Fulminating Autoimmune Demyelination with Optic Neuropathy in a Case of Pediatric Cerebral Adrenoleukodystrophy: Case Report and Review of the Literature

2021 ◽  
Author(s):  
Kanya Singhapakdi ◽  
Kamal Sharma ◽  
Paul Maertens
Keyword(s):  
Optic Neuropathy ◽  
Phenotypic Variability ◽  
Brain Mri ◽  
High Plasma ◽  
Oligoclonal Bands ◽  
Childhood Onset ◽  
Psychomotor Slowing ◽  
Immunomodulating Therapy ◽  
The Central Nervous System ◽  
Autoimmune Demyelination

AbstractX-linked adrenoleukodystrophy (ALD) is a leukodystrophy characterized not only by progressive loss of myelin in the central nervous system due to dysmyelination, but also by acute, subacute, or chronic inflammatory demyelination. This results in the phenotypic variability of cerebral ALD (cerALD), which is independent of the genotype. In this manuscript, we report a fulminant presentation with fluctuating encephalopathy and visual loss in a patient with childhood onset cerALD. Brain MRI showed symmetric confluent occipito-temporal demyelination with severe disruption of the blood–brain barrier and prechiasmal optic neuropathy. The patient's cerebral spinal fluid (CSF) demonstrated an elevated IgG index, myelin basic proteins, and oligoclonal bands. Within 48 hours of receiving immunomodulating therapy, the patient's symptoms of psychomotor slowing, visual impairment, and areflexia partially resolved. High plasma C26:0 levels and high ratios of C24/22 and C26/22 were diagnostic of ALD. It has been shown that environmental factors play an important role in the inflammatory demyelination responsible for the severe phenotypes of cerALD.

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

2020 ◽  
Author(s):  
Margherita Nosadini ◽  
Gianluca D'Onofrio ◽  
Maria Federica Pelizza ◽  
Concetta Luisi ◽  
Davide Padrin ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Impairment ◽  
De Novo Mutation ◽  
Oligoclonal Bands ◽  
Emotional Stimuli ◽  
Childhood Onset ◽  
Ataxic Gait

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C > T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

Sporadic Creutzfeldt-Jakob Disease: Diagnosing Typical and Atypical Presentations under Limited Circumstances

2021 ◽  
pp. 1-7
Author(s):  
Shazma Khan ◽  
Sara Khan
Keyword(s):  
Developing Countries ◽  
Brain Mri ◽  
Tertiary Care ◽  
Rapid Onset ◽  
Spongiform Encephalopathy ◽  
Care Hospital ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Missed Diagnosis ◽  
Atypical Presentations

<b><i>Introduction:</i></b> Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible disorder of the central nervous system caused by the transformation of normal prion protein into an abnormal misfolded form. The process begins spontaneously and runs a vicious cycle to cause spongiform encephalopathy, rapidly resulting in death. Amply described in the western literature, CJD is scarcely reported in Asia due to certain limitations including missed diagnosis, under-reporting, and rarity of the disease. Brain MRI, electroencephalogram, cerebrospinal fluid testing, and biopsy of the infected brain tissue support the diagnosis in cases of clinical suspicion. However, the diagnosis can still be made with limited available resources in developing countries. <b><i>Method:</i></b> A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. <b><i>Results:</i></b> Eleven cases labeled as sCJD are identified based on the European MRI-CJD consortium criteria. This is the first study on CJD from Pakistan, which includes both the typical and atypical presentations. <b><i>Conclusion:</i></b> Even with limited testing available, the diagnosis of CJD can be made with confidence in the developing countries, provided the suspicion is kept high in cases of rapid onset dementia and acute behavioral changes.

scholarly journals Pediatric Multiple Sclerosis in Portugal: A Multicentre Study

2016 ◽  
Vol 29 (7-8) ◽  
pp. 425 ◽  
Author(s):  
Ana Sofia Correia ◽  
Luís Augusto ◽  
Joana Meireles ◽  
Joana Pinto ◽  
Ana Paula Sousa
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Brain Magnetic Resonance Imaging ◽  
Oligoclonal Bands ◽  
Childhood Onset ◽  
Multicentric Study ◽  
Pediatric Multiple Sclerosis ◽  
Adolescent Groups ◽  
Reported Data ◽  
Cerebrospinal Fluid Pleocytosis

