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Neuroimaging in patients with sensory neuronopathy

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Raphael Fernandes Casseb
Total Authors: 1
Document type: Doctoral Thesis
Press: Campinas, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
Defense date:
Examining board members:
Marcondes Cavalcante Franca Junior; Brunno Machado de Campos; Marcio Luiz Figueredo Balthazar; Antonio Carlos dos Santos; Edson Amaro Junior
Advisor: Marcondes Cavalcante Franca Junior

Introduction: Sensory neuronopathies (NS) constitute a subgroup of diseases of the peripheral nervous system, whose most striking feature is the primary degeneration of the dorsal root ganglia, yielding sensory deficits in many points of the body. For the same reason, there is loss of full coordination of movements, even though motor brain areas remain intact. In addition, the disease can anticipate symptoms of the underlying cause (such as lung cancer), and therefore early diagnosis of SNs is critical. Since it is an almost exclusively sensory disease, it is also a valuable model in the study of sensorimotor integration. Objectives: To evaluate the pattern of alteration in the brain and spinal cord of these patients using the MRI technique, in order to identify new diagnostic tools and understand the mechanisms involved with the disease. Methods: Structural (T1-weighted and T2-weighted) and functional (T2-weighted) images of 36 NS patients (52±11 years old; 17 women) defined according to clinical and electrophysiological criteria were acquired. To evaluate the effects of sensory deafferentation in the brain, stratified structural analyzes on gray matter (VBM and volumetry based on "multi-atlas" segmentation - SMA) and white matter (TBSS and SMA-based parameter analysis) were performed. In parallel, we investigated changes in motor activation pattern using a finger-tapping paradigm. To identify a new diagnostic marker, we performed an analysis of the DTI parameters in the posterior funiculus of the spinal cord, comparing SN patients with sensory polyneuropathy patients (PN) and controls. Results: In patients with chronic SNs (duration ? 4 years), we identified symmetrical volumetric increase of the caudate nuclei and volumetric reduction in the posterior portion of the medulla. In the microstructural domain, there were alterations in tracts that connect the thalamus and basal ganglia. Regarding functional alterations, task-related results pointed to a difference in cerebral activation as a consequence of lack of proprioceptive input, specifically in the posterior parietal regions and in medial areas of the cerebellum. SN patients had a significant reduction of mean fractional anisotropy in the posterior funiculi compared to controls and PN patients (p = 0.027). This image parameter was able to discriminate the groups with a sensitivity of 86% and a specificity of 71% (area under the curve = 0.838) Discussion and Conclusion: DTI analysis of the spinal cord seems to be a powerful tool to aid in the diagnosis of SNs, and could be part of the diagnostic work up. Structural findings reinforce the hypothesis that neuronal plasticity takes place in the basal nuclei of the chronically deafferented brain, highlighted by caudate hypertrophy. In addition, white matter alterations surrounding the caudate and thalami favor the hypothesis of damage to circuitries involving the basal nuclei. These findings led us to suggest that a recently identified pathway between the thalamus and the striatum may have an inhibitory role within a sensorimotor integration scheme (AU)

FAPESP's process: 14/15918-6 - Evaluation of motor activation pattern in patients with sensory neuronopathies using fMRI effective connectivity
Grantee:Raphael Fernandes Casseb
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)