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Intracranial hematomas (IHs) occur commonly after severe traumatic brain injury, but their effects on outcomes in patients with prolonged disorders of consciousness (DoC) following coma (i.e., unresponsive wakefulness syndrome and minimally conscious state) are unknown.In this multicenter longitudinal study, we compared clinical outcomes and serum neurofilament light chain (NFL) levels of 52 patients with traumatic DoC with (n = 35) and without (n = 17) IH in the acute phase. Patients were evaluated with the Coma Recovery Scale-Revised (CRS-R) at enrollment (1-3 months post-injury) and with the CRS-R, extended Glasgow Outcome Scale (GOSE), and Functional Independence Measure (FIM) at 6 months post-injury. At the same timepoints, serum NFL levels were compared between patients with and without IHs and with those of 52 sex- and age-matched healthy controls.Patients with and without IH did not differ in terms of DoC or CRS-R scores at admission, or clinical outcomes (death, unresponsive wakefulness syndrome, minimally conscious state, or emergence from minimally conscious state) or CRS-R, GOSE, or FIM scores 6 months post-injury. NFL levels were significantly higher in patients than in controls at admission and 6 months post-injury (both p 0.0001), but they did not differ between patients with and without IH.This study showed that IHs do not affect clinical outcomes or markers of axonal degeneration in patients with traumatic DoC.

The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67 years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* 20 ms). During a mean follow-up of 63.01 ± 24.95 months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88; p = 0.025) and right ventricular (RV) mass index (HR = 1.09; p = 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction 58.9% and an RV mass index 31 g/m

Growing evidence suggests that pathophysiological mechanisms leading to neurodegeneration and neuronal loss take place during the chronic phase of a severe traumatic brain injury (TBI). In this study we evaluated a well-established marker of brain injury, the neuron-specific enolase (NSE), in the serum of 51 patients with severe TBI (86% males, mean age 33.8 ± 11.1 years). All patients' samples were available from a previous study and the mean time between TBI and blood sample collection was 23.2 ± 31.5 months (28 patients were evaluated within 12 months of TBI and 23 patients were evaluated ≥12 months after TBI). Patients' NSE levels were compared with those obtained from 30 age and sex-matched healthy controls (87% males, 33.7 ± 11.3 years). We found that NSE levels were significantly lower in patients (median 3.2 ng/mL; 25th, 75th percentile 2.5, 5.1) than in healthy controls (median 4.1 ng/mL; 25th, 75th percentile 3.1, 7.5) (

Disorders of consciousness (DOCs), i.e., coma, vegetative state, and minimally conscious state are the consequences of a severe brain injury that disrupts the brain ability to generate consciousness. Recovery from DOCs requires functional and structural changes in the brain. The sites where these plastic changes take place vary according to the pathophysiology of the DOC. The ascending reticular activating system of the brainstem and its complex connections with the thalamus and cortex are involved in the pathophysiology of coma. Subcortical structures, such as the striatum and globus pallidus, together with thalamocortical and corticothalamic projections, the basal forebrain, and several networks among different cortical areas are probably involved in vegetative and minimally conscious states. Some mechanisms of plasticity that allegedly operate in each of these sites to promote recovery of consciousness will be discussed in this chapter. While some mechanisms of plasticity work at a local level, others produce functional changes in complex neuronal networks, for example by entraining neuronal oscillations. The specific mechanisms of brain plasticity represent potential targets for future treatments aiming to restore consciousness in patients with severe DOCs.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Background and purpose. Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Since an accurate prognosis is essential for decision-making on patients’ management, we analysed data from an international multicentre prospective cohort study to evaluate two-year mortality rate and bedside predictors of mortality. Methods. We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and non-traumatic brain injury within 3 months post-injury. At enrolment we collected demographic (age; sex), anamnestic (etiology; time post-injury), clinical (Coma Recovery Scale Revised, CRS-R; Disability Rating Scale; Nociception Coma Scale-Revised) and neurophysiologic (EEG; somatosensory evoked and event-related potentials) data. Patients were followed-up to gather data on mortality up to 24 months post- injury. Results. Among 143 traumatic (n=55) and non-traumatic (n=88) patients (VS/UWS=68, 19 females; MCS=75, 22 females), 41 (28.7%) died within 24 months post-injury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p Conclusions. This study demonstrated that a feasible multimodal assessment in the post-acute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients’ families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL, both p &lt, 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

