Diffuse White Matter Involvement Research Articles

Intragenic homozygous duplication in HEPACAM is associated with megalencephalic leukoencephalopathy with subcortical cysts type 2A.

Disease-causing variants in HEPACAM are associated with megalencephalic leukoencephalopathy with subcortical cysts 2A (MLC2A, MIM# 613,925, autosomal recessive), and megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without impaired intellectual development (MLC2B, MIM# 613,926, autosomal dominant). These disorders are characterised by macrocephaly, seizures, motor delay, cognitive impairment, ataxia, and spasticity. Brain magnetic resonance imaging (MRI) in these individuals shows swollen cerebral hemispheric white matter and subcortical cysts, mainly in the frontal and temporal regions. To date, 45 individuals from 39 families are reported with biallelic and heterozygous variants in HEPACAM, causing MLC2A and MLC2B, respectively. A 9-year-old male presented with developmental delay, gait abnormalities, seizures, macrocephaly, dysarthria, spasticity, and hyperreflexia. MRI revealed subcortical cysts with diffuse cerebral white matter involvement. Whole-exome sequencing (WES) in the proband did not reveal any clinically relevant single nucleotide variants. However, copy number variation analysis from the WES data of the proband revealed a copy number of 4 for exons 3 and 4 of HEPACAM. Validation and segregation were done by quantitative PCR which confirmed the homozygous duplication of these exons in the proband and carrier status in both parents. To the best of our knowledge, this is the first report of an intragenic duplication in HEPACAM causing MLC2A.

Expanding the spectrum of neonatal-onset AIFM1-associated disorders.

Pathogenic variants in AIFM1 have been associated with a wide spectrum of disorders, spanning from CMT4X to mitochondrial encephalopathy. Here we present a novel phenotype and review the existing literature on AIFM1-related disorders. We performed EEG recordings, brain MRI and MR Spectroscopy, metabolic screening, echocardiogram, clinical exome sequencing (CES) and family study. Effects of the variant were established on cultured fibroblasts from skin punch biopsy. The patient presented with drug-resistant, electro-clinical, multifocal seizures 6 h after birth. Brain MRI revealed prominent brain swelling of both hemispheres and widespread signal alteration in large part of the cortex and of the thalami, with sparing of the basal nuclei. CES analysis revealed the likely pathogenic variant c.5T>C; p.(Phe2Ser) in the AIFM1 gene. The affected amino acid residue is located in the mitochondrial targeting sequence. Functional studies on cultured fibroblast showed a clear reduction in AIFM1 protein amount and defective activities of respiratory chain complexes I, III and IV. No evidence of protein mislocalization or accumulation of precursor protein was observed. Riboflavin, Coenzyme Q10 and thiamine supplementation was therefore given. At 6 months of age, the patient exhibited microcephaly but did not experience any further deterioration. He is still fed orally and there is no evidence of muscle weakness or atrophy. This is the first AIFM1 case associated with neonatal seizures and diffuse white matter involvement with relative sparing of basal ganglia, in the absence of clinical signs suggestive of myopathy or motor neuron disease.

COVID-19 Associated Encephalopathies and Cerebrovascular Disease

INTRODUCTIONThe coronavirus disease 2019 (COVID-19) pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a dramatic impact on healthcare systems and a variable disease course. Emerging evidence demonstrates that SARS-CoV-2 is associated with central nervous system (CNS) disease. In this series, we describe CNS manifestations in critical COVID-19 patients at our tertiary academic center.METHODSA single center retrospective cross-sectional analysis of all patients admitted to our tertiary care academic center in New Orleans, Louisiana on April 22, 2020, who were in critical condition due to COVID-19 and developed new onset of neurological disease. Patients were grouped into one of three categories according to imaging and clinical features: encephalopathy, acute necrotizing encephalopathy, and vasculopathy.RESULTSA total of 27 of 76 (35.5%) critical COVID-19 patients met inclusion criteria. Mean age was 59.8 years (range 35–91 years) and most had an underlying medical condition, including hypertension (63%), diabetes mellitus type 2 (52%), obesity (26%), and/or chronic kidney disease (22%). Sixty three percent had evidence of neurological injury on CT, 30% on MRI, 15% on non-invasive vascular imaging, and 44% on EEG. CT findings most often included subacute ischemic strokes, diffuse hypoattenuation, subcortical parenchymal hemorrhages, and focal hypodensities within deep structures. MRI findings included diffuse involvement of deep white matter, the corpus callosum, and the basal ganglia. For patients with acute ischemic stroke, vascular findings consisted of irregular proximal focal stenosis of the supraclinoid internal carotid artery. Twenty patients (74%) were designated with COVID-19 associated encephalopathy, two (7%) with COVID-19 associated acute necrotizing encephalopathy, and five (19%) with COVID-19 associated vasculopathy.CONCLUSIONA one-day snapshot of COVID-19 admissions at a tertiary academic center in New Orleans, LA revealed a high percentage of patients with new neurological disease. Although clinical presentations varied, they were broadly categorized. A better understanding of the neurological sequalae and radiographic findings will help clinicians mitigate the impact of this disease.

