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MRI Texture Analysis Reveals Deep Gray Nuclei Damage in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is characterized by extensive corticospinal damage, but extrapyramidal involvement is suggested in pathological studies. Texture analysis (TA) is an image processing technique that evaluates the distribution of gray levels between pixels in a given region of interest (ROI). It provides quantitative data and has been employed in several neurodegenerative disorders. Here, we used TA to investigate possible deep gray nuclei (DGN) abnormalities in a cohort of ALS patients.

Ulnar sensory-motor amplitude ratio: a new tool to differentiate ganglionopathy from polyneuropathy.

UNLABELLED The objective of this study was to evaluate if the ratio of ulnar sensory nerve action potential (SNAP) over compound muscle action potential (CMAP) amplitudes (USMAR) would help in the distinction between ganglionopathy (GNP) and polyneuropathy (PNP). METHODS We reviewed the nerve conductions studies and electromyography (EMG) of 18 GNP patients, 33 diabetic PNP patients and 56 controls. GNP was defined by simultaneous nerve conduction studies (NCS) and magnetic resonance imaging (MRI) abnormalities. PNP was defined by usual clinical and NCS criteria. We used ANOVA with post-hoc Tukey test and ROC curve analysis to compare ulnar SNAP and CMAP, as well as USMAR in the groups. RESULTS Ulnar CMAP amplitudes were similar between GNP x PNP x Controls (p=0.253), but ulnar SNAP amplitudes (1.6±3.2 x 11.9±9.1 × 45.7±24.7) and USMAR values (0.3±0.3 × 1.5±0.9 × 4.6±2.2) were significantly different. A USMAR threshold of 0.71 was able to differentiate GNP and PNP (94.4% sensitivity and 90.9% specificity). CONCLUSIONS USMAR is a practical and reliable tool for the differentiation between GNP and PNP.

Are Human Peripheral Nerves Sensitive to X-Ray Imaging?

Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures.

p16INK4a expression as a potential marker of low-grade cervical intraepithelial neoplasia progression

To evaluate p16INK4a immunoexpression in CIN1 lesions looking for differences between cases that progress to CIN2/3 maintain CIN1 diagnosis, or spontaneously regress. Seventy‐four CIN1 biopsies were studied. In the follow‐up, a second biopsy was performed and 28.7% showed no lesion (regression), 37.9% maintained CIN1, and 33.4% progressed to CIN2/3. Immunostaining for p16INK4a was performed in the first biopsy and it was considered positive when there was strong and diffuse staining of the basal and parabasal layers. Pearsons chi‐square was used to compare the groups (p ≤ 0.05). The age of the patients was similar. There was no significant difference in p16INK4a immunoexpression in the groups, however, statistical analyses showed a significant association when only the progression and regression groups were compared (p = 0.042). Considering p16INK4a positivity and the progression to CIN2/3, the sensitivity, specificity, positive, and negative predictive values in our cohort were 45%, 75%, 47%, and 94%, respectively. We emphasize that CIN1 with p16INK4a staining was associated with lesion progression, but the sensitivity was not high. However, the negative predictive value was more reliable (94%) and p16INK4a may represent a useful biomarker that can identify CIN1 lesions that need particular attention, complementing morphology.

Brazilian consensus on Duchenne muscular dystrophy. Part 1: diagnosis, steroid therapy and perspectives

Significant advances in the understanding and management of Duchenne muscular dystrophy (DMD) took place since international guidelines were published in 2010. Our objective was to provide an evidence-based national consensus statement for multidisciplinary care of DMD in Brazil. A combination of the Delphi technique with a systematic review of studies from 2010 to 2016 was employed to classify evidence levels and grade of recommendations. Our recommendations were divided in two parts. We present Part 1 here, where we describe the guideline methodology and overall disease concepts, and also provide recommendations on diagnosis, steroid therapy and new drug treatment perspectives for DMD. The main recommendations: 1) genetic testing in diagnostic suspicious cases should be the first line for diagnostic confirmation; 2) patients diagnosed with DMD should have steroids prescribed; 3) lack of published results for phase 3 clinical trials hinders, for now, the recommendation to use exon skipping or read-through agents.

Translation and validation into Brazilian Portuguese of the Spastic Paraplegia Rating Scale (SPRS)

OBJECTIVE To translate and validate the Spastic Paraplegia Rating Scale (SPRS) into Brazilian-Portuguese. METHOD Two experienced and English-fluent neurologists translated SPRS into Portuguese, creating SPRS-BR. We then assessed inter and intra-rater reliability of this version using coefficients of correlation and variability in a cohort of 30 patients. RESULTS Mean age of patients and disease duration were 47.7 ± 10.5 and 17.0 ± 10.6 years, respectively. Twenty-one had pure HSP and SPG4 was the most frequent genotype. Mean Rankin and SPRS-BR scores were 2.2 ± 0.9 and 19.9 ± 9.9, respectively. Mean intra and inter-rater correlation coefficients of SPRS-BR scores were 0.951 and 0.934, whereas coefficients of variation were 11.5% (inter-rater) and 9.9% (intra-rater). Cronbachs alpha for the whole SPRS-BR scale was 0.873. CONCLUSION SPRS-BR is a useful, reliable and valid clinical instrument.

