Abstract
Background: The absence of efficient treatments capable to promote central nervous system recovery in patients in vegetative state (VS) due to a severe acquired brain injury highlights the need of exploring alternative neuromodulatory treatments that can lead to neurobehavioral gains. Some encouraging preliminary observations suggest that transcranial direct current stimulation could be effective in disorders of consciousness (DoC) patients, especially when applied on the dorsolateral prefrontal cortex (DLPFC) in patients with minimally conscious state (MCS) but not in those with VS.Objective: The primary aim of the present study was to verify if the application of transcranial random noise stimulation (tRNS) on the DLPFC might favor improvements of consciousness recovery in subacute VS-UWS.Methods: Nine patients with DoC due to traumatic brain injury (n = 1), anoxia (n = 3), and vascular damage (n = 5), have undergone a randomized, double-blind, sham-controlled, neuromodulatory trial with tRNS of bilateral DLPFC. All patients were in a post-acute phase and the DoC onset ranged from 30 days to 4 months. The diagnosis of DoC was based on internationally established criteria from the Multi-Society Task Force on PVS, and classified as VS or MCS using the JFK Coma Recovery Scale-Revised scores (CRS-R). We used CRS-R, Synek Scale, Ad-Hoc semi-quantitative scale and the Clinical Global Impression-Improvement scale to measure behavioral and electrophysiological changes during tRNS intervention. All patients were also treated with daily conventional rehabilitation treatment.Results: No significant differences emerged between active and sham groups regarding improvements of level of consciousness, as well as on electroencephalographic data. Only one patient showed emergence from VS-UWS, evolving from VS to MCS after the tRNS stimulation, at a distance of 3 weeks from the enrolment into the study.Conclusion: Repeated applications of tRNS of the DLPFC, even if applied in a subacute phase of VS-UWS state, did not modify behavioral and neurophysiological outcomes differently than sham stimulation.
Highlights
The term vegetative state (VS) refers to patients who have awakened from coma but remain unresponsive, showing wakefulness without awareness (Jennett and Plum, 1972)
The need to overcome the strong negative connotations that the term “persistent vegetative state (PVS)” continues to have after over 35 years, led the European Task Force on Disorders of Consciousness to introduce the term of Unresponsive Wakefulness Syndrome (UWS) (2010)
No significant differences emerged between real or sham stimulation conditions in Clinical Global Impression-Improvement (CGI-I) scores when the evaluation was performed by the neurologist (T1: Z = 0.295)
Summary
The term vegetative state (VS) refers to patients who have awakened from coma but remain unresponsive, showing wakefulness without awareness (Jennett and Plum, 1972). The need to overcome the strong negative connotations that the term “PVS” continues to have after over 35 years, led the European Task Force on Disorders of Consciousness to introduce the term of Unresponsive Wakefulness Syndrome (UWS) (2010) As this neutral descriptive term indicates, UWS refers to a clinical syndrome describing patients who fail to exhibited voluntary motor responsiveness to commands in the presence of clinical signs of eyes-open wakefulness (Laureys et al, 2010). This complex syndrome is exerting a heavy impact on the health system and the efforts spent to identify patients that could emerge from this state recovering consciousness (Bruno et al, 2012) did not lead to standardization of evidence-based guidelines for the treatment of this condition (Bernat, 2006). Some encouraging preliminary observations suggest that transcranial direct current stimulation could be effective in disorders of consciousness (DoC) patients, especially when applied on the dorsolateral prefrontal cortex (DLPFC) in patients with minimally conscious state (MCS) but not in those with VS
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