Natural history of Krabbe disease \u2013 a nationwide study in Germany using clinical and MRI data

BackgroundKrabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by a defect in the GALC gene leading to a deficiency of the enzyme ß-galactocerebrosidase. The aim of this work was to describe the natural disease course covering the whole spectrum of the disease.MethodsNatural history data were collected with a standardized questionnaire, supplemented by medical record data. We defined different forms of the disease according to Abdelhalim et al. (2014). Developmental and disease trajectories were described based on the acquisition and loss of milestones as well as the time of first clearly identifiable symptoms and needs such as spasticity, seizures and tube feeding. MRI was assessed using the scoring system by Loes et al. (1999) and in addition a pattern recognition approach, based on Abdelhalim et al. (2014).ResultsThirty-eight patients were identified, from 27 of these patients 40 MRIs were available; 30 (79%) had an infantile onset, showing first symptoms in their first year of life, almost all (27 out of 30) starting in the first six months. A later onset after the first year of life was observed in 8 patients (21%, range 18 months to 60 years). Irritability, abnormalities in movement pattern as well as general developmental regression were the first symptoms in the infantile group; disease course was severe with rapid progression, e.g. loss of visual fixation, need for tube feeding and then an early death. Gait disorders were the first symptoms in all patients of the later onset groups; progression was variable. The different forms of the disease were characterized by different MRI patterns (infantile: diffuse white matter involvement and cerebellar structures specifically affected, later onset: parieto-occipital white matter and splenium affected, adult: motor tracts specifically affected).ConclusionThis is the first description of the natural history of Krabbe disease in a larger European cohort using developmental, clinical and MRI data. We would like to highlight the very different clinical and MRI characteristics of the later onset forms. These data are important for counselling affected patients and families and may serve as a basis for future treatment trials.

Coronavirus 2019 (COVID-19)–Associated Encephalopathies and Cerebrovascular Disease: The New Orleans Experience

BackgroundThe coronavirus 2019 (COVID-19) pandemic has had a dramatic impact on health care systems and a variable disease course. Emerging evidence demonstrates that severe acute respiratory syndrome coronavirus 2 is associated with central nervous system disease. We describe central nervous system manifestations in critical patients with COVID-19 at our tertiary center.MethodsWe conducted a single-center retrospective analysis of all actively critical patients with COVID-19 admitted to our tertiary care academic center in New Orleans, Louisiana, on April 22, 2020, with new onset of neurologic disease. Patients were grouped into 1 of 3 categories according to imaging and clinical features; encephalopathy, acute necrotizing encephalopathy, and vasculopathy.ResultsA total of 27 of 76 (35.5%) critical patients with COVID-19 met inclusion criteria. Twenty patients (74%) were designated with COVID-19–associated encephalopathy, 2 (7%) with COVID-19–associated acute necrotizing encephalopathy, and 5 (19%) with COVID-19–associated vasculopathy. Sixty-three percent of neurologic findings were demonstrated on computed tomography, 30% on magnetic resonance imaging, and 44% on electroencephalography. Findings most often included ischemic strokes, diffuse hypoattenuation, subcortical parenchymal hemorrhages, and focal hypodensities within deep structures. Magnetic resonance imaging findings included diffuse involvement of deep white matter, the corpus callosum, and the basal ganglia. For patients with large-territory ischemic stroke, all but one displayed irregular proximal focal stenosis of the supraclinoid internal carotid artery.ConclusionsAnalysis of active critical COVID-19 admissions at our revealed a high percentage of patients with new neurologic disease. Although variable, presentations followed 1 of 3 broad categories. A better understanding of the neurologic sequalae and radiographic findings will help clinicians mitigate the impact of this disease.

Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy.

