Quantification of cauda equina nerve root dispersion through radiomics features in weight-bearing MRI in normal subjects and spinal canal stenosis patients.

OBJECTIVE: To quantify the distribution of cauda equina nerve roots in supine and upright positions using manual measurements and radiomics features both in normal subjects and in lumbar spinal canal stenosis (LSCS) patients. METHODS: We retrospectively recruited patients who underwent weight-bearing MRI in supine and upright positions for back pain. 3D T2-weighted isotropic acquisition (3D-HYCE) sequences were used to develop a 3D convolutional neural network for identification and segmentation of lumbar vertebrae. Para-axial reformatted images perpendicular to the spinal canal and parallel to each vertebral endplate were automatically extracted. From each level, we computed the maximum antero-posterior (AP) and latero-lateral (LL) dispersion of nerve roots; further, radiomics features were extracted to quantify standardized metrics of nerve root distribution. RESULTS: We included 16 patients with LSCS and 20 normal subjects. In normal subjects, nerve root AP dispersion significantly increased from supine to upright position (p < 0.001, L2-L5 levels), and radiomics features showed an increase in non-uniformity. In LSCS subjects, in the upright position AP dispersion of nerve roots and entropy-related features increased caudally to the stenosis level (p < 0.001) and decreased cranially (p < 0.001). Moreover, entropy-related radiomics features negatively correlated with pre-operative Pain Numerical Rating Scale. Comparison between normal subjects and LSCS patients showed a difference in AP dispersion and increase of variance cranially to the stenosis level (p < 0.001) in the upright position. CONCLUSIONS: Nerve root distribution inside the dural sac changed between supine and upright positions, and radiomics features were able to quantify the differences between normal and LSCS subjects. CLINICAL RELEVANCE STATEMENT: The distribution of cauda equina nerve roots and the redundant nerve root sign significantly varies between supine and upright positions in normal subjects and spinal canal stenosis patients, respectively. Radiomics features quantify nerve root dispersion and correlates with pain severity. KEY POINTS: • Weight-bearing MRI depicts spatial distribution of the cauda equina in both supine and upright positions in normal subjects and spinal stenosis patients. • Radiomics features can quantify the effects of spinal stenosis on the dispersion of the cauda equina in the dural sac. • In the orthostatic position, dispersion of nerve roots is different in lumbar spinal stenosis patients compared to that in normal subjects; entropy-related features negatively correlated with pre-operative Pain Numerical Rating Scale.

CT-based radiomics can identify physiological modifications of bone structure related to subjects' age and sex.

PURPOSE: Radiomics of vertebral bone structure is a promising technique for identification of osteoporosis. We aimed at assessing the accuracy of machine learning in identifying physiological changes related to subjects' sex and age through analysis of radiomics features from CT images of lumbar vertebrae, and define its generalizability across different scanners. MATERIALS AND METHODS: We annotated spherical volumes-of-interest (VOIs) in the center of the vertebral body for each lumbar vertebra in 233 subjects who had undergone lumbar CT for back pain on 3 different scanners, and we evaluated radiomics features from each VOI. Subjects with history of bone metabolism disorders, cancer, and vertebral fractures were excluded. We performed machine learning classification and regression models to identify subjects' sex and age respectively, and we computed a voting model which combined predictions. RESULTS: The model was trained on 173 subjects and tested on an internal validation dataset of 60. Radiomics was able to identify subjects' sex within single CT scanner (ROC AUC: up to 0.9714), with lower performance on the combined dataset of the 3 scanners (ROC AUC: 0.5545). Higher consistency among different scanners was found in identification of subjects' age (R2 0.568 on all scanners, MAD 7.232 years), with highest results on a single CT scanner (R2 0.667, MAD 3.296 years). CONCLUSION: Radiomics features are able to extract biometric data from lumbar trabecular bone, and determine bone modifications related to subjects' sex and age with great accuracy. However, acquisition from different CT scanners reduces the accuracy of the analysis.

Prognostic relevance of temporal muscle thickness as a marker of sarcopenia in patients with glioblastoma at diagnosis.

