Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Comparison of T1 mapping and fixed T1 method for dynamic contrast-enhanced MRI perfusion in brain gliomas.

OBJECTIVES: To compare dynamic contrast-enhanced MRI (DCE-MRI) data obtained using different prebolus T1 values in glioma grading and molecular profiling. METHODS: We retrospectively reviewed 83 cases of gliomas: 46 lower-grade gliomas (LGG; grades II and III) and 37 high-grade gliomas (HGG; grade IV). DCE-MRI maps of plasma volume fraction (Vp), extravascular-extracellular volume fraction (Ve), and tracer transfer constant from plasma to tissue (Ktrans) were obtained using a fixed T1 value of 1400 ms and a measured T1 obtained with variable flip angle (VFA). Tumour segmentations were performed and first-order histogram parameters were extracted from volumes of interest (VOIs) after co-registration with the perfusion maps. The two methods were compared using Wilcoxon matched-pairs signed-rank test and Bland-Altman analysis. Diagnostic accuracy was obtained and compared using ROC curve analysis and DeLong's test. RESULTS: Perfusion parameters obtained with the fixed T1 value were significantly higher than those obtained with the VFA. As regards diagnostic accuracy, there were no significant differences between the two methods both for glioma grading and molecular classification, except for few parameters of both methods. CONCLUSIONS: DCE-MRI data obtained with different prebolus T1 are not comparable and the definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI. KEY POINTS: • DCE-MRI data obtained with different prebolus T1 are significantly different, thus not comparable. • The definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI for glioma grading. • The use of a fixed T1 value represents a valid alternative to T1 mapping for DCE-MRI analysis.

Longitudinal quantitative magnetic resonance imaging in adrenomyeloneuropathy.

BACKGROUND AND PURPOSE: Adrenomyeloneuropathy (AMN) is the most frequent metabolic hereditary spastic paraplegia. Accordingly, its main site of pathological changes is the spinal cord. It is difficult to quantify AMN progression because commonly used clinical scales have limitations and reliable biomarkers are lacking. The goal was to investigate whether spinal cord and brain quantitative magnetic resonance imaging may assess structural changes in AMN over a relatively short time period. METHODS: In this longitudinal observational study, the total cord areas (TCAs) from the C2-C3 to T2-T3 level and diffusion tensor imaging (DTI) metrics of the cervical spinal cord and brain portion of the corticospinal tracts in six AMN and six age-matched control subjects at baseline and at a mean follow-up of 22.6 months were assessed. RESULTS: A significant reduction of the mean TCA at the T1-T2 level (-3.79%) and a trend of reduction at the lowest cervical levels were observed only in AMN patients. Additionally, DTI metrics revealed significant changes in fractional anisotropy (-8.84%), mean diffusivity (+12.62%) and radial diffusivity (+25.91%) at the C2-C3 level. DISCUSSION: The study encourages the assessment of TCAs and spinal cord DTI metrics as surrogate outcome measures in AMN, by focusing on the cervical-thoracic junction and the uppermost part of the cervical spinal cord. Despite the limitation of the results due to the small number of investigated subjects, these observations are useful for forthcoming clinical trials in AMN and possibly other hereditary diseases with predominant spinal cord involvement.

Role of Functional Imaging Techniques to Assess Motor and Language Cortical Plasticity in Glioma Patients: A Systematic Review.

Cerebral plasticity is the ability of the central nervous system to reorganize itself in response to different injuries. The reshaping of functional areas is a crucial mechanism to compensate for damaged function. It is acknowledged that functional remodeling of cortical areas may occur also in glioma patients. Principal limits of previous investigations on cortical plasticity of motor and language functions included scarce reports of longitudinal evaluations and limited sample sizes. This systematic review is aimed at elucidating cortical brain plasticity for motor and language functions, in adult glioma patients, by means of preoperative and intraoperative mapping techniques. We systematically reviewed the literature for prospective studies, assessing cortical plasticity of motor and language functions in low-grade and high-grade gliomas. Eight longitudinal studies investigated cortical plasticity, evaluated by motor and language task-based functional MRI (fMRI), motor navigated transcranial magnetic stimulation (n-TMS), and intraoperative mapping with cortical direct electrocortical stimulation (DES) of language and motor function. Motor function reorganization appeared relatively limited and mostly characterized by intrahemispheric functional changes, including secondary motor cortices. On the other hand, a high level of functional reshaping was found for language function in DES studies. Occurrence of cortical functional reorganization of language function was described focusing on the intrahemispheric recruitment of perilesional areas. However, the association between these functional patterns and recovery of motor and language deficits still remains partially clear. A number of relevant methodological issues possibly affecting the finding generalization emerged, such as the complexity of plasticity outcome measures and the lack of large longitudinal studies. Future studies are required to further confirm these evidences on cortical plasticity in larger samples, combining both functional imaging and intraoperative mapping techniques in longitudinally evaluations.