Introduction: Multiple sclerosis is most often diagnosed among young adults but less frequently it may present during childhood or adolescence. In Portugal, there has been only one previous single-center, pediatric multiple sclerosis study. The main objective was the evaluation of the demographic, clinical, laboratorial and neuroradiological characteristics of patients with pediatric-onset multiple sclerosis in Portugal. The secondary objectives were to compare the characteristics of childhood-onset multiple sclerosis and adolescent-onset multiple sclerosis and to characterize the treatments prescribed.Material and Methods: We performed a retrospective observational, multicentric study. We reviewed data of all patients with multiple sclerosis younger than 18 years at the onset of their first multiple sclerosis symptoms.Results: There were 46 patients (72% female) included with a mean age at diagnosis of 16.1 years. Six cases had childhood-onset and 40 cases had adolescence-onset. The median value of Expanded Disability Status Scale was two. Relapsing-remitting multiple sclerosis was most prevalent (98% of cases). In the cerebrospinal fluid study, 74% of patients had positive oligoclonal bands. Brain magnetic resonance imaging studies showed a predominant supratentorial involvement (98% of cases), whereas the cervical segment was the most frequently affected in the spinal cord. All the patients enrolled in the study underwent immunomodulatory therapy, 75% ofpatients with beta-interferon. Concerning differences between the childhood and the adolescent groups, we found a greater proportion of male patients and of individuals with cerebrospinal fluid pleocytosis among the childhood-onset group.Discussion: This study provides new data on pediatric multiple sclerosis characteristics in Portugal and our results are similar to previously reported data in other parts of the worldConclusion: This is the first multicentric study characterizing pediatric multiple sclerosis in Portugal. The mechanisms underlying the particularities of pediatric multiple sclerosis remain largely unknown and further studies are required.

scholarly journals Neurobrucellosis mimicking primary vasculitis of the central nervous system: we should perform a metagenomic analysis of the cerebrospinal fluid prior to brain biopsy

2021 ◽  
Author(s):  
Marina Barrionuevo Mathias ◽  
Fernando Gatti ◽  
Gustavo Bruniera ◽  
Vitor Paes ◽  
Gisele Sampaio Silva ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Symptoms ◽  
Brain Mri ◽  
Genetic Material ◽  
Clinical Manifestations ◽  
Brain Biopsy ◽  
Metagenomic Analysis ◽  
Normal Brain ◽  
The Central Nervous System

Context Primary angiitis of the central nervous system (PACNS) is characterized by the inflammation of small and medium CNS arteries; the clinical manifestations include headache, cognitive impairment and focal neurological deficits. The gold standard test for diagnosis is brain biopsy. Neurobrucellosis is an infection associated with cattle farming, which leads to neurological and psychiatric symptoms. We report a case of neurobrucellosis mimicking PACNS. Case report Male, 32 years old, with fever, headache, dizziness and cognitive impairments for 30 days. History of stroke 2 years before, with mild sequelae right hemiparesis; investigation showed suspected intracranial dissection. On physical examination, he had apathy, preserved strength, reduced reflexes with plantar flexor responses. General laboratory tests, autoantibodies and serology were normal. Brain MRI showed deep left nucleocapsular gliosis and cerebral angiography revealed stenosis of the ICA and MCA. CSF showed 42 cells/ mm³, glucose 46 mg/dL, protein 82 mg/dL. Blood PCR was negative for Brucella. Immunophenotyping of the CSF and PET-CT excluded neoplasia. Brain biopsy was inconclusive for vasculitis. Metagenomic analysis of the CSF detected 78% of Brucella genetic material. Serum agglutination test was 1:40 for brucella. Conclusions PACNS is diagnosed by exclusion. The patient filled criteria for possible PACNS, image compatible with vascular stenosis, but inconclusive brain biopsy. Brucellosis is an endemic disease in underdeveloped countries that can present as CNS vasculitis. Metagenomic analysis allows the detection of different pathogens using a single method. The case illustrates the use of metagenomics in rare diseases characterized by vasculitis, with change in clinical outcomes and conduct.

