Magnetic resonance spectroscopy in MELAS syndrome: correlation with CSF and plasma metabolite levels and change after glutamine supplementation.

PURPOSE: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. METHODS: We conducted an observational case-control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. RESULTS: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). CONCLUSION: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138.

Diagnostic imaging strategies of acute intracerebral hemorrhage in European academic hospitals-a decision-making analysis.

PURPOSE: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. METHODS: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. RESULTS: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. CONCLUSION: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.

High-dose oral glutamine supplementation reduces elevated glutamate levels in cerebrospinal fluid in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome.

BACKGROUND AND PURPOSE: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels. METHOD: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation. RESULTS: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 µmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 µmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety. One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode. DISCUSSION: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT04948138. Initial release 24 June 2021, first patient enrolled 1 July 2021. https://clinicaltrials.gov/ct2/show/NCT04948138.

Elevated glutamate and decreased glutamine levels in the cerebrospinal fluid of patients with MELAS syndrome.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) mutations in the MT-TL1 gene. The pathophysiology of neurological manifestations is still unclear, but neuronal hyperexcitability and neuron-astrocyte uncoupling have been suggested. Glutamatergic neurotransmission is linked to glucose oxidation and mitochondrial metabolism in astrocytes and neurons. Given the relevance of neuron-astrocyte metabolic coupling and astrocyte function regulating energetic metabolism, we aimed to assess glutamate and glutamine CSF levels in MELAS patients. METHODS: This prospective observational case-control study determined glutamate and glutamine CSF levels in patients with MELAS syndrome and compared them with controls. The plasma and CSF levels of the remaining amino acids and lactate were also determined. RESULTS: Nine adult patients with MELAS syndrome (66.7% females mean age 35.8 ± 3.2 years) and 19 controls (63.2% females mean age 42.7 ± 3.8 years) were included. The CSF glutamate levels were significantly higher in patients with MELAS than in controls (18.48 ± 1.34 vs. 5.31 ± 1.09 µmol/L, p < 0.001). Significantly lower glutamine concentrations in patients with MELAS than controls were shown in CSF (336.31 ± 12.92 vs. 407.06 ± 15.74 µmol/L, p = 0.017). Moreover, the CSF levels of alanine, the branched-chain amino acids (BCAAs) and lactate were significantly higher in patients with MELAS. CONCLUSIONS: Our results suggest the glutamate-glutamine cycle is altered probably due to metabolic imbalance, and as a result, the lactate-alanine and BCAA-glutamate cycles are upregulated. These findings might have therapeutic implications in MELAS syndrome.

Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection.

OBJECTIVE: To report a case of a patient infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who acutely developed a hypokinetic-rigid syndrome. METHODS: Patient data were obtained from medical records from the Hospital Universitario 12 de Octubre in Madrid, Spain. [123I]-ioflupane dopamine transporter (DaT) SPECT images were acquired 4 hours after a single dose of 185 MBq of 123I-FP-CIT. Quantitative analysis was performed with DaTQUANT software providing the specific binding ratio and z score values of the striatum. RESULTS: We report a previously healthy 58-year-old man who developed hyposmia, generalized myoclonus, fluctuating and transient changes in level of consciousness, opsoclonus, and an asymmetric hypokinetic-rigid syndrome with ocular abnormalities after a severe SARS-CoV-2 infection. DaT-SPECT confirmed a bilateral decrease in presynaptic dopamine uptake asymmetrically involving both putamina. Significant improvement in the parkinsonian symptoms was observed without any specific treatment. CONCLUSION: This case study provides clinical and functional neuroimaging evidence to support that SARS-CoV-2 can gain access to the CNS, affecting midbrain structures and leading to neurologic signs and symptoms.

Signo de "sal y pimienta" como presentación de una lesión pontina no vascular / "Salt and pepper" sign in the onset of a non-vascular pontine pathology

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Brain Magnetic Resonance Spectroscopy Findings in the Stroke-like Migraine Attacks after Radiation Therapy (SMART) Syndrome.

A 41-year-old male presented with an acute onset of headache, confusion, seizures, and unilateral focal neurological deficit 25 years after receiving whole-brain radiation therapy to treat a cerebellar medulloblastoma. Brain magnetic resonance imaging (MRI) demonstrated a thick unilateral parieto-occipital cortical contrast enhancement. A diagnosis of "Stroke-like Migraine Attacks after Radiation Therapy" (SMART) syndrome was made. Here, we describe the brain MR spectroscopy findings of SMART, showing a decrease in N-acetyl-aspartate and increased levels of creatine and choline, corresponding with neuronal destruction or transient neuronal impairment with mild nonspecific gliosis. The absence of a lactate peak suggests that mitochondrial dysfunction, vasospasm or ischemic mechanisms were not involved.

Subcortical regional morphology correlates with fluid and spatial intelligence.

Neuroimaging studies have revealed associations between intelligence and brain morphology. However, researchers have focused primarily on the anatomical features of the cerebral cortex, whereas subcortical structures, such as the basal ganglia (BG), have often been neglected despite extensive functional evidence on their relation with higher-order cognition. Here we performed shape analyses to understand how individual differences in BG local morphology account for variability in cognitive performance. Structural MRI was acquired in 104 young adults (45 men, 59 women, mean age = 19.83, SD = 1.64), and the outer surface of striatal structures (caudate, nucleus accumbens, and putamen), globus pallidus, and thalamus was estimated for each subject and hemisphere. Further, nine cognitive tests were used to measure fluid (Gf), crystallized (Gc), and spatial intelligence (Gv). Latent scores for these factors were computed by means of confirmatory factor analysis and regressed vertex-wise against subcortical shape (local displacements of vertex position), controlling for age, sex, and adjusted for brain size. Significant results (FDR < 5%) were found for Gf and Gv, but not Gc, for the right striatal structures and thalamus. The main results show a relative enlargement of the rostral putamen, which is functionally connected to the right dorsolateral prefrontal cortex and other intelligence-related prefrontal areas.

