Severe Metabolic Acidosis and Hepatopathy due to Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate.

Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a recently described autosomal recessive mitochondrial disease characterized by early onset of neurological symptoms, a biphasic clinical course, and distinctive neuroimaging. Pathogenic variants in the EARS2 gene that encode for mitochondrial glutamyl-tRNA synthetase are responsible for LTBL. Here, we describe the clinical course of an infant diagnosed with an acute crisis of LTBL and severe liver disease. This article illustrates the utility of blood lactate quantification in addition to basic metabolic testing and brain imaging in a child with low tone and poor growth. In addition, this case demonstrates the utility of current genetic diagnostic testing, in lieu of more invasive procedures, in obtaining rapid answers in this very complicated group of disorders.

A compound heterozygous EARS2 mutation associated with mild leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL).

Mitochondrial glutamyl-tRNA synthetase is a major component of protein biosynthesis that loads tRNAs with cognate amino acids. Mutations in the gene encoding this enzyme have been associated with a variety of disorders related to oxidative phosphorylation. Here, we present a case of leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) presenting a biphasic clinical course characterized by delayed psychomotor development and seizure. High-throughput sequencing revealed a novel compound heterozygous mutation in mitochondrial glutamyl-tRNA synthetase 2 (EARS2), which appears to be causative of disease symptoms.

Delayed leukoencephalopathy after acute carbon monoxide intoxication.

Delayed leukoencephalopathy is an uncommon complication of hypoxic-ischemic events of different etiologies, including carbon monoxide intoxication. We present a case of a 40-year-old male patient who was admitted with rapidly progressive neurocognitive and behavioral deficits. There was a history of accidental carbon monoxide intoxication one month before, presenting with loss of consciousness and short hospitalization, followed by a complete clinical recovery. The imaging studies in the delayed phase depicted confluent, symmetric supra-tentorial white matter lesions in keeping with diffuse demyelinization. Restricted diffusion and metabolite abnormalities in magnetic resonance proton spectroscopy were also seen. The diagnosis of CO-mediated delayed post-hypoxic leukoencephalopathy was assumed after exclusion of other mimickers. Hyperbaric oxygen therapy was tentatively performed and the patient had a favorable clinical and radiological evolution.

White matter abnormalities and working memory impairment in systemic lupus erythematosus.

OBJECTIVE/BACKGROUND: Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy in SLE. METHODS: We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using magnetic resonance spectroscopy, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter. RESULTS: Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant when we considered disease duration and left frontal white matter Ch/Cr against total PASAT score and total dyads. CONCLUSIONS: Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.

Differences in white matter abnormalities between bipolar I and II disorders.

BACKGROUND: Although patients with bipolar I and II disorders exhibit heterogeneous clinical presentations and cognitive functions, it remains unclear whether these two subtypes have distinct neural substrates. This study aimed to differentiate the fiber abnormalities between bipolar I and II patients using diffusion tensor images. METHOD: Fourteen bipolar I patients, thirteen bipolar II patients, and twenty-one healthy subjects were recruited. Fractional anisotropy (FA) values calculated from diffusion tensor images were compared among groups using two-sample t-test analysis in a voxel-wise manner. Correlations between the mean FA value of each survived area and the clinical characteristics as well as the scores of neuropsychological tests were further analyzed. RESULTS: Patients of both subtypes manifested fiber impairments in the thalamus, anterior cingulate, and inferior frontal areas, whereas the bipolar II patients showed more fiber alterations in the temporal and inferior prefrontal regions. The FA values of the subgenual anterior cingulate cortices for both subtypes correlated with the performance of working memory. The FA values of the right inferior frontal area of bipolar I and the left middle temporal area of bipolar II both correlated with executive function. For bipolar II patients, the left middle temporal and inferior prefrontal FA values correlated with the scores of YMRS and hypomanic episodes, respectively. CONCLUSIONS: Our findings suggest distinct neuropathological substrates between bipolar I and II subtypes. The fiber alterations observed in the bipolar I patients were majorly associated with cognitive dysfunction, whereas those in the bipolar II patients were related to both cognitive and emotional processing.

[Posterior reversible encephalopathy related to tacrolimus in a liver transplanted HIV patient]. / Encéphalopathie postérieure réversible liée au tacrolimus chez un patient transplanté hépatique infecté par le VIH.

Tacrolimus-related posterior reversible leukoencephalopathy (PRLE) is a rare complication which should be recognized by clinicians who regularly use immunosuppressive therapy. We report the case of an HIV-positive, hepatitis C-positive liver transplant patient who presented with this complication. Immunosuppression with tacrolimus was started after postsurgery. On the 20th day, the patient suffered two tonic-clonic convulsive attacks against a background of hypertension. Cerebral magnetic resonance imaging and lumbar puncture led to diagnosis of tacrolimus-related PRLE after eliminating other possible diagnoses. Therapeutic management consisted of withdrawing tacrolimus and initiating treatment with antiepileptogenic and antihypertensive drugs, supplemented with magnesium sulphate. The symptoms regressed in the days following withdrawal of tacrolimus and the majority of lesions on magnetic resonance imaging disappeared within two weeks. The aim of which should be to identify patients at risk of developing this complication. This would enable targeted prevention involving magnesium supplementation, strict control of blood pressure and serial monitoring of tacrolimus blood concentrations.

Magnetic resonance imaging techniques in white matter disease: potentials and limitations.

OBJECTIVES: excellent soft tissue contrast, noninvasiveness, assessment of multiple structural and functional parameters, and absence of radiation are the essential properties of magnetic resonance imaging explaining why this modality is the technique of choice for the assessment of cerebral white matter (WM). METHODS: the present review discusses various standard and advance magnetic resonance imaging techniques with respect to WM assessment in a clinical context. Techniques assessing predominantly structure are T2, fluid-attenuated inversion recovery, echo-gradient T2*, and susceptibility weighted imaging. Techniques assessing a mix between structure and function are diffusion-weighted and diffusion tensor imaging to investigate WM tracts, magnetization transfer to assess bound and free water pool, and magnetic resonance spectroscopy investigating brain metabolites. Finally, functional techniques are perfusion-weighted imaging and perfusion reserve imaging to assess cerebral perfusion and cerebral perfusion reserve, respectively. CONCLUSIONS: magnetic resonance imaging may assess various and complementary WM parameters. Because acquisition time is limited in the clinical setting, MR techniques must be adapted to the primary question asked. The basic imaging of WM might include axial T2, diffusion-weighted imaging, and coronal fluid-attenuated inversion recovery. This provides an excellent overview in a relatively short time and 2 imaging planes. The remaining MR techniques can add complementary information, for example, PWI/perfusion reserve imaging in vascular disease, T2*/susceptibility weighted imaging in degenerative disease (iron deposition) and head trauma (microbleeds), magnetic resonance spectroscopy (metabolic disease and neoplasm), magnetization transfer (demyelinating disease), and diffusion tensor imaging (degenerative diseases, presurgical evaluation).