Abstract H3K27-mutant diffuse midline gliomas include a rare group of primary spinal tumours which constitute <1% of all pediatric central nervous system tumors. There is a paucity of data on their clinical and radiological characteristics, genomic landscape, and their respective impact on patient outcomes. Here, we present an interim analysis of an international, multi-institutional retrospective cohort study including patients aged <18 years from the International DIPG/DMG Registry, SIOPE (European Society for Paediatric Oncology) and HIT-HGG groups, assessing overall survival (OS) at 12 months, between January 2012 and December 2023. 86/103 patients met study inclusion criteria (54 female (63%), 32 male (37%) with median age at presentation 8 years. The median symptom interval at presentation was 5.5 weeks. 90% of patients presented with back pain and ataxia, with bladder/bowel incontinence in 10%. Median OS was 12 months. Univariate analyses demonstrated no significant association between age (<10-years vs. >10-years), sex, tumor location (cervical vs. thoracolumbar), extent of resection (subtotal/gross-total, HR = 1.094/1.128, respectively), chemotherapy (HR = 1.14), radiotherapy (photon and proton, HR = 0.93), and targeted therapy (HR = 1.2) with overall survival. Neuroimaging characteristics in 32 patients such as spinal canal widening (91%), posterior vertebral scalloping (77%), minor oedema (50%), moderate enhancement (38%), intratumoral hemorrhage (12%), and necrosis (22%) were not associated with overall survival. Of 41 (48%) patients who underwent molecular profiling, 24/41 (59%) had co-occurring TP53 somatic variants (HR = 0.67) or MAPK pathway alterations (12; 29%). Germline NF1 mutation was identified in one patient. DNA methylation profiles of 24 patients (28%) demonstrated high confidence scores (>0.9) in 7 (29%) and MGMT promoter methylation in 9 (38%). Primary spinal DMG appear to share the same molecular profile and clinical outcome with its intracranial counterpart. Understanding clinical, radiological, and biological features of these rare tumors may help to identify early prognostic indicators and improve patient survival and quality of life.

BackgroundPure neuritic leprosy (PNL) is a distinct form of leprosy characterized by peripheral nerve involvement without skin lesions. Diagnosis is often delayed, and 'silent neuritis' contributes to progressive and irreversible nerve damage. Despite appropriate therapy, many patients develop long-term disability. This study describes the clinical profile, diagnostic patterns, therapeutic outcomes, and predictors of disability in biopsy-confirmed PNL.MethodsWe conducted a retrospective observational cohort study at a tertiary referral centre in South India, enrolling biopsy-confirmed PNL cases from January 2003 to May 2023. Demographic, clinical, electrophysiological, and histopathological data were collected. The primary outcome was the proportion of patients with high disability at follow-up (WHO grade 2). Predictors of disability were identified using multivariate analysis.ResultsNinety-five patients were included (mean age 43.02 years (SD 15.32); 77% male). Over half (55%) presented 1-5 years after symptom onset. Sensory deficits were most common (80%), followed by foot drop (51%), ulnar claw (38%), and trophic ulcers (25%). Electrophysiology revealed mononeuritis multiplex in 52.6% and axonal polyneuropathy in 22.2%. Nerve biopsy showed borderline tuberculoid pathology in 78% and borderline lepromatous in 15.7%. Notably, 6 patients with mononeuropathy had lepromatous pathology. All patients received multidrug therapy; 41 experienced lepra reactions. Higher severity at treatment initiation was significantly associated with persistent disability.ConclusionsPNL often presents late, with many patients already experiencing nerve damage. A substantial subset of clinically mononeuritis patients demonstrated lepromatous pathology, emphasizing the need for nerve biopsy in all suspected cases. Early detection and timely treatment may reduce disability burden. These findings highlight critical gaps in current diagnostic strategies and underscore the importance of aggressive early intervention in PNL.

