Jelena Ostojic

Malignant Peripheral Nerve Sheath Tumor of the Oculomotor Nerve

We present the short-term follow-up magnetic resonance (MR) studies and 1H-MR spectroscopy in a child with malignant peripheral nerve sheath tumor of the oculomotor nerve associated with other less aggressive cranial nerve schwannomas. The tumor revealed perineural extension and diffuse nerve involvement besides rapid growth. 1H-MR spectroscopy was helpful in excluding an intra-axial neoplasm with exophytic growth, mainly due to the absence of creatine and N-acetyl aspartate peaks, and markedly elevated choline peak.

Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues.

Adult-onset autosomal dominant leukodystrophy without early autonomic dysfunctions linked to lamin B1 duplication: a phenotypic variant

The early presentation of autonomic dysfunctions at the disease onset has been considered the mandatory clinical feature in adult-onset autosomal dominant leukodystrophy, which is a rarely recognised leukodystrophy caused by duplication of the lamin B1 gene. We report the first family with adult-onset autosomal dominant leukodystrophy and lamin B1 duplication, without the distinguishing early-appearing autonomic dysfunctions. Subjects from three consecutive generations of a multi-generational Serbian family affected by adult-onset autosomal dominant leukodystrophy underwent clinical, biochemical, neurophysiological, neuroradiological, and genetic studies. The patients atypically exhibited late autonomic dysfunctions commencing at the disease end-stages in some. Genetic findings of lamin B1 duplication verified adult-onset autosomal dominant leukodystrophy, which was supported also by neuroimaging studies. Exclusively, proton magnetic spectroscopy of the brain revealed a possibility of neuro-axonal damage in the white matter lesions, while magnetic resonance imaging of the spinal cord excluded spinal myelin affection as a required finding in this leukodystrophy. The detection of lamin B1 duplication, even when autonomic dysfunctions do not precede the other symptoms of the disease, proves for the first time that lamin B1-duplicated adult-onset autosomal dominant leukodystrophy may have a phenotypic variant with delayed autonomic dysfunctions. Prior to this report, such a phenotype had been speculated to represent an entity different from lamin B1-duplicated leukodystrophy. Hereby we confirm the underlying role of lamin B1 duplication, regardless of the autonomic malfunction onset in this disorder. It is the only report on adult-onset autosomal dominant leukodystrophy from Southeastern Europe.

Hippocampal metabolic dysfunction in juvenile myoclonic epilepsy: 3D multivoxel spectroscopy study

PURPOSE To investigate the metabolic differences in hippocampi of patients with juvenile myoclonic epilepsy (JME) and healthy controls using magnetic resonance spectroscopy (MRS). METHODS A 3D multivoxel SE 135 MRS study on 1.5 T scanner of both hippocampi was performed in 17 patients with JME and normal brain MRI and in 19 age and sex matched controls. Three dominant signals were measured: Choline (Cho), Creatine (tCr) and N-Acetylaspartate (NAA) and expressed as ratios of Cho:tCr, NAA:tCr, NAA:Cho and NAA:(Cho+tCr). Metabolite ratios in head, body and tail of each hippocampus in the JME group of patients were compared with ratios from corresponding structures in the control group. RESULTS We found a significant difference in metabolite ratios of both hippocampi between the JME and the control groups. We detected significant differences of Cho:tCr in the head, NAA:tCr in the head, body and tail, NAA:Cho and NAA:(Cho+tCr) in the body and tail of the left hippocampus, and NAA:Cho and NAA:(Cho+tCr) in the body and tail of the right hippocampus. DISCUSSION Although not previously recognized as a part of the epileptogenic network, our results suggest that the hippocampus, well recognized as a key player in focal epilepsies, may have a certain role in the pathogenesis of JME.

MR and MRS Characteristics of Intraventricular Meningioma

Meningiomas are frequent intracranial, non‐glial tumors of adults. We present the unusual left lateral ventricular localization of meningioma in a 51‐year‐old man. The magnetic resonance (MR) images showed well demarcated, large mass of the atrium of the left lateral ventricle with transependymal extension into the left temporal lobe. MR spectroscopy revealed the presence of “choline only” spectrum, typical for extra axial neoplasms. The mass was completely resected. The diagnosis of transitional type intraventricular meningioma, with psammoma bodies, histologic grade I was made. Progesterone and estrogen receptors were negative.

