Free Mg(2+ )concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by (31)P MRS

BACKGROUND: The increase in cytosolic free Mg(2+ )occurring during exercise and initial recovery in human skeletal muscle is matched by a decrease in cytosolic pH as shown by in vivo phosphorus magnetic resonance spectroscopy ((31)P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg(2+ )is linked to pH in human skeletal muscle, we studied patients with metabolic myopathies due to different disorders of glycogen metabolism that share a lack of intracellular acidification during muscle exercise. METHODS: We assessed by (31)P MRS the cytosolic pH and free magnesium concentration ([Mg(2+)]) in calf muscle during exercise and post-exercise recovery in two patients with McArdle's disease with muscle glycogen phosphorylase deficiency (McArdle), and two brothers both affected by Tarui's disease with muscle phosphofructokinase deficiency (PFK). RESULTS: All patients displayed a lack of intracellular acidosis during muscle exercise. At rest only one PFK patient showed a [Mg(2+)] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg(2+)], while both PFK patients showed decreased free [Mg(2+)] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg(2+)] while in PFK patients the pattern of free [Mg(2+)] was related to the rate of PME recovery. CONCLUSION: i) homeostasis of free [Mg(2+)] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg(2+)] pattern during exercise; ii) the pattern of [Mg(2+)] during exercise and post-exercise recovery in both PFK patients suggests that [Mg(2+)] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal. iii) (31)P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg(2+)] in human skeletal muscle in different metabolic conditions

Distinct MRI pattern of "pseudoresponse" in recurrent glioblastoma multiforme treated with regorafenib: Case report and literature review

: Antiangiogenic agents can induce a distinct MRI pattern in glioblastoma, characterized by a decrease in the contrast enhancement on T1-weighted images and a simultaneous hyperintensity on T2-weighted or fluid-attenuated inversion recovery images

Endoscopic endonasal approach for loco-regional recurrent clivus chordomas

Introduction. Role of surgery for loco-regional recurrences of clivus chordomas (CCs) is still debated. It has been proposed in selected cases with a curative or with palliative intent, eventually followed by radiation or chemo/radiation treatments. Only limited data on the endoscopic endonasal approach (EEA) are available. Research question. To assess the role of EEA for loco-regional recurrent CCs. Materials and Methods. All consecutive loco-regional recurrent CCs operated by EEA at our Institution from 1998 to 2021 were identified. The extension of tumor resection, symptoms control, overall survival (OS), and progression free survival (PFS) were assessed. Results. Series includes 54 patients (53.7% females, mean age 55± 14 years). Surgery was planned with a resective aim in 35 (64.8%) patients, while it was palliative in 19 (35.2%). Gross tumor removal was achieved in 24 cases (44.4%). Main complications consisted of 2 (3.7%) CSF leaks. Further local relapses were observed in 30 (55.5%) patients after 25± 24 months; 29 (53.7%) patients deceased after 34 ± 31 months. OS and PFS were lower in these cases than primary surgeries (p<0.001 and p<0.001), but cases undergone surgery with a resective aim had a significant better OS and PFS than for those treated for palliation (p<0.001). Determinants of recurrences were tumoral size (p=0.48) and previous radiotherapy (p=009). Discussion and Conclusions. EEA has proven to be effective for loco-regional recurrent CCs alleviating patients symptoms and preserving their quality of life with limited morbidities. However, because overall prognosis is poor, EEA should be reserved to selected recurrent cases

Use of Radium-223 Dichloride in Patients With Osteonecrosis of the Jaw Induced by Zoledronic Acid: Report of 2 Cases.

Bisphosphonates, a group of inorganic pyrophosphate analogues that prevent the loss of bone density, are commonly used in patients with bone metastases; the calcium-mimetic a-emitter radium-223 dichloride (Ra223) is a bone-targeting therapy used in patients with metastatic castration-resistant prostate cancer (mCRPC)-related bone metastases. Both treatments reduce pain and disability; Ra223 is associated with significantly improved overall survival in mCRPC. Patients who receive bisphosphonate therapy are at risk of developing osteonecrosis of the jaw, especially in those who do not undergo an accurate oral evaluation and sanitation before the beginning of therapy, and in patients who present with conditions that facilitate the development of this problem, such as inadequate oral and dental care, lack of prophylactic antimicrobial mouth rinsing, patient comorbidity, or suboptimal suturing after tooth extraction. Although there is possible synergism between bisphosphonates and Ra223 therapy, there is no consensus about the use of Ra223 in patients with previous/current osteonecrosis of the jaw induced by zoledronic acid. However, our experience suggests that Ra223 therapy might not be contraindicated in patients with osteonecrosis of the jaw induced by zoledronic acid if an appropriate multidisciplinary approach is followed, and we report 2 cases of patients with current or previous osteonecrosis of the jaw induced by zoledronic acid, who were treated with Ra223 for mCRPCrelated bone metastases. Multidisciplinary management, including accurate clinical and radiological evaluation before beginning therapy with Ra223, together with oral sanitation and periodic controls during treatment, allowed successful administration of Ra223 while reducing side effects, with absent or minimal worsening of osteonecrosis

Role of endoscopic endonasal approach for craniopharyngiomas extending into the third ventricle in adults

