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Introduction/Aims Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and magnetic resonance imaging (MRI) markers with muscle function and strength. Methods Eligible patients were ambulatory males with BMD, aged 18 to 65 years (200 to 450 meters on 6-minute walk test). The following data were obtained: function test results, strength, fat-fraction quantification using chemical shift-encoded MRI (whole thigh and quadriceps), and fibrosis and muscle fiber area (MFA) of the brachial biceps. Results Of 70 patients screened, 51 entered the study. There was substantial heterogeneity between patients in muscle morphology (histology and MRI), with high fat replacement. Total fibrosis correlated significantly and mostly moderately with all functional endpoints, including both upper arm strength assessments (left and right elbow flexion rho -.574 and -.588, respectively [both P < .0001]), as did MRI fat fraction (whole thigh and quadriceps), for example, with four-stair-climb velocity -.554 and -.550, respectively (both P < .0001). Total fibrosis correlated significantly and moderately with both MRI fat fraction assessments (.500 [P = .0003] and .423 [.0024], respectively). Discussion In this BMD cohort, micro- and macroscopic morphological muscle parameters correlated moderately with each other and with functional parameters, potentially supporting the use of MRI fat fraction and histology as surrogate outcome measures in patients with BMD, although additional research is required to validate this.

OBJECT Surgery of brainstem lesions is increasingly performed despite the fact that surgical indications and techniques continue to be debated. The deep pons, in particular, continues to be a critical area in which the specific risks related to different surgical strategies continue to be examined. With the intention of bringing new knowledge into this important arena, the authors systematically examined the results of brainstem surgeries that have been performed through the lateral infratrigeminal transpontine window. METHODS Between 1990 and 2013, 29 consecutive patients underwent surgery through this window for either biopsy sampling or for removal of a deep pontine lesion. All of this work was performed at the Department of Neurosurgery of the Istituto Nazionale Neurologico "Carlo Besta", in Milan, Italy. A retrospective analysis of the findings was conducted with the intention of bringing further clarity to this important surgical strategy. RESULTS The lateral infratrigeminal transpontine window was exposed through 4 different approaches: 1) classic retrosigmoid (15 cases), 2) minimally invasive keyhole retrosigmoid (10 cases), 3) translabyrinthine (1 case), and 4) combined petrosal (3 cases). No deaths occurred during the entire clinical study. The surgical complications that were observed included hydrocephalus (2 cases) and CSF leakage (1 case). In 6 (20.7%) of 29 patients the authors encountered new neurological deficits during the immediate postoperative period. All 6 of these patients had undergone lesion removal. In only 2 of these 6 patients were permanent sequelae observed at 3 months follow-up. These findings show that 93% of the patients studied did not report any permanent worsening of their neurological condition after this surgical intervention. CONCLUSIONS This retrospective study supports the idea that the lateral infratrigeminal transpontine window is both a low-risk and safe corridor for either biopsy sampling or for removal of deep pontine lesions.

BACKGROUND The aim of this paper was to evaluate the synergic strategy comprising intraoperative neurophysiological monitoring and ultrasound sonography in terms of clinical motor scores and extent of resection. METHODS Patients harboring tumors in close relationship with the motor cortex were operated on with image-guided mini-invasive approach and multimodal neurophysiological monitoring. The peculiarity is the partial exposure of the motor cortex and the limited electrophysiological mapping used to search for negative spots. Multimodal neurophysiological monitoring comprised the electrocortical stimulation, somatosensory evoked potentials, motor evoked potentials and subcortical stimulation. Ultrasound sonography guided the tumor removal. The post-op clinical motor scores and the extent of resection were assessed. RESULTS Twelve patients were operated on with the combined approach and were further analyzed. Six had high grade gliomas, 1 anaplastic astrocytoma, 1 oligodendroglioma, 1 pilocytic astrocytoma and three had metastasis. One out of 12 had a worsening of the motor scores at the last follow-up. The mean extent of resection was 90% ranging from 60% to 100%, but in 9 out of 12 patients, it reached or exceeded 90%. CONCLUSIONS The synergic strategy comprising intraoperative multimodal neurophysiological monitoring and the ultrasound sonography is feasible in all surgeries. Data are promising in terms of both clinical motor scores and extent of resection. This strategy represents an alternative approach to the treatment of supratentorial tumors, although further studies are necessary to confirm the long-term efficacy of this procedure.

