Subcortical White Matter Changes Research Articles

Methotrexate Induced Central Nervous System Manifestations in Children Receiving Treatment for Acute Lymphoid Malignancies

Methotrexate (MTX) is an essential part of most chemotherapy regimens for acute lymphoblastic leukemia (ALL). It is administered intrathecally (IT), intravenously, and orally during ALL therapy. We performed a retrospective chart review to assess the central nervous system (CNS) manifestations induced by MTX in all children who received ALL therapy at our institution between July 2013 and June 2023. A list of patients with the ICD-9/10 codes for ALL or ALLy was obtained from the Electronic Medical Records for the study time period. Data collected included demographics, cytogenetics, laboratory test results, MTX pharmacological data if available, and details of the treatment of CNS manifestations attributable to MTX. Lastly, we had a single neuroradiologist re-review all the brain Magnetic Resonance Imaging (MRI) obtained in patients with MTX induced CNS manifestations. Sixty-five children were treated for ALL during the study decade. The average age at diagnosis was 4.7 ± 4 years. Our cohort consisted of 38 males and 27 females. Twelve of 65 patients (19%) developed MTX-induced CNS manifestations. The average age at the onset of symptoms was 5.3 ± 2 years. Ten patients had received a dose of IT MTX within 2 weeks of experiencing symptoms. Symptoms included raised intracranial pressure (ICP) (64%), headache (36%), confusion (36%), altered mental status (29%), and altered level of consciousness (29%). Treatment of MTX-induced CNS manifestations consisted of therapeutic drainage of cerebrospinal fluid (CSF) with their scheduled IT chemotherapy administration (65%), acetazolamide (57%), theophylline + leucovorin + dextromethorphan (64%), and addition of hydrocortisone with IT medications (36%). In 3 (25%) patients the subsequent doses of MTX were delayed. The symptoms of CNS manifestations resolved in 100% of cases and MTX was able to be readministered in all the patients. Only one patient had recurrence of CNS manifestations twice after rechallenging with MTX; however, with specific symptomatic treatment, was able to tolerate the remainder of the IT therapy inclusive of MTX. Brain MRIs were obtained in all patients. Initial imaging studies yielded normal results in 6 (50%) patients. Abnormal findings included subcortical white matter changes, vividly observed on T2/FLAIR MRI. These changes were represented by regions of acute hyperintensity seen in diffuse bilateral cerebral hemispheres (33%), parietal regions (33%), frontoparietal regions (17%), occipital regions (17%) and the left parietooccipital region (17%). A follow up MRI was performed 3 to 8 months after the initial MRI and was repeated up to 6 times over a course of 6 years in a patient. The earliest MRI improvement was evident after 3 months of initial imaging. About 20% of patients developed MTX induced CNS manifestations in our cohort. IT MTX was the most common culprit. Raised ICP, on opening pressure measured during IT procedures happened to be the most common finding. This has not widely been reported previously under MTX induced CNS complications in published data. One of the suspected etiologies is the inflammation of arachnoid villi impairing CSF drainage. These patients responded well to acetazolamide and therapeutic drainage of CSF. Finally subcortical while matter changes on T2/FLAIR MRI was a common CNS manifestation.

Inadvertent Discovery of Gerstmann's Syndrome During a Skull MRI and Its Anatomical Basis: A Case Report

A rare neurological disorder in which an individual is unable to perform tasks related to language, spatial recognition,mathematics, and cognition is known as Gerstmann's syndrome(GS). Gerstmann hypothesised that the four symptoms thatmakeup Gerstmann's syndrome are caused by a shared cognitive problem (Grundstörung). Gerstmann asserted that it is a bodyschema disorder that only affects the hand and fingers. Since then, the existence of a Grundstörung has been disputed. The studyproposed a shared psychoneurological element, but it should be connected to changes in mental pictures rather than the bodilyschema. The significant facts appear to be the common simultaneous impairment of writing, computation, and bodily awarenessafter left parietal lesion, beyond the diagnostic label of "pure" and "non-pure" Gerstamann's syndrome instances. Some functionaldomains can be linked to patients' symptoms despite being heterogeneous. A 65-year-old male was brought to the hospital witha history of injury to the head and complaints of confusion, speech difficulty, inability to perform simple calculations, severeheadache, and drowsiness. The patient was sent to the radiology department of Sree Balaji Medical College and Hospital,Chennai, for a Magnetic Resonance Imaging of Skull (MRI). The MRI study revealed chronic ischemic changes in periventricularand subcortical white matter in the parietal lobes. Certain ischemic changes were also observed in the frontal lobe, suggestingage-related changes and Gerstmann's syndrome. By cutting off various portions of the inferior parietal cortex, a lesion affectingsubcortical and subangular bundles of fibers affects many circuits with distinct roles. Therefore, the deficits seen in the patientare best explained by this anatomical explanation.

