Diffusion tensor imaging in the musculoskeletal and peripheral nerve systems : from experimental to clinical applications

Magnetic resonance imaging (MRI) is a well-established imaging modality which is used in all districts of the musculoskeletal and peripheral nerve systems. More recently, initial studies have applied multiparametric MRI to evaluate quantitatively different aspects of musculoskeletal and peripheral nerve diseases, thus providing not only images but also numbers and clinical data. Besides 1H and 31P magnetic resonance spectroscopy, diffusion-weighted imaging (DWI) and blood oxygenation level-dependent imaging, diffusion tensor imaging (DTI) is a relatively new MRI-based technique relying on principles of DWI, which has traditionally been used mainly for evaluating the central nervous system to track fibre course. In the musculoskeletal and peripheral nerve systems, DTI has been mostly used in experimental settings, with still few indications in clinical practice. In this review, we describe the potential use of DTI to evaluate different musculoskeletal and peripheral nerve conditions, emphasising the translational aspects of this technique from the experimental to the clinical setting

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain

Ophthalmoplegia due to Miller Fisher syndrome in a patient with myasthenia gravis

Here, we describe a 79-year-old man, admitted to our unit for worsening diplopia and fatigue, started a few weeks after an episode of bronchitis and flu vaccination. Past medical history includes myasthenia gravis (MG), well-controlled by Pyridostigmine, Azathioprine, and Prednisone. During the first days, the patient developed progressive ocular movement abnormalities up to complete external ophthalmoplegia, severe limb and gait ataxia, and mild dysarthria. Deep tendon reflexes were absent in lower limbs. Since not all the symptoms were explainable with the previous diagnosis of myasthenia gravis, other etiologies were investigated. Brain MRI and cerebrospinal fluid analysis were normal. Electromyography showed a pattern of predominantly sensory multiple radiculoneuritis. Suspecting Miller Fisher syndrome (MFS), the patient was treated with plasmapheresis with subsequent clinical improvement. Antibodies against GQ1b turned out to be positive. MFS is an immune-mediated neuropathy presenting with ophthalmoplegia, ataxia, and areflexia. Even if only a few cases of MFS overlapping with MG have been described so far, the coexistence of two different autoimmune disorders can occur. It is always important to evaluate possible differential diagnosis even in case of known compatible diseases, especially when some clinical features seem atypical

Dystonia-ataxia syndrome with permanent torsional nystagmus caused by ECHS1 deficiency

Biallelic mutations in ECHS1, encoding the mitochondrial enoyl-CoA hydratase, have been associated with mitochondrial encephalopathies with basal ganglia involvement. Here, we describe a novel clinical presentation consisting of dystonia-ataxia syndrome with hearing loss and a peculiar torsional nystagmus observed in two adult siblings. The presence of a 0.9-ppm peak at MR spectroscopy analysis suggested the accumulation of branched-chain amino acids. Exome sequencing in index probands identified two ECHS1 mutations, one of which was novel (p.V82L). ECHS1 protein levels and residual activities were reduced in patients' fibroblasts. This paper expands the phenotypic spectrum observed in patients with impaired valine catabolism

A new case of limb girdle muscular dystrophy 2g in a greek patient, founder effect and review of the literature

Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Bilateral Cavernous Carotid Aneurysms: Atypical Presentation of a Rare Cause of Mass Effect. A Case Report and a Review of the Literature

Bilateral cavernous carotid aneurysms (CCAs) represent a rare medical condition that can mimic other disorders. We present a rare case of bilateral CCAs simulating an ocular myasthenia. A 76-year-old woman presented with a history of fluctuating bilateral diplopia and unilateral ptosis, which led to the suspicion of ocular myasthenia. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain showed the presence of large bilateral aneurysms of the carotid cavernous tract. After an unsuccessful attempt with steroid therapy, the patient underwent endovascular treatment, with mild improvement. Bilateral CCAs can cause pupil sparing third nerve palsies and other cranial neuropathies which can mimic signs and symptoms of disorders of the neuromuscular junction. Therefore, the possibility of a vascular lesion simulating ocular myasthenia should be considered especially in older patients

Paroxysmal Nocturnal Hemoglobinuria (Pnh) : Brain Mri Ischemic Lesions in Neurologically Asymtomatic Patients

This study investigated for the first time brain ischemic involvement in 19 consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged 5 mm, and 5 cases a score >4 by the age-related white matter changes (ARWMC) scale. Compared with age and sex-matched controls (1:2 ratio), patients showed an increased frequency of periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher overall ARWMC scale score (3.5 \uc2\ub1 1.07 versus 2.0 \uc2\ub1 0.8, mean \uc2\ub1 SD, p < 0.0001). Notably, vascular abnormalities suspected for prior partial venous thrombosis, were observed in PNH cases only. MRI lesions were not related to blood counts, hemolytic markers, clone size, disease duration, and therapy with eculizumab. Neurological examination was unremarkable in all patients but one (Parkinson disease). Psychiatric assessment revealed a case of generalized anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In conclusion, brain MRI may be useful at diagnosis and during the course of the disease to explore subclinical neurological involvement

CSF &#946;-amyloid predicts prognosis in patients with multiple sclerosis

Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognized, and hence reliable biomarkers are needed. Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) amyloid beta 1\u201342 (A\u3b2) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white matter (WM) and grey matter (GM) damage at early disease stages. Methods: Sixty patients were recruited and followed up for 3\u20135 years. Patients underwent clinical assessment, brain magnetic resonance imaging (MRI; at baseline and after 1 year), and CSF analysis to determine A\u3b2 levels. T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads. Results: Lower CSF A\u3b2 levels were observed in patients with a worse follow-up Expanded Disability Status Scale (EDSS; r = 120.65, p &lt; 0.001). The multiple regression analysis confirmed CSF A\u3b2 concentration as a predictor of patients\u2019 EDSS increase (r = 120.59, p &lt; 0.0001). Generating a receiver operating characteristic curve, a cut-off value of 813 pg/mL was determined as the threshold able to identify patients with worse prognosis (95% confidence interval (CI): 0.690\u20130.933, p = 0.0001). No differences in CSF tau and neurofilament light chain (NfL) levels were observed (p &gt; 0.05). Conclusion: Low CSF A\u3b2 levels may represent a predictive biomarker of disease progression in MS