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.

Impact of Ovarian Endometrioma and Surgery on Reproductive Outcomes: A Single-Center Spanish Cohort Study.

Anti-Müllerian hormone (AMH) and antral follicular count (AFC) decrease in women with ovarian endometrioma (OMA) and in vitro fertilization (IVF). In addition, these parameters drop even further when women with OMA undergo surgery. In this study, the primary aim was to compare the reproductive variables in IVF-treated women with and without endometriosis. The secondary aim was to explore if the reproductive variables were modified by endometrioma surgery. In this retrospective study, 244 women undergoing IVF were enrolled at the Hospital Universitario La Paz (Madrid, Spain). Women were categorized as OMA not surgically treated (OMA; n = 124), OMA with surgery (OMA + S; n = 55), and women with infertility issues not related to OMA (control; n = 65). Demographic and clinical variables, including age, body mass index (BMI), and reproductive (AMH, AFC, number of extracted oocytes, and transferred embryos) and obstetrical data (biochemical pregnancy and fetal heart rate at 6 weeks) were collected. Adjusted logistic regression models were built to evaluate reproductive and pregnancy outcomes. The models showed that women with OMA (with and without surgery) had significantly decreased levels of AMH and AFC and numbers of cycles and C + D embryos. Women with OMA + S had similar rates of pregnancy to women in the control group. However, women with OMA had lower biochemical pregnancy than controls (aOR = 0.08 [0.01; 0.50]; p-value = 0.025). OMA surgery seems to improve pregnancy outcomes, at least until 6 weeks of gestation. However, it is important to counsel the patients about surgery expectations due to the fact that endometrioma itself reduces the quality of oocytes.

Lewis-Sumner syndrome: contribution of diffusion tensor imaging in its differential diagnosis.

Lewis-Sumner syndrome (LSS) is an atypical variant of chronic inflammatory demyelinating polyneuropathy characterized by an asymmetric sensory-motor neuropathy with multifocal distribution. The diagnosis is typically clinical and electrophysiological but in some cases might be challenging causing a significant therapeutic delay. Diffusion tensor imaging (DTI) has been progressively used for the in vivo assessment of peripheral nerves integrity. In this study, we aimed to elucidate if DTI was able to detect the specific nerve damage in a patient with suspected LSS, and determine if DTI presented a specific pattern that could be useful in its differential diagnosis. A 38-year-old male with a right foot drop was studied. Physical examination, electrodiagnostic, and MRI studies were performed. MRI of the lower limb was acquired in a 3-T scanner and included T1-wi, T2-TSE-SPIR, and PD-TSE-SPAIR images in axial and coronal planes. Axial DTI was acquired using a single-shot EPI sequence with diffusion encoding in 32 directions. The electrodiagnostic tests suggested a demyelinating sensorimotor neuropathy with conduction blocks. Conventional MRI was normal. DTI showed pathological results in Tibial and Peroneal nerves consisting of thinning and discontinuities along both nerves but more significant in the Peroneal. Compared with MRI, DTI offered a significant improvement to detect the specific nerve damage and its characteristics. The observed nerve damage in DTI suggested polyneuropathy and was compatible with the electrophysiological findings, endorsing the LSS diagnosis. This is the first report in the literature presenting the DTI findings in LSS.

Quality of Life in Women after Deep Endometriosis Surgery: Comparison with Spanish Standardized Values.

The quality of life (QoL) of women who have been surgically treated for endometriosis may be severely impaired. Therefore, QoL can be a determining factor in the recovery of these patients. The aims of this study were to evaluate if the QoL of women surgically treated for deep endometriosis differs from a healthy age-matched population from Catalonia (Spain) and to analyze the QoL of these women considering concomitant events. This is an observational cross-sectional study, where 112 women (between 18 and 48 years old), with endometriosis treated by surgery at Hospital Universitario La Paz (Madrid, Spain), were enrolled to assess the QoL using the second version of the 12-item short form (SF-12) questionnaire. The QoL in these women were tested against a reference population of healthy women using a standardized one-sample comparison method. In addition, the QoL was compared according to the pathophysiology and type of surgery. In women with endometriosis, the physical health component, but not mental health component, was positively correlated with age (r = 0.19; p-Value = 0.048). In addition, physical (20.3 ± 29.2) and social functions (29.7 ± 38.3) and the overall physical health component (37.8 ± 19.4) were significantly lower than the reference population. On the contrary, the body pain (64.1 ± 41.2), emotional role (62.5 ± 42.2), mental health (54.4 ± 26.0), vitality (59.3 ± 31.2), and the overall mental health component (59.4 ± 26.6) had significantly higher scores than the reference. The anatomical compartment of endometriosis, reintervention, bowel nodule resection, and fertility preservation did not show statistical differences in QoL. Women with deep endometriosis had worse physical and social functions, and the overall physical health, compared to the norm in Spanish women. Bodily pain, emotional role, vitality, and the overall mental health improved. These areas could be considered protective factors in this disease. Considering the importance of QoL in adjustments in mental and physical health, it would be necessary to improve these areas of QoL in women surgically treated for deep endometriosis.

