Polymicrogyria is estimated to be one of the most common brain malformations, accounting for ∼16% of malformations of cortical development. However, the prevalence and incidence of polymicrogyria is unknown. Our aim was to estimate the prevalence, incidence rate, neuroimaging diversity, aetiology, and clinical phenotype of polymicrogyria in a population-based paediatric cohort. We performed a systematic search of MRI scans at neuroradiology department databases in Stockholm using the keyword polymicrogyria. The study population included all children living in the Stockholm region born from January 2004 to June 2021 with polymicrogyria. Information on the number of children living in the region during 2004–21 was collected from records from Statistics Sweden, whereas the number of births for each year during the study period was collected from the Swedish Medical Birth Register. All MRI scans were re-evaluated, and malformations were classified by a senior paediatric neuroradiologist. The prevalence and yearly incidence were estimated. Clinical data were collected from medical records. A total of 109 patients with polymicrogyria were included in the study. The overall polymicrogyria prevalence in Stockholm was 2.3 per 10 000 children, and the overall estimated yearly incidence between 2004 and 2020 was 1.9 per 10 000 person-years. The most common polymicrogyria distribution was in the frontal lobe (71%), followed by the parietal lobe (37%). Polymicrogyria in the peri-sylvian region was observed in 53%. Genetic testing was performed in 90 patients revealing pathogenic variants in 32%. Additionally, 12% had variants of uncertain significance. Five patients had a confirmed congenital infection, and in six individuals, the cause of polymicrogyria was assumed to be vascular. Epilepsy was diagnosed in 54%. Seizure onset during the first year of life was observed in 44%. The most common seizure types were focal seizures with impaired awareness, followed by epileptic spasms. Thirty-three of 59 patients with epilepsy (56%) were treated with more than two anti-seizure medications, indicating that pharmacoresistant epilepsy is common in polymicrogyria patients. Neurodevelopmental symptoms were observed in 94% of the individuals. This is the first population-based study on polymicrogyria prevalence and incidence. Confirmed genetic aetiology was present in one-third of individuals with polymicrogyria. Epilepsy was common in this patient group, and the majority had pharmacoresistant epilepsy. These findings increase our knowledge about polymicrogyria and will help in counselling patients and their families.

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. Methods: Children aged <18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). Results: Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. Conclusions: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.

Neurodegeneration (ND) is a severe complication of Langerhans cell histiocytosis (LCH), yet its underlying biology and reliable biomarkers remain poorly defined. The aim of this study was to (1) gain insight into neuroimmunological mechanisms governing ND and (2) assess the clinical value of established and novel biomarkers for ND‐LCH. We applied targeted proteomics and neurofilament light chain (NFL) assays to cerebrospinal fluid (CSF) and plasma from LCH patients with and without ND, with control cohorts. ND‐LCH exhibited a distinct CSF proteomic profile characterized by increased decoy receptors, including interleukin‐1 receptor type 2 (IL‐1RT2), macrophage activation markers, and cytotoxic and immunoregulatory proteins. CSF IL‐1RT2 showed higher specificity for ND‐LCH than CSF NFL (0.99 [0.99–1.0] vs. 0.88 [0.80–0.96]) and tracked longitudinal disease changes. Plasma analyses revealed a complementary immune signature in which NFL correlated with CSF markers, including IL‐1RT2, and distinguished ND‐LCH from controls. In independent plasma NFL cohorts from France and Japan, elevated levels were confirmed in adults with histiocytosis‐associated ND. These findings define a neuroinflammatory signature of ND‐LCH and identify IL‐1RT2 as a novel candidate biomarker for diagnosis and monitoring.

PAX6 encodes a dosage‐sensitive transcription factor that is essential for eye development. Heterozygous PAX6 disease is well characterized, but biallelic disease is extremely rare and has been associated with anophthalmia, severe brain malformations, and perinatal lethality. Here we report the first adult patient with biallelic pathogenic PAX6 variants and describe a novel phenotype that includes severe microphthalmia, anosmia, and autism spectrum disorder, Level 1. Notably, intellectual function was preserved. Genome sequencing revealed compound heterozygosity for the missense variant c.622C>T p.(Arg208Trp), inherited from the patient's mother diagnosed with sclerocornea and iris hypoplasia, and the nonsense variant c.718C>T p.(Arg240*), inherited from the patient's father diagnosed with aniridia. We compare the phenotype and genotype with previously reported biallelic patients and observe that the neurological phenotype of the patient fits the pattern observed in PAX6 haploinsufficiency. We propose that the severe microphthalmia is the result of haploinsufficiency and a hypomorphic, eye‐restricted effect of the missense variant, which is predicted to affect the DNA‐binding homeodomain of PAX6 . Together, these findings expand the phenotypic spectrum of biallelic PAX6 disease and suggest that the homeodomain may have a tissue‐specific role that is critical for eye development but largely dispensable for brain development.