Magnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis.

Patients with multiple sclerosis (MS) display reduced structural connectivity among brain regions, but the pathogenic mechanisms underlying network disruption are still unknown. We aimed to investigate the association between the loss of diffusion-based structural connectivity, measured with graph theory metrics, and magnetic resonance (MR) markers of microstructural damage. Moreover, we evaluated the cognitive consequences of connectivity changes. We analysed the frontoparietal network in 102 MS participants and 25 healthy volunteers (HV). MR measures included radial diffusivity (RD), as marker of demyelination, and ratios of myo-inositol, N-acetylaspartate and glutamate+glutamine with creatine in white (WM) and grey matter as markers of astrogliosis, neuroaxonal integrity and glutamatergic neurotoxicity. Patients showed decreased global and local efficiency, and increased assortativity (p < 0.01) of the network, as well as increased RD and myo-inositol, and decreased N-acetylaspartate in WM compared with HV (p < 0.05). In patients, the age-adjusted OR of presenting abnormal global and local efficiency was increased for each increment of 0.01 points in RD and myo-inositol, while it was decreased for each increment of 0.01 points in N-acetylaspartate (the increase of N-acetylaspartate reduced the risk of having abnormal connectivity), all in WM. In a multiple logistic regression analysis, the OR of presenting abnormal global efficiency was 0.95 (95% confidence interval, CI: 0.91-0.99, p = 0.011) for each 0.01 increase in N-acetylaspartate, and the OR of presenting abnormal local efficiency was 1.39 (95% CI: 1.14-1.71, p = 0.001) for each 0.01 increase in RD. Patients with abnormal efficiency had worse performance in attention, working memory and processing speed (p < 0.05). In conclusion, patients with MS exhibit decreased structural network efficiency driven by diffuse microstructural impairment of the WM, probably related to demyelination, astroglial and neuroaxonal damage. The accumulation of neuroaxonal pathological burden seems to magnify the risk of global network collapse, while demyelination may contribute to the regional disorganization. These network modifications have negative consequences on cognition.

Putamina involvement in Wernicke encephalopathy induced by Janus Kinase 2 inhibitor.

OBJECTIVE: The aim of the study was to report a case of Wernicke encephalopathy (WE) due to fedratinib (Janus Kinase 2 inhibitor) treatment with atypical neuroimaging findings. METHODS: We present a detailed report of the case and literature review. RESULTS: A 68-year-old woman under treatment with fedratinib (investigational JAK2 inhibitor) developed memory impairment, diplopia, and ataxia compatible with WE. Brain magnetic resonance imaging showed extensive lesions involving medial thalami, periaqueductal gray, caudate nuclei, and putamina. Thiamine supplementation provided clinical recovery and radiological improvement of the lesions described. Basal ganglia lesions have been previously described in children with this disease, but this is rarely found in adults. Clinical trials including fedratinib have been recently discontinued, and its involvement in pathogenesis of WE may be related to thiamine-transporter inhibition. CONCLUSIONS: Our case represents an example of drug-related WE, with a rare radiological pattern. Precocious diagnosis and treatment are essential to prevent irreversible brain injury.