Little is known about cognition and predictors of neuropsychological outcomes in pediatric low-grade glioma (PLGG) survivors treated without radiation therapy. This research expands upon our previous work by further identifying the cognitive profile of PLGG patients treated without radiation therapy, investigating the specific medical and demographic variables that predict functioning, and examining white matter structure and its relationship to neuropsychological performance. Nineteen PLGG patients (11-19 years) were administered the Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale, and subtests from the Woodcock-Johnson Tests of Cognition (visual matching, rapid picture naming, and pair cancellation) and Cambridge Neuropsychological Test Automated Battery (pattern recognition memory, delayed matching to sample, intra-extra dimensional set shift, motor screening task, rapid visual information processing, and spatial span). The sample had normative weaknesses in verbal working memory, brief attention/vigilance, psychomotor speeded output, visual perception and matching, overall cognition, working memory, and processing speed. Increased surgeries or subtotal resections, hydrocephalus, shunting procedures, chemotherapy, NF1, and supratentorial location were predictive of cognitive deficits. Broad white matter involvement of the frontal, temporal, parietal, and occipital lobes as well as the cerebellum, as inferred from diffusion tensor imaging indices of decreased fiber orientation and increased water diffusion, was related to many cognitive difficulties. This study comprehensively examines cognitive functioning in PLGG patients treated without radiation therapy, predictors of cognition, and its relation to white matter structure. Our findings indicate that medical and demographic variables other than radiation therapy can lead to cognitive late effects with diffuse white matter involvement.

CLCN2-related leukoencephalopathy: a case report and review of the literature

BackgroundLoss-of-function mutations in the CLCN2 gene were recently discovered to be a cause of a type of leukodystrophy named CLCN2-related leukoencephalopathy (CC2L), which is characterized by intramyelinic edema. Herein, we report a novel mutation in CLCN2 in an individual with leukodystrophy.Case presentationA 38-year-old woman presented with mild hand tremor, scanning speech, nystagmus, cerebellar ataxia in the upper limbs, memory decline, tinnitus, and dizziness. An ophthalmologic examination indicated macular atrophy, pigment epithelium atrophy and choroidal capillary atrophy. Brain magnetic resonance imaging (MRI) showed the diffuse white matter involvement of specific white matter tracts. Decreased diffusion anisotropy was detected in various brain regions of the patient. Diffusion tensor tractography (DTT) showed obviously thinner tracts of interest than in the controls, with a decreased fiber number (FN), increased radial diffusivity (RD) and unchanged axial diffusivity (AD). A novel homozygous c.2257C > T (p.Arg753Ter) mutation in exon 20 of the CLCN2 gene was identified.ConclusionCC2L is a rare condition characterized by diffuse edema involving specific fiber tracts that pass through the brainstem. The distinct MRI patterns could be a strong indication for CLCN2 gene analysis. The findings of our study may facilitate the understanding of the pathophysiology and clinical symptoms of this disease.

Posttraumatic movement disorders: A clinical and imaging profile of 30 patients.

Posttraumatic movement disorders (PTMDs) are frequently associated with severe head injury. There are very few studies on the clinical phenomenology and radiological correlation of PTMD. To study the clinical phenomenology of patients with PTMD and correlate it with the site of lesion on brain imaging. This was a prospective study of patients with suspected PTMD. All of these patients underwent neurological evaluation to characterize the phenomenology and imaging, such as computed tomography/magnetic resonance imaging (CT/MRI), to localize the site of lesion. The age of the patients was 32.6 ± 16.4 years and the age at onset was 29.1 ± 16.0 years. Right upper limb was the initial body part affected in 36.7% patients. Tremor (alone or with dystonia) was the most common movement disorder (MD; 44.7%) followed by parkinsonism (17.2%), dystonia (13.8%), dystonia plus (dystonia associated with choreoathetosis: 10.3%), mixed MD (more than one MD: 10.3%), and myoclonus (3.4%). MRI was performed in 23 patients and the rest seven patients underwent CT brain. Normal MRI was observed in one patient with parkinsonism. Isolated, discrete lesions were found in six (27.3%) patients. Basal ganglia was the most common site of involvement (66.7%) followed by thalamus (16.7%) and brainstem (16.7%). Diffuse white matter involvement was the most common radiological lesion in patients with tremor. Our study describes the clinical phenomenology of patients with PTMDs and its radiological correlation. Tremor (alone or in combination with dystonia) was the most common MD observed and diffuse white matter lesions without affection of the basal ganglia was the most common site of lesion.