OBJECTIVES: Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia, correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. We evaluated the prognostic relevance of TMT measured on brain MRIs acquired at diagnosis in patients affected by glioblastoma. METHODS: We retrospectively enrolled 51 patients in our Institution affected by methylated MGMT promoter, IDH1-2 wild-type glioblastoma, who underwent complete surgical resection and subsequent radiotherapy with concomitant and maintenance temozolomide, from January 1, 2015, to April 30, 2017. The last clinical/radiological follow-up date was set to September 3, 2019. TMT was measured bilaterally on reformatted post-contrast 3D MPRAGE images, acquired on our 3-T scanner no more than 2 days before surgery. The median, 25th, and 75th percentile TMT values were identified and population was subdivided accordingly; afterwards, statistical analyses were performed to verify the association among overall survival (OS) and TMT, sex, age, and ECOG performance status. RESULTS: In our cohort, the median OS was 20 months (range 3-51). Patients with a TMT ≥ 8.4 mm (median value) did not show a statistically significant increase in OS (Cox regression model: HR 1.34, 95% CI 0.68-2.63, p = 0.403). Similarly, patients with a TMT ≥ 9.85 mm (fourth quartile) did not differ in OS compared to those with TMT ≤ 7 mm (first quartile). The statistical analyses confirmed a significant association among TMT and sex (p = 0.0186), but none for age (p = 0.642) and performance status (p = 0.3982). CONCLUSIONS: In our homogeneous cohort of patients with glioblastoma at diagnosis, TMT was not associated with prognosis, age, or ECOG performance status. KEY POINTS: • Temporal muscle thickness (TMT) is a surrogate marker of sarcopenia and has been correlated with survival expectancy in patients suffering from brain metastases and recurrent or treated glioblastoma. • We appraised the correlation among TMT and survival, sex, age at surgery, and performance status, measured on brain MRIs of patients affected by glioblastoma at diagnosis. • TMT did not show any significant correlation with prognosis, age at surgery, or performance status, and its usefulness might be restricted only to patients with brain metastases and recurrent or treated glioblastoma.

Microstructural characterization of corticospinal tract in subacute and chronic stroke patients with distal lesions by means of advanced diffusion MRI.

PURPOSE: The aim of the paper is to evaluate if advanced dMRI techniques, including diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI), could provide novel insights into the subtle microarchitectural modifications occurring in the corticospinal tract (CST) of stroke patients in subacute and chronic phases. METHODS: Seventeen subjects (age 68 ± 11 years) in the subacute phase (14 ± 3 days post-stroke), 10 of whom rescanned in the chronic phase (231 ± 36 days post-stroke), were enrolled. Images were acquired using a 3-T MRI scanner with a two-shell EPI protocol (20 gradient directions, b = 700 s/mm2, 3 b = 0; 64 gradient directions, b = 2000 s/mm2, 9 b = 0). DTI-, DKI-, and NODDI-derived parameters were calculated in the posterior limb of the internal capsule (PLIC) and in the cerebral peduncle (CP). RESULTS: In the subacute phase, a reduction of FA, AD, and KA values was correlated with an increase of ODI, RD, and AK parameters, in both the ipsilesional PLIC and CP, suggesting that increased fiber dispersion can be the main structural factor. In the chronic phase, a reduction of FA and an increase of ODI persisted in the ipsilesional areas. This was associated with reduced Fic and increased MD, with a concomitant reduction of MK and increase of RD, suggesting that fiber reduction, possibly due to nerve degeneration, could play an important role. CONCLUSIONS: This study shows that advanced dMRI approaches can help elucidate the underpinning architectural modifications occurring in the CST after stroke. Further follow-up studies on bigger cohorts are needed to evaluate if DKI- and NODDI-derived parameters might be proposed as complementary biomarkers of brain microstructural alterations.

Prediction of Isocitrate Dehydrogenase Genotype in Brain Gliomas with MRI: Single-Shell versus Multishell Diffusion Models.

