Single unit activities recorded in the thalamus and the overlying parietal cortex of subjects affected by disorders of consciousness.

The lack of direct neurophysiological recordings from the thalamus and the cortex hampers our understanding of vegetative state/unresponsive wakefulness syndrome and minimally conscious state in humans. We obtained microelectrode recordings from the thalami and the homolateral parietal cortex of two vegetative state/unresponsive wakefulness syndrome and one minimally conscious state patients during surgery for implantation of electrodes in both thalami for chronic deep brain stimulation. We found that activity of the thalamo-cortical networks differed among the two conditions. There were half the number of active neurons in the thalami of patients in vegetative state/unresponsive wakefulness syndrome than in minimally conscious state. Coupling of thalamic neuron discharge with EEG phases also differed in the two conditions and thalamo-cortical cross-frequency coupling was limited to the minimally conscious state patient. When consciousness is physiologically or pharmacologically reversibly suspended there is a significant increase in bursting activity of the thalamic neurons. By contrast, in the thalami of our patients in both conditions fewer than 17% of the recorded neurons showed bursting activity. This indicates that these conditions differ from physiological suspension of consciousness and that increased thalamic inhibition is not prominent. Our findings, albeit obtained in a limited number of patients, unveil the neurophysiology of these conditions at single unit resolution and might be relevant for inspiring novel therapeutic options.

Personalized objects can optimize the diagnosis of EMCS in the assessment of functional object use in the CRS-R: a double blind, randomized clinical trial.

BACKGROUND: Behavioral assessment has been acted as the gold standard for the diagnosis of disorders of consciousness (DOC) patients. The item "Functional Object Use" in the motor function sub-scale in the Coma Recovery Scale-Revised (CRS-R) is a key item in differentiating between minimally conscious state (MCS) and emergence from MCS (EMCS). However, previous studies suggested that certain specific stimuli, especially something self-relevant can affect DOC patients' scores of behavioral assessment scale. So, we attempted to find out if personalized objects can improve the diagnosis of EMCS in the assessment of Functional Object Use by comparing the use of patients' favorite objects and other common objects in MCS patients. METHODS: Twenty-one post-comatose patients diagnosed as MCS were prospectively included. The item "Functional Object Use" was assessed by using personalized objects (e.g., cigarette, paper) and non-personalized objects, which were presented in a random order. The rest assessments were performed following the standard protocol of the CRS-R. The differences between functional uses of the two types of objects were analyzed by the McNemar test. RESULTS: The incidence of Functional Object Use was significantly higher using personalized objects than non-personalized objects in the CRS-R. Five out of the 21 MCS studied patients, who were assessed with non-personalized objects, were re-diagnosed as EMCS with personalized objects (χ2 = 5, df = 1, p < 0.05). CONCLUSIONS: Personalized objects employed here seem to be more effective to elicit patients' responses as compared to non-personalized objects during the assessment of Functional Object Use in DOC patients. TRIAL REGISTRATION: Clinical Trials.gov: NCT02988206 ; Date of registration: 2016/12/12.

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.

Predicting long-term neurological outcomes after severe traumatic brain injury requiring decompressive craniectomy: A comparison of the CRASH and IMPACT prognostic models.

BACKGROUND: Predicting long-term neurological outcomes after severe traumatic brain (TBI) is important, but which prognostic model in the context of decompressive craniectomy has the best performance remains uncertain. METHODS: This prospective observational cohort study included all patients who had severe TBI requiring decompressive craniectomy between 2004 and 2014, in the two neurosurgical centres in Perth, Western Australia. Severe disability, vegetative state, or death were defined as unfavourable neurological outcomes. Area under the receiver-operating-characteristic curve (AUROC) and slope and intercept of the calibration curve were used to assess discrimination and calibration of the CRASH (Corticosteroid-Randomisation-After-Significant-Head injury) and IMPACT (International-Mission-For-Prognosis-And-Clinical-Trial) models, respectively. RESULTS: Of the 319 patients included in the study, 119 (37%) had unfavourable neurological outcomes at 18-month after decompressive craniectomy for severe TBI. Both CRASH (AUROC 0.86, 95% confidence interval 0.81-0.90) and IMPACT full-model (AUROC 0.85, 95% CI 0.80-0.89) were similar in discriminating between favourable and unfavourable neurological outcome at 18-month after surgery (p=0.690 for the difference in AUROC derived from the two models). Although both models tended to over-predict the risks of long-term unfavourable outcome, the IMPACT model had a slightly better calibration than the CRASH model (intercept of the calibration curve=-4.1 vs. -5.7, and log likelihoods -159 vs. -360, respectively), especially when the predicted risks of unfavourable outcome were <80%. CONCLUSIONS: Both CRASH and IMPACT prognostic models were good in discriminating between favourable and unfavourable long-term neurological outcome for patients with severe TBI requiring decompressive craniectomy, but the calibration of the IMPACT full-model was better than the CRASH model.