Van Der Knaap disease; A case having a defined mutation and novel mutation

Context: Van der Knaap Syndrome (MLC1) is a slowly progressive neurodegenerative diseasecharacterized by macrocephaly, megalencephaly, ataxia, spasticity, motor retardation, moderatemental retardation, diffuse cerebral white matter, subcortical cysts (MEGALENCEPHALICLEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 1,OMIM 604004). The prevalence is reportedapproximately 1/1,000,000. MLC1 is a autosomal recessive disorder due to mutations in the MLC1gene at 22q13.33 locus localization. In this study, aimed to diagnose a girl who is guided by ataxicwalking and pathologic cranial MR findings of a family with first degree cousin marriage and to givegenetic counseling to the family. Methods: Affected girls and their parents were included in the study. The cranial MR and examination findings of the index case were evaluated and MLC1 gene have been analyzed by a next generation sequencing methods. Results: Parent 7 years old , ataxic walking, spasticity, slowing of motor movements and intrinsic tremor, cranial MR showed a pathologic signal increase in cerebral white matter compatible with neurometabolic disease. Macrocephaly in infantile period. The amino acid and acylcarnitine profiles were evaluated as normal with the tandem mass spectrometry. MLC1 gene sequence analysis including all coding exons and exon-intron boundiries was done and MLC1 gene NM_015166.3: IVS2+1G>T (c.177+1G>T) homozygous mutation was detected. This mutation was previously described and have been reported (HGMD No: CS035660). In the familial segregation this mutation was detected heterozygous in parents. In addition, previously undeA (c.1059+6T>A) heterozygous mutation was detected in the parent. In silico analysis with Mutation Taster, Polyphen2, SIFT was predict this variant as a disease causing mutation. Prenatal, preimplantation genetic diagnosis for new pregnancies was recommended especially for those who are married to relatives. Since MLC1 is a rare form of megaencephalic leukoencephalopathy, it is presented to emphasize that parents with macrocephaly, ataxic gait and diffuse white matter involvement should be kept in mind.

Early Radiologic Pattern in a Patient with Megaloencephalic Leukoencephalopathy Due to Homozygous MLC1 Mutation

Background/Purpose: Megaloencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare autosomal recessive disease caused by mutations in the MLC1 or GLIALCAM genes. MLC is characterized by infantile-onset macrocephaly and diffuse white matter involvement with subcortical cysts. Depending on the genetic background, motor deterioration with ataxia and spasticity, cognitive decline, and seizures occur. We aim to illustrate clinical features and MRI findings in a very early stage of MLC.

Cytokine Storm may Play a Role in the Pathogenesis of Human Parechovirus Type 3-Associated Acute Encephalopathy in Neonates: A Case Report

Background: Human parechovirus type 3 (HPeV3) is an important cause of acute encephalitis in the neonatal and early infantile periods. Typical HPeV3-associated acute encephalitis paradoxically shows no cerebrospinal fluid (CSF) pleocytosis despite virus detection in CSF and diffuse deep white matter involvement of the corpus callosum on magnetic resonance images (MRI). Patient: An 8-day-old full-term infant was found to have HPeV3 infection of the central nervous system (CNS), which was confirmed using diffusion-weighted MRI showing poor diffusivity in the bilateral deep white matter and the corpus callosum without CNS pleocytosis, as seen in previously reported cases. Interestingly, this patient had extremely elevated serum ferritin and urinary beta-2-microglobulin levels, which indicated a surge of the cytokines tumor necrotizing factor alpha and interferon gamma. Conclusion: These findings suggest that the cytokine storm can promote the pathogenesis of white matter lesions in HPeV3-associated acute encephalopathy rather than direct infection of the brain.

Neuropathology of Zika Virus Infection.

Zika virus (ZIKV) is a member of the Flaviviridae family that had been associated only with mild disease prior to the 2015 outbreak in Brazil. A dramatic increase in reported cases of microcephaly and Guillain-Barré syndrome during this time prompted significant research into possible associations with ZIKV and its neurotropic properties. Infection of neural progenitor cells and organoids have been shown to induce apoptosis and dysregulation of growth, and mouse studies have demonstrated viral replication in brain tissue in adults, as well as vertical transmission resulting in embryonic brain abnormalities. Large case series of clinical and radiological findings of congenital ZIKV infection have begun to be published; however, pathology reports have been limited to two case reports and two small case series. Thus far, the findings have largely been restricted to the brain and include diffuse grey and white matter involvement consisting of dystrophic calcifications, gliosis, microglial nodules, neuronophagia, and scattered lymphocytes. Mild chronic villitis was observed in the placental tissue in some cases, and the remaining organs were essentially uninvolved. Larger, systematic studies, including correlation of histological findings with gestational age at the time of maternal infection, will be required to determine the full range of Zika virus-induced abnormalities and to help guide future clinical decision making.