BACKGROUND:Although short-term outcomes are generally favourable in Cerebral venous sinus thrombosis (CVT), there are limited data on long-term complications and sequelae. METHODS:This ambispective study is from the Vellore CVT Registry, the largest single-centre CVT registry in the world. Two thousand four hundred and eighty-four adults with CVT enrolled between 2000 and 2024 were analysed for functional status and complications with follow-up up to 12 years. RESULTS:Out of 2,484 patients, 2,380 (95.8%) survived the acute phase with a mean follow-up of 3.2 years (range, 0-12 years). During follow-up, 41 patients (1.7%) died, the majority being within 1 year. Excellent functional outcomes (mRS ≤ 2) were achieved by 92% of patients within 2 years. Complications were observed in 799 (33.5%) at follow-up, with 405 (50.6%) requiring rehospitalization. More than half (55.1%) of these complications occurred more than 2 years after the initial diagnosis of CVT. Common complications were seizures (9.6%) and headaches (7.7%). Bleeding events occurred in 3.9% of cases, predominantly due to anticoagulant use. Recurrent CVT developed in 1.3%, and other thrombotic events in 2.4%. Occurrences of malignancies (1%) and secondary dural arteriovenous fistulas (dAVFs) (0.6%) were significant complications that occurred after 2 years. Of the 108 pregnancies that occurred during follow-up, thrombotic events occurred in 2.7% in the absence of antithrombotic prophylaxis. CONCLUSIONS:Most patients with CVT achieve long-term functional independence, yet one-third develop delayed complications. These findings underscore the importance of long-term surveillance in CVT survivors and give important insights into the natural history of CVT.

Early childhood stunting (ECS) affects millions of children globally and conjectured to result in suboptimal brain and cognitive development later in life. Charting out the trajectory of brain network development and most importantly how the compensation of function can be achieved gives windows of intervention to clinicians, educators and policy makers. In this study, advanced network neuroscience tools, graph theoretical methods applied on diffusion weighted MR-imaging (DWI) revealed the effects of ECS on white matter (WM) organization in a community-based birth cohort of 170 children (mean age = 9.18 years, SD = 0.28) from Vellore, India. Based on stunting status at ages two, five, and nine years, children were categorised into four groups: always stunted (AS; n =21), stunted until five with catch-up at nine (S5C9; n =31), stunted until two with catch-up at five (S2C5; n =28), and never stunted or typically developing (TD; n =90). The catch-up groups showed strikingly similar anthropometric measures compared to TD. However, all stunted groups (AS, S5C9, S2C5) showed significantly lower performance and verbal IQ scores compared to TD children. DWI data revealed AS children exhibited shorter tract lengths across select cortico-cortical connections, an increased number and strength of short- and medium-range connections, and a corresponding reduction in long-range connections and strength. Network analyses further revealed that AS and S5C9 groups displayed higher local clustering and local efficiency relative to TD, reflecting greater local segregation of brain networks. Hub-like modules was broadly conserved across groups, although both catch-up groups (S2C5 and S5C9) showed additional hubs, suggesting compensatory network reorganization via a more modular architecture. Together, these findings provide novel evidence that ECS is linked to altered structural reorganization of brain networks and reduced cognitive performance in later childhood. While persistent stunting (AS) is associated with the most pronounced alterations, partial catch-up (S2C5 and S5C9) is accompanied by compensatory adaptations, such as increased short-range connectivity and recruitment of additional hubs. These results underscore the critical importance of early nutritional interventions to support optimal brain network development.

We report a highly selective manifestation of pathological laughter in which speech initiation consistently triggers laughter, resulting in disrupted articulation. A 55-year-old male with bilateral pontine infarction exhibited laughter that was time-locked to speech, most prominent during speech production and absent during non-speech tasks. Functional MRI during speech demonstrated activation of language regions, medial prefrontal cortex, amygdala, and ventral pons, with concurrent subjective laughter. We propose that ventral pontine lesions disrupt inhibitory pathways, leading to disinhibition of brainstem laughter circuits. We use the descriptive term ‘gelastic dysarthria’ to characterize the selectively speech-triggered manifestation of pathological laughter and propose a pontine gating mechanism to account for its observed phenomenology.