Glioma imaging in Europe: A survey of 220 centres and recommendations for best clinical practice.

OBJECTIVES: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. METHODS: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists' societies and distributed via social media. RESULTS: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24-72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). CONCLUSION: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. KEY POINTS: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol. • Perfusion MRI is recommended for diagnosis and follow-up of glioma. • Use of advanced imaging could be promoted with increased education activities. • Most response assessment is currently performed qualitatively. • Reporting templates are not widely used, and could facilitate standardisation.

Multiple biomarkers improve the prediction of multiple sclerosis in clinically isolated syndromes.

OBJECTIVES: Since its introduction, MRI had a major impact on the early and more precise diagnosis of multiple sclerosis (MS), and the 2010 diagnostic criteria even allow a diagnosis to be made just after a single attack if stringent MRI criteria are met. Several other clinical and paraclinical markers have been reported to be associated with an increased risk of MS independently of MRI in patients with clinically isolated syndromes (CIS), but the incremental usefulness of adding them to the current criteria has not been evaluated. In this study, we determined whether multiple biomarkers improved the prediction of MS in patients with CIS in a real-world clinical practice. MATERIALS AND METHODS: This was a retrospective study involving patients with CIS admitted to our department between 2000 and 2013. We evaluated baseline clinical, MRI, neurophysiological, and cerebrospinal fluid (CSF) data. RESULTS: During follow-up (median, 7.2 years), 127 of 243 participants (mean age, 31.6 years) developed MS. Cox proportional-hazards models adjusted for established MRI criteria, age at onset, number of T1 lesions, and presence of CSF oligoclonal bands significantly predicted the risk of developing MS at 2 and 5 years. The use of multiple biomarkers led to 29% net reclassification improvement at 2 years (P<.001) and 30% at 5 years (P<.001). CONCLUSIONS: The simultaneous addition of several biomarkers significantly improved the risk stratification for MS in patients with CIS beyond that of a model based only on established MRI criteria.

Effects of muscle composition and architecture on specific strength in obese older women.

NEW FINDINGS: What is the central question of this study? Do obesity-specific factors affect skeletal muscle performance in older individuals? What is the main finding and its importance? Older obese women have a larger quadriceps femoris size but develop lower tension per unit of skeletal muscle than their normal-weight counterparts. Muscle impairment and excess body mass are very common among older people. Given that the effect of obesity on strength production has scarcely been studied in older individuals, we analysed functional and structural characteristics of quadriceps femoris (QF) in obese (OB) and normal-weight (NW) older women with comparable habitual physical activity. In five OB (body mass index 36.8 ± 1.9 kg m(-2), age 72.4 ± 2.3 years) and six NW well-functioning older women (body mass index 24.3 ± 1.8 kg m(-2), age 72.7 ± 1.9 years), peak knee-extension torque (KET) was measured in isometric (90 deg knee flexion) and isokinetic conditions (240, 180, 120 and 60 deg s(-1)). Mid-thigh QF cross-sectional area (CSA) and muscle tissue fat content (MF%) were determined with magnetic resonance imaging (Dixon sequence). Muscle fascicle length and pennation angle (PA) were assessed with ultrasonography for each muscle belly of the QF (vastus lateralis, vastus intermedius, rectus femoris and vastus intermedius). Despite similar values of KET, CSA was 17.0% larger in OB than in NW women (P < 0.05), so that KET/CSA was significantly lower (P < 0.05) in OB women. Compared with NW women, OB women had 28.7% higher MF% (P < 0.05) and 24.9% higher average PA (P < 0.05), while fascicle length was similar. Overall, isometric KET/CSA was negatively affected by both MF% (P < 0.05) and PA (P < 0.05), while isokinetic KET/CSA was negatively affected only by MF% (P < 0.01). Muscle composition and architecture seem to be important determinants of KET/CSA in elderly women. In fact, owing to the effect of obesity overload, OB women have a larger QF size than NW women, but unfavourable muscle composition and architecture. The higher MF% and steeper PA observed in OB women are associated with reduced levels of muscle specific strength.