Symptomatic treatment of unresponsive wakefulness syndrome with transcranially focused extracorporeal shock waves.

OBJECTIVE: Can stimulation of nerve growth factors by focused transcranial extracorporeal shock wave therapy (TESWT) be made effective for persons within unresponsive wakefulness syndrome (apallic syndrome)? DESIGN: Between eight and 18 years after the brain lesion, five patients with unresponsive wakefulness syndrome of differing severity received TESWT with the device Duolith (Storz Medical) during four-week physicomedical complex therapies. In the previous years they had been treated with the same complex therapies without TESWT. The vigilance did not change. RESULTS: After two-four years and an average of 5.2 treatment series, the patients' abilities improved by 135.9% on the German Coma Remission Scale (KRS) and by 43.6% on the Glasgow Coma Scale. In the motor area of the KRS, the patients improved by 64.3%. Three PEG feeding tubes could be removed, nonverbal communication initiated four times. CONCLUSION: In this longitudinal observation study, focused TESWT stimulated vigilance in patients with unresponsive wakefulness syndrome. The precise neurophysiological effects remain to be verified by a study of the clinical results.

Brainstem neurons survive the identical ischemic stress that kills higher neurons: insight to the persistent vegetative state.

Global ischemia caused by heart attack, pulmonary failure, near-drowning or traumatic brain injury often damages the higher brain but not the brainstem, leading to a 'persistent vegetative state' where the patient is awake but not aware. Approximately 30,000 U.S. patients are held captive in this condition but not a single research study has addressed how the lower brain is preferentially protected in these people. In the higher brain, ischemia elicits a profound anoxic depolarization (AD) causing neuronal dysfunction and vasoconstriction within minutes. Might brainstem nuclei generate less damaging AD and so be more resilient? Here we compared resistance to acute injury induced from simulated ischemia by 'higher' hippocampal and striatal neurons versus brainstem neurons in live slices from rat and mouse. Light transmittance (LT) imaging in response to 10 minutes of oxygen/glucose deprivation (OGD) revealed immediate and acutely damaging AD propagating through gray matter of neocortex, hippocampus, striatum, thalamus and cerebellar cortex. In adjacent brainstem nuclei, OGD-evoked AD caused little tissue injury. Whole-cell patch recordings from hippocampal and striatal neurons under OGD revealed sudden membrane potential loss that did not recover. In contrast brainstem neurons from locus ceruleus and mesencephalic nucleus as well as from sensory and motor nuclei only slowly depolarized and then repolarized post-OGD. Two-photon microscopy confirmed non-recoverable swelling and dendritic beading of hippocampal neurons during OGD, while mesencephalic neurons in midbrain appeared uninjured. All of the above responses were mimicked by bath exposure to 100 µM ouabain which inhibits the Na+/K+ pump or to 1-10 nM palytoxin which converts the pump into an open cationic channel. Therefore during ischemia the Na+/K+ pump of higher neurons fails quickly and extensively compared to naturally resilient hypothalamic and brainstem neurons. The selective survival of lower brain regions that maintain vital functions will support the persistent vegetative state.