A rare lentiform fork sign in a patient with methanol intoxication with neurological sequelae of parkinsonism and cognitive dysfunction: A case report and literature review

Methanol intoxication is rare in developed countries. Early identification and elimination of the methanol metabolites are vital to an optimal prognosis. A characteristic brain imaging finding is bilateral basal ganglia necrosis and subcortical white matter changes. Here, we report a rare neuroradiological feature called the lentiform fork sign in a patient with methanol intoxication who survived the acute poisoning stage. We report a 31-year-old woman who presented to the emergency department with acute-onset incoherent speech, consciousness disturbance, and a high-anion-gap metabolic acidosis caused by methanol intoxication. She was treated with antidote administration of fomepizole and enhanced methanol elimination through hemodialysis. Neurological sequelae of cognitive decline and parkinsonism developed, with preserved vision. Brain MRI showed bilateral putaminal necrosis and subcortical white matter changes. The apparent diffusion coefficient map showed low signal intensities in the putamen and globus pallidus bilaterally, with brightly hyperintense rims surrounding both putamina that resembled a fork, indicating a lentiform fork sign. She then had sequelae of cognitive decline and delayed parkinsonism feature, which are compatible with the brain lesions on neuroimage studies. Methanol poisoning is an uncommon life-threatening event, and neurological sequelae result from the accumulation of formic acid, a methanol metabolite that inhibits cytochrome c oxidase in mitochondria, leading to neuronal injury. Methanol intoxication should be considered in patients with imaging findings of bilateral basal ganglia necrosis with lentiform fork sign and a metabolic acidosis of unknown origin.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

L-2-hydroxyglutaric aciduria - review of literature and case series.

The authors report two sisters with L2HGA from Pakistan born to consanguineous parents. The 15- and 17-year-old girls presented with psychomotor delay, seizures, ataxia, intentional tremors, and dysarthria. Both had normal anthropometric measurements for age. Exaggerated tendon reflexes and bilateral sustained ankle clonus were observed in addition to cerebellar signs. Urine organic acids analysis showed marked excretion of 2-hydroxyglutaric acid, chiral differentiation of 2-hydroxyglutaric acid showed it to be L2HGA. Brain MRI of the 15-year-old showed diffuse subcortical white matter changes evident by T2/FLAIR hyperintense signals bilaterally, particularly in the frontal region in the centripetal distribution with some diffusion restriction along involvement of globus pallidus. The characteristic MRI pattern raised the suspicion of L2HGA. Targeted L2HGDH sequencing identified a homozygous pathogenic variant, c.829C>T (p.Arg227*) in L2HGDH gene in both girls. Both parents were heterozygous carriers of the familial variant. Neuroradiological features of centripetal subcortical leukoencephalopathy with basal ganglia and dentate nuclei involvement are rather specific to L2HGA and should lead to further biochemical investigations to look for L2HGA and L2HGDH gene sequencing.

Abstract Number ‐ 224: Stroke Mimic—Patient with Symptomatic Amyloid‐Related Imaging Abnormalities Presenting with Stroke‐like Symptoms.

