The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.
Cerebral small vessel disease (cSVD) is the leading cause of vascular cognitive impairments and dementia, cerebral hemorrhages and lacunar strokes, as well as the most common form of asymptomatic vascular brain lesion. Major forms of cSVD are age- and arterial hypertension (AH)-associated arteriolosclerosis and cerebral amyloid angiopathy. The etiologies and the underlying mechanisms of disease development and progression remain unclear for a substantial group of cSVD types. Significant difficulties in the study of this pathology are explained by technical limitations in assessing smallest vessels in vivo. A modified correlation between MRI equivalents and their morphological manifestations in cSVD to use them subsequently as a surrogate marker of lesions in small vessels has allowed clinicians to establish disease progression regularities and the association of the latter with clinical symptoms. This review presents the results of studies showing the clinical significance and role of the leading MRI features in the assessment of disease progression, including white matter hyperintensity (WMH, formerly known as leukoaraiosis), lacunes, enlarged perivascular spaces, and microbleeds. The recognition of MRI features as diagnostic criteria for cSVD was specified by international experts in the Standards for Reporting Vascular Changes on Neuroimaging (the STRIVE criteria). Despite the enormous importance of this standardization for the improvement of concepts about the significance of different factors in the development and understanding of heterogeneity of cSVD forms, this categorization cannot provide for the prediction of the disease course in a particular patient and assess the treatment efficacy in short- and medium-term prospects. One of the approaches to solution was based on the use of diffusion methodologies for assessing a microstructural lesion in the visually unaltered brain matter. The obtained consistent association of the expressiveness of microstructural alterations with clinical impairments substantiates the expediency of multimodal MRI studies aimed to evaluate the pathophysiological mechanisms of disease progression, beginning from the subclinical brain lesion stage.