Progressive multifocal leukoencephalopathy (PML) is a rare, life-threatening, infectious, lytic, demyelinating disease that results from reactivation of the virulent JC polyomavirus (JCV) \"major opportunistic infection\" in immunosuppressed individuals. We reported a case of a young girl who presented with new onset focal neurological defect, evaluated, and laboratory and radiological findings in the context of a clinical setting confirmed HIV-related-PML infection. However, remyelination does not occur, the patients may develop complications in the long term including cognitive impairment, sensory deficits, motor deficits, and disturbances in balance. We must increase our knowledge about HIV- related PML in any patient with reduced immunity and who presented with new onset neurological defect.

OBJECTIVE: Chemotherapy is commonly used for treatment in children over three years old with high-risk medulloblastoma(MB). However, little is currently known about the therapeutic benefits and side effects of intrathecal methotrexate(MTX), warranting further research.
METHODS: In this retrospective study, patients who received intrathecal MTX during chemotherapy were included in the MTX group (n = 32), and patients that only underwent cerebrospinal fluid (CSF) cytology analysis were assigned to the control group (n = 14).
RESULTS: In the MTX group, 27(84.38%) patients had metastatic disease, 3(9.38%) had diffuse anaplasia, and 3(9.38%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 28(87.5%) patients. In the control group, 8(57.14%) patients had metastatic disease, 3(27.27%) had diffuse anaplasia, and 6(42.86%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 6(42.86%) patients. The 5-year progression-free survival was 70.99% and the 5-year overall survival was 72.99% for the MTX group, and the corresponding values were 41.67% and 50% for the control group, respectively. 6 (18.75%) patients in the MTX group with group 4 disease developed MTX-related acute leukoencephalopathy and one of them died.
CONCLUSIONS: Our findings support the addition of intrathecal MTX during chemotherapy as the optimal management for children with group 3 and SHH high-risk MB. However, it is not recommended for group 4 MB patients, especially in resource-limited regions.
BACKGROUND: Retrospective registered No.(2020 - 117).

Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls.
TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated.
Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities.
Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.

Background  Varied neurological manifestations in pediatric patients with coronavirus disease 2019 (COVID-19) have been increasingly reported from all across the world in the scientific literature. Objective  We aimed to evaluate pediatric cases with neurological symptoms and neuroimaging findings with COVID-19 infection in our hospital. Materials and Methods  Children from 0 to 12 years with laboratory evidence of COVID-19 infection and acute neurological manifestations within 3 months, who have undergone magnetic resonance imaging (MRI) were included in the study. We categorized them based on neurological findings into four groups: acute encephalitis syndrome (AES), acute flaccid paralysis (AFP), cerebrovascular event/stroke, and miscellaneous consisting of acute seizures without encephalopathy. Results  A total of 19 children with neurological manifestations related to COVID-19 infection were included in the study. AES was the most common neurological syndrome seen in 47.36%, followed by AFP in 26.31% and cardiovascular event/stroke in 21.05%. Seizure was the most common neurological symptoms in 62.15%, followed by encephalopathy in 42.10% and AFP in 26.31%. On neuroimaging, pattern observed were immune-mediated cauda equina nerve roots enhancement in 26.31% or acute disseminated encephalitis in 5.26%, small acute infarcts, hippocampal, and bilateral thalamic signal changes seen in 21.05% each, microhemorrhages and leukoencephalopathy in 15.78%, and coinfection in 5.26%. Conclusion  In our study, seizures and encephalopathy were the most common neurological symptoms with COVID-19 infection. Postinfectious immune-mediated cauda equina nerve root enhancement or acute demyelinating encephalomyelitis-like brain imaging, followed by small acute infarcts and hippocampal/thalamic signal changes were most common imaging patterns. We found overlapping neurological and MRI patterns in many children, suggesting that various pathophysiological mechanisms act individually or synergistically.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter degenerative disease manifesting as progressive cognitive decline, pyramidal, and extrapyramidal features resulting from mutations in the colony-stimulating factor-1 receptor (CSF1R) gene. We describe a sporadic case of a young man who developed five months history of progressive cognitive decline with predominant neuropsychiatric symptoms, suggestive of frontotemporal dementia. Brain magnetic resonance imaging (MRI) showed bilateral frontotemporal atrophy, high signal intensities in frontal and high parietal deep white matter with persistent diffusion restriction on follow-up imaging. Genetics showed a novel heterozygous mutation in CSF1R gene confirming the diagnosis of ALSP. Being a rare disease, and given its particular adult-onset presentation especially presenile cognitive impairment, it can pose a unique diagnostic challenge. The study highlights the importance of recognizing the disease early and broadens the clinical, genetic, and imaging spectrum of CSF1R gene mutation.

