White Matter Signal Changes Research Articles

Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS.

Objective: Amyotrophic lateral sclerosis (ALS) exhibits several different presentations and clinical phenotypes. Of these, classic ALS (ALS-Cl), which is the most common phenotype, presents with relatively equal amounts of upper motor neuron and lower motor neuron signs. Magnetic resonance imaging (MRI) provides a noninvasive way to assess central nervous system damage in these patients. To our knowledge no study is available where exploratory whole brain grey matter (GM) and white matter (WM) network analysis is performed considering only the ALS-Cl subgroup of ALS patients. Methods: GM voxel-based morphometry analysis and WM network analysis using graph theory was performed in the MRI dataset of 14 neurologic controls and 25 ALS-Cl patients. Results and Conclusions: No significant GM differences were observed between ALS-Cl and neurologic controls. WM network revealed significant (p < 0.05) reduction and increase in degree measure in several extramotor brain regions of ALS-Cl patients. Both global and local graph metrics revealed significant abnormal values in ALS-Cl patients when compared to neurologic controls. Significant WM changes in ALS-Cl patients with no significant GM changes suggest that neurodegeneration may onset as an "axonopathy" in this ALS subtype.

10215-ML-7 CLINICAL OUTCOME OF TIRABRUTINIB IN PCNSL REFRACTORY TO R-MPV THERAPY

Abstract In recent years, R-MPV therapy has been widely used for treatment of primary central nervous system lymphoma (PCNSL). Although a high response rate and favorable prognosis have been reported with R-MPV therapy using multiple drugs, the treatment strategy for cases refractory to induction therapy has not been established. High-dose radiotherapy is currently recommended for refractory cases, however, the efficacy and frequency of adverse events such as leukoencephalopathy are not yet clear. Tirabrutinib has been available for recurrent or refractory PCNSL cases since 2020. However, there have been few reports on the results of tilabrutinib in these refractory cases. We have been using tirabrutinib for these refractory cases since its introduction. Here, we compared the results of tirabrutinib with those before the introduction of tirabrutinib. We investigated 30 cases with PCNSL treated with R-MPV at our hospital since 2013. 5 (16.7%) of the 30 cases revealed refractory to R-MPV. Two cases were promptly treated with irradiation (total 40-45 Gy) and both remitted, but one (a 70's male) had extensive white matter changes. One case (40's female) also had white matter changes but maintained CR for 4 years and 8 months. All three patients treated with tirabrutinib achieved CR or PR immediately, and two patients (a 60's woman and a 70's man) received whole brain irradiation of 23.4 Gy at 26 and 28 days after tirabrutinib introduction and remained in remission for 2 years 3 months and 2 years 4 months respectively with no significant white matter changes. The results suggest that tirabrutinib may be useful for cases refractory to R-MPV therapy. Because the long-term results of tirabrutinib are not yet clear, careful consideration should be given to the necessity of radiotherapy for cases who have achieved remission with tirabrutinib.

Abstract #1411492: Loss-of-Function EGFR Mutation in Bartter Syndrome with Neonatal Epithelial Autoinflammation

Bartter syndrome (BS) manifests as hypokalemic and hypochloremic metabolic alkalosis and hyperreninemic hyperaldosteronism. Loss-of-function (LoF) mutations in any of seven genes cause different subtypes of BS. We sought the genetic cause of BS in a 17-year-old patient who presented with progressive nephrocalcinosis, hypercalciuria, polyuria, metabolic alkalosis, hypokalemia, significantly high urine chloride, failure-to-thrive, hypergammaglobulinemia, abnormal cerebral white matter signal changes, autoinflammation, and moderate intellectual disability. No mutations were identified in previously BS-associated genes in this patient with consanguineous parents, and all seven genes resided outside of genomic regions of homozygosity (ROH). Instead, whole-exome sequencing and homozygosity mapping identified a homozygous intronic mutation, c.2702-2A >G, in the epidermal growth factor receptor (EGFR) gene within an ROH of ∼28 Mb in chromosome 7p. Examination of the patient's RNA by RNA-Seq and RT-PCR confirmed the pathogenicity of this variant, causing aberrant splicing resulting in an in-frame retention of 27 nucleotides of intron 22 of EGFR. Immunofluorescence of proband's skin, with a monoclonal antibody, revealed reduced protein level of EGFR, instead of complete protein absence, presumably justifying the life compatibility of this mutation. Previously, three loss-of-function EGFR mutations have been reported in patients with neonatal lethal inflammatory skin lesions and bowel disease. Thus, these observations provide an association of an autosomal recessive BS with hypomorphic EGFR mutation, expanding the phenotypic spectrum of the EGFR-associated disorders.