Affective blindsight, the capacity to discriminate emotional stimuli despite bilateral damage to the primary visual cortex (V1) and without conscious awareness, offers a unique model of non-conscious visual processing. Subcortical pathways involving the pulvinar and amygdala have been proposed, but putative cortical contributions remain unclear. We examined 182 patients, including 31 with bilateral V1 lesions. Among these, 15 had cortical visual loss and seven showed affective blindsight. Using behavioral testing, lesion symptom mapping, and tractography, we found that preserved pulvinar connectivity with both the posterior superior temporal sulcus (pSTS) and the amygdala is necessary for affective blindsight. These findings provide causal evidence for a multi-route architecture, identifying the pulvinar-pSTS pathway, alongside the pulvinar-amygdala pathway, as a critical substrate for non-conscious affective processing.

Early childhood stunting can result in sub-optimal executive functions (EF), affecting academic achievements and economic potential in later life. This study hypothesized that children always stunted (AS) at ages 2, 5 and 9 years had lower EF than those who were never stunted (NS). A birth-cohort in Vellore, India was followed up with periodic anthropometric and development/cognitive measures over 2, 5 and 9 years of age. Based on stunting status at these time points, children were classified as NS, stunted at 2 years and caught up by 5 years (S2N5), stunted at 2 and 5 years but caught up later (S5N9), and AS. At 9th year, children underwent neuroimaging using 3T MRI scanner and EF assessment using FAS phonemic fluency test, colour cancellation test and colour trials tests (CTT). From the original birth-cohort of 251, 205 children were reviewed at 9 years. FAS phonemic fluency test showed NS group had significantly higher test scores compared to AS (11.52 vs. 7.4, p = 0.02). In CTT, a significant difference in near misses score was observed between NS and AS groups (0.12 vs. 0.38, p = 0.03). Upon evaluating unimodal brain association areas, volumes of right occipital fusiform gyrus (9991 mm3 vs. 9313 mm3; p = 0.04; η2 = 0.11), and left lateral occipital cortex (13458 mm3 vs. 12559 mm3; p = 0.03; η2 = 0.07) were significantly higher among NS compared to AS group. Considering higher order association areas, only left pars triangularis was found to be significantly reduced among AS children compared to NS group (4284 mm3 vs. 3291 mm3; p = 0.01; η2 = 0.07). Similarly, there were also significance visible in the basal ganglia regions and the cerebellum. Current study demonstrated EF dysfunction in verbal fluency and inhibitory control in a dose response fashion in groups AS-to-NS with corresponding EF-related brain volumetric changes, highlighting the need for focused nutritional and nurturing approaches in early childhood for gain in human capital.

The manifestations of HPeV infection vary from asymptomatic to serious conditions like meningitis, encephalitis, and neonatal sepsis.[1,2] While the infection is common among children, especially newborns, recent studies have demonstrated that HPeV can lead to severe cases of meningitis and encephalitis in adults.[3] We present the first cases of acute HPeV CNS infections from India, meningitis in an adult and meningoencephalitis in a paediatric patient.

Affective blindsight, the capacity to discriminate emotional stimuli despite bilateral damage to the primary visual cortex (V1) and without conscious awareness, offers a unique model of non-conscious visual processing. Subcortical pathways involving the pulvinar and amygdala have been proposed, but putative cortical contributions remain unclear. We examined 182 patients, including 31 with bilateral V1 lesions. Among these, 15 had cortical visual loss and 7 showed affective blindsight. Using behavioral testing, lesion symptom mapping, and tractography, we found that preserved pulvinar connectivity with both the posterior superior temporal sulcus (STS) and the amygdala is necessary for affective blindsight. These findings provide causal evidence for a multi-route architecture, identifying the pulvinar–STS pathway, alongside the pulvinar–amygdala pathway, as a critical substrate for non-conscious affective processing. ### Competing Interest Statement The authors have declared no competing interest.

