psychologists and pediatricians in India to identify items concerning for cultural bias. Results MSEL stimuli unfamiliar to children in this setting were identified and modified within Visual Reception, Fine-Motor, Receptive Language and Expressive Language Scales. Item category was maintained for adaptations of items visually or linguistically different from those observed in daily life. Adjusted items were administered to six typically developing children to determine modification utility. Two children diagnosed with confirmed TBM (ages 11 and 29 months) were evaluated with the adapted MSEL before receiving study medications. Skills were below age-expectation across visual reception, fine motor and expressive language domains. Conclusions This is the first study to assess children with TBM using the MSEL adapted for use in India. Future studies in larger groups of Indian children are warranted to validate the adapted measure.

Backround Traumatic brain injury (TBI) has an estimated prevalence rate of 1.7 million occurrences a year in the United States with over 75% of traumatic brain injuries classified as 'mild.' The majority of individuals with mild traumatic brain injuries resume their daily functioning fairly quickly, and many fully within the first year. However, a minority of persons with mild TBI (mTBI), with estimates ranging between 1% and 20%, develop persistent cognitive, emotional, behavioral, and physical symptoms. Clinicians vary considerably in their clinical opinions regarding these individuals and there is no consensus on the treatment protocol for this population. Objective This manuscript presents four case studies of mild TBI with persistent symptoms treated by a transdisciplinary team in an outpatient neurorehabilitation setting based on community reintegration. Clinical challenges and insights involved in conceptualizing and effectively treating these individuals are discussed to facilitate future direction. Methods Four different mild TBI cases, each with persistent symptoms, but different injury mechanisms, dynamics, and factors affecting symptom persistence, expression, course, and outcome were included in the analysis of their treatment course and outcome. The treatment protocol included: brain injury education combined with supportive counseling for cultivation of positive expectancy effects, symptom-based, graded treatment involving most disciplines, frequent treatment team consultations, collaborations, and planning, and consistent team messages about post-injury recovery and expected return to community activities. Treatment outcomes were assessed with self and family reports, as well as the Mayo Portland Adaptability Inventory (MPAI-4) at admission and at discharge. Results and conclusions Each of the individuals made functional progress during rehabilitation, as evidenced by self and family reports and the MAPI-4. The cases posed various challenges to the treatment team, though a transdisciplinary team under the guidance of a rehabilitation physician and rehabilitation neuropsychologist was able to help patients navigate the path to their functional recovery. In addition to the specific treatment protocol, transdisciplinary team collaboration guided by rehabilitation neuropsychology contributed to treatment success.

The global public health burden of the novel coronavirus disease 2019 (COVID-19) is immense and has yet to be measured and understood in its entirety. Leading to and since the time it was declared ...

SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population.

Turner syndrome is recognized now as a syndrome familiar not only to pediatricians and pediatric specialists, medical geneticists, adult endocrinologists, and cardiologists, but also increasingly to primary care providers, internal medicine specialists, obstetricians, and reproductive medicine specialists. In addition, the care of women with Turner syndrome may involve social services, and various educational and neuropsychologic therapies. This article focuses on the recognition and management of Turner syndrome from adolescents in transition, through adulthood, and into another transition as older women. It can be viewed as an interpretation of recent international guidelines, complementary to those recommendations, and in some instances, an update. An attempt was made to provide an international perspective. Finally, the women and families who live with Turner syndrome and who inspired several sections, are themselves part of the broad readership that may benefit from this review.