Clinical and Neurophysiological Features of Epilepsy in Pediatric Patients with Vanishing White Matter Disease-A single institute experience and literature review (P12-9.006)

<h3>Objective:</h3> Refractory epilepsy is a common presentation in Vanishing white matter disease (VWMD) patients. However, there is little literature describing the nature and evolution of seizures. We aim to study the electroencephalograpic findings in patients with a genetically confirmed diagnosis of VWMD, and their correlation with MRI progression and clinical status longitudinally. <h3>Background:</h3> Vanishing White Matter Disease (VWMD) is one of the most prevalent leukodystrophies in pediatric patients with unique clinical, pathological, and molecular features. It mostly affects children, but may develop at all ages, from birth to senescence. Incidence in one study is reported to be 1 in 80,000 live births. The molecular basis of the disease has been shown to be due to mutations in subunits of Eukaryotic Translation Initiation Factor 2B (eIF2B) ie eIF2B 1–5. <h3>Design/Methods:</h3> An IRB approved retrospective chart review was conducted at Children’s Medical Center, Dallas TX. The initial search pulled up 42 patients that had an associated diagnosis of leukodystrophy. Four of these 42 patients were found to have a genetically confirmed diagnosis of VWMD. <h3>Results:</h3> In our cohort, there were 3males and 1female. Age of diagnosis ranged between 2–10 years and mutations in EIF2B5 was the most common. The earliest seizure onset was noted at 2 years of age at the time of diagnosis. Patients that presented with intractable seizures were noted to have significant MRI changes. Average time of seizure onset from time of diagnosis was 1.6 years. Our patient that was diagnosed with VWMD at 10 years of age did not go on to develop seizures and his EEG did not have any epileptiform discharges. His MRI did not show significant white matter changes and clinically patient had mild to moderate deficits. <h3>Conclusions:</h3> We observe that there is a wide range of severity of epilepsy in these patients &amp; not all patients with a diagnosis of VWMD go on to develop seizures. <b>Disclosure:</b> Dr. Laheji has nothing to disclose. Dr. Lowden has nothing to disclose.

Automation of a Rule-based Workflow to Estimate Age from Brain MR Imaging of Infants and Children Up to 2 Years Old Using Stacked Deep Learning.

Myelination-related MR signal changes in white matter are helpful for assessing normal development in infants and children. A rule-based myelination evaluation workflow regarding signal changes on T1-weighted images (T1WIs) and T2-weighted images (T2WIs) has been widely used in radiology. This study aimed to simulate a rule-based workflow using a stacked deep learning model and evaluate age estimation accuracy. The age estimation system involved two stacked neural networks: a target network-to extract five myelination-related images from the whole brain, and an age estimation network from extracted T1- and T2WIs separately. A dataset was constructed from 119 children aged below 2 years with two MRI systems. A four-fold cross-validation method was adopted. The correlation coefficient (CC), mean absolute error (MAE), and root mean squared error (RMSE) of the corrected chronological age of full-term birth, as well as the mean difference and the upper and lower limits of 95% agreement, were measured. Generalization performance was assessed using datasets acquired from different MR images. Age estimation was performed in Sturge-Weber syndrome (SWS) cases. There was a strong correlation between estimated age and corrected chronological age (MAE: 0.98 months; RMSE: 1.27 months; and CC: 0.99). The mean difference and standard deviation (SD) were -0.15 and 1.26, respectively, and the upper and lower limits of 95% agreement were 2.33 and -2.63 months. Regarding generalization performance, the performance values on the external dataset were MAE of 1.85 months, RMSE of 2.59 months, and CC of 0.93. Among 13 SWS cases, 7 exceeded the limits of 95% agreement, and a proportional bias of age estimation based on myelination acceleration was exhibited below 12 months of age (P = 0.03). Stacked deep learning models automated the rule-based workflow in radiology and achieved highly accurate age estimation in infants and children up to 2 years of age.