Evaluation of Women's Age and Ultrasonographic Features to Choose Surgical Treatment for Endometriosis Associated with Ovarian Cancer.

Adequate surgical management of malignant endometriosis remains a clinical challenge in gynecology. Age, sonography variables, and tumor biomarkers have been reported as candidates in the clinical decision. This study aims were to analyze the factors of women's age, body mass index, ultrasound features, and tumor biomarkers to predict endometriosis-associated ovarian cancer in a large series of endometriomas and to study the surgical treatment performed in this cohort. In this retrospective study, we reviewed the medical records of patients with ultrasound diagnosis of ovarian cyst classified as endometrioma (benign as well as with risk of malignancy), surgically treated in the endometriosis unit of Hospital Universitario La Paz (Madrid, Spain) between January 2019 and July 2021. According to the final histology examination, the women were clustered as non-endometriosis-associated ovarian cancer (OE, benign endometriomas, n = 59) and endometriosis-associated ovarian cancer (EAOC) (n = 17). Demographic, clinical, and surgical data were collected from these women. International Ovarian Tumor Analysis (IOTA) criteria were assessed for the ultrasound examination. The age of the women in the EAOC group was 50.0 [43.0; 63.0] years, which was significantly higher than OE (39.0 [34.0; 46.0] years; p-value < 0.001). In addition, the body mass index for the OE group (24.9 ± 5.3 kg/m2) was significantly higher than for the EAOC group (23.3 ± 4.6 kg/m2; p-value < 0.001). However, the tumor biomarker levels (CA 125, CA 19.9 and He4) were not significantly different among the groups. We performed 51.4% cystectomies and 48.6% adnexectomies, with an association between the adnexectomy and EAOC group (p-value < 0.001). In addition, a significant association was found between ultrasound features suspicious for malignancy and the EAOC group. Conclusively, women's age and ultrasound features, such as papillary projections, septa, and positive echo-Doppler, were the main factors to consider when evaluating the malignancy risk associated with endometriosis.

Contribution of Gray Matter Atrophy and White Matter Damage to Cognitive Impairment in Mildly Disabled Relapsing-Remitting Multiple Sclerosis Patients.

Cognitive impairment (CI) is frequently present in multiple sclerosis patients. Despite ongoing research, the neurological substrates have not been fully elucidated. In this study we investigated the contribution of gray and white matter in the CI observed in mildly disabled relapsing-remitting multiple sclerosis (RRMS) patients. For that purpose, 30 patients with RRMS (median EDSS = 2), and 30 age- and sex-matched healthy controls were studied. CI was assessed using the symbol digit modalities test (SDMT) and the memory alteration test. Brain magnetic resonance imaging, diffusion tensor imaging (DTI), voxel-based morphometry (VBM), brain segmentation, thalamic vertex analysis, and connectivity-based thalamic parcellation analyses were performed. RRMS patients scored significantly lower in both cognitive tests. In the patient group, significant atrophy in the thalami was observed. Multiple regression analyses revealed associations between SDMT scores and GM volume in both hemispheres in the temporal, parietal, frontal, and occipital lobes. The DTI results pointed to white matter damage in all thalamocortical connections, the corpus callosum, and several fasciculi. Multiple regression and correlation analyses suggested that in RRMS patients with mild disease, thalamic atrophy and thalamocortical connection damage may lead to slower cognitive processing. Furthermore, white matter damage at specific fasciculi may be related to episodic memory impairment.

Main genetic differences in high-grade gliomas may present different MR imaging and MR spectroscopy correlates.