Introduction Amyloid‐related imaging abnormalities (ARIA) are rare phenomena in patients taking monoclonal antibodies directed against amyloid beta in Alzheimer’s disease clinical trials. The pathogenesis is unclear, but may be due to an induced inflammatory microangiopathy. While the majority of cases are asymptomatic and resolve without intervention, a small subset can experience symptoms of sudden or uncertain onset. Given the relative rarity of this phenomena and the striking imaging findings, ARIA can be misdiagnosed as ischemic stroke or primary microangiopathy when presenting with acute‐subacute symptoms. Following diagnosis there is no clinical consensus on the optimal management and approaches range from withdrawal of the study drug to pulse‐dose steroids. Methods We present a case study of a patient admitted to our inpatient stroke service after 4 days of rapidly progressive confusion and sudden vision loss with MRI workup reporting subacute stroke. The findings were ultimately determined to be secondary to ARIA. Results A 67‐year‐old man with early onset Alzheimer’s disease enrolled in a clinical trial for donamemab presented with four days of marked cognitive decline including increased forgetfulness, confusion, and episodic hallucinations following an episode of abrupt vision loss. An outpatient MRI brain demonstrated subcortical hyperintensity that was initially reported as a subacute left occipital stroke. Notably, an MRI performed 3 months prior showed no abnormality. Neurological exam was remarkable for right superior quadrantanopia, memory impairment, and mild confabulation. Repeat MRI demonstrated FLAIR white matter hyperintensities and extensive susceptibility artifact in the left parieto‐occipital lobe, consistent with an inflammatory cerebral amyloid angiopathy (or ARIA). Spot EEG demonstrated no associated epileptiform discharges. Patient was treated with 7‐day course of IV Solumedrol and had improvement in visual symptoms. He was discharged on a prednisone taper and a followup MRI brain 4 weeks later showed near‐ complete resolution of the previously noted subcortical white matter changes. Conclusions ARIA can be seen in patients receiving anti‐amyloid monoclonal antibody treatments. Surveillance MRIs have been implemented to screen for such cases as a minority of patients with ARIA present with symptoms. As noted with this case study, a relatively acute presentation and imaging characteristics can lead to an initial misdiagnosis as subacute ischemic stroke. Vascular neurologists should be aware of this clinical entity, noting the natural history and treatment are not well established. This patient was treated aggressively as an inflammatory cerebral amyloid angiopathy with IV steroids and noted positive outcome. More research is required to establish the optimal acute medical management of patients with ARIA.

Structural Relationship between Cerebral Gray and White Matter Alterations in Degenerative Cervical Myelopathy.

Patients with degenerative cervical myelopathy (DCM) undergo adaptive supraspinal changes. However, it remains unknown how subcortical white matter changes reflect the gray matter loss. The current study investigated the interrelationship between gray matter and subcortical white matter alterations in DCM patients. Cortical thickness of gray matter, as well as the intra-cellular volume fraction (ICVF) of subcortical whiter matter, were assessed in a cohort of 44 patients and 17 healthy controls (HCs). The results demonstrated that cortical thinning of sensorimotor and pain related regions is associated with more severe DCM symptoms. ICVF values of subcortical white matter underlying the identified regions were significantly lower in study patients than in HCs. The left precentral gyrus (r = 0.5715, p < 0.0001), the left supramarginal gyrus (r = 0.3847, p = 0.0099), the left postcentral gyrus (r = 0.5195, p = 0.0003), the right superior frontal gyrus (r = 0.3266, p = 0.0305), and the right caudal (r = 0.4749, p = 0.0011) and rostral anterior cingulate (r = 0.3927, p = 0.0084) demonstrated positive correlations between ICVF and cortical thickness in study patients, but no significant correlations between ICVF and cortical thickness were observed in HCs. Results from the current study suggest that DCM may cause widespread gray matter alterations and underlying subcortical neurite loss, which may serve as potential imaging biomarkers reflecting the pathology of DCM.

Morphological changes in the brain in liver cirrhosis of alcoholic and viral etiology

Background. Hepatic encephalopathy is an actual problem of modern medicine. However, its pathogenesis and histological picture are currently insufficiently studied. Less is known about the impact of the nature of primary liver disease on pathogenesis and histological picture of hepatic encephalopathy. This determines the relevance of further morphological studies of the brain in the late stages of liver cirrhosis of various etiologies.The aim. To establish and compare the morphological changes in the brain in alcoholic liver cirrhosis and viral (hepatitis C virus (HCV)) cirrhosis.Materials and methods. The morphological study of the brain of 40 deceased in outcome of HCV-associated cirrhosis and 23 patients died in outcome of chronic alcoholism was carried out. Histological changes in various parts of the brain were studied using survey and elective stains. The immunohistochemical study of HCV NS3 and CD68 expression in different brain regions was performed in cases of HCV-infection.Results. The changes of neurons, glial cells and cerebral microvessels underlie in the basis of morphological picture of brain damage in both studied groups underlie that corresponds to the “classical” model of hepatic encephalopathy pathogenesis. At the same time, a number of morphological features were observed. The most prominent differences concerned the manifestations of the glial reaction. The productive changes of macroglial cells with the appearance of multiple Alzheimer’s astrocytes type 2 as well as spongious changes in subcortical white matter dominated in the observations of alcoholic cirrhosis. In contrast, microglia cells reaction (microgliosis) in white matter was noticed in HCV-associated cirrhosis.Conclusions. The differences in histological signs of brain in the terminal stages of liver disease of viral and alcoholic etiology are shown. They broaden current idea of morphological picture of hepatic encephalopathy, and may be used to study its pathogenesis.