Resgate biográfico como estratégia de assistência a pacientes com condições neurológicas muito graves / Biographic Rescue as a strategy to assist patients with severe neurological conditions

Este artigo é um relato de experiência, apresentando uma prática de Terapia Ocupacional junto a pacientes comcondições neurológicas muito graves, pautada no resgate biográfico destes sujeitos, utilizando-se do diário de campo da primeira autora. Tem como referencial norteador o Cuidado,entendido como a designação da atenção à saúde interessada no sentido existencial da experiência do adoecimento. Busca-se o resgate da subjetividade destas pessoas, compreendida como o modo de organizar as diferentes experiências, a partir e com relação à atribuição de significado par a o seu cotidiano. A população assistida nesta experiência refere-se àquelas que sofreram umaperda muito grande de sua funcionalidade (motora e cognitiva), apartir de acometimentos neurológicos, especialmente pessoas em estado vegetativo persistente e em estado mínimo de consciência. Memória, história, identidade, dignidade, subjetividade especificam a prática do terapeuta ocupacional, independentemente das reações neurológicas apresentadas, como alguém que ajuda reconstruir os sentidos e significados do cotidiano do paciente em condição de tão severa incapacidade.

This article aims to describe an occupational therapy intervention for patients with severe neurological conditions, based on biographical rescue. It was used records and fi eld diaries of the first author. The concept of Comprehensive Care is the mainreference, designed as care interested in the existential sense of the illness process. It seeks to rescue the subjectivity of these people, understood as a way of organizing all the different experiences in life, from their relations with meaning. The assisted populationrefers to those who have suffered great loss of its functionality (motor and cognitive), from neurological affections, especially persons in a persistent vegetative state and minimally conscious state. Memory, history, identity, dignity, subjectivity specify thepractice of occupational therapist, regardless of neurological reactions presented by the patients, as someone who helps reconstruct the meanings of the daily life of person with so severedisability.

Zolpidem arouses patients in vegetative state after brain injury: quantitative evaluation and indications.

BACKGROUND: To investigate the efficacy and indications of zolpidem, a nonbenzodiazepine hypnotic, inducing arousal in vegetative state patients after brain injury. METHODS: One hundred sixty-five patients were divided into 4 groups, according to area of brain damage and injury mechanism. All patients' brains were imaged by Tc-ECD single-photon emission computerized tomography (SPECT), before and 1 hour after treatment with 10 mg of zolpidem. Simultaneously, 3 quantitative indicators of brain function and damage were obtained using cerebral state monitor. Thirty-eight patients withdrew from the study after the first zolpidem dose. The remaining 127 patients received a daily dose of 10 mg of zolpidem for 1 week and were monitored again at the end of this week. RESULTS: One hour after treatment with zolpidem, cerebral state index was increased and burst suppression reduced in both brain contrecoup contusion and space-occupying brain compression groups (P < 0.05). SPECT showed, 1 hour after medication, that cerebral perfusion was improved in both brain contrecoup contusion and space-occupying brain compression groups, but no changes were seen in primary and secondary brain stem injury groups. In the 127 patients' group, after 1 week of zolpidem treatment, all parameters obtained from cerebral state monitor were not statistically different compared with those after the initial medication (P > 0.05). CONCLUSIONS: Zolpidem is an effective medicine to restore brain function in patients in vegetative state after brain injury, especially for those whose brain injuries are mainly in non-brain-stem areas. Improvement of brain function is sudden rather than gradual.

Bedside assessment of residual functional activation in minimally conscious state using NIRS and general linear models.

Near Infrared Spectroscopy (NIRS) was employed for the detection of possible residual functional activations in two patients in minimally conscious state. An "ad hoc" protocol for somatosensory and motor stimulations was created and administered to the patients, synchronously to NIRS recordings. One healthy subject was also assessed with the same task for comparison. Results from the healthy subject globally agree with the literature. Moreover, we could obtain significant results from the patients data. Indeed, in one patient, the NIRS channels showing activation completely correspond to regions of residual cortex underneath. In the second patient, though, together with possible residual intact cortex insulae, some channels match large cystic formations, with fluid gathering.

Neuromodulation of vegetative state through spinal cord stimulation: where are we now and where are we going?