Role of Electroencephalogram (EEG) and Magnetic Resonance Imaging (MRI) Findings in Early Recognition and Diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 Disease.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a very rare neurodegenerative lysosomal storage disorder. Progression is rapid and irreversible, making early diagnosis crucial for timely treatment. A group of pediatric neurologists and neuroradiologists with expertise in CLN2 convened to discuss early electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings in CLN2 diagnosis. Of 18 CLN2 cases, 16 (88.9%) had background slowing and 16 (88.9%) had epileptiform discharges on initial EEG. Seven of 17 (41.2%) patients who received intermittent low-frequency photic stimulation had a photoparoxysmal response. Initial MRIs showed subtle cerebellar (n = 14, 77.8%) or cerebral (n = 9, 50.0%) atrophy, white matter abnormalities (n = 11, 61.1%), and basal ganglia T2 hypointensity (n = 6, 33.3%), which became more apparent on follow-up MRI. The recognition of even subtle cerebellar atrophy and white matter signal changes in children aged 2-5 years who present with language delay, new-onset seizures, and an EEG with epileptiform discharges and background slowing should prompt investigation for CLN2. Because these early signs are not unique to CLN2, genetic testing is essential early in the diagnostic journey.

Symptomatic care of late-onset Alexander disease presenting with area postrema-like syndrome with prednisolone; a case report

BackgroundAlexander disease (AxD) is classified into AxD type I (infantile) and AxD type II (juvenile and adult form). We aimed to determine the potential genetic cause(s) contributing to the AxD type II manifestations in a 9-year-old male who presented area postrema-like syndrome and his vomiting and weight loss improved after taking prednisolone.Case presentationA normal cognitive 9-year-old boy with persistent nausea, vomiting, and a significant weight loss at the age of 6 years was noticed. He also experienced an episode of status epilepticus with generalized atonic seizures. He showed non-febrile infrequent multifocal motor seizures at the age of 40 days which were treated with phenobarbital. He exhibited normal physical growth and neurologic developmental milestones by the age of six. Occasionally vomiting unrelated to feeding was reported. Upon examination at 9 years, a weak gag reflex, prominent drooling, exaggerated knee-deep tendon reflexes (3+), and nasal tone speech was detected. All gastroenterological, biochemical, and metabolic assessments were normal. Brain magnetic resonance imaging (MRI) revealed bifrontal confluent deep and periventricular white matter signal changes, fine symmetric frontal white matter and bilateral caudate nucleus involvements with garland changes, and a hyperintense tumefactive-like lesion in the brain stem around the floor of the fourth ventricle and area postrema with contrast uptake in post-contrast T1-W images. Latter MRI at the age of 8 years showed enlarged area postrema lesion and bilateral middle cerebellar peduncles and dentate nuclei involvements. Due to clinical and genetic heterogeneities, whole-exome sequencing was performed and the candidate variant was confirmed by Sanger sequencing. A de novo heterozygous mutation, NM_001242376.1:c.262 C > T;R88C in exon 1 of the GFAP (OMIM: 137,780) was verified. Because of persistent vomiting and weight loss of 6.0 kg, prednisolone was prescribed which brought about ceasing vomiting and led to weight gaining of 3.0 kg over the next 3 months after treatment. Occasional attempts to discontinue prednisolone had been resulting in the reappearance of vomiting.ConclusionsThis study broadens the spectrum of symptomatic treatment in leukodystrophies and also shows that R88C mutation may lead to a broad range of phenotypes in AxD type II patients.

