A Patient With Minimally Conscious Syndrome Due to Cerebrovascular Accident Whose Symptoms Resolved With Zolpidem.

OBJECTIVE: In this report, we discuss the case of a patient with minimally conscious state (MCS) whose clinical condition significantly improved after Zolpidem therapy. We aim to provide supportive evidence for inclusion of zolpidem trials in patients with MCS. METHODS: Our team used electronic medical records, direct patient care experiences, and literature review to obtain information for this case report. RESULTS: Twice daily zolpidem therapy led to significant clinical improvement in our patient with MCS. In addition, this improvement was maintained throughout an increasingly arduous medical course. CONCLUSIONS: Minimally conscious state is a disorder with limited proven therapeutic options. Zolpidem administration has demonstrated immense benefit in a select population of patients, including ours. Given the potential for great improvement with limited downside, zolpidem trial presents an intriguing treatment option. Further clarification of prognostic features to stratify responders and nonresponders to therapy is needed.

Speech recovery after single-dose zolpidem in two minimally conscious patients with severe traumatic brain injuries: a case report.

BACKGROUND: In rare cases, zolpidem administration has been found to paradoxically improve cognition in patients with brain injury in disorders of consciousness. CASE PRESENTATION: Two minimally conscious plus (MCS+) patients at baseline, a 24-year-old woman 8 weeks post-traumatic brain injury (TBI) and 23-year-old man 6 weeks post-TBI, demonstrated behavioral improvements after off-label, single-dose administration of 10 mg of zolpidem. DISCUSSION/CONCLUSION: The patients demonstrated improved cognition on Coma Recovery Scale-Revised assessment after ingesting zolpidem. In particular, speech was substantially restored as one patient recovered functional communication and both demonstrated intelligible verbalizations for the first-time post-injuries following zolpidem. Overall, evidence is limited regarding the underlying mechanisms of various cognitive improvements in zolpidem response although studies incorporating neuroimaging are promising. The outcomes and similarities between these cases contribute to the current literature and highlight the need for rigorous studies in the future to guide zolpidem trials in patient care for those with DOC.

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. OBJECTIVES: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS: Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. MAIN RESULTS: We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias.  Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence).  Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). AUTHORS' CONCLUSIONS: The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines.

Persistent vegetative state after severe cerebral hemorrhage treated with amantadine: A retrospective controlled study.

Amantadine is currently recommended for use in patients of posttraumatic brain injury with unconsciousness. However, the application of amantadine in consciousness disturbance after cerebral hemorrhage has only been rarely reported. This allows for a further exploration of the role of amantadine in the treatment of PVS resulting from severe cerebral hemorrhage.Retrospective cohort study from 1/2015 to 7/2019 in Beijing Chaoyang hospital. We included adult patients treated with amantadine after severe cerebral hemorrhage in PVS. Primary outcome was time of consciousness recovery and Glasgow Out Scale scores after 5 months from onset. We compared characteristics and outcomes to a control cohort. matched on age, Coma Recovery Scale-Revised score, volume and location of hemorrhage.Among the 12 patients who received amantadine treatment, 6 patients regained consciousness (50%) after 5 months of disease onset, but were still severely disabled. Besides, the time for regaining consciousness was within 3 months of disease onset. The remaining 6 patients were still in a PVS. Compared with the amantadine group, the consciousness recovery rate (50% vs 33.3%, P = .68) after 5 months in the nested control group was not significantly different. The awakening time for patients in the amantadine group was earlier than the control group (100% vs 25%, P = .03).In this study, amantadine can accelerate the recovery of consciousness in patients following severe cerebral hemorrhage. We recommend further randomized controlled studies to determine the efficacy of amantadine.

The use of amantadine in patients with unresponsive wakefulness syndrome after severe cerebral hemorrhage.

BACKGROUND: Amantadine is currently recommended for use in patients of post-traumatic brain injury with unresponsive wakefulness syndrome (UWS). However, the application of amantadine in UWS after cerebral hemorrhage has only been rarely reported. This allows for a further exploration of the role of amantadine in the treatment of UWS resulting from a severe cerebral hemorrhage. METHODS: We observed the changes of seven patients with UWS of intracerebral hemorrhage after taking amantadine. We also carried out a detailed neurological examination of the patient with disorders of consciousness to include or exclude subjects for the study. CRS-R score was used to evaluate the neurological recovery. RESULTS: An improvement in consciousness was observed within 3-6 days after the start of amantadine administration in all seven cases (n = 7/7; 100%). Five patients recovered conscious and left aphasia, hemiplegia and other sequelae, and two patients recovered from UWS to minimally conscious state (MCS). CONCLUSIONS: In this study, amantadine administration showed substantial positive effects on recovery following severe cerebral hemorrhage. We recommend further randomized controlled studies to determine the efficacy of amantadine.