Purpose The primary aim of this prospective observational study was to assess whether diffusion MRI metrics correlate with isocitrate dehydrogenase (IDH) status in grade II and III gliomas. A secondary aim was to investigate whether multishell acquisitions with advanced models such as neurite orientation dispersion and density imaging (NODDI) and diffusion kurtosis imaging offer greater diagnostic accuracy than diffusion-tensor imaging (DTI). Materials and Methods Diffusion MRI (b = 700 and 2000 sec/mm2) was performed preoperatively in 192 consecutive participants (113 male and 79 female participants; mean age, 46.18 years; age range, 14-77 years) with grade II (n = 62), grade III (n = 58), or grade IV (n = 72) gliomas. DTI, diffusion kurtosis imaging, and NODDI metrics were measured in regions with or without hyperintensity on diffusion MR images and compared among groups defined according to IDH genotype, 1p/19q codeletion status, and tumor grade by using Mann-Whitney tests. Results In grade II and III IDH wild-type gliomas, the maximum fractional anisotropy, kurtosis anisotropy, and restriction fraction were significantly higher and the minimum mean diffusivity was significantly lower than in IDH-mutant gliomas (P = .011, P = .002, P = .044, and P = .027, respectively); areas under the receiver operating characteristic curve ranged from 0.72 to 0.76. In IDH wild-type gliomas, no difference among grades II, III, and IV was found. In IDH-mutant gliomas, no difference between those with and those without 1p/19q loss was found. Conclusion Diffusion MRI metrics showed correlation with isocitrate dehydrogenase status in grade II and III gliomas. Advanced diffusion MRI models did not add diagnostic accuracy, supporting the inclusion of a single-shell diffusion-tensor imaging acquisition in brain tumor imaging protocols. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Brain Gliomas: Multicenter Standardized Assessment of Dynamic Contrast-enhanced and Dynamic Susceptibility Contrast MR Images.

Purpose To evaluate the feasibility of a standardized protocol for acquisition and analysis of dynamic contrast material-enhanced (DCE) and dynamic susceptibility contrast (DSC) magnetic resonance (MR) imaging in a multicenter clinical setting and to verify its accuracy in predicting glioma grade according to the new World Health Organization 2016 classification. Materials and Methods The local research ethics committees of all centers approved the study, and informed consent was obtained from patients. One hundred patients with glioma were prospectively examined at 3.0 T in seven centers that performed the same preoperative MR imaging protocol, including DCE and DSC sequences. Two independent readers identified the perfusion hotspots on maps of volume transfer constant (Ktrans), plasma (vp) and extravascular-extracellular space (ve) volumes, initial area under the concentration curve, and relative cerebral blood volume (rCBV). Differences in parameters between grades and molecular subtypes were assessed by using Kruskal-Wallis and Mann-Whitney U tests. Diagnostic accuracy was evaluated by using receiver operating characteristic curve analysis. Results The whole protocol was tolerated in all patients. Perfusion maps were successfully obtained in 94 patients. An excellent interreader reproducibility of DSC- and DCE-derived measures was found. Among DCE-derived parameters, vp and ve had the highest accuracy (are under the receiver operating characteristic curve [Az] = 0.847 and 0.853) for glioma grading. DSC-derived rCBV had the highest accuracy (Az = 0.894), but the difference was not statistically significant (P > .05). Among lower-grade gliomas, a moderate increase in both vp and rCBV was evident in isocitrate dehydrogenase wild-type tumors, although this was not significant (P > .05). Conclusion A standardized multicenter acquisition and analysis protocol of DCE and DSC MR imaging is feasible and highly reproducible. Both techniques showed a comparable, high diagnostic accuracy for grading gliomas. © RSNA, 2018 Online supplemental material is available for this article.

Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma.

PURPOSE: We evaluated the relationship between 11C-methionine PET (11C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11C-METH PET were analysed. Semiquantitative evaluation of the 11C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). RESULTS: In all patients, the tumour was identified on 11C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. CONCLUSION: 11C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).

Imaging biomarkers in primary brain tumours.

We are getting used to referring to instrumentally detectable biological features in medical language as "imaging biomarkers". These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context.