LYRM7-associated mitochondrial complex III deficiency has classically been described in the literature as a childhood-onset episodic leukoencephalopathy with neuroimaging findings of cavitating periventricular and subcortical white matter loss. We describe the heterogeneous clinical and neuroimaging profile of six individuals from south India with the specific homozygous pathogenic variant in the LYRM7 gene (c.2T>C, (p.Met1?)). This is a retrospective case series featuring six cases (four pediatric, one adult, and one adolescent-onset) with the pathogenic start loss LYRM7 variant. The spectrum of neurologic manifestations and brain imaging findings documented over multiple clinic visits was analyzed and described. Vision loss and lactic acidosis were seen in all but one individual. A novel phenotype with adult-onset isolated bilateral simultaneous optic neuropathy was noted. Characteristic cavitating leukoencephalopathy in supratentorial white matter was seen in the brain MRI of three out of six individuals. A comprehensive description of our cases along with the previously published cases is provided in the table highlighting the clinical and imaging variability and the disease course. The phenotype of adult-onset isolated acute optic neuropathy can be a manifestation of LYRM7-related mitochondrial disorder. LYRM7-associated Mitochondrial Complex III deficiency should be considered in the differential diagnosis of para- and post-infectious demyelinating/inflammatory disorders, especially if there is a background of variable developmental delay, recurrence of the episodes, family history, cystic changes in cerebral white matter on imaging, or poor response to immunomodulation. The case series also exemplifies the intra-and inter-familial variability seen with this rare disorder.

In 7.7% cases of spontaneous cerebrospinal fluid (CSF) rhinorrhea, the site of leak is lateral recess of sphenoid sinus (LRS). There is paucity of studies comparing LRS leaks and demographics in general, and BMI in particular. This study aims to evaluate the clinicoradiological characteristics, treatment and outcomes of these patients. In this retrospective review of electronic medical records and imaging (Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan of the nose and paranasal sinuses) conducted at the department of ENT at a tertiary care center in South India, all data regarding demography, symptomatology, radiological features, operative findings, treatment, outcome, and postoperative complications were recorded. All patients diagnosed with sphenoid sinus CSF leak from 2010 to 2021 were included. Among the 11 patients with 12 sites of leak, the average BMI was 24.45, with a normal BMI in five patients. Of the ten patients with spontaneous CSF rhinorrhea, 60% were female. The most common comorbidity was hypertension, particularly in women. Ten patients had unilateral leaks, 60% of which were on the left side. All patients had empty sella on MRI, with the majority showing grade 4 empty sella. Intraoperatively, meningoceles were present in 72.73% of patients, with half having concomitant encephaloceles. All patients were managed endoscopically. Spontaneous CSF leaks in sphenoid sinus tend to be unilateral, more common on the left side, and involve the lateral recess. Contrary to previous studies, there was no significant gender predominance or association with obesity in this cohort.