[Intrathecal baclofen therapy in brain injury and recovery of persistent vegetative state. Apropos of a case]. / Baclofeno intratecal en daño cerebral y recuperación de estado vegetativo persistente. A propósito de un caso.

Patients with brain injury and spasticity are candidates for intrathecal baclofen therapy (ITB) when maximal doses of oral antispastic drugs fail. Some authors have described an improvement in the level of consciousness in patients with brain injury and disorder of consciousness treated with ITB for spasticity. We present the case of a 43-year-old patient with brain injury, spasticity, and permanent vegetative state (PVS) who showed an improvement in the level of consciousness after ITB for spasticity. We performed an ITB infusion test, assessing the spasticity with the Modified Ashworth Scale (MAS) and level of consciousness with the Coma Recovery Scale-Revised (CRS-R) and observed an improvement in the spasticity and the level of consciousness. Consequently, the ITB pump was implanted and the patient recovered from PVS to minimal conscious state (MCS). We conclude that ITB is indicated in patients with brain injury and spasticity. We suggest the improvement in the level of consciousness as a possible additional benefit. There is a lack of evidence to recommend ITB in patients with altered level of consciousness.

Rotigotine effect in prolonged disturbance of consciousness. Brief report of two cases.

Two patients with post-coma reactivation deficiency who showed a "dramatic" response to rotigotine therapy are described. They had suffered from prolonged coma due to lesions in the mesencephalic ventral tegmental area. The authors believe that rotigotine effect in these cases could be due to restoration of dopaminergic transmission in medial frontal areas previously "de-afferented" from the lesions. Some comatous patients may experience a prolonged difficulty in recovering a normal state of consciousness. This phenomenon may be due to dysfunction of amynergic activating pathways connecting brainstem to the frontal cerebral cortex. In particular, dysfunction of dopaminergic pathways from the mesencephalon to the frontal cortical areas may be responsible for clinical pictures characterized by preserved alertness and total loss of interactions with the surrounding environment; the so called "waking coma" cases.

[Bromocriptine in disorders of consciouness due to traumatic brain injury]. / Uso de bromocriptina en pacientes con alteración de conciencia secundaria a traumatismo craneoencefálico.

INTRODUCTION: The aim of this study was to assess the results and adverse effects of bromocriptine in patients with traumatic brain injury-vegetative state (TBI-VS) or traumatic brain injury-minimally conscious state (TBI-MCS). METHODS: We conducted a retrospective review of 10 patients, six with TBI-VS and four with TBI-MCS. All patients received bromocriptine at a starting dose of 2.5mg twice daily. Bromocriptine was titrated up to 7.5 or 12.5mg twice daily according to response and was maintained for at least 4 weeks. Various assessment scales were used in the following stages: before bromocriptine administration, at 4 weeks post bromocriptine prescription, and at hospital discharge. The assessment scales used were the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale, Glasgow Coma Scale, Barthel Scale, and Marshall Scale. RESULTS: Of the 10 patients, four with TBI-MCS and four with TBI-VS achieved a score of 23 points at discharge in the CRS-R, thus emerging from VS or MCS and regaining functional status. There were only two patients who emerged from VS but remained in MCS (8 to 11 and 5 to 10 points in CRS-R). CONCLUSIONS: Considering the poor prognosis for recovery in these patients, bromocriptine use has a positive risk-benefit ratio at a dosage of at least 7.5mg twice daily for 4 weeks.

Effect of amantadine on vegetative state after traumatic brain injury: a functional magnetic resonance imaging study.

