No effects of 20 Hz-rTMS of the primary motor cortex in vegetative state: A randomised, sham-controlled study.

We assessed the effects of a non-invasive neuromodulatory intervention with repetitive transcranial magnetic stimulation (rTMS) of the motor cortex in patients with vegetative state (VS) by a randomised, sham-controlled study with a cross-over design. Eleven patients classified as being in VS (9 post-anoxic, 2 post-traumatic, time elapsed from the injury 9-85 months) were included in the study. Real or sham 20 Hz rTMS were applied to the left primary motor cortex (M1) for 5 consecutive days. Primary outcome measures were changes in the JFK Coma Recovery Scale-Revised (CRS-R) scale total score and Clinical Global Impression Improvement (CGI-I) scale. Additional measures were EEG changes and impression of the patients' relatives using the CGI-I scale. Evaluations were blindly performed at baseline, after the first day of treatment, immediately after the end of the 5-days treatment, 1 week and 1 month later. Slight changes observed in the CRS-R and CGI-I scores did not significantly differ between real or sham stimulation conditions. EEG was not significantly changed on average, although spots of brain reactivity were occasionally found underneath the stimulation point. Findings did not provide evidence of therapeutic effect of 20 Hz rTMS of the M1 in chronic VS, at least with conventional coils and current safety parameters. Therefore, they might be useful to better allocate human and financial resources in future trials.

Vegetative versus minimally conscious states: a study using TMS-EEG, sensory and event-related potentials.

Differential diagnoses between vegetative and minimally conscious states (VS and MCS, respectively) are frequently incorrect. Hence, further research is necessary to improve the diagnostic accuracy at the bedside. The main neuropathological feature of VS is the diffuse damage of cortical and subcortical connections. Starting with this premise, we used electroencephalography (EEG) recordings to evaluate the cortical reactivity and effective connectivity during transcranial magnetic stimulation (TMS) in chronic VS or MCS patients. Moreover, the TMS-EEG data were compared with the results from standard somatosensory-evoked potentials (SEPs) and event-related potentials (ERPs). Thirteen patients with chronic consciousness disorders were examined at their bedsides. A group of healthy volunteers served as the control group. The amplitudes (reactivity) and scalp distributions (connectivity) of the cortical potentials evoked by TMS (TEPs) of the primary motor cortex were measured. Short-latency median nerve SEPs and auditory ERPs were also recorded. Reproducible TEPs were present in all control subjects in both the ipsilateral and the contralateral hemispheres relative to the site of the TMS. The amplitudes of the ipsilateral and contralateral TEPs were reduced in four of the five MCS patients, and the TEPs were bilaterally absent in one MCS patient. Among the VS patients, five did not manifest ipsilateral or contralateral TEPs, and three of the patients exhibited only ipsilateral TEPs with reduced amplitudes. The SEPs were altered in five VS and two MCS patients but did not correlate with the clinical diagnosis. The ERPs were impaired in all patients and did not correlate with the clinical diagnosis. These TEP results suggest that cortical reactivity and connectivity are severely impaired in all VS patients, whereas in most MCS patients, the TEPs are preserved but with abnormal features. Therefore, TEPs may add valuable information to the current clinical and neurophysiological assessment of chronic consciousness disorders.

Can we scientifically and reliably measure the level of consciousness in vegetative and minimally conscious States? Rasch analysis of the coma recovery scale-revised.

OBJECTIVES: (1) To appraise, by the means of Rasch analysis, the internal validity and reliability of the Coma Recovery Scale-Revised (CRS-R) in a sample of patients with disorder of consciousness (DOC); and (2) to provide information about the comparability of CRS-R scores across persons with DOC across different settings and groups, including different etiologies. DESIGN: Multicenter observational prospective study. SETTING: Two rehabilitation wards, 1 intermediate care facility, and 2 nursing homes in Italy. PARTICIPANTS: Consecutively admitted patients (N=129) for which assessments at 2 different time points were available, giving a total sample of 258 observations. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: CRS-R. RESULTS: After controlling for any possible dependency between persons' measures collected at different time points, and for uniform differential item functioning by etiology showed by the visual subscale, Rasch analysis demonstrated adequate satisfaction of all the model's requirements, including adequate ordering of scoring categories, unidimensionality, local independence, invariance (χ(2)21=27.798, P=.146), and absence of differential item functioning across patients' sex, age, time, and setting. The reliability (person separation index=.896) was adequate for individual person measurement. We devised a practical raw score to measure conversion tables based on the CRS-R calibrations. CONCLUSIONS: The CRS-R is a psychometrically sound and robust measurement tool. The linear measures of ability derived from the CRS-R total scores do satisfy all the principles of scientific measurement and are sufficiently reliable for high stakes assessments, such as the diagnosis of the level of consciousness in individual patients. Future studies are needed to directly explore the capabilities of the CRS-R measures to reduce the risk of vegetative state misdiagnosis.