scholarly journals Exome-Sequence Analyses of Four Multi-Incident Multiple Sclerosis Families

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 988
Author(s):  
Tobias Zrzavy ◽  
Fritz Leutmezer ◽  
Wolfgang Kristoferitsch ◽  
Barbara Kornek ◽  
Christine Schneider ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genome Wide Association Study ◽  
Rare Variants ◽  
Demyelinating Disease ◽  
Phenotypic Variability ◽  
Convincing Evidence ◽  
Risk Variants ◽  
Unbiased Manner ◽  
The Central Nervous System ◽  
Reduced Penetrance

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). Currently, it is estimated that 30–40% of the phenotypic variability of MS can be explained by genetic factors. However, low susceptibility variants identified through Genome Wide Association Study (GWAS) were calculated to explain about 50% of the heritability. Whether familial high-risk variants also contribute to heritability is a subject of controversy. In the last few years, several familial variants have been nominated, but none of them have been unequivocally confirmed. One reason for this may be that genetic heterogeneity and reduced penetrance are hindering detection. Sequencing a large number of MS families is needed to answer this question. In this study, we performed whole exome sequencing in four multi-case families, of which at least three affected individuals per family were analyzed. We identified a total of 138 rare variants segregating with disease in each of the families. Although no single variant showed convincing evidence for disease causation, some genes seemed particularly interesting based on their biological function. The main aim of this study was to provide a complete list of all rare segregating variants to provide the possibility for other researchers to cross-check familial candidate genes in an unbiased manner.

Leber’s hereditary optic neuropathy associated with a multiple-sclerosis-like picture in a man

2011 ◽  
Vol 17 (6) ◽  
pp. 763-766 ◽  
Author(s):  
Antonella La Russa ◽  
Rita Cittadella ◽  
Virginia Andreoli ◽  
Paola Valentino ◽  
Francesca Trecroci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Optic Neuropathy ◽  
Brain Mri ◽  
Resonance Imaging ◽  
Gadolinium Enhancement ◽  
Demyelinating Lesions ◽  
Male Patients ◽  
Magnetic Resonance Imaging Mri ◽  
Symptoms And Signs

A 35-year-old young man displayed Leber’s optic neuropathy (LHON) due to T14484C and multiple sclerosis (MS) phenotype that was dominated by symptoms and signs of spinal cord impairment. Magnetic resonance imaging (MRI) revealed demyelinating lesions extending from D6 to D11 in the spinal cord with gadolinium enhancement, while only three linear demyelinating lesions were seen on brain MRI. In the literature, a major involvement of the spinal cord was already reported in three of four male patients with the 14484 LHON mutation who developed MS, but the reasons of this peculiar association remain unknown, and further research in this area is needed.

scholarly journals Giant hyperostosis after sphenoid ridge en plaque meningioma removal

2014 ◽  
Vol 21 (4) ◽  
pp. 471-476
Author(s):  
Danil Adam ◽  
Toma Papacocea ◽  
Ioana Hornea ◽  
Cristiana Moisescu
Keyword(s):  
Brain Mri ◽  
Growth Patterns ◽  
Neurological Deficits ◽  
X Rays ◽  
Blurred Vision ◽  
Orbital Cavity ◽  
Orbital Wall ◽  
The Central Nervous System ◽  
The Right ◽  
Sphenoid Ridge