Background:In May 2023, we investigated a cluster of neuromelioidosis notified from Tamil Nadu state in southern India to describe case characteristics and identify the infection source. Methods:We searched for probable cases presenting with fever and brainstem syndrome, supported by radiological findings suggestive of neuromelioidosis. Cases were confirmed by isolation of Burkholderia pseudomallei from tissue, blood, or cerebrospinal fluid (CSF), or by PCR. The cases were described by time (epidemic curve), place (spot map), and person (clinical characteristics). Infection sources and virulence markers were identified by genome sequencing of the clinical and environmental isolates. Whole genome sequencing data were analysed to investigate the expression of Burkholderia mallei-like bimA Bm gene, and a phylogenetic tree was constructed to study sequence similarity to the global isolates. Findings:We identified 21 probable cases between July 2022 and April 2023 (median age = 33 years; 11 females; five confirmed) across four districts in Northern Tamil Nadu. Seventeen cases were from a single district and 10 reported prior dental treatment at a clinic. Cases with dental exposure had higher fatality (8/10 vs. 1/11) and shorter time to death (median 17 days vs. 1 death at day 56) than sporadic cases. The bimA Bm gene, which is associated with neurotropism, was identified in all three clonal isolates (two from the cases and one from the environmental isolate from the in-use saline bottle). Whole genome sequencing identified the ST1553 strain as being associated with the current outbreak. Genetic analysis of 209 isolates available in the public database with metadata revealed that ST1553, the strain responsible for the outbreak, clustered with isolates from India and Australia that expressed the B. mallei-like bimA Bm allele. Interpretation:We confirmed a large cluster of neuromelioidosis from South India, likely representing sporadic cases from environmental sources and cases linked to an iatrogenic source at a dental clinic. Rapid and high case fatality among dental cases supports the direct trans-neural spread of B. pseudomallei to the brainstem following inoculation via contaminated saline. Expression of B. mallei-like bimA Bm allele may have contributed to the increased neurological manifestations of melioidosis. Funding:None.

BACKGROUND:Early childhood stunting affects around 150 million young children worldwide and leads to suboptimal human potential in later life. However, there is limited data on the effects of early childhood stunting and catch-up growth on brain morphometry. METHODS:We evaluated childhood brain volumes at nine years of age in a community-based birth-cohort follow-up study in Vellore, south India among four groups based on anthropometric assessments at two, five, and nine years namely 'Never Stunted' (NS), 'Stunted at two years and caught up by five years' (S2N5), 'Stunted at two and five years and caught up by nine years' (S2N9), and 'Always Stunted' (AS). T1-weighted magnetic resonance imaging (MRI) images were acquired using a 3T MRI scanner, and brain volumes were quantified using FreeSurfer software. Analysis of Variance (ANOVA) was used to determine the differences in brain volumetry between the stunting groups, with age and sex as covariates. The effect size ANOVA models was evaluated using Eta squared. FINDINGS:Amongst 251 children from the initial cohort, 178 children with a mean age of 9.54 underwent neuroimaging and considered for further analysis. The total brain volume, subcortical volume, bilateral cerebellar white matter, and posterior corpus callosum showed a declining trend from NS to AS. Regional cortical brain analysis showed significant lower bilateral lateral occipital volumes, right pallidum, bilateral caudate, and right thalamus volumes between NS and AS. INTERPRETATION:To the best of our knowledge, this first neuroimaging analysis to investigate the effects of persistent childhood stunting and catch-up growth on brain volumetry indicates impairment at different brain levels involving total brain and subcortical volumes, networking/connecting centres (thalamus, basal ganglia, callosum, cerebellum) and visual processing area of lateral occipital cortex.

To prospectively identify the prevalence of idiopathic intracranial hypertension (IIH) in a cohort of patients with spontaneous cerebrospinal fluid rhinorrhoea (SCSFR) using the previously published clinico-radiological Vellore criteria for IIH. Patients diagnosed with SCSFR over a 23-month period were prospectively evaluated using clinical methods and neuroimaging. Clinical evaluation included ophthalmological examination by fundoscopy and optical coherence tomography. Optic nerve sheath diameter (ONSD) measurement was performed using ultrasound scanning. Neuroimaging was performed by the acquisition of heavily T2 weighted MR images of the brain and skull base. Patients were categorised into definite, probable and no IIH using the Vellore diagnostic criteria. Fifty-five patients (45 (81.8