BACKGROUND: Vegetative state (VS) is a complex condition that represents a challenging frontier for medicine and neuroscience research. Nowadays there is no scientifically validated treatment for VS patients, and their chronic long-term assistance is very demanding for healthcare systems worldwide. OBJECTIVES: The present paper is a systematic review of the role of spinal cord stimulation (SCS) as a treatment of patients with VS. METHODS: Published literature on this topic was analyzed systematically. Clinical and epidemiological characteristics of VS, present therapeutic options and social costs of VS were also evaluated. RESULTS: Only 10 papers have been published since 1988, and overall 308 VS patients have been treated with SCS worldwide; 51.6% displayed a clinical improvement and an amelioration of the environmental interaction. These effects are probably mediated by the stimulation of the reticular formation-thalamus-cortex pathway and by cerebral blood flow augmentation induced by SCS. CONCLUSIONS: The experience on this topic is still very limited, and on this basis it is still hard to make any rigorous assessment. However, the most recent experiments represent significant progress in the research on this topic and display SCS as a possible therapeutic tool in the treatment of VS.

The vegetative state--a syndrome in search of a name.

In 2002, Bryan Jennett chose the caption "A syndrome in search of a name" for the first chapter of his book "The vegetative state--medical facts, ethical and legal dilemmas", which, in summary, can be taken as his legacy. Jennett coined the term "VegetativeState" (VS), which became the preferential name for the syndrome of wakeful unresponsiveness in the English literature, with the intention to specify the concern and dilemmas in connection with the naming "vegetative", "persistent" and "permanent". In Europe, Apallic Syndrome (AS) is still in use. The prevalence of VS/AS in hospital settings in Europe is 0.5-2/100.000 population year; one-third traumatic brain damage, 70% following intracranial haemorrhages, tumours, cerebral hypoxemia after cardiac arrest, and end stage of certain progressive neurological diseases. VS/AS reflects brain pathology of (a) consciousness, self-awareness, (b) behaviour, and (c) certain brain structures, so that patients are awake but total unresponsive. The ambiguity of the naming "vegetative" (meant to refer to the preserved vegetative (autonomous nervous system) can suggest that the patient is no more a human but "vegetable" like. And "apallic" does not mean being definitively and completely anatomically disconnected from neocortical structures. In 2009, having joined the International Task Force on the Vegetative State, we proposed the new term "Unresponsive Wakefulness Syndrome" (UWS) to enable (neuro-)scientists, the medical community, and the public to assess and define all stages accurately in a human way. The Unresponsive Wakefulness Syndrome (UWS) could replace the VS/AS nomenclature in science and public with social competence.

Prediction of minimally conscious state with somatosensory evoked potentials in long-term unconscious patients after traumatic brain injury.

BACKGROUND: To evaluate the predictive power of somatosensory evoked potentials (SEPs) for minimally conscious state (MCS) in long-term unconscious patients after traumatic brain injury (TBI). METHODS: SEPs were recorded in 58 patients with duration of unconsciousness >30 days after TBI. SEPs were classified into three grades. Predictors including age, sex, Glasgow Coma Scale (GCS), and cause of injury were also analyzed, respectively. The outcome was divided into two groups including unconscious group and MCS group. The outcome was assessed at 12 months after TBI. RESULTS: In 58 patients, 22 of 58 were minimally conscious, 3 of 58 dead, and 33 of 57 were still in vegetative state at 12 months after TBI. SEPs grade (p = 0.001) and GCS (p = 0.010) were significantly associated with the outcome. The area under the receiver operator characteristic curve of SEPs was 0.891 ± 0.048 (p < 0.001; 95% confidence interval, 0.798-0.984) for predicting outcome, and of GCS score was only 0.746 ± 0.066 (p = 0.002; 95% confidence interval, 0.616-0.876). The accuracy of the whole model for predicting unconscious and MCS was 91.7% and 86.4%, respectively. The overall correct prediction was as high as 89.7% (p < 0.001). CONCLUSIONS: SEPs are excellent in predicting the outcome of long-term unconscious patients after TBI. SEPs should be considered more often and more routinely used after TBI.

Predict recovery of consciousness in post-acute severe brain injury: the role of EEG reactivity.