OBJECTIVE: We assessed the use of functional magnetic resonance imaging (fMRI) to observe residual brain function and responsiveness to amantadine in a patient in a vegetative state (VS) following traumatic brain injury. METHOD: We observed cerebral cortex activation in a 52-year-old man in a VS, and in a healthy individual using fMRI during passive listening and motor-imagery tasks. The patient received oral amantadine for 3 months. fMRI was repeated after treatment. RESULTS: Activation around the left insular regions occurred during stimulation by a familiar voice, and activity in the left temporal and bi-occipital cortices occurred during stimulation by a familiar/unfamiliar voice. Activity in the bilateral frontal and parietal cortices occurred during the motor-imagination task. Brain cortex activation was reduced in the VS patient compared with the healthy volunteer. However, the patient responded to certain auditory stimuli and motor imagery, suggesting that he retained some intact auditory and motor cortical functions. fMRI scans after 3 months of treatment showed increased activation of brain areas corresponding to task instructions. CONCLUSION: fMRI could be used to observe the effects of amantadine on brain function, and to aid the diagnosis and prognostic prediction in VS patients in terms of recovery and rehabilitation planning.

An analysis of the effects of using Zolpidem and an innovative multimodal interdisciplinary team approach in prolonged disorders of consciousness (PDOC).

Zolpidem has been used with mixed effects in patients presenting with Prolonged Disorders of Consciousness (PDOC). This single case report describes an interdisciplinary team (IDT) protocol combined with Zolpidem 10 mg in a single case of a patient in PDOC. 'Emily', a 44-year-old lady was admitted to a rehabilitation unit in Ireland one year post onset of subarachnoid haemorrhage. Standardized assessments diagnosed her as being in a minimally conscious state (MCS). An IDT protocol was devised to stimulate and record responses to sensory and pharmacological stimuli. The protocol was applied pre and post administration of Zolpidem 10 mg. Across standardized measures of awareness, improved results post-Zolpidem were recorded. Spontaneous, appropriate verbalization was the most significant change observed 30 min after administration of Zolpidem 10 mg. This ceased after approximately 2 h with Emily reverting to a non-verbal state. The combined effect of Zolpidem and the IDT protocol applied over an eight-week period resulted in durable functional and communicative gains for Emily, inferring neuro-plasticity. This report highlights the impact of a combined approach of intensive IDT intervention in conjunction with Zolpidem. The use of Zolpidem with this patient population warrants further investigation.

Selegiline in Patients With Disorder of Consciousness: An Open Pilot Study.

This open study investigated the clinical effects of 10-week selegiline administration in six patients in vegetative state and in four patients in a minimally conscious state, at least 6 months after onset. Clinical outcome was assessed by Coma Recovery Scale-Revised once a week during selegiline administration and 1 month later. Three patients stopped treatment because of possible side effects. After treatment and at 1 month of follow-up, four patients showed improvements in clinical diagnosis, and three patients showed an increase in arousal level only. Selegiline might represent a relatively safe option to enhance arousal and promote recovery in brain-injured patients with disorders of consciousness.

Awakening with amantadine from a persistent vegetative state after subarachnoid haemorrhage.

We report the case of a 36-year-old woman with a subarachnoid haemorrhage (SAH) caused by a rupture of a right-sided middle cerebral artery aneurysm and subsequent malignant infarction of the right hemisphere leading to a persistent vegetative state and severe spastic tetraparesis with recurrent myocloni. Nine months after disease onset, the patient was transferred to our department for diagnostic and therapeutic re-evaluation. The poor clinical condition could not be explained by the brain lesion caused by the SAH or infarction. Moreover, glucose metabolism was normal in brain regions not affected by SAH and infarction as shown by positron emission tomography with 18F-fluorodeoxyglucose. We terminated baclofen and reduced antiepileptics known to impair vigilance and cognitive functions. However, only after starting amantadine treatment we observed a stunning awakening of the patient fully orientated within days. Our findings warrant trials to investigate amantadine in the treatment of unresponsive wakefulness syndromes due to acute central nervous system diseases.

Improved Arousal and Motor Function Using Zolpidem in a Patient With Space-Occupying Intracranial Lesions: A Case Report.

Patients with disorders of consciousness (DOC) have profound functional limitations with few treatment options for improving arousal and quality of life. Zolpidem is a nonbenzodiazepine hypnotic used to treat insomnia that has also been observed to paradoxically improve arousal in those with DOC, such as the vegetative or minimally conscious states. Little information exists on its use in patients with DOC who have intracranial space-occupying lesions. We present a case of a 24-year-old man in a minimally conscious state due to central nervous system lymphoma who was observed to have increased arousal and improved motor function after the administration of zolpidem. LEVEL OF EVIDENCE: V.