Clinical, Neuroimaging, and Genetic Characteristics of Megalencephalic Leukoencephalopathy With Subcortical Cysts in Egyptian Patients

BackgroundMegalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare and genetically heterogeneous cerebral white matter disease. Clinically, it is characterized by macrocephaly, developmental delay, and seizures. We explore the clinical spectrum, neuroimaging characteristics, and gene involvement in the first patients with megalencephalic leukoencephalopathy with subcortical cysts described from Egypt. PatientsSix patients were enrolled from three unrelated families. Patient inclusion criteria were macrocephaly, developmental delay, normal urinary organic acids, and brain imaging of diffuse cerebral white matter involvement. Direct sequencing of the MLC1 gene in patients' families and GliaCAM in one questionable case was performed using BigDye Terminator cycle sequencing. ResultsClinical heterogeneity, both intra- and interfamilial, was clearly evident. Developmental delays ranged from globally severe or moderate to mild delay in achieving walking or speech. Head circumference above the ninety-seventh percentile was a constant feature. Neuroimaging featured variability in white matter involvement and subcortical cysts. However, findings of posterior fossa changes and brain stem atrophy were frequently (66.6%) identified in these Egyptian patients. Discrepancy between severe brain involvement and normal mental functions was evident, particularly in patients from the third family. MLC1 mutations were confirmed in all patients. Deletion/insertion mutation in exon 11 (c.908-918delinsGCA, p.Val303 Gly fsX96) was recurrent in two families, whereas a missense mutation in exon 10 (c.880 C > T, p.Pro294Ser) was identified in the third family. ConclusionsThis report extends our knowledge of the clinical and neuroimaging features of megalencephalic leukoencephalopathy with subcortical cysts. It confirms the apparent lack of selective disadvantage of MLC1 mutations on gamete conception and transmission as supported by the presence of multiple affected siblings in Egyptian families.

Cocaine-Induced Recurrent Leukoencephalopathy

Cocaine-induced leukoencephalopathy is a rare neurological complication. It is most likely related to the substances used to adulterate the cocaine. Levamisole is one of the most common adulterants of cocaine and causes reversible leukoencephalopathy. Patients display severe neurological symptoms that resolve at termination of the exposure. MRI shows diffuse white matter involvement with sparing of the U fibers, without brain stem or cerebellar involvement. We describe the case of a woman with three neurologic episodes and remitting and recurrent brain white matter lesions.

MRI patterns of global hypoxic-ischemic injury in adults

To assess MRI patterns and associated clinical outcome in adults with global hypoxic-ischemic injury. In order to identify the patients with evidence of global hypoxic-ischemic injury, we retrospectively searched our radiology information system for reports of brain MRI studies from 01/01/2004 to 12/31/2010, containing the keywords - "hypoxia", "hypoxic", "anoxia" and "anoxic". A board certified neuroradiologist visually inspected the corresponding MR images for the presence, location and extent (focal versus diffuse) of ischemic findings. Clinical data for these patients was collected from the electronic medical records, including mechanism of the hypoxic-ischemic injury, and clinical outcome was measured using modified Rankin Scale (mRS). Review of radiology reports identified 151 cases, of which 64 patients remained after exclusion of normal studies ("no hypoxia" in the report), pediatric patients and patients with remote perinatal hypoxia. Five patients had relatively favorable clinical outcome (mRS of 1 to 3) and 59 had poor outcome (mRS of 4 to 6). Patterns associated with relatively favorable clinical outcome were: a) watershed pattern and b) basal ganglia without cortical involvement. Patterns associated with poor clinical outcome were: a) diffuse cortical and deep grey matter pattern, with and without perirolandic sparing; (b) medial occipital with perirolandic involvement; c) precentral gyrus involvement; d) diffuse white matter involvement; e) brainstem involvement; f) cerebellar involvement and g) hippocampal involvement. The vast majority of patients with MRI patterns of hypoxic-anoxic injury have a poor clinical outcome, independently of the observed pattern, with the only relative exception being the watershed pattern and the basal ganglia pattern without cortical involvement.