Accuracy of MRI criteria for dissemination in space for the diagnosis of multiple sclerosis in patients with clinically isolated syndromes.

The MRI Barkhof-Tintoré criteria have proved to be highly specific for predicting conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes (CIS), but lacked an optimal sensitivity. In order to improve the accuracy of early multiple sclerosis diagnosis, new imaging criteria have been proposed by Swanton et al. We aimed to evaluate the accuracy of both MRI criteria for dissemination in space to predict conversion from CIS to clinically definite multiple sclerosis. We studied 79 CIS patients with baseline MRI performed within the first 3 months after onset. The sensitivity and specificity of both MRI criteria to predict conversion to clinically definite multiple sclerosis were analysed. The time to develop clinically definite multiple sclerosis from CIS onset, according to each imaging criteria, was studied by Kaplan-Meier survival curves. The overall conversion rate was 75.7% with a median follow-up of 57 months. Barkhof- Tintoré's criteria showed a sensitivity of 71.9% and a specificity of 77.2%. Swanton's criteria had a sensitivity of 91.2% and a specificity of 68.1%. Both MRI criteria identified CIS patients with higher risk and faster conversion to clinically definite multiple sclerosis. Swanton's criteria are simpler and more sensitive than Barkhof-Tintoré's criteria, with a slight decrease in specificity. These results reinforce their use in multiple sclerosis diagnosis.

Sex does not influence prognosis in diabetic patients. The Barbanza Diabetes study.

INTRODUCTION AND OBJECTIVES: To determine the influence of sex on cardiovascular complications in diabetic patients. METHODS: This multicenter prospective cohort study involved 1423 consecutive patients with diabetes mellitus who were recruited during consultations with 31 primary care physicians. The patients' characteristics were recorded and they were followed up for 45 + or - 10 months. RESULTS: The mean age of the patients (50% female) was 66 years, 64% had hypertension, 70% had dyslipidemia, and 26% had had a previous cardiovascular event. Cardiovascular disease, predominantly ischemic heart disease, was observed more frequently in men and a higher percentage had end-organ damage (57.7% of males versus 45.4% of females; P< .0001). Women had poorer glycemic control, higher total cholesterol levels and lower high-density lipoprotein cholesterol levels. By the end of follow-up, 81 patients had died (5.7% of males versus 6.7% of females; P=.513). There were no sex differences in cardiovascular complications during follow up (15.8% in males versus 13.7% in females; P=.368). Multivariate analysis identified the following factors as independent predictors of morbidity or mortality: age (hazard ratio [HR]=1.04; 95% confidence interval [CI], 1.02-1.06), existing cardiovascular disease (HR=1.96; 95% CI, 1.38-2.79), diuretic treatment (HR=1.62; 95% CI, 1.10-2.38), and albuminuria (HR=1.86; 95% CI, 1.33-2.61). CONCLUSIONS: No difference was observed in mediumterm prognosis, with regard to mortality and cardiovascular selecmorbidity, between male and female diabetics from the same geographical area, despite the presence of clinical differences between the sexes.

Hemiparkinsonismo secundario a meningioma en el ala del esfenoides / No disponible

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[Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging]. / Complicaciones neurológicas en el postoperatorio inmediato de la cirugía cardíaca. Aportación de la resonancia magnética cerebral.

INTRODUCTION AND OBJECTIVES: Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. MATERIAL AND METHOD: We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. RESULTS: In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. CONCLUSIONS: The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications.

Complicaciones neurológicas en el postoperatorio inmediato de la cirugía cardíaca. Aportación de la resonancia magnética cerebral / Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging

Introducción y objetivos. Las complicaciones neurológicas (CN) causan una importante morbimortalidad en el postoperatorio inmediato de la cirugía cardíaca. La comprensión de la etiopatogenia, la prevención y el tratamiento de éstas están en constante evolución. Material y método. Se describen las CN y su evolución en una serie quirúrgica, y se analizan las aportaciones de la resonancia magnética cerebral (RMC) con secuencias T1, T2 y la supresión de líquido cefalorraquídeo, en los pacientes que presentan ictus o encefalopatía poscirugía y tomografía computarizada (TC) craneal sin hallazgos que justifiquen la situación clínica. Resultados. Se estudió a 688 postoperados; se observaron 57 CN (8,3%): 25 ictus, 24 encefalopatías, 5 pacientes con crisis convulsivas, 2 muertes cerebrales y una hemorragia intracerebral. La TC craneal inicial no mostró hallazgos relevantes en el 70% de las ocasiones. Se realizó RMC en 18 pacientes, 11 de ellos con ictus: excepto en un estudio, en la RMC encontramos áreas de infarto agudo o subagudo (hiperintensas en la secuencia T2 y FLAIR) en diferentes localizaciones. También se realizó en 4 pacientes con encefalopatía leve-moderada y mostró en 3 de ellos lesiones similares a las descritas en los ictus. En los restantes 3 casos con encefalopatía severa, la RMC mostró áreas con múltiples infartos corticales. Conclusiones. Las CN tras cirugía cardíaca se presentan con una incidencia no despreciable. La TC craneal puede no presentar hallazgos patológicos en un alto porcentaje. En pacientes seleccionados, la RMC puede presentar lesiones, y demostrar áreas isquémicas no detectadas en la TC que ayudan a comprender a los clínicos la etiopatogenia, la fisiopatología, la clínica y la evolución de estas complicaciones (AU)

Introduction and objectives. Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. Matherial and method. We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. Results. In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. Conclusions. The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications (AU)