Craniovertebral junction pathological features and their management in the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are multisystemic inherited metabolic diseases caused by the deficiency of the enzymes involved in the degradation of glycosaminoglycans (GAGs), which variably involve the central nervous system, heart, lungs, and bones.Undegraded or only partly degraded GAGs accumulate in the extracellular matrix, joint fluid, and connective tissue leading to widespread tissue and organ dysfunction.The introduction of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) has positively affected the natural history of MPS patients and their life expectancy. However, the presence of spinal abnormalities and deposition of GAGs in soft tissues remains nearly unaltered.Abnormalities of the craniovertebral junction (CVJ) and GAG deposits can result in spinal cord compression with slowly progressive myelopathy or acute posttraumatic tetraplegia.The current paper discusses neuroimaging findings in a consecutive series of 42 MPS patients followed at our Center for Metabolic Diseases and their neurosurgical issues.Current recommendations for decompression and fusion will be discussed according to our experience and review of the literature.

CT Cadaveric dataset for Radiomics features stability assessment in lumbar vertebrae.

Radiomics features (RFs) studies have showed limitations in the reproducibility of RFs in different acquisition settings. To date, reproducibility studies using CT images mainly rely on phantoms, due to the harness of patient exposure to X-rays. The provided CadAIver dataset has the aims of evaluating how CT scanner parameters effect radiomics features on cadaveric donor. The dataset comprises 112 unique CT acquisitions of a cadaveric truck acquired on 3 different CT scanners varying KV, mA, field-of-view, and reconstruction kernel settings. Technical validation of the CadAIver dataset comprises a comprehensive univariate and multivariate GLM approach to assess stability of each RFs extracted from lumbar vertebrae. The complete dataset is publicly available to be applied for future research in the RFs field, and could foster the creation of a collaborative open CT image database to increase the sample size, the range of available scanners, and the available body districts.

Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy.

BACKGROUND: Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce. OBJECTIVES: To determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT). METHODS: Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1-16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales. RESULTS: Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes. CONCLUSIONS: The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.

Precocious puberty and empty sella syndrome in a girl cured of acute lymphoblastic leukemia.

We describe a case of precocious puberty in a girl treated with chemoradiotherapy according to the Italian Association of Pediatric Hematology and Oncology ALL 9503 protocol for acute lymphoblastic leukemia (ALL) from the age of 15 months until the age of 3 years and 4 months. The patient was treated with chemotherapy and cranial irradiation (18 Gy in 12 fractions). At 7 years of age, during topical estrogenic treatment for congenital adhesions of the labia minora, she showed bilateral breast development that evolved into precocious puberty. A magnetic resonance imaging of the brain showed an "empty sella" (ES); the etiology of the ES, and the consequent precocious puberty, being presumably iatrogenic. Children treated with cranial radiotherapy should be carefully checked for signs of precocious puberty and the exogenous administration of estrogens should be avoided, as far as possible, because these could act as a trigger factor in a population at higher risk of precocious puberty.

Natural Course and Diagnosis of Lumbar Spinal Stenosis: WFNS Spine Committee Recommendations.

Lumbar spinal stenosis (LSS) is defined as a degenerative disorder showing a narrowing of the spinal canal. The diagnosis is straightforward in cases with typical neurogenic claudication symptoms and unequivocal imaging findings. However, not all patients present with typical symptoms, and there is obviously no correlation between the severity of stenosis and clinical complaint. The radiologic diagnosis of LSS is widely discussed in the literature. The best diagnostic test for the diagnosis of LSS is magnetic resonance imaging (MRI). However, canal diameter measurements have not gained much consensus from radiologists, whereas qualitative measures, such as cerebrospinal fluid space obliteration, have achieved greater consensus. Instability can best be defined by standing lateral radiograms and flexion-extension radiograms. For cases showing typical neurogenic claudication symptoms and unequivocal imaging findings, the diagnosis is straightforward. However, not all patients present with typical symptoms, and there is obviously no correlation between the severity of stenosis (computed tomography and MRI) and clinical complaint. In fact, recent MRI studies have shown that mild-to-moderate stenosis can also be found in asymptomatic individuals. Routine electrophysiological tests such as lower extremity electromyography, nerve conduction studies, F-wave, and H-reflex are not helpful in the diagnosis and outcome prediction of LSS. The electrophysiological recordings are complementary to the neurologic examination and can provide confirmatory information in less obvious clinical complaints. However, in the absence of reliable evidence, imaging studies should be considered as a first-line diagnostic test in the diagnosis of degenerative LSS.

fMRI-Targeted High-Angular Resolution Diffusion MR Tractography to Identify Functional Language Tracts in Healthy Controls and Glioma Patients.