Does Modafinil improve the level of consciousness for people with a prolonged disorder of consciousness? a retrospective pilot study.

BACKGROUND AND AIM: Modafinil is best known as a sleep regulator among healthy individuals, but studies suggest that it reduces excessive daytime sleepiness in patients with brain injury. This retrospective pilot study evaluated the effectiveness of Modafinil for people with a prolonged disorder of consciousness and whether those with a traumatic brain injury did better than those with a non-traumatic brain injury. METHOD: Twenty four prolonged disorder of consciousness patients who were prescribed Modafinil, were assessed at least four times both before and during treatment. The Coma Recovery Scale-Revised was used to determine if patients had a disorder of consciousness and the Wessex Head Injury Matrix was used to monitor behavior during baseline and treatment periods. Patients with a traumatic brain injury (N = 12) were compared with those with non-traumatic brain injury (N = 12). A chi-square test with significance at 0.05 was used and when frequencies were below 5 a Fisher's Exact Test was used. RESULTS: Cognitive improvements were noted in domains of wakefulness, awareness, concentration, tracking and following commands. Significant differences were found for the whole group between baseline and Modafinil (x2 = 9.80; p = 0.002). Eleven of the 12 traumatic brain injury patients had higher Wessex Head Injury Matrix scores when on Modafinil (x2 = 8.33, p < 0.004). Six non-traumatic brain injury patients had higher scores with Modafinil, two had lower scores and four showed no change. There was no significant difference in the number of patients showing an increase compared to those showing a decrease (Fisher's exact test p = 0.29). CONCLUSION: Modafinil appears to be beneficial for enhancing cognition in prolonged disorder of consciousness patients. Traumatic brain injury patients benefited more than non-traumatic brain injury patients. Implications for Rehabilitation People with prolonged disorders of consciousness are those in coma, a vegetative state or a minimally conscious state. Sensorimotor and neuromodulations (pharmacological and brain stimulation) are the available treatment strategies to this group. Modafinil promotes attention, concentration and maintains wakefulness in a patient with narcolepsy, obstructive sleep apnea and shift work sleep disorders. In a relatively small sample, this retrospective pilot study shows the effectiveness of Modafinil in conjunction with good care, suitable medications and multidisciplinary rehabilitation in enhancing arousal in prolonged disorders of consciousness patients.

Influence of intrathecal baclofen on the level of consciousness and mental functions after extremely severe traumatic brain injury: brief report.

BACKGROUND: Whenever oral treatment or botulinum toxin injections fail to control severe spasticity, a trial with intrathecal baclofen is recommended no earlier than 1 year after brain injury. When irreversible contractures are to be avoided, such a trial might be done earlier. Some have briefly reported cognitive modifications with this treatment. METHODS: During the trial period, intrathecal baclofen is continuously infused by a portable external pump through an intrathecal catheter. The daily dose is adjusted according to the clinical response. If the expected response is obtained by reduction of spasticity, a programmable pump is then implanted. Throughout the procedure, close neuropsychological follow-up is pursued. RESULTS: Two persons with extremely severe brain injury and spasticity received a programmable pump less than 10 months after trauma. Unexpectedly, one emerged from the minimally conscious state and the other from post-traumatic amnesia. CONCLUSIONS: Intrathecal baclofen should be considered within the first year after brain injury whenever spasticity does not respond to medication. ITB lessens the degree of spasticity which in turn facilitates care and, thus, has the potential to limit contractures. After severe brain injury, this treatment might trigger recovery from altered states of consciousness, improve cognition and facilitate rehabilitation.

A case of post-traumatic minimally conscious state reversed by midazolam: Clinical aspects and neurophysiological correlates.