The sinking skin flap syndrome (SSFS), or syndrome of the trephined, is a pathological condition arising from the presence of large bone defects of the skull. Originally described by Grant and Norcross in patients with a skin flap depression following craniectomy [1], SSFS has a multifaceted clinical presentation, including chronic fatigue, headache, dizziness, impaired vigilance, motor deficits, cognitive deficits, epileptic seizures, and visual symptoms [2]. SSFS pathophysiology is related to the atmospheric pressure exerted on the brain through the craniectomy, inducing brain compression, changes in the cerebrospinal fluid (CSF) dynamics, impaired venous return, and decrease in the regional blood flow, alone or in combination [2]. In this report we describe a case of SSFS complicated by paradoxical uncal herniation due to diuretic therapy.

INTRODUCTION/AIMS Neurophysiological patterns in patients with foodborne botulism are rarely described after the acute phase. We report data from a large Italian outbreak of botulism, with patients evaluated at different timepoints after poisoning. METHODS Eighteen male patients (mean age 47 ± 8.4 y) underwent 22 clinical and neurophysiological evaluations (4 patients were re-evaluated). The resting compound muscle action potential (CMAP) amplitude, postexercise CMAP amplitude, CMAP change after high-frequency (50 Hz) repetitive nerve stimulation (HFRNS), and motor unit action potentials (MUAPs) were assessed in the acute (4-8 days after poisoning; 5 patients), early post-acute (32-39 days after poisoning; 5 patients), and late post-acute (66-80 days after poisoning; 12 patients) phases. RESULTS In the acute, early post-acute, and late post-acute phases, respectively, reduced CMAP amplitudes were found in 100%, 20%, and 17% of patients; abnormal postexercise CMAP facilitation was observed in 100%, 40%, and 0% of patients; and pathological incremental responses to HFRNS were found in 80%, 50%, and 8% of patients. Baseline CMAP amplitudes, postexercise CMAP facilitation, and CMAP increases in response to HFRNS differed significantly between the acute and post-acute phases. Small MUAPs were found in 100% of patients in the acute and early post-acute phases and in 50% of patients in the late post-acute phase. DISCUSSION The neurophysiological findings of foodborne botulism vary considerably according to the evaluation time point. In the post-acute phase, different neurophysiological techniques must be applied to support a diagnosis of botulism.

Objective To prospectively investigate relationships of cortical somatosensory evoked potential (SEP) amplitudes with consciousness recovery and disability in the year following brain injury in patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Methods SEPs of 42 patients with VS/UWS were recorded 51.7 ± 23.3 days post-injury. N20–P25 amplitudes were compared between patients with and without consciousness recovery at 6 months and 1 year post-injury. Results SEPs were present in 21 patients and bilaterally absent in 21 patients. N20–P25 amplitudes were significantly higher in patients who recovered consciousness than in those who died or did not recover consciousness at 6 months (median, 4.6 vs. 1.9 μV; P = 0.004) and 1 year (median, 4.6 vs. 2.1 μV; P = 0.02) after injury. The lowest N20–P25 amplitude in a patient who recovered consciousness was 2.15 μV. N20–P25 amplitudes correlated significantly with Coma Recovery Scale-Revised and Disability Rating Scale scores at 6 months and 1 year post-injury (both P Conclusions In patients with VS/UWS, SEP amplitudes are related to consciousness recovery and disability at 6 months and 1 year post-injury. Significance The evaluation of SEP amplitudes can help to refine prognoses for patients with VS/UWS.

Highlights • Muscle weakness after COVID-19 can be caused by critical illness myopathy. • Critical illness myopathy should be suspected in patients with long ICU stay. • Health systems must plan access to rehabilitative facilities after COVID-19., We describe a patient who developed diffuse and symmetrical muscle weakness after a long stay in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). The patient underwent a neurophysiological protocol, including nerve conduction studies, concentric needle electromyography (EMG) of the proximal and distal muscles, and direct muscle stimulation (DMS). Nerve conduction studies showed normal sensory conduction and low-amplitude compound muscle action potentials (CMAPs). EMG revealed signs of myopathy, which were more pronounced in the lower limbs. The post-DMS CMAP was absent in the quadriceps and of reduced amplitude in the tibialis anterior muscle. Based on these clinical and neurophysiological findings, a diagnosis of critical illness myopathy was made according to the current diagnostic criteria. Given the large number of patients with COVID-19 who require long ICU stays, many of these patients are very likely to develop ICU-acquired weakness, as did the patient described here. Health systems must plan to provide adequate access to rehabilitative facilities for both pulmonary and motor rehabilitative treatment after COVID-19.

Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25th and 75th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25th and 75th percentiles, 2100 and 2875 pg/ml; p<0.001). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (p=0.5). Moreover, BDNF levels did not differ between patients with UWS and MCS (p=0.2), or between patients with traumatic and nontraumatic brain injuries (p=0.6). BDNF level correlated positively with the time since brain injury (p=0.025). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.

The aim of this study was to evaluate whether standardized responses to nociceptive pain, assessed with the revised Nociception Coma Scale (NCS-R), were correlated with the outcomes of patients with unresponsive wakefulness syndrome (UWS) 6 months after admission to a rehabilitation department. We recruited 24 consecutive patients with UWS. Patients’ consciousness levels were assessed with the revised Coma Recovery Scale (CRS-R) at admission and 6 months later, and their CRS-R scores were correlated with the NCS-R scores at admission. Ten of the 24 patients with UWS recovered consciousness after 6 months. The NCS-R score at admission was correlated with the CRS-R score at admission (P = 0.02), but not after 6 months (P = 0.6). Patients with and without consciousness improvement after 6 months showed no significant difference in the NCS-R total score and sub-scores at admission (P values > 0.05). In conclusion, the correlation between NCS-R and CRS-R scores at admission suggests that the standardized assessment of pain parallels patients’ levels of consciousness, and may be helpful in the clinical evaluation of patients with UWS. Pain response assessed with the NCS-R was not related to the 6-month outcomes of patients with UWS.

Introduction: Peripheral neuropathy can affect patients with heart failure, though its prevalence is unknown. After heart transplantation, it can influence the postoperative course and quality of life, but screening for neuromuscular disease is not routinely performed. Objective: The aim of this study was to identify the factors associated with neuropathy in a population of patients with heart failure who are candidates for heart transplantation. Study Design: Data regarding patients’ clinical history, including recent hospitalizations, were collected. All patients underwent a complete neurological examination and a neurophysiological protocol including nerve conduction studies and concentric needle electromyography. Results: Thirty-two patients were included in the study, and neuropathy was diagnosed in 10 (31.3%). Neuropathy was associated with the number of admissions ( P = .023; odds ratio [OR]: 1.96) and the total number of days of hospitalization in the year prior to inclusion in the study ( P = .010; OR: 1.03). The majority of hospitalizations occurred in the step-down unit (85%), with acute heart failure the leading cause of admission (42%). Conclusions: This study shows that neuropathy is frequent in patients with advanced heart failure and that hospitalization for cardiac care, also in the absence of intensive care, is a marker of high risk of neurologic damage. These data can help physicians in selecting and managing candidates for transplantation and can guide decisions on the best immunosuppressive regimen or rehabilitation strategy.

The mechanisms involved in secondary brain injury after the acute phase of severe traumatic brain injury (TBI) are largely unknown. Ongoing axonal degeneration, consequent to the initial trauma, may lead to secondary brain injury. To test this hypothesis, we evaluated the cerebrospinal fluid (CSF) level of neurofilament light chain (NF-L), a proposed marker of axonal degeneration, in 10 patients who developed a severe disorder of consciousness after a TBI, including 7 in a minimally conscious state and 3 with unresponsive wakefulness syndrome (time since brain injury, 309 ± 169 days). CSF NF-L level was measured with a commercially available NF-L enzyme-linked immunosorbent assay. CSF NF-L level was very high in all 10 patients, ranging from 2.4- to 60.5-fold the upper normal limit (median value, 4458 pg/mL; range, 695-23,000). Moreover, NF-L level was significantly higher after a severe TBI than in a reference group of 9 patients with probable Alzheimer's disease, a population with elevated levels of CSF NF-L attributed to neuronal degeneration (median value, 1173 pg/mL; range, 670-3643; p 0.01). CSF NF-L level was correlated with time post-TBI (p = 0.04). These results demonstrate prolonged secondary brain injury, suggesting that patients exhibit ongoing axonal degeneration up to 19 months after a severe TBI.