HIV-associated neurodegeneration and neuroimmunity: multivoxel MR spectroscopy study in drug-naïve and treated patients

AbstractObjectivesThe aim of this study was to test neurobiochemical changes in normal appearing brain tissue in HIV+ patients receiving and not receiving combined antiretroviral therapy (cART) and healthy controls, using multivoxel MR spectroscopy (mvMRS).MethodsWe performed long- and short-echo 3D mvMRS in 110 neuroasymptomatic subjects (32 HIV+ subjects on cART, 28 HIV+ therapy-naïve subjects and 50 healthy controls) on a 3T MR scanner, targeting frontal and parietal supracallosal subcortical and deep white matter and cingulate gyrus (NAA/Cr, Cho/Cr and mI/Cr ratios were analysed). The statistical value was set at p < 0.05.ResultsConsidering differences between HIV-infected and healthy subjects, there was a significant decrease in the NAA/Cr ratio in HIV+ subjects in all observed locations, an increase in mI/Cr levels in the anterior cingulate gyrus (ACG), and no significant differences in Cho/Cr ratios, except in ACG, where the increase showed trending towards significance in HIV+ patients. There were no significant differences between HIV+ patients on and without cART in all three ratios.ConclusionNeuronal loss and dysfunction affects the whole brain volume in HIV-infected patients. Unfortunately, cART appears to be ineffective in halting accelerated neurodegenerative process induced by HIV but is partially effective in preventing glial proliferation.Key Points• This is the first multivoxel human brain 3T MRS study in HIV. • All observed areas of the brain are affected by neurodegenerative process. • Cingulate gyrus and subcortical white matter are most vulnerable to HIV-induced neurodegeneration. • cART is effective in control of inflammation but ineffective in preventing neurodegeneration.

Guanidinoacetic acid increases skeletal muscle creatine stores in healthy men

Guanidinoacetic acid (GAA; also known as glycocyamine, betacyamine, or guanidinoacetate) is an experimental dietary additive that enhances serum creatine bioavailability and affects blood-derived metabolic markers of methylation in humans [1]. Because creatine is an important compound in cellular bioenergetics [2], consumption of GAA has been recognized as an effective investigational intervention to facilitate creatine-mediated energy provision in health and disease [3]. At the same time, the methylation of GAA to form creatine consumes w40% of available methyl groups, potentially depleting the sources of methyl groups in the body, including methionine, folate, betaine, and choline [4]. However, to our knowledge, no human study so far has evaluated the effects of GAA consumption on creatine bioavailability and/or use of methyl groups in tissues with high-energy requirements, such as skeletal muscle or brain. In this pilot study, we evaluated the effects of 4-wk GAA supplementation on total creatine and choline levels in human skeletal muscle of healthy men. Four healthy young and physically active men (age 25 3 y, body mass index 24.3 1.6 kg/m2, physical activity 15 2 h/wk) were assigned to receive 3 g/d of oral GAA for 4 wk in this open-label, repeated-measure pilot study. Sample size (N 1⁄4 4) was in accordance with the power analysis (effect size 1⁄4 0.9, a error probability 1⁄4 0.05, power 1⁄4 0.95) for the primary outcome measure. Our primary outcome measure was the change in total creatine levels in the right vastus medialis muscle assessed at baseline and at 4 wk. Secondary outcome measures were total choline levels, intramyocellular and extramyocellular triacylglycerol contents, and muscle water. In vivo metabolite concentrations were determined by 1.5 T magnetic resonance spectroscopy using a four-element body matrix receiver coil (Siemens Avanto Tim, Erlangen, Germany) and calculated using the muscle water signal as an internal intensity reference [5]. Participants were obliged to maintain their usual diets (apart from the intervention) and physical activity levels during the study. All participants gave written informed consent before

Human skeletal muscle contains no detectable guanidinoacetic acid

We analyzed data from previously completed trials to determine the effects of supplemental guanidinoacetic acid (GAA) on markers of muscle bioenergetics in healthy men using 1.5 T magnetic resonance spectroscopy. No detectable GAA (<0.1 μmol/L) was found in the vastus medialis muscle at baseline nor at follow-up. This implies deficient GAA availability in the human skeletal muscle, suggesting absent or negligible potential for creatine synthesis from GAA inside this tissue, even after GAA loading.

Dietary guanidinoacetic acid does not accumulate in the brain of healthy men

We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations. No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used.

White Matter Changes in Two Leber's Hereditary Optic Neuropathy Pedigrees: 12-Year Follow-Up.

We are presenting two Lebers hereditary optic neuropathy (LHON) pedigrees with abnormal magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (H-MRS) findings but without neurological manifestation associated with LHON. The study included 14 LHON patients and 41 asymptomatic family members from 12 genealogically unrelated families. MRI showed white matter involvement and H-MRS exhibited metabolic anomalies within 12 LHON families. Main outcome measures were abnormal MRI and H-MRS findings in two pedigrees. MRI of the proband of the first pedigree showed a single demyelinating lesion in the right cerebellar hemisphere, while the proband of the second family displayed multiple supratentorial and infratentorial lesions, compatible with the demyelinating process, and both the absolute choline (Cho) concentration and Cho/creatinine ratio were increased. MRI and H-MRS profiles of both affected and unaffected mitochondrial DNA mutation carriers suggest more widespread central nervous involvement in LHON. Although even after 12 years our patients did not develop neurological symptoms, MRI could still be used to detect possible changes during the disease progression.