PURPOSE: We describe the case of a subject in a post-traumatic Minimally Conscious State (MCS) who retrieved full interaction with the environment after midazolam infusion. We studied EEG correlates of the "awakening reaction" in the different domains of frequency, time and cortical topography, along with the intrinsic connectivity within both the task-positive and the linguistic network. METHODS: EEG recorded before and after midazolam administration has been submitted to spectral power analysis, sLORETA analysis and intrinsic connectivity analysis within both functional networks. RESULTS: A critical change in the power spectrum profile was observed after midazolam: a) the power between 1 and 12 Hz decreased, reaching its maximum difference with respect to pre-infusion at about 7 Hz and b) the power between 12 and 30 Hz increased, with a maximum difference at about 15 Hz. At the same time, midazolam induced significant connectivity changes, especially for these two frequency bands, within both functional networks. CONCLUSIONS: We advance some hypotheses about certain aspects of the recovery from the MCS both in terms of anatomo-functional correlations and functional brain systems and we make inferences about the role that some kind of 'catatonic' symptoms might play in determining and/or maintaining this peculiar clinical state.

[Vegetative state treated with acupoint injection combined with plum-blossom needle in children: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy difference on vegetative state in children between acupoint injection combined with plum-blossom needle and western medication based on basic treatment. METHODS: Forty-eight children of vegetative state were randomized into an observation group and a control group, 24 cases in each one. On the basis of the treatment of transcranial magnetic stimulation apparatus, balancing treatment apparatus and massage, the acupoint injection and tapping method with plum-blossom needle were adopted in the observation group, in which Xingnaojing injection, mouse nerve growth factor (mNGF) injection, monosialotetrahexosylganglioside sodium injection (MSI), compound Danshen injection were divided in 6 pairs and were injected respectively in Baihui (GV 20), Yongquan (KI 1), Fengfu (GV 16), Yamen (GV 15) and the others, 0.5 mL in each acupoint, once a day for continuous 10 days. Additionally, the tapping method with plum-blossom needle was used on the Governor Vessel and Jiaji (EX-B 2) on the back. In the control group, the intravenous infusion was adopted with citicoline sodium injection, mannitol injection and dexamethasone injection. The treatment was given once a day, 20 days of treatment made one session and totally 3 sessions were required in the two groups. The clinical efficacy, the vegetative state score and the mean curing time were observed after 20 days, 40 days and 60 days of treatment between the two groups. RESULTS: The effective rates were 58.3% (14/24), 70.8% (17/24) and 79.2% (19/24) in 20 days, 40 days and 60 days of treatment in the observation group and 20.8% (5/24), 45.8% (11/24) and 58.3% (14/24) in the control group respectively. The efficacy in the observation group was superior to those in the control group (P < 0.01, P < 0.05). The vegetative state score was improved apparently after 20 days, 40 days and 60 days of treatment as compared with those before treatment separately (all P < 0.05). It was improved obviously at the each time point after treatment in the observation group as compared with that in the control group (3.34 +/- 2.41 vs 2.64 +/- 11.56, 6.20 +/- 1.46 vs 4.34 +/- 1.64, 11.26 +/- 2.63 vs 8.75 +/- 2.18, all P < 0.05). The mean curing time was (45.67 +/- 16.24) days in the observation group, which was shorter apparently than that of (55.34 +/- 4.57) days in the control group (P < 0.05). CONCLUSION: Based on basic treatment acupoint injection combined with tapping method of plum-blossom needle achieve the reliable efficacy on vegetative state in children.

Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation?

Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.

Posttraumatic parkinsonism.

Amantadine hydrochloride is one of the most commonly used drugs in the pharmacotherapeutic treatment of disorders of consciousness (DOCs) following traumatic brain injury (TBI). Indeed, its actions as a pro-dopaminergic drug and as an N-methyl-D-aspartate antagonist makes amantadine an interesting candidate to improve consciousness and responsiveness in individuals with DOC, including vegetative state and minimally conscious state. Giacino et al (N Engl J Med. 2012;366(9):819-826) recently reported that amantadine was able to accelerate the functional recovery course of subjects after TBI with DOC, during a 4-week treatment period. Some patients with DOC following severe TBI have been reported to have parkinsonian symptoms. Severe TBI and posttraumatic parkinsonism may share a common midbrain network dysfunction. In fact, both vegetative state and minimally conscious state following severe TBI can include features of akinetic mutism and parkinsonism. Responsiveness to pro-dopaminergic agents in some patients and to deep brain stimulation in others, might depend, respectively, on the integrity, or lack thereof, of the dopaminergic postsynaptic receptors. We are of the strong opinion that more attention should be given to parkinsonian findings in persons with DOC after severe TBI and would advocate for multicenter, randomized, controlled trials to assess risk factors for parkinsonism following severe TBI.