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Context About one-third of diabetic patients suffer from neuropathic pain, which is poorly responsive to analgesic therapy and associated with greater autonomic dysfunction. Previous research on diabetic neuropathy mainly links pain and autonomic dysfunction to peripheral nerve degeneration resulting from systemic metabolic disturbances, but maladaptive plasticity in the central pain and autonomic systems following peripheral nerve injury has been relatively ignored. Objective This study aimed to investigate how the brain is affected in painful diabetic neuropathy (PDN), in terms of altered structural connectivity (SC) of the thalamus and hypothalamus that are key regions modulating nociceptive and autonomic responses. Methods We recruited 25 PDN and 13 painless (PLDN) diabetic neuropathy patients, and 27 healthy adults as controls. The SC of the thalamus and hypothalamus with limbic regions mediating nociceptive and autonomic responses was assessed using diffusion tractography. Results The PDN patients had significantly lower thalamic and hypothalamic SC of the right amygdala compared with the PLDN and control groups. In addition, lower thalamic SC of the insula was associated with more severe peripheral nerve degeneration, and lower hypothalamic SC of the anterior cingulate cortex was associated with greater autonomic dysfunction manifested by decreased heart rate variability. Conclusion Our findings indicate that alterations in brain structural connectivity could be a form of maladaptive plasticity after peripheral nerve injury, and also demonstrate a pathophysiological association between disconnection of the limbic circuitry and pain and autonomic dysfunction in diabetes.

Radiation vasculopathy is one of the rare causes of ischemic stroke. Carotid stenosis with large volume infarction may occur years after radiation therapy for head or neck cancer. We report a case of a patient with bilateral internal carotid artery occlusion presenting with left middle cerebral artery infarct 10 years after receiving treatment for tongue cancer. A literature review and discussion of treatment for such patients are presented.

Objective Small‐fiber neuropathy (SFN) is characterized by neuropathic pain due to degeneration of small‐diameter nerves in the skin. Given that brain reorganization occurs following chronic neuropathic pain, this study investigated the structural and functional basis of pain‐related brain changes after skin nerve degeneration. Methods Diffusion‐weighted and resting‐state functional MRI data were acquired from 53 pathologically confirmed SFN patients, and the structural and functional connectivity of the pain‐related network was assessed using network‐based statistic (NBS) analysis. Results Compared with age‐ and sex‐matched controls, the SFN patients exhibited a robust and global reduction of functional connectivity, mainly across the limbic and somatosensory systems. Furthermore, lower functional connectivity was associated with skin nerve degeneration measured by reduced intraepidermal nerve fiber density and better therapeutic response to anti‐neuralgia medications, particularly for the connectivity between the insula and the limbic areas including the anterior and middle cingulate cortices. Similar to the patterns of functional connectivity changes, the structural connectivity was robustly reduced among the limbic and somatosensory areas, and the cognition‐integration areas including the inferior parietal lobule. There was shared reduction of structural and functional connectivity among the limbic, somatosensory, striatal, and cognition‐integration systems: (1) between the middle cingulate cortex and inferior parietal lobule and (2) between the thalamus and putamen. These observations indicate the structural basis underlying altered functional connectivity in SFN. Interpretation Our findings provide imaging evidence linking structural and functional brain dysconnectivity to sensory deafferentation caused by peripheral nerve degeneration and therapeutic responses for neuropathic pain in SFN. ANN NEUROL 2023;93:655–667