Brain Mapping of Abnormal Neural Networks in Patients with Various Neurological Disorders
A novel study hints that brain mapping of neural network can allow doctors and researchers to characterize previously unidentified central nervous system (CNS) involvement more precisely and/or to elucidate the underlying mechanisms of CNS abnormalities in patients with various neurological disorders, which may be determined by genetic subtypes in hereditary neurological disorders. Structural or functional brain mapping of neural networks could not only identify normal functional neural networks, but also could elucidate abnormal network alternations in various neurological disorders. Prof. Hyang Woon Lee and her research group reported in a recent study of the structural brain network mapping by using diffusion tensor imaging (DTI) in patients with Charcot-Marie-Tooth disease (CMT), one of the most common hereditary sensorimotor peripheral neuropathies. Although CNS involvement has occasionally been described in patients with CMT2A (GJB1 mutation) and CMTX (MFN2 mutation), it is difficult to identify other genetic subtypes or define the pathomechanism. Moreover, CMT patients with NEFL mutation, dominant-intermediate subtype were described to have CNS symptoms, such as cerebellar ataxia and nystagmus. However, the underlying mechanisms of CNS involvement in CMT patients were elusive. Thus, in this study, we investigated the structural and functional abnormalities of the CNS white matters in CMT patients including MFN2, GJB1 and NEFL mutations, and tried to find the different underlying pathomechanism among various pathologies involving peripheral nervous system such as demyelinating, axonal and intermediate type neuropathies. In addition, Prof. Lee and her group investigated the structural evidence of cerebral white matter abnormalities in CMT patients and the relationship between these abnormalities and clinical disability. We evaluated the structural evidence of CNS involvement by using diffusion tensor imaging (DTI) in 75 subjects including 45 patients with CMT2A (MFN2 mutation), CMT1X (GJB1 mutation), and dominant intermediate CMT (DI-CMT) (NEFL mutation) compared with 30 controls. CMT patients with MFN2, GJB1, and NEFL mutations revealed microstructural CNS white matter abnormalities with alternations in various DTI indices such as decreased fractional anisotropy (FA), axial diffusivity (AD), and increased radial diffusivity (RD), mean diffusixity (MD) values. Interestingly, the DTI abnormalities were correlated with severity of clinical disabilities manifested as Medical Research Counsil (MRC) motor power, CMT neuropathy scale (CMTNS) and/or functional disability score (FDS). In this study, we demonstrated structural and functional evidence of CNS motor pathway involvement using DTI in CMT patients with MFN2, GJB1, and NEFL mutations. Distinct DTI abnormalities and their clinical correlations in these genetic subgroups of CMT suggest co-morbidity of central nervous system damage of motor pathways in addition to pathology in peripheral nervous system in these genetic subtypes of CMT patients.
Figure 1. A. White matter abnormalities demonstrated by diffusion tensor imaging in various genetic subtypes of Charcot-Marie-Tooth disease (CMT), a hereditary sensorimotor neuropathy.
Figure 2. B. Clinical correlations between CNS abnormality of diffusion tensor imaging and severity of clinical symptoms in CMT patients.
The research is based on a relatively new method of brain mapping identifying neural networks that are structurally wired and functionally connected in normal and abnormal brains. This new analysis method can be done to explore various neural networks where normal higher brain functional modules are connected or part of abnormal brain connectomes wired in various neurological disorders. This kind of approach can apply to explore the abnormalities in brain neural networks and to contribute for developing a novel treatment methods based on pathophysiologic mechanisms in various neurological disorders.
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Lee M, Park CH, Chung HK, Kim HJ, Choi Y, Yoo JH, Yoon YC, Hong YB, Chung KW, Choi BO, Lee HW. Cerebral white matter abnormalities in patients with Charcot-Marie-Tooth disease. Ann Neurol 2017;81: in press. doi: 10.1002/ana.24824. [Epub ahead of print]