Adverse childhood experiences influence white matter microstructure in patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with adverse childhood experiences (ACE), which worsen the lifetime course of illness, and with signs of widespread disruption of white matter (WM) integrity in adult life. ACE are associated with changes in WM microstructure in healthy humans. METHOD: We tested the effects of ACE on diffusion-tensor imaging (DTI) measures of WM integrity in 80 in-patients affected by a major depressive episode in the course of BD. We used whole-brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial, radial and mean diffusivity, and fractional anisotropy. RESULTS: ACE hastened the onset of illness. We observed an inverse correlation between the severity of ACE and DTI measures of axial diffusivity in several WM fibre tracts contributing to the functional integrity of the brain and including the corona radiata, thalamic radiations, corpus callosum, cingulum bundle, superior longitudinal fasciculus, inferior fronto-occipital fasciculus and uncinate fasciculus. CONCLUSIONS: Axial diffusivity reflects the integrity of axons and myelin sheaths, and correlates with functional connectivity and with higher-order abilities such as reasoning and experience of emotions. In patients with BD axial diffusivity is increased by lithium treatment. ACE might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.

Influence of the topography of brain damage on depression and fatigue in patients with multiple sclerosis.

OBJECTIVES: Involvement of selected central nervous system (CNS) regions has been associated with depression and fatigue in MS. We assessed whether specific regional patterns of lesion distribution and atrophy of the gray (GM) and white matter (WM) are associated with these symptoms in MS. METHODS: Brain dual-echo and 3D T1-weighted images were acquired from 123 MS patients (69 depressed (D), 54 non-depressed (nD), 64 fatigued, 59 non-fatigued) and 90 controls. Lesion distribution, GM and WM atrophy were estimated using VBM and SPM8. RESULTS: Gender, age, disease duration and conventional MRI characteristics did not differ between D-MS and nD-MS patients. Fatigued patients experienced higher EDSS and depression than non-fatigued ones. Lesion distribution and WM atrophy were not related to depression and fatigue. Atrophy of regions in the frontal, parietal and occipital lobes had a combined effect on depression and fatigue. Atrophy of the left middle frontal gyrus and right inferior frontal gyrus were selectively related to depression. No specific pattern of GM atrophy was found to be related to fatigue. CONCLUSIONS: Depression in MS is linked to atrophy of cortical regions located in the bilateral frontal lobes. A distributed pattern of GM atrophy contributes to the concomitant presence of depression and fatigue in these patients.

Forceps minor damage and co-occurrence of depression and fatigue in multiple sclerosis.

OBJECTIVE: Using diffusion tensor magnetic resonance imaging (DT MRI), we analyzed the architectural integrity of the brain white matter (WM) from a large cohort of MS patients to identify the structural substrates of the concomitant presence of depression and fatigue. METHODS: Brain dual-echo, 3D T1-weighted and DT MRI scans were acquired from 147 MS patients and 90 gender- and age-matched healthy controls (HCs). Patients were stratified by the presence of depression (92 depressed (D), 55 not depressed (nD)) and fatigue (81 fatigued (F), 66 not fatigued (nF)). Sixty-five patients had co-occurrence of depression and fatigue (DF). Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). Tract-specific analyses were run in brain WM tracts using standard-space templates. RESULTS: Whole-brain voxel-wise analysis yielded no significant differences between patient subgroups. At tract-specific analysis, DF patients had reduced fractional anisotropy (FA) of the forceps minor. Reduced FA of the right anterior thalamic radiation and right uncinate fasciculus was found in F-MS vs not F-MS patients after correcting for depression. No significant differences were found between D vs not D-MS patients, after correcting for fatigue. CONCLUSIONS: This study provides evidence for partially overlapping damage to frontal and fronto-temporal pathways underlying depression and fatigue in MS.