OBJECTIVE: This study tested the hypothesis of electroencephalographic reactivity (EEG-R) as a reliable tool for the prognostic evaluation of consciousness recovery in post-acute brain injury. METHODS: EEG was recorded in 50 unconscious patients. All patients had a GCS ≤8 and LCF score ≤2. They suffered from traumatic brain injury, cerebrovascular disease or anoxia. EEG was classified according to Synek classification (1988) as benign, malignant and 'uncertain significance'. EEG-R to painful stimuli was tested. RESULTS: Twenty per cent of patients fulfilled the criteria for benign prognosis, 38% for malignant prognosis, while 42% of them were included in the 'uncertain' category, preventing them from stating a prognosis. EEG-R was detected in 48% of patients classified 'uncertain' and 92% of them recovered consciousness within 5 months from EEG recording. Multivariable analysis indicates that an unconscious patient admitted to the Rehabilitation Unit within 2 months from brain injury, with a LCF score equal to 2 and the presence of EEG-R has a probability of recovery of consciousness higher than 97%. CONCLUSION: EEG-R is a good positive factor for the prognosis of recovery of consciousness in the post-acute phase of brain injury, with a high specificity (88.9%). Nevertheless, its absence is not invariably associated with a poor prognosis.

Post-coma persons with extensive multiple disabilities use microswitch technology to access selected stimulus events or operate a radio device.

The present two studies extended research evidence on the use of microswitch technology by post-coma persons with multiple disabilities. Specifically, Study I examined whether three adults with a diagnosis of minimally conscious state and multiple disabilities could use microswitches as tools to access brief, selected stimulus events. Study II assessed whether an adult, who had emerged from a minimally conscious state but was affected by multiple disabilities, could manage the use of a radio device via a microswitch-aided program. Results showed that the participants of Study I had a significant increase of microswitch responding during the intervention phases. The participant of Study II learned to change radio stations and seemed to spend different amounts of session time on the different stations available (suggesting preferences among the programs characterizing them). The importance of microswitch technology for assisting post-coma persons with multiple disabilities to positively engage with their environment was discussed.

Cerebral vasculopathy after 4-bromo-2,5-dimethoxyphenethylamine ingestion.

BACKGROUND: 4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a designer-drug variant of 3,4-methylenedioxymethamphetamine (ecstasy) whose recreational use has increased significantly over the last 10 years. Neurologic consequences of 2C-B usage are currently unknown. CASE REPORT: A 43-year-old woman experienced severe headaches within 48 hours of taking liquid 2C-B, after which time she developed progressive encephalopathy and quadraparesis, which did not improve over several months. MRA and cerebral angiogram imaging demonstrated profound vascular abnormalities of large, medium, and small-caliber vessels with subsequent watershed infarction. Brain biopsy and cerebrospinal fluid studies ruled out an inflammatory process. CONCLUSIONS: This case demonstrates an idiosyncratic and devastating neurologic response to 2C-B, a recreational drug whose popularity has increased with widespread availability of online guides for its synthesis.

A clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and outcome after cardiac arrest.

BACKGROUND: Anoxic coma following cardiac arrest is a common problem with ethical, social, and legal consequences. Except for unfavorable somatosensory-evoked potentials (SSEP) results, predictors of unfavorable outcome with a 100% specificity and a high sensitivity are lacking. The aim of the current research was to construct a clinical and EEG scoring system that predicts early cortical response (N20) to somatosensory evoked potentials and 6-months outcome in comatose patients after cardiac arrest. METHODS: We retrospectively reviewed the records of all consecutive patients who suffered cardiac arrest outside our hospital and were subsequently admitted to our facility from November 2002 to July 2006. We scored each case based on early clinical and EEG factors associated with unfavorable SSEPs, and we assessed the ability of this score to predict SSEP results and outcome. RESULTS: Sixty-six patients qualified for inclusion in the cohort. Among them, 34 (52%) had unfavorable SSEP results. At day three, factors independently associated with unfavorable SSEPs were: absence of corneal (14 points) and pupillary (21 points) reflexes, myoclonus (25 points), extensor or absent motor response to painful stimulation (28 points), and malignant EEG (11 points). A score >40 points had a sensitivity of 85%, a specificity of 84%, and a positive predictive value (PPV) of 85% to predict unfavorable SSEP results. A score >88 points had a PPV of 100%, but a sensitivity of 18%. Overall, this score had an area under ROC curves of 0.919. In addition, at day three, a score > 69 points had a PPV of 100% with a sensitivity of 32% to predict death or vegetative state. CONCLUSION: A scoring system based on a combination of clinical and EEG findings can predict the absence of early cortical response to SSEPs. In settings without access to SSEPs, this score may help decision-making in a subset of comatose survivors after a cardiac arrest.