Limbic encephalitis (LE) is a rare neurological disorder characterized by inflammation of the brain caused by autoimmunity or infection. LE has been a difficult to define and diagnose disorder due to the insidious and nonspecific (e.g., irritability, low mood, short-term memory complaints) presentation of early symptoms, as well as inconsistent findings on neuroimaging, lumbar puncture serum analysis, and electroencephalogram. Seizures, memory problems, and psychiatric disturbance are among the earliest and most prominent clinical features. This manuscript describes three adolescent males who developed LE and became psychotic, needed inpatient care, were trialed on various psychotropic medications, and exhibited lingering cognitive and psychiatric issues, though generally had very positive recoveries and return to community activities. There was no history of psychiatric disturbance, developmental disorder, or learning difficulties in any of these three young men. Two of the three cases exhibited a long, insidious symptom onset. None of the adolescents benefitted from antipsychotic medications and did not begin to experience improvement and eventual recovery until intravenous immunoglobulin (IVIG) was added to their treatment regimen. Neuropsychological consultation and team education was helpful in each of these cases. Neuropsychological findings for each individual are presented.

This study compared neurologic disability and adaptive function in children and adults >1 year following anti- N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis diagnosis. Retrospective record review identified 12 patients with anti-NMDAR encephalitis. At last follow-up, all surviving patients had “good” modified Rankin Score (0-2). Four children, 6 adults, and their families participated in a telephone interview. Median duration since diagnosis was similar for children (2.42 years, interquartile range 2.12-3.32) and adults (3.55 years, interquartile range 2.08-5.50 years). 3/4 (75%) pediatric and 3/5 (60%) adult patients reported neuropsychiatric symptoms (fatigue, emotional lability, short-term memory deficits or concentration deficits). On the Adaptive Behavior Assessment System (ABAS-3), although overall adaptive function was intact for adults (general adaptive composite standard score: median 104.5, interquartile range 98.8-112.5), the median for children was below average (General Adaptive Composite Standard Score: median 82.0, interquartile range 79.0-89.0). Children with anti-NDMAR encephalitis may have long-term effects impacting daily life while adults regain normal function.

This study evaluates long-term neurobehavioral function in patients with clinically diagnosed autoimmune encephalitis (AE) of various etiologies through retrospective chart review and a cross-sectional structured telephone interview. Of 77 patients meeting clinical diagnostic criteria for AE over a ten year period, 39/77 (51%) patients had known AE-associated antibodies, and 38/77 (49%) had no detected antibody. 9/77 (12%) died, and 26/77 (34%) had "poor" neurologic disability score (mRS 3-5) at the last documented follow-up. 44 participants enrolled in the telephone interview, of whom 38/44 (86%) endorsed ongoing difficulties with fatigue, emotional lability, short-term memory, and/or concentration. On standardized assessment of adaptive behavior (ABAS-3), 23/44 (52%) scored "below average" (general adaptive composite: mean 86.95, standard deviation 18.45). Of the participants with "good" neurologic disability outcome (mRS 0-2), 12/30 (40%) scored "below average" in adaptive behavior. In summary, patients with AE frequently have persistent impairments in neurologic disability, neurocognitive symptomatology, and adaptive behavior, which may not be adequately captured by routine neurologic assessments. Comprehensively elucidating these persistent neurobehavioral impairments and predicting which patients are at highest risk will allow for optimal care of patients and their families.

In those who survive tuberculous meningitis (TBM), the long-term outcome is uncertain; individuals may suffer neurocognitive, functional and psychiatric impairment, which may significantly affect their ability to lead their lives as they did prior to their diagnosis of TBM. In children who survive, severe illness has occurred at a crucial timepoint in their development, which can lead to behavioural and cognitive delay. The extent and nature of this impairment is poorly understood, particularly in adults. This is in part due to a lack of observational studies in this area but also inconsistent inclusion of outcome measures which can quantify these deficits in clinical studies. This leads to a paucity of appropriate rehabilitative therapies available for these individuals and their caregivers, as well as burden at a socioeconomic level. In this review, we discuss what is known about neurocognitive impairment in TBM, draw on lessons learnt from other neurological infections and discuss currently available and emerging tools to evaluate function and cognition and their value in TBM. We make recommendations on which measures should be used at what timepoints to assess for impairment, with a view to optimising and standardising assessment of neurocognitive and functional impairment in TBM research.