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Background and Purpose: Human neuropathological studies indicate that the pontine nucleus Locus Coeruleus (LC) undergoes significant and early degeneration in Alzheimer's disease. This line of evidence alongside experimental data suggests that the LC functional/structural decay may represent a critical factor for Alzheimer's disease pathophysiological and clinical progression. In the present prospective study, we used Magnetic Resonance Imaging (MRI) with LC-sensitive sequence (LC-MRI) to investigate in vivo the LC involvement in Alzheimer's disease progression, and whether specific LC-MRI features at baseline are associated with prognosis and cognitive performance in amnestic Mild Cognitive Impairment., Methods: LC-MRI parameters were measured at baseline by a template-based method on 3.0-T magnetic resonance images in 34 patients with Alzheimer's disease dementia, 73 patients with amnestic Mild Cognitive Impairment, and 53 cognitively intact individuals. A thorough neurological and neuropsychological assessment was performed at baseline and 2.5-year follow-up., Results: In subjects with Mild Cognitive Impairment who converted to dementia (n = 32), the LC intensity and number of LC-related voxels were significantly lower than in cognitively intact individuals, resembling those observed in demented patients. Such a reduction was not detected in Mild Cognitive Impairment individuals, who remained stable at follow-up. In Mild Cognitive Impairment subjects converting to dementia, LC-MRI parameter reduction was maximal in the rostral part of the left nucleus. Structural equation modeling analysis showed that LC-MRI parameters positively correlate with cognitive performance., Conclusions: Our findings highlight a potential role of LC-MRI for predicting clinical progression in Mild Cognitive Impairment and support the key role of LC degeneration in the Alzheimer clinical continuum., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The locus coeruleus is the main noradrenergic nucleus of the brain and is often affected in neurodegenerative diseases. Recently, magnetic resonance imaging with specific T1-weighted sequences for neuromelanin has been used to evaluate locus coeruleus integrity in patients with these conditions. In some of these studies, abnormalities in locus coeruleus signal have also been found in healthy controls and related to ageing. However, this would be at variance with recent post-mortem studies showing that the nucleus is not affected during normal ageing. The present study aimed at evaluating locus coeruleus features in a well-defined cohort of cognitively healthy subjects who remained cognitively intact on a one-year follow-up. An ad-hoc semiautomatic analysis of locus coeruleus magnetic resonance was applied. Sixty-two cognitively intact subjects aged 60-80 years, without significant comorbidities, underwent 3 T magnetic resonance with specific sequences for locus coeruleus. A semi-automatic tool was used to estimate the number of voxels belonging to locus coeruleus and its intensity was obtained for each subject. Each subject underwent extensive neuropsychological testing at baseline and 12 months after magnetic resonance scan. Based on neuropsychological testing 53 subjects were cognitively normal at baseline and follow up. No significant age-related differences in locus coeruleus parameters were found in this cohort. In line with recent post-mortem studies, our in vivo study confirms that locus coeruleus magnetic resonance features are not statistically significantly affected by age between 60 and 80 years, the age range usually evaluated in studies on neurodegenerative diseases. A significant alteration of locus coeruleus features in a cognitively intact elderly subject might be an early sign of pathology., (© 2021. The Author(s).)

Locus Coeruleus (LC) is the main noradrenergic nucleus of the brain, which is involved in many physiological functions including cognition; its impairment may be crucial in the neurobiology of a variety of brain diseases. Locus Coeruleus-Magnetic Resonance Imaging (LC-MRI) allows to identify in vivo LC in humans. Thus, a variety of research teams have been using LC-MRI to estimate LC integrity in normal aging and in patients affected by neurodegenerative disorders, where LC integrity my work as a biomarker. A number of variations between LC-MRI studies exist, concerning post-acquisition analysis and whether this had been performed within MRI native space or in ad hoc-built MRI template space. Moreover, the reproducibility and reliability of this tool is still to be explored. Therefore, in the present study, we analyzed a group of neurologically healthy, cognitively intact elderly subjects, using both a native space- and a template space-based LC-MRI analysis. We found a good inter-method agreement, particularly considering the LC Contrast Ratio. The template space-based approach provided a higher spatial resolution, lower operator-dependency, and allowed the analysis of LC topography. Our ad hoc-developed LC template showed LC morphological data that were in line with templates published very recently. Remarkably, present data significantly overlapped with a recently published LC "metaMask", that had been obtained by averaging the results of a variety of previous LC-MRI studies. Thus, such a template space-based approach may pave the way to a standardized LC-MRI analysis and to be used in future clinic-anatomical correlations., (© 2022. The Author(s).)

Background: Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms). The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis., Methods: We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology., Results: Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The "complicated" forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls., Conclusion: We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping.