A man with Erb’s disease

A man, currently aged 72, developed a spastic paraparesis without sensory abnormalities progressing to wheel-chair dependence and late urinary incontinence over 14 years. Apart from a history of type 2 diabetes mellitus, he was otherwise well. Extensive blood and CSF investigations including screening for HIV, HTLV1, syphilis, and Lyme disease were normal or negative. There was no evidence of neuropathy or denervation on EMG. MRI showed mild non-specific white matter signal change in both cerebral hemi- spheres. A provisional diagnosis of primary lateral sclerosis (PLS) was revised with the finding of elevated Very Long Chain Fatty Acids (VLCFAs). Genetic testing revealed a novel missense variant c.1771C&gt;Gp. (Arg591Gly) in exon 7 of the ABCD1 gene. Mutation in ABCD1 transporter leads to accumulation of VLCFAs in the peroxisomes and cytosol which is toxic, causing oxidative stress and demyelination in the CNS and PNS. Literature review did not reveal reports of AMN mimicking PLS. Our patient highlights the importance of screening VLCFAs (abnormal in ~99% of men with AMN) in suspected PLS, a diagnosis of exclusion. Diagnosis of ALD/AMN allows genetic counselling, screening for adrenal failure, and access to stem cell therapy for children with asymptomatic cerebral onset ALD.sara.leddy1@nhs.net

Phenotypic Pleiotropy in Arginase Deficiency: A Single Center Cohort.

Arginase deficiency is considered a masquerader of diplegic cerebral palsy. The rarity of hyperammonemic crisis and the slowly progressive course has made it a unique entity among the urea cycle defects. The aim of our study is to describe the varied phenotypic spectrum of children with arginase deficiency. This retrospective study included children and adolescents aged <18 years with a biochemical or genetic diagnosis of arginase deficiency from May 2011 to May 2022. Data were collected from the hospital's electronic database. The clinical presentation, laboratory parameters at baseline and during metabolic decompensation, neuroimaging, electroencephalography findings, and molecular studies were analyzed. About 11 children from nine families with biochemically or genetically proven arginase deficiency were analyzed. The male: female ratio was 2.7:1. Consanguineous parentage was observed in all children. The median age at presentation was 36 months (Range: 5 months-18 years). All children with onset of symptoms in early childhood had a predominant delay in motor milestones of varying severity. Metabolic decompensation with encephalopathy occurred in all except two children (n = 9, 81.8%). Pyramidal signs were present in all patients and additional extrapyramidal signs in two children. Positive family history was present in four probands. Seizures occurred in all children. Epilepsy with electrical status in slow wave sleep and West syndrome was noted in three children. All children had elevated ammonia and arginine at the time of metabolic crisis. The spectrum of neuroimaging findings includes periventricular, subcortical, and deep white matter signal changes and diffusion restriction. The mean duration of follow-up was 38.6 ± 34.08 months. All patients were managed with an arginine-restricted diet and sodium benzoate with or without ornithine supplementation. Spastic diparesis, recurrent encephalopathy, presence of family history, and elevated serum arginine levels must alert the clinician to suspect arginase deficiency. Atypical presentations in our cohort include frequent metabolic crises and epileptic encephalopathy. Early identification and management will ensure a better neurodevelopmental outcome.

Breast cancer-associated opsoclonus-myoclonus syndrome: a case report

BackgroundParaneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.Case presentationA 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.ConclusionsIn conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.

Progressive Ataxia and Neurologic Regression in RFXANK-Associated Bare Lymphocyte Syndrome.