Background and purpose Previous studies have demonstrated that individuals suffering from disorder of consciousness (DOC) maintain some minor neural processing of percepts mediated by senses that early in their pathway intersect the thalamus, a key dysfunctional area in DOC patients. Here the degree of sensory preservation within the olfactory system, a system that lacks an obligatory thalamic relay, and its relationship to the consciousness level in DOC patients of various etiologies was assessed. Methods Clinical Coma Recovery Scale – Revised (CRS-R) as well as cerebral responses to odors by means of functional magnetic resonance were obtained in a group of vegetative state/unresponsive wakefulness syndrome (n = 26) patients, minimally conscious state (n = 7) patients and healthy controls (n = 25). Results A majority of vegetative state/unresponsive wakefulness syndrome patients (58%) and 100% of minimally conscious state patients demonstrated a significant preservation of olfactory neural processing, manifested by activation within the piriform cortex, an area considered as a primary olfactory region. Degree of preservation of olfactory processing differed linearly in line with the patients’ etiologies where groups demonstrating greater conscious awareness demonstrated more significant processing. Viewed over all DOC patients, there was a significant negative association between odor-related activity in the orbitofrontal cortex and CRS-R scores. Conclusions It is demonstrated that DOC patients exhibit a significant preservation of olfactory neural processing with a clear relationship to etiopathologies and clinical measures even years after of chronification of DOC.

Mutations in the CLCN2 gene encoding ClC-2, a chloride channel implicated in brain ion and water homeostasis, have been recently associated with a rare autosomal recessive leukoencephalopathy, characterized by specific MRI findings caused by chronic white matter edema.1 Acknowledgment: The authors thank Mario Savoiardo, an Italian pioneer in neuroradiology, who died during the revision process of this article, for his help, insightful comments, and diagnoses. The authors and his friends around the world will miss him.

Diffusion tensor imaging (DTI) is a magnetic resonance modality that permits to characterize the orientation and integrity of white matter (WM). DTI-based tractography techniques, allowing the virtual reconstruction of WM tract pathways, have found wide application in preclinical neurological research. Recently, anatomically detailed rat brain atlases including DTI data were constructed from ex vivo DTI images, but tractographic atlases of normal rats in vivo are still lacking. We propose here a probabilistic tractographic atlas of the main WM tracts in the healthy rat brain based on in vivo DTI acquisition. Our study was carried out on 10 adult female Sprague-Dawley rats using a 7T preclinical scanner. The MRI protocol permitted a reliable reconstruction of the main rat brain bundles: corpus callosum, cingulum, external capsule, internal capsule, anterior commissure, optic tract. The reconstructed fibers were compared with histological data, proving the viability of in vivo DTI tractography in the rat brain with the proposed acquisition and processing protocol. All the data were registered to a rat brain template in the coordinate system of the commonly used atlas by Paxinos and Watson; then the individual tracts were binarized and averaged, obtaining a probabilistic atlas in Paxinos-Watson space of the main rat brain WM bundles. With respect to the recent high-resolution MRI atlases, the resulting tractographic atlas, available online, provides complementary information about the average anatomical position of the considered WM tracts and their variability between normal animals. Furthermore, reference values for the main DTI-derived parameters, mean diffusivity and fractional anisotropy, were provided. Both these results can be used as references in preclinical studies on pathological rat models involving potential alterations of WM.