Microstructural magnetic resonance imaging of cortical lesions in multiple sclerosis.

BACKGROUND: Pathologic and magnetic resonance imaging (MRI) studies have shown that cortical lesions (CLs) are a frequent finding in multiple sclerosis (MS). OBJECTIVE: To quantify microstructural damage in CLs and normal appearing (NA) cortex in relapse-onset MS patients at different stages of the disease. METHODS: Brain double inversion recovery (DIR), diffusion tensor (DT) MRI and 3D T 1-weighted scans were acquired from 35 relapsing-remitting (RR) patients, 23 secondary progressive (SP) patients, 12 benign (B) MS patients and 41 healthy controls (HC). Diffusivity values in CLs, cortex, white matter (WM) lesions and normal-appearing white matter (NAWM) were assessed. RESULTS: Compared to HC, MS patients had a significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the cortex and NAWM. CLs had higher FA vs HC cortex and vs patients' cortex. Compared to RRMS patients, SPMS patients had higher WM lesion volume, higher MD in the cortex, and more severe damage to the NAWM and WM lesions. Compared to SPMS patients, BMS patients had lower MD and FA of CLs. Damage in other compartments was similar between SPMS and BMS patients. Damage in CLs had a high power to discriminate BMS from SPMS (area under the curve: 79-91%), with high specificity (85%), sensitivity (100%) and accuracy (90%). CONCLUSIONS: Microstructural imaging features of CLs differ from those of WM lesions and are likely to reflect neuronal damage and microglial activation. The nature and extent of CL damage can be used to help distinguish the different MS clinical phenotypes.

White matter damage in frontotemporal lobar degeneration spectrum.

White matter (WM) tract damage was assessed in patients with the behavioral variant frontotemporal dementia (bvFTD) and the 3 primary progressive aphasia (PPA) variants and compared with the corresponding brain atrophy patterns. Thirteen bvFTD and 20 PPA patients were studied. Tract-based spatial statistics and voxel-based morphometry were used. Patients with bvFTD showed widespread diffusion tensor magnetic resonance imaging (DT MRI) abnormalities affecting most of the WM bilaterally. In PPA patients, WM damage was more focal and varied across the 3 syndromes: left frontotemporoparietal in nonfluent, left frontotemporal in semantic, and left frontoparietal in logopenic patients. In each syndrome, DT MRI changes extended beyond the topography of gray matter loss. Left uncinate damage was the best predictor of frontotemporal lobar degeneration diagnosis versus controls. DT MRI measures of the anterior corpus callosum and left superior longitudinal fasciculus differentiated bvFTD from nonfluent cases. The best predictors of semantic PPA compared with both bvFTD and nonfluent cases were diffusivity abnormalities of the left uncinate and inferior longitudinal fasciculus. This study provides insights into the similarities and differences of WM damage in bvFTD and PPA variants. DT MRI metrics hold promise to serve as early markers of WM integrity loss that only at a later stage may be detectable by volumetric measures.

Contribution of magnetic resonance imaging to the diagnosis and monitoring of multiple sclerosis.

Magnetic resonance (MR) imaging is an extremely sensitive modality for detecting focal changes to the white matter (WM) in patients with multiple sclerosis (MS). For this reason, it has become an integral part of the diagnostic workup of patients with clinically isolated syndromes who are at risk of developing definite MS, and it is always recommended in patients with definite MS to confirm the diagnosis and monitor the disease course. Crucial to the use of MR imaging for diagnostic purposes is the identification of lesion features - in terms of site, shape and size - that may be considered suggestive or typical for MS, and thus help in the differential diagnosis with other neurological diseases with similar clinical presentation to MS. This need has led to the publication of several guidelines for characterising MS lesions on both dual-echo (T2 and proton density) and T1-weighted sequences after administration of contrast material. Developments in clinical research into MS have highlighted the need to formulate a diagnosis as far as possible on the basis of objective and reproducible criteria. Currently, when making a clinical diagnosis and monitoring patients with suspected MS, neurologists and neuroradiologists make use of specific diagnostic criteria that have changed over the years and will probably continue to be updated. It is therefore crucial for radiologists to become familiar with these criteria in order to improve the quality of their diagnostic assessment. In patients with a definite diagnosis of MS, on the other hand, the main problem is to define standard procedures for monitoring the course of the disease and response to pharmacological treatments. even though no guidelines currently exist, it is possible to suggest some strategies to improve the assessment in this setting.