An Unsuspecting Recurrent Cryptogenic Stroke: A Case Report

Cerebral Autosomal Dominant Arteriopathy with Sub-Cortical Infarcts and Leukoencephalopathy (CADASIL) is a rare autosomal genetic disorder that affects the brain’s small vessels. It is recognized among the leading causes of stroke in the young.&#x0D; This is a case report of a 35-year-old female with underlying migraine with auras who presented with recurrent cryptogenic strokes. She presented no vascular risk factors or any family history of neurological disease. An investigation into her presentation leads us to a diagnosis of CADASIL following typical subcortical and deep white matter changes seen on her Magnetic Resonance Imaging (MRI).

Changes in subcortical white matter in the unaffected hemisphere following unilateral spontaneous intracerebral hemorrhage: a tract-based spatial statistics study.

We investigated changes in the subcortical white matter in the unaffected hemisphere in patients with unilateral intracerebral hemorrhage (ICH) by applying tract-based spatial statistics (TBSS) analysis. Twenty-four patients with ICH and 17 healthy control subjects were recruited for this study. Diffusion tensor imaging (DTI) data were obtained at least four weeks after ICH onset. TBSS analysis was performed using fractional anisotropy (FA) DTI data. We calculated mean FA values across the tract skeleton and within 27 regions of interest (ROIs) based on the observed intersections between the FA skeleton and the probabilistic Johns Hopkins University white matter atlases. The FA values of 27 ROIs in the unaffected hemisphere in the patient group were significantly lower than those of the control group (p < 0.05). In terms of a causal relationship between possible confounding factors (sex, age, lateralization [right], lesion volume), a negative correlation coefficient was observed in five ROIs (the tapetum, sagittal stratum, column and body of the fornix, posterior corona radiate, inferior cerebellar peduncle, superior cerebellar peduncle) in the regression analysis (p < 0.05). In the patient group, moderate negative correlations were detected between ICH volume and the FA values of two ROIs: the sagittal stratum, r = -0.479, p < 0.05; the tapetum, r = -0.414, p < 0.05. We detected extensive neural injury of the subcortical white matter in the unaffected hemisphere in patients with unilateral ICH. In addition, injury severities of neural structures located around the mid-sagittal line or periventricular areas were correlated with ICH volume.

The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care

Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.

Expanding the phenotype of SPARC-related osteogenesis imperfecta: clinical findings in two patients with pathogenic variants in SPARC and literature review

BackgroundSecreted protein, acidic, cysteine rich (SPARC)-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report...

Hyperglycemia‐induced seizures and visual symptoms due to reversible occipital damage: A case series

AbstractSeizures associated with hyperglycemia are mostly partial motor with or without secondary generalization. Occipital lobe seizures due to hyperglycemia have been reported in few case studies. The clinical characteristics, electroencephalogram (EEG), and imaging findings of the patients with poorly controlled sugars, visual impairment, and seizures were analyzed. Three patients presented with poorly controlled sugars, seizures, and visual symptoms including visual impairment and occipital seizures over a period of 6 months. EEG showed frequent occipital spikes and electrical seizures of occipital origin. Magnetic resonance imaging brain showed T2 FLAIR hypointensity over the subcortical white matter and gyral changes over the parieto‐occipital area. All of them showed good clinical improvement with antiepileptic medications and good glycemic control. The imaging repeated on follow‐up in two patients showed complete resolution of T2 FLAIR hypointensity. Hyperglycemia‐induced changes can occur with a predeliction for occipital lobe. The visual impairment and occipital seizures respond to glycemic control and anticonvulsants.

Brain MRI features of methylmalonic acidemia in children: the relationship between neuropsychological scores and MRI findings