Multimodal neuroimaging analysis in patients with SYNE1 Ataxia

BACKGROUND The gene SYNE1 is highly expressed in the cerebellum and its dysfunction is related to an autosomal recessive ataxia (SYNE1-ataxia). The disease was firstly considered a pure cerebellar ataxia however, recent studies have described a broader clinical presentation, including motor neuron disease symptoms. OBJECTIVES To investigate cerebellar and potential extra-cerebellar changes in SYNE1-ataxia using multimodal neuroimaging analyses. METHODS Six patients completed clinical and imaging exams, and were compared to age-gender-matched healthy controls. Gray matter was analyzed using FreeSurfer and CERES for brain and cerebellum, respectively. White matter was analyzed with DTI-TBSS while we used SpineSeg for spinal cord analysis. RESULTS We found significantly reduced cortical thickness (p < 0.05, FDR-corrected) in primary and association cortices, and volume reduction in subcortical structures, brainstem and cerebellum. White matter was found disrupted in both brain and cerebellum (p < 0.05, FWE-corrected). These results are consistent with the expression of the SYNE1 mRNA and its encoded protein in the brain. We failed to demonstrate spinal cord changes. CONCLUSIONS SYNE1-ataxia is, therefore, a relatively common cause of recessive ataxia characterized by complex multisystemic neurostructural changes consistent with the phenotypic heterogeneity and neuroimaging configures a potential marker of the disease.

S158. F wave persistence of the peroneal and tibial nerves in the differential diagnosis of sensory polyneuropathies and neuronopathies

Introduction The distinction between sensory polyneuropathies (SP) and neuronopathies (SN) is important for etiologic investigation and for prognosis estimation. However, this task is often challenging for the clinical neurophysiologist. In this scenario, we hypothesize that F wave assessment might be helpful, since it is able to detect subtle signs of motor involvement, which are found in SP, but not in SN. The aim of this study was to determine whether lower limb F waves are useful in the differential assessment of SP and SN. Methods Twenty-nine patients were selected: 8 with SP - 6 diabetic, 1 familial amyloidosis and 1 with leprosy - and 21 with SN - caused by Sjogren’s syndrome, autoimmune hepatitis, HTLV or idiopathic. We collected data on height for every subject. For each patient, we obtained 20 supramaximal distal stimuli in the peroneal and tibial nerves to record F waves using a Neuropack M1 unit (Nihon Kohden Co., Japan). The values of F wave latencies (minimum, mean and maximal) and persistence for the peroneal and tibial nerves in both groups were compared. Non-parametric tests were used and p values Results The mean age of patients was 52 years and there were 16 women. There were no significant between-group differences regarding ages (p  = 0.191) and the F wave latencies adjusted for height (p  = 0.918). The F waves persistence for the right fibular (27.5% vs 62%, p  = 0.019), right tibial (69% vs 91%, p  = 0.029) and left tibial nerves (72.5 vs 98%, p  = 0.003 ) was significantly lower in the SP group compared to SN. Conclusion Although preliminary, these results suggest that F waves may be useful in the differential diagnosis between SP and SN. The persistence of responses seems to be the most sensitive parameter. Studies with larger series should be performed to validate these findings.

S36. Neuropathic pain is common in sensory neuronopathy and may play a role in its diagnostic delay

Introduction Sensory neuronopathies (SN) are a distinct group of peripheral nerve disorders that emerge from the dorsal root ganglia damage. The resultant phenotype is characterized by multifocal non-length dependent sensory deficits. This pattern of sensory impairment produces a sensory symptoms spectrum with different combinations of sensory ataxia and pain. Neuropathic pain (NP) is often present in the context of SN, however its description and its impact on SN diagnosis delay have not been previously addressed. Objective To describe neuropathic pain in SN patients and to evaluate its impact on the diagnosis delay of these patients. Methods We evaluated 40 consecutive patients with SN who were regularly followed in a tertiary neuromuscular clinic. For each patient, we obtained data regarding the presence of pain, the Leeds assessment of neuropathic symptoms and signs (LANSS) score was obtained and all patients were actively interrogated regarding the onset of the SN symptoms, previous diagnoses for which they were eventually treated, the number and the specialty of previous physicians consulted. Non-parametric tests were used and p values  Results The mean age of SN patients was 50.9 ± 11.3 years and there were 30 women. For 33 SN patients pain was part of the clinical picture and for22 of those, the pain was described as neuropathic accordingly to LANSS (LANSS scores ⩾ 12). None of these patients was first evaluated in our center by the time of the settlement of SN symptoms. Every patient was evaluated by a mean of 4.32 ± 2.21 specialists and received a mean of 3.1 ± 1.4 wrong different diagnoses. The mean time between the SN symptoms onset and the proper SN diagnosis was 5.47 ± 5.3 years. Considering those patients with and without NP the mean time to the SN diagnose was 7.13 ± 6.3 and 3.44 ± 2.7 years (p = 0.026) respectively. Conclusion These results suggest that pain, specially the NP, is a common feature in SN and may impose a significant delay for its correct diagnosis.

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION: T2 RELAXOMETRY AS A DIAGNOSTIC TOOL

The deposition of iron in the basal ganglia is an age-dependent physiological event, however, increased deposits has been shown in the central nervous system in many neurodegenerative diseases (including Friedreichs Ataxia FA, Machado-Joseph Disease MJD, Amyotrophic Lateral Sclerosis ALS and Parkinsons Disease PD) and, in this context, the use of Magnetic Resonance Imaging (MRI) trhough the analyses of transversal relaxation time (RT2) can be a powerfull diagnostic tool by the detection of brain iron deposits. We selected 191 patients (32 AF, 48 MJD, 58 ALS, 53 PD) and compared four structures of basal ganglia (thalamus, dentate nucleus, pallidum and substantia nigra) RT2 values with control group (n = 207, using normal values from previous study of the same group of researchers), trying to determine paterns of brain iron depositions that can be used as diagnostic tool. We found statistically significance in the avaliation of left dentate nucleus in FA patients (p = 0,03), rght substantia nigra in MJD (p = 0,01) and left thalamus in ALS (0,01), with probable physiopathological and clinical correlations. The RT2 MRI is a relevant technique in the evaluation of neurodegenerative diseases and can be used as an important diagnostic tool in the clinical practice.