BACKGROUND: MR Tractography enables non-invasive preoperative depiction of language subcortical tracts, which is crucial for the presurgical work-up of brain tumors; however, it cannot evaluate the exact function of the fibers. PURPOSE: A systematic pipeline was developed to combine tractography reconstruction of language fiber bundles, based on anatomical landmarks (Anatomical-T), with language fMRI cortical activations. A fMRI-targeted Tractography (fMRI-T) was thus obtained, depicting the subsets of the anatomical tracts whose endpoints are located inside a fMRI activation. We hypothesized that fMRI-T could provide additional functional information regarding the subcortical structures, better reflecting the eloquent white matter structures identified intraoperatively. METHODS: Both Anatomical-T and fMRI-T of language fiber tracts were performed on 16 controls and preoperatively on 16 patients with left-hemisphere brain tumors, using a q-ball residual bootstrap algorithm based on High Angular Resolution Diffusion Imaging (HARDI) datasets (b = 3000 s/mm2; 60 directions); fMRI ROIs were obtained using picture naming, verbal fluency, and auditory verb generation tasks. In healthy controls, normalized MNI atlases of fMRI-T and Anatomical-T were obtained. In patients, the surgical resection of the tumor was pursued by identifying eloquent structures with intraoperative direct electrical stimulation mapping and extending surgery to the functional boundaries. Post-surgical MRI allowed to identify Anatomical-T and fMRI-T non-eloquent portions removed during the procedure. RESULTS: MNI Atlases showed that fMRI-T is a subset of Anatomical-T, and that different task-specific fMRI-T involve both shared subsets and task-specific subsets - e.g., verbal fluency fMRI-T strongly involves dorsal frontal tracts, consistently with the phonogical-articulatory features of this task. A quantitative analysis in patients revealed that Anatomical-T removed portions of AF-SLF and IFOF were significantly greater than verbal fluency fMRI-T ones, suggesting that fMRI-T is a more specific approach. In addition, qualitative analyses showed that fMRI-T AF-SLF and IFOF predict the exact functional limits of resection with increased specificity when compared to Anatomical-T counterparts, especially the superior frontal portion of IFOF, in a subcohort of patients. CONCLUSION: These results suggest that performing fMRI-T in addition to the 'classic' Anatomical-T may be useful in a preoperative setting to identify the 'high-risk subsets' that should be spared during the surgical procedure.

Is IDH status the only factor predicting prognosis in newly diagnosed anaplastic glioma patients? Outcome evaluation and prognostic factor analysis in a single-institution large series.

OBJECTIVE: Anaplastic gliomas (AGs) are an extremely heterogeneous group of primary brain tumors. More recently, new discoveries have indicated that isocitrate dehydrogenase (IDH) mutation status is the most important parameter predicting survival. The primary aim of the present analysis was to identify prognostic factors, other than IDH status, that eventually impact survival. METHODS: Patients with available clinical, imaging, and molecular profile data who were amenable to resection were evaluated. The extent of resection (EOR) was defined as gross-total resection (GTR), near-total resection (NTR), subtotal resection (STR), or partial resection (PR). Residual tumor volume (RTV) was quantified. Following surgery, patients received adjuvant chemotherapy alone, radiation therapy plus concomitant and adjuvant temozolomide (TMZ), or sequential radio-chemotherapy. Clinical outcome was evaluated by neurological examination and MRI 1 month after treatment and every 4 months thereafter. Tumor progression was defined according to the Response Assessment in Neuro-Oncology (RANO) working group. RESULTS: Among 402 patients referred to the authors' institution for AG, 142 were included in the present analysis. Eighty-eight (62%) were male and 54 (38%) were female, with a median age of 43 years (range 19-70 years). At admission, most patients had a Karnofsky Performance Scale score of 90-100 (84.5%) and were symptomatic (93.7%). Forty-eight (33.8%) patients had newly diagnosed anaplastic oligodendrogliomas (AOs), and 94 (66.2%) had anaplastic astrocytomas (AAs). Most of them had mutant IDH tumors (67.6%) and methylated O 6-methylguanine-DNA-methyltransferase (MGMT) promoter status (71.8%). GTR was performed in more than half of the patients (56.3%). RTV was detected in 83 (58.5%) patients. Following surgery, 72 (50.7%) patients received radiotherapy with concomitant and adjuvant TMZ, 48 (33.8%) received sequential radio-chemotherapy, and 22 (15.5%) received adjuvant chemotherapy alone. The median follow-up time was 40 months (range 16-146 months). The median PFS time and the 1-, 3-, and 5-year PFS rates were 35 months (95% CI 27-76) and 78.9% ± 3.4%, 49.7% ± 4.6%, and 42.7% ± 5.4%, respectively. The median OS time and the 1-, 3-, and 5-year OS rates were 91 months (95% CI 66-95) and 90.1% ± 2.5%, 70.9% ± 4.2%, and 61.8% ± 4.9%, respectively. Prognostic factors predicting survival other than molecular profile were the EOR and the RTV (p < 0.0001). Sequential radio-chemotherapy was the more effective treatment administered. CONCLUSIONS: In addition to IDH status, EOR and the RTV have proved to statistically impact survival. The pivotal role of adjuvant radiotherapy has been recorded in all AG patients, regardless of tumor features.