OBJECTIVE: To assess whether the main genetic differences observed in high-grade gliomas (HGG) will present different MR imaging and MR spectroscopy correlates that could be used to better characterize lesions in the clinical setting. METHODS: Seventy-nine patients with histologically confirmed HGG were recruited. Immunohistochemistry analyses for isocitrate dehydrogenase gene 1 (IDH1), alpha thalassemia mental retardation X-linked gene (ATRX), Ki-67, and p53 protein expression were performed. Tumour radiological features were examined on MR images. Metabolic profile and infiltrative pattern were assessed with MR spectroscopy. MR features were analysed to identify imaging-molecular associations. The Kaplan-Meier method and the Cox regression model were used to identify survival prognostic factors. RESULTS: In total, 17.7% of the lesions were IDH1-mutated, 8.9% presented ATRX-mutated, 70.9% presented p53 unexpressed, and 22.8% had Ki-67 > 5%. IDH1 wild-type tumours had higher levels of mobile lipids (p = 0.001). The tumour-infiltrative pattern was higher in HGG with unexpressed p53 (p = 0.009). Mutated ATRX tumours presented higher levels of glutamate and glutamine (Glx) (p = 0.001). An association was observed between Glx tumour levels (p = 0.038) and Ki-67 expression (p = 0.008) with the infiltrative pattern. Survival analyses identified IDH1 status, age, and tumour choline levels as independent predictors of prognostic significance. CONCLUSIONS: Our results suggest that IDH1-wt tumours are more necrotic than IDH1-mut. And that the presence of an infiltrative pattern in HGG is associated with loss of p53 expression, Ki-67 index, and Glx levels. Finally, tumour choline levels could be used as a predictive factor in survival in addition to the IDH1 status to provide a more accurate prediction of survival in HGG patients. KEY POINTS: • IDH1-wt tumours present higher levels of mobile lipids than IDH1-mut. • Mutated ATRX tumours exhibit higher levels of glutamate and glutamine. • Loss of p53 expression, Ki-67 expression, and glutamate and glutamine levels may contribute to the presence of an infiltrative pattern in HGG.

MRI evidence of brain atrophy, white matter damage, and functional adaptive changes in patients with cervical spondylosis and prolonged spinal cord compression.

OBJECTIVES: To investigate the effect of cervical spondylosis (CS) in the brain with a combination of advanced neuroimaging techniques. METHODS: Twenty-seven patients with CS and 24 age- and gender-matched healthy controls were studied. Disease severity was quantified using the Modified Japanese Orthopaedic Association Scoring System (mJOHA). Magnetic resonance (MR) imaging of the brain and spinal cord, functional MR imaging (fMRI) with a bilateral rest/finger-tapping paradigm, brain diffusion tensor imaging (DTI), voxel-based morphometry (VBM), and MR spectroscopy of the sensorimotor cortex were performed. RESULTS: A total of 92.3% of patients had more than one herniated disc. In the MRI, 33.33% presented signs of myelopathy. The mJOHA score was 13.03 ± 2.83. Compared with controls, DTI results showed significant lower FA values in Corpus callosum, both corticospinal tracts and middle cerebellar peduncles (p < 0.05 corrected). Only in CS patients fMRI results showed activation in both globus pallidi, caudate nucleus, and left thalamus (p < 0.001). Subject-specific activation of the BOLD signal showed in CS patients lower activation in the sensorimotor cortex and increased activation in both cerebellum hemispheres (p < 0.05 corrected). VBM showed bilateral clusters of gray matter loss in the sensorimotor cortex and pulvinar nucleus (p < 0.05 corrected) of CS patients. NAA/Cr was reduced in the sensorimotor cortex of CS patients (p < 0.05). Linear discriminant and support vector machine analyses were able to classify > 97% of CS patients with parameters obtained from the fMRI, DTI, and MRS results. CONCLUSION: CS may lead to distal brain damage affecting the white and gray matter of the sensorimotor cortex causing brain atrophy and functional adaptive changes. KEY POINTS: • This study suggests that patients with cervical spondylosis may present anatomical and functional adaptive changes in the brain. • Cervical spondylosis may lead to white matter damage, gray matter volume loss, and functional adaptive changes in the sensorimotor cortex. • The results reported in this work may be of value to better understand the effect of prolonged cervical spine compression in the brain.

Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.

The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

BRAIM: A computer-aided diagnosis system for neurodegenerative diseases and brain lesion monitoring from volumetric analyses.

BACKGROUND AND OBJECTIVE: This paper presents BRAIM, a computer-aided diagnosis (CAD) system to help clinicians in diagnosing and treatment monitoring of brain diseases from magnetic resonance image processing. BRAIM can be used for early diagnosis of neurodegenerative diseases such as Parkinson, Alzheimer or Multiple Sclerosis and also for brain lesion diagnosis and monitoring. METHODS: The developed CAD system includes different user-friendly tools for segmenting and determining whole brain and brain structure volumes in an easy and accurate way. Specifically, three types of measurements can be performed: (1) total volume of white, gray matter and cerebrospinal fluid; (2) brain structure volumes (volume of putamen, thalamus, hippocampus and caudate nucleus); and (3) brain lesion volumes. RESULTS: As a proof of concept, some study cases were analyzed with the presented system achieving promising results. In addition to be used to quantify treatment effectiveness in patients with brain lesions, it was demonstrated that BRAIM is able to classify a subject according to the brain volume measurements using as reference a healthy control database created for this purpose. CONCLUSIONS: The CAD system presented in this paper simplifies the daily work of clinicians and provides them with objective and quantitative volume data for prospective and retrospective analyses.