OBJECTIVE: The vast clinical and radiological spectrum of pyruvate dehydrogenase complex (PDHc) deficiency continue to pose challenges both in diagnostics and disease monitoring. Prompt diagnosis is important to enable early initiation of ketogenic diet.
METHODS: The patients were recruited from an ongoing population-based study in Sweden. All patients with a genetically confirmed diagnosis that had been investigated with an MRI of the brain were included. Repeated investigations were assessed to study the evolution of the MRI changes.
RESULTS: Sixty-two MRI investigations had been performed in 34 patients (23 females). The genetic cause were mutations in PDHA1 in 29, PDHX and DLAT in two each and PDHB in one. The lesions were prenatal developmental in 16, prenatal clastic in 18 and postnatal clastic in 15 individuals. Leigh-like lesions with predominant involvement of globus pallidus were present in 12, while leukoencephalopathy was present in six and stroke-like lesions in three individuals. A combination of prenatal developmental and clastic lesions was present in 15 individuals. In addition, one male with PDHA1 also had postnatal clastic lesions.
CONCLUSIONS: The most common lesions found in our study were agenesis or hypoplasia of corpus callosum, ventriculomegaly or Leigh-like lesions. Furthermore, we describe a broad spectrum of other MRI changes that include leukoencephalopathy and stroke-like lesions. We argue that a novel important clue, suggesting the possibility of PDHc deficiency on MRI scans, is the simultaneous presence of multiple lesions on MRI that have occurred during different phases of brain development. This article is protected by copyright. All rights reserved.

BACKGROUND: The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs).
METHODS: The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group.
RESULTS: This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3.
CONCLUSIONS: The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.

Delayed post-hypoxic leukoencephalopathy (DPHL) is a syndrome that may occur as a result of the hypoxic event, including opiate overdose. The pathophysiology of this entity is not fully known. Within a neuropsychiatric context, the diagnosis of this rare disease is important. A 39-year-old man with a history of methadone overdose presented with loss of consciousness and fever. After clinical evaluations, laboratory analysis, including various tests on blood and cerebrospinal fluid and magnetic resonance imaging, the patient was diagnosed with methadone-induced DPHL. Treatment with antioxidants, including vitamins E, C and B complex, produced a favorable outcome. In rare cases, methadone overdose may lead to DPHL. Antioxidants therapy should be considered in the treatment of this rare disorder.

OBJECTIVE: To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT).
METHODS: We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods.
RESULTS: The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients.
CONCLUSIONS: GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.

In order to evaluate the usefulness of presymptomatic MRI, we performed 3T brain MRI and Sanger gene sequencing in a proband with suspected but not confirmed CADASIL and her apparently asymptomatic father. The 35-year-old proband presented with migraine with visual aura. Brain MRI showed diffuse leukoencephalopathy, suggesting CADASIL. NOTCH3 gene sequencing (exons 3-6) was negative. Family history was unclear. The MRI study of the father documented severe, diffuse leukoencephalopathy, with involvement of the temporal poles and external capsules (not observed in the proband), and lacunar infarcts in the absence of cardiac disease or risk factors. The MRI findings were in favour of an autosomal dominant mode of transmission and reinforced the hypothesis of CADASIL. Full NOTCH3 gene sequencing uncovered a novel exon 8 mutation (c.1337G>A; p.Cys446Tyr) outside the most commonly mutated region of NOTCH3. The novel mutation leads to a typical MRI pattern but a variable overall phenotype. The study underlines the usefulness of combining full gene sequencing with familial MRI studies.