Severely symptomatic craniovertebral junction abnormalities in children: long-term reliability of aggressive management.

OBJECTIVES: The treatment of symptomatic cranio-vertebral junction (CVJ) instability in children affected by CVJ abnormalities is a challenge. A series of severely symptomatic children has been reviewed to understand the controversial long-term effectiveness of the aggressive management of CVJ abnormalities, in terms of clinical improvement, spinal stability and growth. METHODS: Three Down syndrome patients, 1 with mucopolysaccharidosis and 1 with os odontoideum (range 3-6 years old) with a CVJ instability determining spinal cord compression with severe neurological deficits (the patients presented at admission a Ranawat III A/III B neurological condition), were consecutively treated at our institution. Medical records, imaging studies, adopted surgical techniques and long-term results were reviewed. Details of the presenting symptoms, clinical and radiological signs were compared to the signs and symptoms at follow-up. RESULTS: The perioperative use of an halo-orthosis, the operative techniques and the timing of rehabilitation were always tailored to the patient's anatomical features. All the patients showed remarkable neurological improvements, along with construct stability and bone fusion without abnormalities of the developing spine. CONCLUSIONS: Considering the effective long-term results, we recommend, even in severely symptomatic children with CVJ abnormalities, a multidisciplinary aggressive tailored treatment of instability with rigid internal fixation.

Anatomo-functional characterisation of the human "hand-knob": A direct electrophysiological study.

The cortical area within the human primary motor cortex (M1) that hosts the representation of the hand and fingers is known as the 'hand-knob' and is essential for voluntary hand movement. The anatomo-functional heterogeneity described within the monkey primary motor cortex (M1) in a rostro-caudal direction suggests an internal subdivision in two sectors originating different systems of connections to the spinal cord. Direct investigation of the human hand-knob has been prevented, so far, by methodological constraints. The unique setting of brain tumour resection with the brain mapping technique in awake patients enables direct electrophysiological investigation of the functional properties of the human hand-knob. Motor-evoked potentials (MEPs) elicited by Direct Electrical Stimulation (DES) at high frequency (HF-DES) delivered along the hand-knob in rostro-caudal direction, i.e., from the central to the precentral sulcus, were recorded from the hand/arm muscles in patients at rest. The sites located near the precentral sulcus identified with HF-DES were then stimulated with low-frequency DES (LF-DES) during a hand manipulation task (HMt) to assess whether DES affected task execution. From the stimulated sites, corticofugal projections and U-shaped tracts connecting with adjacent gyri were traced using diffusion tensor and spherical deconvolution tractography. Analysis of MEPs showed a rostro-caudal gradient of cortical excitability along the hand-knob (the rostral sector being less excitable). Stimulation of rostral sites during the HMt impaired the task by inducing dysfunctional recruitment or, alternatively, suppression of distal muscles. Diffusion tractography showed different patterns of rostro-caudal connectivity for the U-shaped tracts. Overall data suggests, in humans, the anatomo-functional subdivision of the human hand-knob in two sectors, possibly subserving different roles in motor control.