Abstract Meningioma is in most cases a benign tumor of the central nervous system with two growth patterns: en masse and en plaque. Hyperostosis is associated in 13 - 49 % of the cases with en plaque meningioma. We describe the case of a 47 years old woman with meningotelial sphenoid ridge meningioma which was totally removed. At the first admission she presented with no neurological deficits, seizures and a mild right exophthalmos. This had an indolent growth. After 10 years, the patient was readmitted for headache, blurred vision and right exophthalmos. Skull X-rays and brain MRI revealed an important thickening of the right superior orbit wall and sphenoid ridge. She underwent a new surgery. There was no intradural tumor found. Instead, bones of the superior and lateral right orbit walls were very hiperostotic. A hole of 3/2 cm in the right superior orbital wall was drilled and the orbital cavity was decompressed. In the postoperative period, the symptoms were remitted and the exophthalmos reduced. We discuss the causes and management of hyperostosis associated with meningiomas.

scholarly journals Neurodevelopmental regression, severe generalized dystonia, and metabolic acidosis caused by POLR3A mutations

2020 ◽  
Vol 6 (6) ◽  
pp. e521
Author(s):  
Vanessa Zanette ◽  
Aurelio Reyes ◽  
Mark Johnson ◽  
Daniel do Valle ◽  
Alan J. Robinson ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Phenotypic Variability ◽  
Brain Mri ◽  
Rna Polymerase Iii ◽  
Resonance Spectroscopy ◽  
Compound Heterozygous ◽  
Expression Levels ◽  
Abnormal Movements ◽  
Generalized Dystonia ◽  
Pol Iii

ObjectiveTo expand the clinical phenotype of POLR3A mutations by assessing the functional consequences of a missense and a splicing acceptor mutation.MethodsWe performed whole-exome sequencing for identification of likely pathogenic mutations in a 9-year-old female patient with severe generalized dystonia, metabolic acidosis, leukocytosis, hypotonia, and dysphagia. Brain MRI showed basal ganglia atrophy and presence of lactate and lipid peaks by [1H]-magnetic resonance spectroscopy. Expression levels of Pol III target genes were measured by quantitative real-time (qRT)-PCR to study the pathogenicity of the biallelic mutations in patient fibroblasts.ResultsThe patient is a compound heterozygous for a novel missense c.3721G>A (p.Val1241Met) and the splicing region c.1771-6C>G mutation in POLR3A, the gene coding for the catalytic subunit of RNA polymerase III (Pol III). Aberrant splicing was observed for the c.1771-6C>G mutation. Decreased RNA expression levels of Pol III targets (HNRNPH2, ubiquitin B, lactotransferrin, and HSP90AA1) were observed in patient fibroblasts with rescue to normal levels by overexpression of the wild-type protein but not by the p.Val1241Met variant.ConclusionsMutations in the POLR3A gene cause POLR3A-related hypomyelinating leukodystrophy with or without oligodontia or hypogonadotropic hypogonadism (HLD7, OMIM: 607694) and neonatal progeroid syndrome (OMIM: 264090), both with high phenotypic variability. We demonstrated the pathogenicity of c.1771-6C>G and c.3721G>A mutations causing an early-onset disorder. The phenotype of our patient expands the clinical presentation of POLR3A-related mutations and suggests a new classification that we propose designating as Neurodevelopmental Disorder with Regression, Abnormal Movements, and Increased Lactate.

scholarly journals Rasmussen’s Encephalitis: A Report of a Tunisian Pediatric Case and Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hedia Klaa ◽  
Thouraya Ben Younes ◽  
Hanene Benrhouma ◽  
Sonia Nagi ◽  
Aida Rouissi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Imaging ◽  
Brain Mri ◽  
Rasmussen Encephalitis ◽  
Pediatric Case ◽  
Rasmussen’S Encephalitis ◽  
Progressive Neurological Deficit ◽  
The Central Nervous System

Rasmussen’s encephalitis (RE) is a rare progressive inflammatory disease of the central nervous system. It is characterized by unilateral hemispheric atrophy, pharmacoresistant focal seizures, and progressive neurological deficit. The exact etiopathogenesis still remains unknown. Brain imaging plays an important role in diagnosis and follow-up. Fluctuation of lesions in brain imaging was reported in few cases. Herein, we report an additional pediatric case of Rasmussen encephalitis with fluctuating changes in brain MRI.

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