Background and Purpose: The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain., Materials and Methods: Tract-based spatial statistics analysis was performed to compare fractional anisotropy and mean, axial, and radial diffusivities of the WM skeleton in a group of 12 patients with pure hereditary spastic paraplegia and 12 healthy volunteers. Data were analyzed counting age and sex as nuisance covariates. The threshold-free cluster-enhancement option was applied, and the family-wise error rate was controlled by using permutation tests for nonparametric statistics., Results: In pure hereditary spastic paraplegia, group widespread fractional anisotropy decreases and radial diffusivity and mean diffusivity increases (P < .05, corrected) were found. No voxelwise difference was observed for the axial diffusivity map. Percentage of voxels within the WM skeleton that passed the significance threshold were 51%, 41.6%, and 11.9%, respectively, for radial diffusivity, fractional anisotropy, and mean diffusivity clusters. An anteroposterior pattern with preferential decrease of fractional anisotropy in the frontal circuitry was detected., Conclusions: In patients with pure hereditary spastic paraplegia, alterations in multiple DTI indices were found. Radial diffusivity seems more sensitive to hereditary spastic paraplegia-related WM pathology and, in line with the lack of axial diffusivity changes, might indicate a widespread loss of myelin integrity. A decrease of fractional anisotropy alone in the frontal circuitry may reflect subtle disruption of the frontal connections., (© 2014 by American Journal of Neuroradiology.)

Mucoceles are slow-growing, benign, expansile, mucoid-filled masses developing after obstruction of the sinus ostium. Late post-traumatic mucoceles are relatively rare entities and the literature is limited to single case reports. We describe an unusual case of post-traumatic fronto-ethmoidal mucocele, evaluated with computed tomography (CT), magnetic resonance imaging (MRI) and proton MR-spectroscopy ((1)H-MRS). As a contribution to the diagnostic work-up of the mucocele, (1)H-MRS demonstrates a dominant peak at 2.0 ppm at long echo time (TE) and an additional component at 3.8 ppm at short TE due to mucus glycoprotein compounds of the mucocele.

Upper motor neuron (UMN) dysfunction in Amyotrophic Lateral Sclerosis (ALS) is not easy to identify clinically: Diffusion Tensor Imaging (DTI) and single-voxel Magnetic Resonance Spectroscopy (H-MRS) can identify markers of UMN involvement. The aim of this study was to correlate brain DTI and MRS data with clinical parameters in ALS patients (PALS). We studied 32 PALS using Magnetic Resonance Imaging. The subjects were subdivided into definite/probable (D/P) and possible/suspected (P/S). DTI indices included Fractional Anisotropy (FA) and averaged Apparent Diffusion Coefficient (avADC). Anatomical areas were sampled by positioning regions of interest along corticospinal tracts, from the precentral cortex to the bulb. H-MRS voxels were localized bilaterally in precentral regions. D/P-PALS showed significantly lower FA values than healthy controls in almost all regions, whereas P/S-PALS FA values were significantly lower only in the left precentral gray matter (GM), right precentral white matter (WM), cerebral peduncles (CP), left hemipons, and left bulbar pyramid (BP). Significantly higher avADC values were observed in the D/P-PALS right precentral GM, precentral WM, right semioval center-posterior limb of the internal capsule (SC-PLIC), and left CP; and in the precentral WM, right SC-PLIC, left CP, and right hemipons of P/S-PALS. With increasing disability, only D/P-PALS showed significantly reduced FA values in the left precentral WM and hemipons, and increased avADC values in the precentral WM. Significantly lower N-acetylaspartate (NAA)/creatine-phosphocreatine complex (Cr) and higher choline (Cho)/Cr and myoinositol (mI)/Cr ratios were found in D/P-PALS, while only higher Cho/Cr and mI/Cr ratios were found in P/S-PALS. Our data highlight the usefulness of DTI and H-MRS in assessing UMN involvement. Given FA sensitivity and specificity, despite the small number of PALS, our findings support its use as a diagnostic marker in D/P-PALS.

An improvement in the clinical results obtained using total body irradiation (TBI) with photon beams requires precise TBI treatment planning, reproducible irradiation, precise in vivo dosimetry, accurate documentation and careful evaluation. In vivo dosimetry using LiF Harshaw TLD-100 chips was used during the TBI treatments performed in our department. The results of in vivo thermoluminescence dosimetry (TLD) show that using TLD measurements and interactive adjustment of some treatment parameters based on these measurements, like monitor unit calculations, lung shielding thickness and patient positioning, it is possible to achieve high precision in absorbed dose delivery (less than 0.5%) as well as in homogeneity of irradiation (less than 6%).