Objective: Acute encephalitis syndrome (AES) in children results in significant neurocognitive deficits or mortality. It is pertinent to study the AES patterns periodically to identify the changes in the etiological trends and outcomes. Our objective was to find the etiological agents of AES, mode of diagnosis, treatment given, and outcomes. Methods: We reviewed the electronic records of children aged 1 month to 15 years who were admitted with AES in our centre from January 2015 to December 2019. We analyzed the the clinical, laboratory, and radiological profile of these children and adolescents in relation to their outcome. Poor outcome was defined as death, discharge against medical advice with neurological deficits, or Glasgow Outcome Score Extended (GOS-E) d <= 5 at the time of discharge. Results: Among 250 patients admitted with AES during the study period, a definitive etiological diagnosis was established in 56.4% of children (30.4% viral, 22% bacterial). Scrub typhus (11.2%) and dengue (9%) were the two most common underlying illnesses. Serology helped in clinching the diagnosis in 30% of children. A surge in AES cases in the post-monsoon season was observed in our cohort. Third-generation cephalosporin drugs (85.7%) and acyclovir (77.7%) were the most commonly used empiric antimicrobial drugs. About one-third of children (n = 80) had a poor outcome. GCS <= 8 at presentation and requirement for invasive ventilation were found to be significant predictors of poor outcome. Conclusion: A definitive diagnosis was obtained in about half of the children with AES. Viral (30.4%) and rickettsial infections (22%) were the common etiologies identified. Poor outcome was observed in 32 % of patients.

Idiopathic intracranial hypertension (IIH) is a diagnosis of exclusion characterized by features of raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. Commonly used other terms for this entity include benign intracranial hypertension (BIH) or pseudotumor cerebri. Few case reports of systemic lupus erythematosus (SLE) presenting as IIH are available in the literature. We report a 12-year-old girl presented with chronic holocranial headache and occasional episodes of projectile vomiting for the last 6 months and then developed blurring of vision for the last month. She fulfilled the criteria for IIH. Subsequent evaluation revealed a diagnosis of SLE. The occurrence of IIH in SLE is not coincidental and is reported in 1%-5.4% of patients with SLE. Though corticosteroids have not been widely used in IIH, underlying SLE warranted administering corticosteroids with subsequent complete resolution of IIH. Pediatricians, neurologists, intensivists, and ophthalmologists should consider SLE as a differential diagnosis in children presenting with IIH.

Background The WHO 2021 introduced the term pituitary neuroendocrine tumours (PitNETs) for pituitary adenomas and incorporated transcription factors for subtyping, prompting the need for fresh diagnostic methods. Current biomarkers struggle to distinguish between high- and low-risk non-functioning PitNETs. We explored if radiomics can enhance preoperative decision-making. Methods Pre-treatment magnetic resonance (MR) images of patients who underwent surgery between 2015 and 2019 with available WHO 2021 classification were used. The tumours were manually segmented on the T1w, T1-contrast enhanced, and T2w images using 3D Slicer. One hundred Pyradiomic features were extracted from each MR sequence. Models were built to classify (1) somatotroph and gonadotroph PitNETs and (2) high- and low-risk subtypes of non-functioning PitNETs. Feature were selected independently from the MR sequences and multi-sequence (combining data from more than one MR sequence) using Boruta and Pearson correlation. Support vector machine (SVM), logistic regression (LR), random forest (RF), and multi-layer perceptron (MLP) were the classifiers used. Data imbalance was addressed using the Synthetic Minority Oversampling TEchnique (SMOTE). Performance of the models were evaluated using area under the receiver operating curve (AUC), accuracy, sensitivity, and specificity. Results A total of 222 PitNET patients (train, n = 149; test, n = 73) were enrolled in this retrospective study. Multi-sequence-based LR model discriminated best between somatotroph and gonadotroph PitNETs, with a test AUC of 0.84, accuracy of 0.74, specificity of 0.81, and sensitivity of 0.70. Multi-sequence-based MLP model perfomed best for the high- and low-risk non-functioning PitNETs, achieving a test AUC of 0.76, accuracy of 0.67, specificity of 0.72, and sensitivity of 0.66. Conclusions Utilizing pre-treatment MRI and radiomics holds promise for distinguishing high-risk from low-risk non-functioning PitNETs based on the latest WHO classification. This could assist neurosurgeons in making critical decisions regarding surgery or alternative management strategies for PitNETs after further clinical validation.