Magnetic Resonance Imaging “Tigroid Pattern” in Alexander Disease

Alexander disease (AD) is a rare white matter disorder resulting from mutations in the gene encoding for the glial fibrillary acidic protein. Diffuse white matter involvement with frontal predominance is typical of infantile AD that is clinically characterized by progressive motor and mental retardation, seizures, and megaloencephaly. We describe the case of a 10-year-old patient harboring a de novo missense mutation c.235C > T (p.R79C) in the GFAP gene, showing a relatively slow clinical and neuroradiologic progression of disease associated with a previously unreported magnetic resonance imaging (MRI) finding consistent with the so-called tigroid pattern. This pattern has been previously described in only a few different neurologic conditions, including Pelizaeus-Merzbacher disease and some lysosomal disorders. This report expands the spectrum of MRI features in AD.

FMRI evaluation of cochlear implant candidacy in diffuse cortical cytomegalovirus disease

Congenital cytomegalovirus infection is the most frequent nongenetic cause of pediatric hearing loss in the United States, affecting approximately 8,000 children each year. Due in part to variable cytomegalic involvement of the auditory cortex, cochlear implantation outcomes have varied widely. Functional magnetic resonance imaging (fMRI) has the potential to assist in determining candidacy for cochlear implantation through the detection of intact auditory pathways including the cortex. We report a case of a 21-month-old girl with cytomegalovirus-related deafness and diffuse white matter involvement in which fMRI was a determining factor for cochlear implantation and side selection.

Characteristics of Early MRI in Children and Adolescents with Vanishing White Matter

MRI in vanishing white matter typically shows diffuse abnormality of the cerebral white matter, which becomes increasingly rarefied and cystic. We investigated the MRI characteristics preceding this stage. In a retrospective observational study, we evaluated all available MRIs in our database of DNA-confirmed VWM patients and selected MRIs without diffuse cerebral white matter abnormalities and without signs of rarefaction or cystic degeneration in patients below 20 years of age. A previously established scoring list was used to evaluate the MRIs. An MRI of seven patients fulfilled the criteria. All had confluent and symmetrical abnormalities in the periventricular and bordering deep white matter. In young patients, myelination was delayed. The inner rim of the corpus callosum was affected in all patients. In early stages of VWM, MRI does not necessarily display diffuse cerebral white matter involvement and rarefaction or cystic degeneration. If the MRI abnormalities do not meet the criteria for VWM, it helps to look at the corpus callosum. If the inner rim (the callosal-septal interface) is affected, VWM should be considered.

A Japanese Adult Case of Megalencephalic Leukoencephalopathy with Subcortical Cysts with a Good Long-term Prognosis

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a recently recognized neurological disease, and mutations in the MLC1 gene have been identified as the cause of the disorder. A 54-year-old Japanese woman with macrocephaly presented with progressive mental decline, gait disturbance due to spasticity and ataxia, and choreoathetotic movement in the left upper extremity. Brain magnetic resonance imaging (MRI) revealed characteristic subcortical cysts in addition to diffuse white matter involvement. Genetic analysis of the MLC1 gene identified an S93L mutation in a homozygous state. This case is particularly valuable because of the lack of knowledge on the long-term prognosis of MLC.

Unusual Neuroimaging in a Young Boy with Cerebral X-Linked Adrenoleukodystrophy

We describe the case of a 7-year-old boy with cerebral X-linked adrenoleukodystrophy presenting with neurobehavioral symptoms. Attention deficit with hyperactive behavior was followed by progressive memory retrieval deficits and difficulty in writing. A detailed review of the clinical history, clinical examination and contrast-enhanced brain nuclear magnetic resonance imaging disclosed indeed an atypical cerebral form of X-linked adrenoleukodystrophy with diffuse anterior and posterior white matter involvement with a typical rim of contrast enhancement. A severe clinical deterioration occurred despite dietary treatment and hormonal replacement therapy. These rare but severe forms of atypical cerebral X-linked adrenoleukodystrophy can more often mimic attention deficit/hyperactivity disorder and should, therefore, be considered in young males with progressive neurobehavioral symptoms, particularly when possibly related to frontal white matter involvement. An accurate clinical history and examination should determine whenever a contrast-enhanced head MRI should be indicated.