Objectives Premanifest Huntington’s disease mutation carriers (preHD) are known to present functional and neuroradiological abnormalities before the motor onset. This study evaluated brain morphometry and posture in preHD. Participants and methods 29 preHD (13F/16 M, mean age 36.5 years, CAG range 37–48) and 25 sex-age matched controls were enrolled (14F/11 M, mean age 35.7 years). Inclusion criteria were: CAG expansion > 36; UHDRS-TMS Results PreHD and controls did not differ in total intracranial volume, caudate volumes, and cortical thickness. Only in close-to-onset preHD caudate volumes and occipital cortical thickness were reduced in comparison with controls (p = 0.002; p = 0.0098) and far-from-onset preHD (p = 0.002; p = 0.007). Caudate volumes and occipital cortical thickness directly correlated with years to onset (ρ = 0.58, 0.74; p = 0.003, p Posturography parameters were similar in pre-HD and controls for all conditions, except for wide-base-closed-eyes test, in which preHD presented a greater number of sway peaks (p = 0.006). In close-to-onset preHD the number of sway peaks was greater than controls (p = 0.001) and far-from-onset preHD (p = 0.016). Conclusions Our study confirms that caudate volumes and occipital cortical thickness are the earliest markers of brain degeneration in the preHD. Posturography may represent a simple and rapid test to investigate early stance abnormalities.

Objectives We aimed to identify markers of cognitive and structural brain abnormalities in premanifest Huntington’s disease subjects (preHD). Participants and methods We enrolled 29 preHD (13F/16 M, age 36.5 years, CAG range 37–48; UHDRS-TMS Results PreHD and controls did not differ in total intracranial volume, caudate volumes, and cortical thickness, and presented scores within normal range in all cognitive tests. However, preHD scored significantly worse than controls in SDMT (p = 0.048), in MMSE (p = 0.0013) and in Calculation test (p = 0.014). Analyses of sub-item of the Calculation test showed that preHD, and in particular the group of close-to-onset preHD (−16 years), made specifically more mistakes than controls in the subtraction task (p = 0.0089), while preHD and controls did not differ in multiplications. The SDMT score correlated with left occipital cortical thickness (p = 0.0029) and Calculation test total score with caudate nucleus volumes (p = 0.032). Conclusions We confirm that SDMT can identify very early abnormalities in preHD and the scores directly correlate with occipital cortical thickness. The results of the Calculation test suggest that preHD have selective executive deficits in calculation, as demonstrated in the subtraction process, while in the multiplication task, implying mainly memory retrieval, no differences were found.

Introduction Lesions in the ventrolateral region of the dominant frontal lobe have been historically associated with aphasia. Recent imaging results suggest that frontal language regions extend beyond classically defined Broca’s area to include the ventral precentral gyrus (VPCG) and the arcuate fasciculus (AF). Frontal gliomas offer a unique opportunity to identify structures that are essential for speech production. The aim of this prospective study was to investigate the correlation between language deficits and lesion location in patients with gliomas. Methods Nineteen patients with glioma and 10 healthy subjects were evaluated with diffusion tensor imaging magnetic resonance (MR) tractography, functional MR (verb generation task) and the Aachener Aphasie Test. Patients were divided into two groups according to lesion location with respect to the ventral precentral sulcus: (i) anterior ( n = 8) with glioma growing in the inferior frontal gyrus (IFG) and underlying white matter; (ii) posterior ( n = 11) with glioma growing in the VPCG and underlying white matter. Virtual dissection of the AF, frontal intralobar tract, uncinate fasciculus (UF) and inferior frontal occipital fasciculus (IFOF) was performed with a deterministic approach. Results Seven posterior patients showed aphasia classified as conduction (4), Broca (1), transcortical motor (1) and an isolated deficit of semantic fluency; one anterior patient had transcortical mixed aphasia. All posterior patients had invasion of the VPCG, however only patients with aphasia had also lesion extension to the AF as demonstrated by tractography dissections. All patients with language deficits had high grade glioma. Groups did not differ regarding tumour volume. A functional pars opercularis was identified with functional MR imaging (fMRI) in 17 patients. Conclusions Gliomas growing in the left VPCG are much more likely to cause speech deficits than gliomas infiltrating the IFG, including Broca’s area. Lesion extension to the AF connecting frontal to parietal and temporal regions is an important mechanism for the appearance of aphasia.