Lower Grade Gliomas: Relationships Between Metabolic and Structural Imaging with Grading and Molecular Factors.

BACKGROUND: Positron emission tomography (PET) is a valuable tool for the characterization of brain tumors in vivo. However, few studies have investigated the correlation between carbon-11-methionine (11C-METH) PET metrics and the clinical, radiological, histological, and molecular features of patients affected by lower grade gliomas (LGGs). The present observational study evaluated the relationships between 11C-METH PET metrics and structural magnetic resonance imaging (MRI) findings with the histomolecular biomarkers in patients with LGGs who were candidates for surgery. METHODS: We enrolled 96 patients with pathologically proven LGG (51 men, 45 women; age 44.1 ± 13.7 years; 45 with grade II, 51 with grade III), who had been referred from March 2012 to January 2015 for tumor resection and had undergone preoperative 11C-METH PET. The semiquantitative metrics for 11C-METH PET included maximum standardized uptake value (SUVmax), SUV ratio to normal brain, and metabolic tumor burden (MTB). The PET semiquantitative metrics were analyzed and compared with the MRI features, histological diagnosis, isocitrate dehydrogenase-1/2 status, and 1p/19q codeletion. RESULTS: Histological grade was associated with SUVmax (P = 0.002), SUV ratio (P = 0.011), and MTB (P = 0.001), with grade III lesions showing higher values. Among the nonenhancing lesions on MRI, SUVmax (P = 0.001), SUV ratio (P = 0.003) and MTB (P < 0.001) were significantly different statistically for grade II versus grade III. The MRI lesion volume correlated poorly with MTB (r2 = 0.13). The SUVmax and SUV ratio were greater (P < 0.05) in isocitrate dehydrogenase-1/2 wild-type lesions, and the SUV ratio was associated with the presence of the 1p19q codeletion. CONCLUSIONS: The 11C-METH PET metrics correlated significantly with histological grade and the molecular profile. Semiquantitative PET metrics can improve the preoperative evaluation of LGGs and thus support clinical decision-making.

The role of imaging in the skeletal involvement of mucopolysaccharidoses.

This article discusses the role of imaging modalities including radiography, multi-detector computed tomography, magnetic resonance imaging, and ultrasound in diagnosing and monitoring skeletal abnormalities in mucopolysaccharidoses (MPS). The advantages and disadvantages of these different imaging tools will be discussed, along with their feasibility in this class of patients. As the musculoskeletal involvement is common to all MPS and is one of the main reasons for seeking medical attention, an increased awareness among paediatricians, rheumatologists, orthopaedists, radiologists, and other musculoskeletal specialists on the possible spectrum of abnormalities observed could facilitate a timely diagnosis, an appropriate severity evaluation, and better management.

Anatomical identification of active contacts in subthalamic deep brain stimulation.

BACKGROUND: Subthalamic Deep Brain Stimulation is a valid surgical procedure for the treatment of idiopathic PD, although its precise mechanism of action is still unclear; moreover, there are no conclusive data about the functional anatomy of the human subthalamic region. Identifying the location of active contacts for StnDBS can yield interesting insights on the mechanisms of action of DBS and the different role played by the anatomical structures of the subthalamic region. METHODS: Twenty-five patients operated on for bilateral StnDBS were considered. During the surgical procedure, a complete intraoperative neurophysiological study was obtained by means of semimicrorecordings and stimulations. After surgery, an MRI study confirmed the position of the electrodes; MR images were subsequently superimposed onto a stereotactic atlas by using a dedicated workstation. The coordinates relative to the tip of the electrodes and active contacts were then calculated. RESULTS: Most of the electrode tips are located inside the subthalamus or immediately ventrally to it. Of the active contacts used for chronic stimulation, 96.5% are located in a well-defined anatomical region, which includes subthalamus, zona incerta, and FF. CONCLUSIONS: Our findings seem to suggest that other structures beyond the subthalamus itself play a clinical role in symptoms control after DBS for PD.