ObjectiveTo identify the genetic cause of a late-onset immunodeficiency and subacute progressive neurodegenerative disease affecting cognition, motor, visual, and cerebellar systems in a patient with a family history of 2 younger siblings with an early-onset immunodeficiency disease.MethodsPhysical examinations, immunologic, brain MRI, whole-exome sequencing, and segregation studies were used to identify the genetic and neuroimmunologic etiology of disease in this family.ResultsWe identified a homozygous loss-of-function (LOF) mutation (c.271+1G>C) in the RFXANK gene in the index patient and one of his younger affected siblings. Biallelic mutations in the RFXANK gene are known to cause bare lymphocyte syndrome (BLS) type II, complementation group B. The clinical and immunologic investigations were consistent with a clinical diagnosis of BLS type II. MRI demonstrated global cerebral and cerebellar atrophy with white matter signal changes in the index case.ConclusionsIn addition to BLS type II, our study has expanded and further characterized the phenotype associated with the LOF of RFXANK to include progressive neurodegenerative disease. Our study also provides evidence for the impact of LOF on brain development and function. Thus, early bone marrow transplantation, as a standard of care for BLS, could prove to be protective against the neurologic phenotypes in this group of patients.

A novel missense variant in the LMNB2 gene causes progressive myoclonus epilepsy.

Progressive myoclonus epilepsies (PMEs) are a group of disorders embracing myoclonus, seizures, and neurological dysfunctions. Because ofthe genetic and clinicalheterogeneity, a large proportion ofPMEs cases have remained molecularly undiagnosed. Thepresent study aimed to determine the underlying genetic factors that contribute to the PME phenotype in an Iranian female patient. We describe a consanguineous Iranian family with autosomal recessive PME that had remained undiagnosed despite extensive genetic and pathological tests. After performing neuroimaging and clinical examinations, due to heterogeneity of PMEs, the proband was subjected to paired-end whole-exome sequencing and the candidate variant was confirmed by Sanger sequencing. Various in-silico tools were also used to predict the pathogenicity of the variant. In this study, we identified a novel homozygous missense variant (NM_032737.4:c.472C > T; p.(Arg158Trp)) in the LMNB2 gene (OMIM: 150341) as the most likely disease-causing variant. Neuroimaging revealed a progressive significant generalized atrophy in the cerebral and cerebellum without significant white matter signal changes. Video-electroencephalography monitoring showed a generalized pattern of high-voltage sharp waves in addition to multifocal spikes and waves compatible with mixed type seizures and epileptic encephalopathic pattern. Herein, we introduce the second case of PME caused by a novel variant in the LMNB2 gene. This study also underscores the potentiality of next-generation sequencing in the genetic diagnosis of patients with neurologic diseases with an unknown cause.

A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses.

Mutations in CLN3 (OMIM: 607042) are associated with juvenile neuronal ceroid lipofuscinoses (JNCL)-a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration. The study aimed to determine the underlying genetic factors justifying the NCL phenotype in a large Iraqi consanguineous family. Four affected individuals with an initial diagnosis of NCL were recruited. By doing neuroimaging and also pertinent clinical examinations, e.g. fundus examination, due to heterogeneity of neurodevelopmental disorders, the proband was subjected to the paired-end whole-exome sequencing to identify underlying genetic factors. The candidate variant was also confirmed by Sanger sequencing. Various in silico predictions were used to show the pathogenicity of the variant. This study revealed a novel homozygous frameshift variant-NM_000086.2: c.1127del; p.(Leu376Argfs*15)-in the exon 14 of the CLN3 gene as the most likely disease-causing variant. Three out of 4 patients showed bilateral vision loss (< 7years) and retinal degeneration with macular changes in both eyes. Electroencephalography demonstrated the loss of normal posterior alpha rhythm and also low amplitude multifocal slow waves. Brain magnetic resonance imaging of the patients with a high degree of deterioration showed mild cerebral and cerebellar cortical atrophy, mild ventriculomegaly, thinning of the corpus callosum and vermis, and non-specific periventricular white matter signal changes in the occipital area. The novel biallelic deletion variant of CLN3 was identified that most probably led to JNCL with variable expressivity of the phenotype. This study also expanded our understanding of the clinical and genetic spectrum of JNCL.