Monolateral type I proatlantal artery with bilateral absence of vertebral arteries: description of a case and review of the literature.

We report a case of a patient with right type I proatlantal intersegmental artery associated with right fetal posterior cerebral artery and absence of both vertebral arteries and of the left posterior communicating artery. We also describe the clinical relevance of these findings for this patient. A 56-year-old woman with vertigo and tinnitus underwent contrast enhanced Magnetic Resonance Angiography (MRA) of the supra-aortic arteries using a 1.5 Tesla scanner. Maximum intensity projection and volume rendering reconstructions were obtained. MRA demonstrated the persistence of an anastomotic artery between the right internal carotid artery and basilar artery, passing through the foramen magnum, suggesting a type I proatlantal intersegmental artery. The examination also showed the absence of both vertebral arteries and the presence of a right fetal-type posterior cerebral artery. To our knowledge, this is the first report of a type I proatlantal intersegmental artery associated with an omolateral fetal-type posterior cerebral artery and the absence of both vertebral arteries and of the left posterior communicating artery. This condition requires a watchful monitoring of the patient and has to be considered in case of surgical procedures of the carotid arteries.

Predictive value of inferior fronto-occipital fasciculus (IFO) DTI-fiber tracking for determining the extent of resection for surgery of frontal and temporal gliomas preoperatively.

AIM: This work reports the analysis of the relationship between inferior fronto-occipital fasciculus (IFO), neoplastic lesions and surgical resection, in patients operated for gliomas located in the frontal, temporal and insular lobes of the dominant hemisphere. Aim of the study is evaluating the predictive value of inferior fronto-occipital fasciculus DTI-fiber tracking (FT) for determining the extent of resection preoperatively. METHODS: We selected 38 cases affected by lesions located in the frontal, temporal and insular lobes of the dominant hemisphere, which were related to the trajectory of the IFO. For each patient preoperative and postoperative MR images and DTI-FT were loaded into the neuronavigation system and merged; volumetric scan analysis was used for establishing tumor location and topography, as well as the volume of the lesion and of the residual tumor. All preoperative fiber tracking datasets were evaluated and the position of the tract (IFO) compared to the tumor was recorded. Postoperative MR scans were then compared with DTI-FT, in order to evaluate the correspondence between the resection boundaries and the trajectory of the fiber tract. RESULTS: Amongst the cases in which the IFO was inside the lesion, we found only incomplete resections (5 subtotal and 6 partial resections), while considering the cases in which the IFO was located outside the tumor, it was possible to perform a relevant (total/subtotal) resection in 18 of them (78%). CONCLUSION: FT of the inferior frontal-occipital fasciculus predicts the possibility and the extent of the resection for a frontal, temporal and/or insular lesion of the dominant hemisphere.

Emotional reactivity in chronic schizophrenia: structural and functional brain correlates and the influence of adverse childhood experiences.