Introduction. Recent advancements in endoscopic endonasal approach (EEA) have favored its adoption for craniopharyngiomas extended to 3rd ventricle (3VCPs). However, for lack of extensive series, its outcome, limits, and indications remain debated. Research question. To assess the EEA results of for 3VCPs and identify those factors determining the choice of this approach. Material and Methods. Records of patients with 3VCPs, consecutively operated through an EEA at our Institution were retrospectively analyzed. Demographic and clinico-radiological data, rate of tumor resection, complications and outcome at follow-up were collected. Results. Thirty-six patients (19 females, mean age: 51.1 ± 15.9 yrs) were included. Extended transplanum-transtuberculum approach was performed in all cases Radical resection was achieved in 33 patients (91.7%). At follow-up, visual deficits improved/normalized in 21 cases (58.3%), and 35 (97.2%) presented with panhypopituitarism and DI. Anatomical (displacement of the chiasm and hypothalamus), clinical (age and pre-operative visual and endocrinological function) and tumoral (consistency, presence of hydrocephalus) parameters resulted relevant in determining the choice of this approach. Discussion and Conclusion. EEA offers a valid and direct route for 3VCPs, which permits to safely manage these tumors. In our series, EEA was chosen for tubero-infundibular forms with chiasm displaces antero-superiorly, and preferred in younger patients, with visual disturbances, comprimesed endocrinological function and no hydrocephalus. It requires a specific training and should be reserved in dedicated centers. Because no single approach is ideal for every 3VCP, all surgical options should be considered as complementary and selected basing on clinical, anatomical and tumoral features of each case

Current State-of-the-Art of AI Methods Applied to MRI

Di Noia, C., Grist, J. T., Riemer, F., Lyasheva, M., Fabozzi, M., Castelli, M., Lodi, R., Tonon, C., Rundo, L., & Zaccagna, F. (2022). Predicting Survival in Patients with Brain Tumors: Current State-of-the-Art of AI Methods Applied to MRI. Diagnostics, 12(9), 1-16. [2125]. https://doi.org/10.3390/diagnostics12092125Given growing clinical needs, in recent years Artificial Intelligence (AI) techniques have increasingly been used to define the best approaches for survival assessment and prediction in patients with brain tumors. Advances in computational resources, and the collection of (mainly) public databases, have promoted this rapid development. This narrative review of the current state-of-the-art aimed to survey current applications of AI in predicting survival in patients with brain tumors, with a focus on Magnetic Resonance Imaging (MRI). An extensive search was performed on PubMed and Google Scholar using a Boolean research query based on MeSH terms and restricting the search to the period between 2012 and 2022. Fifty studies were selected, mainly based on Machine Learning (ML), Deep Learning (DL), radiomics-based methods, and methods that exploit traditional imaging techniques for survival assessment. In addition, we focused on two distinct tasks related to survival assessment: the first on the classification of subjects into survival classes (short and long-term or eventually short, mid and long-term) to stratify patients in distinct groups. The second focused on quantification, in days or months, of the individual survival interval. Our survey showed excellent state-of-the-art methods for the first, with accuracy up to ∼98%. The latter task appears to be the most challenging, but state-of-the-art techniques showed promising results, albeit with limitations, with C-Index up to ∼0.91. In conclusion, according to the specific task, the available computational methods perform differently, and the choice of the best one to use is non-univocal and dependent on many aspects. Unequivocally, the use of features derived from quantitative imaging has been shown to be advantageous for AI applications, including survival prediction. This evidence from the literature motivates further research in the field of AI-powered methods for survival prediction in patients with brain tumors, in particular, using the wealth of information provided by quantitative MRI techniques.publishersversionpublishe

Association of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions

Background: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads also to a Leigh-like phenotype. Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1 mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6) subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H background, were also present. Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the primary LHON mutation

Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis

Truncating mutations in PRNP have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel PRNP stop-codon mutations (p.Y163X, p.Y169X) in two Italian kindreds. Disease typically presented in the third or fourth decade with progressive autonomic failure and diarrhea. Moreover, one proband (p.Y163X) developed late cognitive decline, whereas some of his relatives presented with isolated cognitive and psychiatric symptoms. Our results strengthen the link between PRNP truncating mutations and systemic abnormal PrP deposition and support a wider application of PRNP screening to include unsolved cases of familial autonomic neuropathy

Relationship of white and gray matter abnormalities to clinical and genetic features in myotonic dystrophy type 1

AbstractBackgroundMyotonic dystrophy type 1 (DM1) represents a multisystemic disorder in which diffuse brain white and gray matter alterations related to clinical and genetic features have been described. We aimed to evaluate in the brain of adult patients with DM1 (i) white and gray matter differences, including cortical-subcortical gray matter volume and cortical thickness and (ii) their correlation with clinical disability, global neuropsychological performance and triplet expansion.MethodsWe included 24 adult genetically-confirmed DM1 patients (14 males; age: 38.5±11.8years) and 25 age- and sex-matched healthy controls (14 males; age: 38.5±11.3years) who underwent an identical brain MR protocol including high-resolution 3D T1-weighted, axial T2 FLAIR and DTI sequences. All patients underwent an extensive clinical and neuropsychological evaluation. Voxel-wise analyses of white matter, performed by using Tract Based Spatial Statistics, and of gray matter, with Voxel-based Morphometry and Cortical Thickness, were carried out in order to test for differences between patients with DM1 and healthy controls (p<0.05, corrected). The correlation between MRI measures and clinical-genetic features was also assessed.ResultsPatients with DM1 showed widespread abnormalities of all DTI parameters in the white matter, which were associated with reduced gray matter volume in all brain lobes and thinning in parieto-temporo-occipital cortices, albeit with less extensive cortical alterations when congenital cases were removed from the analyses. White matter alterations correlated with clinical disability, global cognitive performance and triplet expansions.ConclusionIn patients with DM1, the combined smaller overall gray matter volume and white matter alterations seem to be the main morpho-structural substrates of CNS involvement in this condition. The correlation of white matter differences with both clinical and genetic findings lends support to this notion