Methylmalonic acidemia (MMA) is a severe, heterogeneous disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism with a poor prognosis that can cause brain damage. Identifying the magnetic resonance imaging (MRI) findings of MMA might help to make accurate diagnoses earlier in the disease course and exploring the relationship between neuropsychological scores and MRI findings, when therapy is more effective and to improve therapeutic efficacy. Cerebral MRI studies from 37 children with MMA were evaluated by a neuroradiologist. Clinical and imaging data were collected from each patient. All tests were performed during routine investigations and in accordance with the ethical principles of the Declaration of Helsinki. Informed consent was obtained from the guardians of all patients for inclusion in the study. The most common and significant findings were periventricular white matter changes (78.4%), ventricular dilation (29.7%) and cerebral atrophy (40.5%). According to the developmental quotient, the 37 patients were divided into the normal intelligence subgroup (NI, developmental quotient ≥ 85) and the low intelligence subgroup (LI, developmental quotient < 85). The incidence of corpus callosal thinning, cortical atrophy, subcortical white matter changes, and ventricular dilation (grades 0–3) was significantly higher in the LI subgroup than in the NI subgroup (P < 0.05). The incidence of no-mild and moderate-severe ventricular dilation was significantly higher in the LI subgroup than in the NI subgroup (P < 0.05). Ventricular dilatation, cerebral atrophy, white matter changes, and corpus callosal thinning are the main MRI abnormalities in MMA patients, and these manifestations are significantly correlated with delayed development in children.

Indication of Thalamo-Cortical Circuit Dysfunction in Idiopathic Normal Pressure Hydrocephalus: A Diffusion Tensor Imaging Study

Idiopathic normal pressure hydrocephalus (iNPH) is a disorder with unclear pathophysiology. The diagnosis of iNPH is challenging due to its radiological similarity with other neurodegenerative diseases and ischemic subcortical white matter changes. By using Diffusion Tensor Imaging (DTI) we explored differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in iNPH patients (before and after a shunt surgery) and healthy individuals (HI) and we correlated the clinical results with DTI parameters. Thirteen consecutive iNPH-patients underwent a pre- and post-operative clinical work-up: 10 m walk time (w10mt) steps (w10ms), TUG-time (TUGt) and steps (TUGs); for cognitive function MMSE. Nine HI were included. DTI was performed before and 3 months after surgery, HI underwent DTI once. DTI differences analyzed by manually placing 12 regions-of-interest. In patients motor and balance function improved significantly after surgery (p = 0.01, p = 0.025). Higher nearly significant FA values found in the patients vs HI pre-operatively in the thalamus (p = 0.07) accompanied by an almost significant lower ADC (p = 0.08). Significantly FA and ADC-values were found between patients and HI in FWM (p = 0.02, p = 0.001) and almost significant (p = 0.057) pre- vs postoperatively. Postoperatively we found a trend towards the HIs FA values and a strong significant negative correlation between FA changes vs. gait results in the FWM (r = −0.7, p = 0.008). Our study gives a clear indication of an ongoing pathological process in the periventricular white matter, especially in the thalamus and in the frontal white matter supporting the hypothesis of a shunt reversible thalamo-cortical circuit dysfunction in iNPH.

A Neurological Appearance of Celiac Disease: Is There Any Associated Factor?

Celiac disease may present with one or more neurological signs and/or symptoms. We aimed to define the incidence of accompanying neurological manifestations in children diagnosed as having celiac disease. The prospective study included 146 children diagnosed as having celiac disease. The medical records (presentation symptoms, clinical findings, serological test, duodenal biopsy results, lack/deficiency of vitamin, tissue type, accompanying autoimmune disorders) and demographic data of all patients were also reviewed. Thirty-five (23.9%) of the 146 celiac patients exhibited one or more neurological findings. Headache (11.6%) and dizziness (6.1%) were the most common symptoms among neurological manifestations. There was a significant difference between the patients with and without neurological manifestations in terms of sex, biopsy result, and tissue type (P < 0.05). Moreover, there was a statistically significant difference between tissue types of the patients with and without headache (P < 0.05). We found that grade 3a by Marsh classification was the most common type among the patients with and without neurological findings in celiac disease. On neuroimaging evaluation of patients, 1 patient with chronic focal ischemic lesion, 1 patient with Chiari type 1 malformation, and 1 patient with subcortical white matter changes were identified. Pathophysiology of neurological involvement in celiac disease is liable for various neurological findings. This study contributes to data suggesting that female sex, mild histopathological form, and human leukocyte antigen DQ2 heterozygosity are related to neurological manifestations, and also human leukocyte antigen DQ2 heterozygosity is associated with headache in celiac disease.

Evaluation of clinical, neuroradiologic, and genotypic features of patients with L-2-hydroxyglutaric aciduria.