A pilot study of the impact of an exercise intervention on brain structure, cognition, and psychosocial symptoms in individuals with relapsing-remitting multiple sclerosis

BackgroundDespite pharmacological treatment, many individuals with multiple sclerosis (MS) continue to experience symptoms and medication side effects. Exercise holds promise for MS, but changes in brain structure following exercise have not been thoroughly investigated, and important cognitive and psychosocial variables are rarely primary outcomes. The aim of this pilot study was to investigate whether a 12-week exercise intervention would improve white matter integrity in the brain, or cognition, symptoms of fatigue, and depressed mood for individuals with relapsing-remitting MS (RRMS).MethodThirteen participants completed 12 weeks of speeded walking. Baseline and post-intervention testing included 3T diffusion tensor imaging (DTI) to assess white matter and neuropsychological testing to assess cognition, fatigue, and mood. Image pre-processing and analyses were performed in functional magnetic resonance imaging of the Brain Software Library.ResultsPost-intervention, there were no significant changes in white matter compared to baseline. Post-intervention, individuals with RRMS performed significantly better on the Symbol Digit Modalities Test (SDMT), reported fewer perceived memory problems, and endorsed less fatigue. Performance was not significantly different on Trails or Digit Span, and there were no significant changes in reports of mood.ConclusionAlthough 12 weeks of speeded walking did not improve white matter integrity, exercise may hold promise for managing some symptoms of RRMS in the context of this study population.

Giant axonal neuropathy with novel GAN pathogenic variant in a patient of consanguineous origin from Poonch Jammu and Kashmir-India

Giant axonal neuropathy (GAN) is a severe and rare autosomal recessive neurodegenerative disorder of childhood affecting both the peripheral and central nervous systems (CNS). It is caused by mutations in the GAN (gigaxonin) gene linked to chromosome 16q24. Here, we present a 15-year-old male patient with GAN from a consanguineous family of Poonch, Jammu and Kashmir (J&K)-India. Whole-exome sequencing (WES) was employed to unravel the genetic cause of GAN in the proband. Pathogenic variant identified with WES was confirmed in other affected sibling using Sanger sequencing. Magnetic resonance imaging (MRI) and detailed clinical investigation was also carried out on proband. WES revealed a novel homozygous stopgain GAN mutation (NM_022041, c.C1028G, p.S343X) in the patient. MRI of brain displayed bilateral symmetrical confluent areas of deep white matter signal changes affecting periventricular regions (withsparing ofsubcortical U-fibers), posterior limbs of internal capsules, thalami, external capsules, and semioval centers. The patient was initially suspected to be a case of metachromatic leukodystrophy. However, WES analysis revealed a pathogenic variant in GAN gene as causative. No other pathogenic variant relevant to any other type of dystrophy was reported in WES. Our findings extend the geographical distribution of GAN to even a very remote region in India, extend the mutational and imaging spectrum of GAN and substantiate the need for introducing genetic testing and counselling in primary referral centers/district hospitals in India.

Cyclosporine-induced Leukoencephalopathy Precipitated Following Interaction with Ciprofloxacin.

ABSTRACTA bone marrow transplant recipient on cyclosporine initiated on ciprofloxacin for a renal abscess presented with encephalopathy, right hemiparesis, and multiorgan dysfunction. Imaging revealed white matter signal changes characteristic of cyclosporine leukoencephalopathy. This case illustrates the potential drug interaction of cyclosporine with ciprofloxacin and the need to exercise caution while prescribing antibiotics with cyclosporine.

Neurological Manifestations of Congenital Cytomegalovirus Infection at a Tertiary Care Centre from Southern India.