BACKGROUND: Despite behavioural signs of flattened affect, patients affected by schizophrenia show enhanced sensitivity to negative stimuli. The current literature concerning neural circuitry for emotions supports dysregulations of cortico-limbic networks, but gives contrasting results. Adverse childhood experiences (ACEs) could persistently influence emotional regulation and neural correlates of response to emotional stimuli in healthy humans. This study evaluated the effect of ACEs and chronic undifferentiated schizophrenia on neural responses to emotional stimuli (negative facial expression). METHOD: Brain blood-oxygen-level-dependent functional magnetic resonance imaging neural responses to a face-matching paradigm, and regional grey matter (GM) volumes were studied at 3.0 T in the amygdala, hippocampus, anterior cingulated cortex (ACC) and prefrontal cortex (PFC). The severity of ACEs was assessed. Participants included 20 consecutively admitted in-patients affected by chronic undifferentiated schizophrenia, and 20 unrelated healthy volunteers from the general population. RESULTS: Patients reported higher ACEs than controls. Worse ACEs proportionally led to decreasing responses in the amygdala and hippocampus, and to increasing responses in the PFC and ACC in all participants. Patients showed higher activations in the amygdala and hippocampus, and lower activations in the PFC and ACC. Higher ACEs were associated with higher GM volumes in the PFC and ACC, and schizophrenia was associated with GM reduction in all studied regions. CONCLUSIONS: Structural and functional brain correlates of emotional reactivity are influenced by both current chronic undifferentiated schizophrenia and the severity of past ACEs.

Quantitative muscle mass biomarkers are independent prognosis factors in primary central nervous system lymphoma: The role of L3-skeletal muscle index and temporal muscle thickness.

OBJECTIVE: To investigate the role of quantitative muscle biomarkers assessed with skeletal muscle index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) in predicting progression-free and overall survival in patients with primary central nervous system lymphoma (PCNSL) undergoing first-line high-dose methotrexate-based chemotherapy. METHODS: L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted MR images, respectively, using predefined validated methods. Standardized sex-specific cut-off values were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS: Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12-40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95% CI 1.66-11.61, p = 0.003; HR 4.40, 95% CI 1.68-11.49, p = 0.003, respectively) and overall survival (HR 3.16, 95% CI 1.09-9.11, p = 0.034; HR 4.93, 95% CI 1.78-13.65, p = 0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSIONS: Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.

Treatment of Wernicke's encephalopathy with high dose of thiamine in a patient with pyloric sub-stenosis: description of a case.

Wernicke's encephalopathy (WE) is an acute or subacute syndrome that results from a deficiency in vitamin B1 (thiamine). The syndrome is characterised by a classical triad of symptoms: nystagmus and ophthalmoplegia,mental-status changes, and unsteadiness of stance and gait. When patients with WE are inappropriately treated with low doses of thiamine, mortality rates average out at 20% and Korsakoff's Psychosis develops in about 85% of survivors(Sechi and Serra in Lancet Neurol 6(5):442­455,2007). We report the case of a patient with a pyloric substenosis that developed a WE, and was treated with high doses of thiamine showing after few days of treatment a great improvement of neurological and neuroradiological assessment, even though cognitive impairment was still severe at discharge and at 6 months follow-up.

Selective diffusion changes of the visual pathways in patients with migraine: a 3-T tractography study.

Using diffusion tensor (DT) tractography, we quantified optic radiation (OR) structural changes in seven migraine patients with (MA) and eight without visual aura (MoA) and their relation to clinical manifestations and T2-visible burden. The corticospinal tract and the corpus callosum were studied as 'control' white matter (WM). No difference was found for any of the WM fibre bundles metrics between controls and MoA patients. MA patients had reduced average fractional anisotropy (FA) of both OR compared with controls and reduced average FA of the right OR compared with MoA patients. They also showed higher right OR mean diffusivity than controls. OR metrics were not correlated with clinical and magnetic resonance imaging (MRI) metrics. DT tractography reveals OR changes in MA patients that might represent a phenotypic biomarker of the disease given the lack of correlation with clinical and structural MRI metrics.

Voxel-wise analysis of diffusion tensor MRI improves the confidence of diagnosis of corticobasal degeneration non-invasively.

Corticobasal degeneration (CBD) presents with symptoms that often overlap with other neurological conditions. In many cases, diagnosis, prognosis and consequent clinical management remain uncertain. Structural and functional asymmetric brain changes represent the most consistent imaging findings that may assist in CBD diagnosis. Diffusion Tensor MRI (DT-MRI) is a quantitative technique that allows microscopic tissue abnormalities to be non-invasively assessed in vivo. A single case of clinically suspected CBD with symmetric diffuse brain atrophy on conventional-MRI scans was studied using DT-MRI by voxel-wise comparison with eight healthy subjects. The lateralized distribution of DT-MRI abnormalities was consistent with clinical features providing a substantial support to the diagnosis.