Aim:L-2-hydroxyglutaric aciduria is a slowly progressive neurometabolic disorder caused by an enzymatic deficiency of L-2-hydroxyglutarate dehydrogenase. Here, we aimed to evaluate the clinical, neuroradiologic, and genotypic characteristics of patients with L-2-hydroxyglutaric aciduria who were followed in our outpatient clinic.Material and Methods:Twenty-five patients with L-2-hydroxyglutaric aciduria were enrolled in the study. Data regarding demographic, clinical, and neuroradiologic findings and molecular analysis were evaluated retrospectively.Results:The mean age of patients at the time of diagnosis was 12.09±8.02 years, whereas the mean age at the time of the first symptoms was 39.47±29.96 months. Diagnostic delay was found as 9.95±7.78 years. Developmental delay, decrease in school success, and seizures were the most common initial symptoms; however, behavioral problems and seizures became more prominent in the disease course. At the time of diagnosis, mental retardation and at least one pathologic cerebellar finding were detected in all symptomatic patients. Three patients developed brain tumors. The most common neuroimaging findings were subcortical white matter changes and cerebellar dentate nucleus involvement. In one patient, there was only isolated basal ganglia involvement without white matter lesions. Patients with similar genotypic features exhibited different clinical and radiologic findings.Conclusion:Although clinical symptoms appear early in L-2-hydroxyglutaric aciduria, there is approximately a ten-year delay in diagnosis. In subjects in whom brain tumor is detected in early childhood, L-2-hydroxyglutaric aciduria should be considered in the differential diagnosis in the presence of mental retardation accompanied by developmental delay, cerebellar and pyramidal findings, and behavior disorders in a wide spectrum ranging from autism spectrum disorder to psychosis. In patients with L-2-hydroxyglutaric aciduria, incipient headache, tinnitus, altered consciousness, and seizures can be indicative of brain tumors.

Prenatal or Perinatal Injury? Diagnosing the Cortically Blind Infant

To document the association of prenatal brain disruption with secondary perinatal distress in children diagnosed as having cortical visual impairment (CVI). Retrospective case series. Eight children with severe CVI and clinical history of perinatal events were included. Case histories and neuroimaging studies were reviewed. The main outcome measures were perinatal history, visual and neurologic findings, and magnetic resonance (MR) imaging. In our patient cohort, MR imaging showed signs of cortical dysgenesis leading to congenital brain malformations such as polymicrogyria consistent with a prenatal timing of CNS injury. Although subcortical white matter changes were common, signs of watershed injury to the visual cortex were absent, suggesting that the visual loss was attributable to a prenatal etiology with secondary birth complications. Some children with CVI and a history of perinatal distress have prenatal dysgenesis of the developing brain. Therefore, a clinical history of perinatal hypoxia-ischemia is nonspecific and merits neuroimaging to identify antecedent brain malformations and timing of injury, which can influence patient diagnosis and management.

Neuroimaging in mitochondrial disorders

MRI and 1H magnetic resonance spectroscopy (1HMRS) are the main neuroimaging methods to study mitochondrial diseases. MRI can demonstrate seven 'elementary' central nervous system (CNS) abnormalities in these disorders, including diffuse cerebellar atrophy, cerebral atrophy, symmetric signal changes in subcortical structures (basal ganglia, brainstem, cerebellum), asymmetric signal changes in the cerebral cortex and subcortical white matter, leukoencephalopathy, and symmetric signal changes in the optic nerve and the spinal cord. These elementary MRI abnormalities can be variably combined in the single patient, often beyond what can be expected based on the classically known clinical-pathological patterns. However, a normal brain MRI is also possible. 1HMRS has a diagnostic role in patients with suspected mitochondrial encephalopathy, especially in the acute phase, as it can detect within the lesions, but also in normal appearing nervous tissue or in the ventricular cerebrospinal fluid (CSF), an abnormally prominent lactate peak, reflecting failure of the respiratory chain with a shift from the Krebs cycle to anaerobic glycolysis. So far, studies correlating MRI findings with genotype in mitochondrial disease have been possible only in small samples and would greatly benefit from data pooling. MRI and 1HMRS have provided important information on the pathophysiology of CNS damage in mitochondrial diseases by enabling in vivo non-invasive assessment of tissue abnormalities, the associated changes of blood perfusion and cellular metabolic derangement. MRI and 1HMRS are expected to serve as surrogate biomarkers in trials investigating therapeutic options in mitochondrial disease.

P47. Voxel-based Morphometry (VBM) subcortical white matter changes correlate with D50 model disease progression in amyotrophic lateral sclerosis

P47. Voxel-based Morphometry (VBM) subcortical white matter changes correlate with D50 model disease progression in amyotrophic lateral sclerosis