Background Cytomegalovirus (CMV) is a ubiquitous herpes virus. It is the most common congenital viral infection. Data on congenital CMV in India are lacking and hence the present study was undertaken. Objectives The aim of the study is to evaluate the clinical and radiological profile of neurological manifestations of congenital CMV infections in tertiary care hospital. Methods This is a retrospective chart review of the clinical and laboratory profile of congenital CMV infections presenting from January 2018 to February 2020 to a tertiary care hospital in Southern India. Details of clinical profile, serological and neuroimaging data were obtained and analyzed. Results A total of 42 cases with female preponderance (57%) were reported during the study period. The mean age of presentation was 2.9 years. Clinical features were developmental delay (81%), microcephaly (93%), seizures (33%), intrauterine growth restriction (19%), neonatal encephalopathy (10%), anemia (9%), jaundice (10%), hepato-splenomegaly (7%), and eye abnormalities (14%). Antenatal maternal fever was reported by 12%. Sensorineural hearing loss was present in 57%. Neuroimaging showed periventricular calcification (79%), cerebral atrophy (69%), ventricular dilatation (55%), malformations (26%), dysmyelination (12%), and temporal lobe cysts (5%). CMV-immunoglobulin-M positivity was seen in 14 cases (33%), urinary polymerase chain reaction for CMV was positive in 21 cases (50%), and clinical diagnosis was done in seven cases (16%). Conclusion Common findings in congenital CMV are microcephaly, developmental delay, seizures, anemia, and sensorineural hearing loss. Common neuroimaging findings are periventricular calcification, cerebral atrophy, malformation, white matter signal changes, and cysts. CMV can mimic like cerebral palsy, malformations of the brain, demyelinating disorders, and calcified leukoencephalopathies like Aicardi-Goutières syndrome.

Incidence of brain lesions in moderate-late preterm infants assessed by cranial ultrasound and MRI: The BIMP-study

PurposeTo evaluate the incidence and characteristics of brain lesions in moderate-late preterm (MLPT) infants, born at 32–36 weeks’ gestation using cranial ultrasound (cUS) and magnetic resonance imaging (MRI). MethodsProspective cohort study carried out at Isala Women and Children’s Hospital between August 2017 and November 2019. cUS was performed at postnatal day 3–4 (early-cUS), before discharge and repeated at term equivalent age (TEA) in MLPT infants born between 32+0 and 35+6 weeks’ gestation. At TEA, MRI was also performed. Several brain lesions were assessed e.g. hemorrhages, white matter and deep gray matter injury. Brain maturation was visually evaluated. Lesions were classified as mild or moderate-severe. Incidences and confidence intervals were calculated. Results166 MLPT infants were included of whom 127 underwent MRI. One or more mild lesions were present in 119/166 (71.7 %) and moderate-severe lesions in 6/166 (3.6 %) infants on cUS and/or MRI. The most frequent lesions were signs suggestive of white matter injury: inhomogeneous echogenicity in 50/164 infants (30.5 %) at early-cUS, in 12/148 infants (8.1 %) at TEA-cUS and diffuse white matter signal changes (MRI) in 27/127 (23.5 %) infants. Cerebellar hemorrhage (MRI) was observed in 16/127 infants (12.6 %). Delayed maturation (MRI) was seen in 17/117 (13.4 %) infants. Small hemorrhages and punctate white matter lesions were more frequently detected on MRI than on cUS. ConclusionsIn MLPT infants mild brain lesions were frequently encountered, especially signs suggestive of white matter injury and small hemorrhages. Moderate-severe lesions were less frequently seen.

Rapid Progression of White Matter Signal Changes and Frontotemporal Atrophy in Globular Glial Tauopathy.

Rapid Progression of White Matter Signal Changes and Frontotemporal Atrophy in Globular Glial Tauopathy.

Teaching Neuroimages: COVID-19-Associated Acute Disseminated Encephalomyelitis With Corpus Callosal Hemorrhage.

A 55-year-old man with severe coronavirus disease 2019 (COVID-19) required ventilation and hemofiltration. Central venous catheter thrombosis necessitated heparin infusion. On day 20 postadmission, impaired conscious level, complex ophthalmoplegia, and hyperreflexia prompted noncontrast neuroimaging, demonstrating corpus callosal and right subinsular hemorrhage with diffuse white matter signal change (figure). CSF analysis was not performed due to clinical concerns regarding raised intracranial pressure. Administration of high-dose corticosteroids led to clinical and radiologic improvement (figure).