Indication of peripheral nerve hyperexcitability in adult-onset subacute sclerosing panencephalitis (SSPE).

Subacute sclerosing panencephalitis (SSPE) is a rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection of immune-resistant measles virus. Diagnostic hallmarks include widespread cortical dysfunction on EEG, myoclonus, white matter abnormalities on neuroradiological examination and the presence of IgG anti-measles antibodies in the cerebrospinal fluid. We present the first case of SSPE with signs of peripheral nerve hyperexcitability, observed as extra discharges following the compound motor action potential at motor nerve stimulation. In addition we demonstrate the importance of SSPE in the differential diagnosis of adult patients with psychiatric and neurological symptoms.

Cranioplasty of large cranial defect at an early stage after decompressive craniectomy performed for severe head trauma.

Large cranial defects resulting from decompressive craniectomy performed for refractory intracranial hypertension after head trauma is one of the indications for cranioplasty, and this procedure is commonly performed 3 months after craniectomy. However, the large cranial defect would lead to the kinds of complications early during the phase of these patients' recovery, which would go against rehabilitation. This study retrospectively reviewed 23 patients undergoing early cranioplasty (5-8 weeks after craniectomy) in the last 4 years with a detailed choice of patients, outcome of complications after head trauma and large craniectomy, as well as assessment of prognosis. The early outcome (1 month later) revealed most of the patients who had conscious disturbance before the cranioplasty recovered their consciousness and presented an improved neurologic function. The long-dated prognosis (18 months later) revealed that 17 patients were good (independent patients) in this series (74%), whereas four patients survived with a severe disability (17%) and two remained in a vegetative state (9%). No dead patients or intracranial infection after the procedure were found in this study. Most patients' complications were relieved after the cranioplasty with improvements of symptoms or image of computed tomography scan. In conclusion, we consider that with the appropriate choice of patients and materials, early cranioplasty for large cranial defects after decompressive craniectomy would be safe and helpful for the improvement of patients' neurologic function and prognosis. To our knowledge, this series may be the first detailed report in English about early cranioplasty after decompressive craniectomy. We are going to perform prospective and retrospective contrastive studies to further confirm the effects of this procedure on the patients with large cranial defects after decompressive craniectomy.

Persistent but reversible coma in encephalitis.

INTRODUCTION: Nontraumatic coma in adults has a poor prognosis, and late recovery of consciousness is unlikely. Functional recovery is usually extremely poor. However, a few nontraumatic comatose patients have shown late recovery of both awareness and function. METHODS: A retrospective survey was conducted by reviewing the medical records of all inpatients to our department during the 1990s. Patients with persistent but reversible nontraumatic coma were identified according to the following criteria: (a) deep coma with a Glasgow Coma Scale (GCS) score of 7 or less on admission; (b) nontraumatic cause; (c) persistence of unconsciousness for longer than 1 month; and (d) subsequent recovery of GCS (total) to normal. The clinical spectrum of patients meeting these criteria was evaluated. RESULTS: Six patients (ages 16-75 years) met the criteria. Viral encephalitis was diagnosed in five (two with herpes simplex virus, two with cytomegalovirus, and one with Epstein-Barr virus or cytomegalovirus). Two young female patients with encephalitis manifested extremely protracted coma persisting for 3 and 18 months, respectively. Complications included nonconvulsive status epilepticus in two patients and relative overdose of clonazepam in one patient. CONCLUSION: Recognition of the clinical spectrum of persistent but reversible nontraumatic coma is important.