To identify changes in the standard electroencephalograms (EEGs) of patients with unresponsive wakefulness syndrome (UWS) who did or did not recover consciousness 6 months after admission to a rehabilitation department.Prospective cohort study.Unit for severe acquired brain injuries.Consecutive patients with UWS (N=28).Not applicable.EEG amplitude (reduced or normal), dominant frequency (alpha, theta, or delta), and reactivity (absent or present) were scored at admission and 6 months later. The cumulative Amplitude-Frequency-Reactivity score was evaluated. Clinical assessments were made using the Coma Recovery Scale-Revised.Sixteen (57.1%) of the 28 patients with UWS recovered consciousness after 6 months, while 12 patients (42.9%) did not recover consciousness. EEG improvements occurred in 14 patients with consciousness recovery (87.5%) and 2 patients without consciousness recovery (16.7%) only. Improvements in EEG dominant frequency (from the theta to the alpha band or from the delta to the theta band), reappearance of EEG reactivity, and Amplitude-Frequency-Reactivity score increase (P.01) differentiated patients with consciousness improvement from those without consciousness improvement. Six months after admission for rehabilitation, patients with EEG improvements showed higher Coma Recovery Scale-Revised scores than did those without EEG changes (P.01).Most patients who emerge from UWS demonstrate improvement in basic EEG characteristics over time. EEG changes in patients with UWS may aid in the timely recognition of patients transitioning into a minimally conscious state.

Acquired neuralgic amyotrophy, described for the first time by Parsonage and Turner, is a rare idiopathic disease that may occur in otherwise normal healthy individuals. It typically begins with sudden, unilateral shoulder pain that may also involve the neck and/or arm. Less frequently, the disease involves nerves other than those of the brachial plexus, such as phrenic nerves, resulting in dyspnoea. The diagnosis is based on the clinical presentation and is generally supported by electroneurography/electromyography. We report the case of a 45-year-old white man who was referred to our clinic for acute dyspnoea preceded by severe neck and right shoulder pain. Corticosteroid therapy ameliorated the clinical picture, but without a complete recovery. Keywords: Dyspnoea, Parsonage-turner syndrome, Neuralgic amyotrophy

It has been argued that complex subjective sense of self is linked to the brain default-mode network (DMN). Recent discovery of heterogeneity between distinct subnets (or operational modules - OMs) of the DMN leads to a reconceptualization of its role for the experiential sense of self. Considering the recent proposition that the frontal DMN OM is responsible for the first-person perspective and the sense of agency, while the posterior DMN OMs are linked to the continuity of ‘I’ experience (including autobiographical memories) through embodiment and localization within bodily space, we have tested in this study the hypothesis that heterogeneity in the operational synchrony strength within the frontal DMN OM among patients who are in a vegetative state (VS) could inform about a stable self-consciousness recovery later in the course of disease (up to six years post-injury). Using EEG operational synchrony analysis we have demonstrated that among the three OMs of the DMN only the frontal OM showed important heterogeneity in VS patients as a function of later stable clinical outcome. We also found that the frontal DMN OM was characterized by the process of active uncoupling (stronger in persistent VS) of operations performed by the involved neuronal assemblies.

Neuropathies may affect heart reinnervation and functional outcome after heart transplantation (HT). In this study, neurological evaluations, standard nerve conduction studies, and electromyography were performed in 32 HT candidates without a previous history of neuromuscular disorder. Ten patients underwent HT and were revaluated 3 months later. We found that before HT 10 (31.3%) patients had sensorimotor polyneuropathy (18.8%) or sensory polyneuropathy (12.5%). After HT, the percentage of patients with a neuromuscular disorder increased to 70%, most of them showing new or worsening neuropathies or neuromyopathies. The most sensitive abnormality that indicated neuromuscular involvement after HT was a reduction of the compound muscle action potential (CMAP) of the deep peroneal nerve. In conclusion, neuromuscular disorders are common in HT candidates, and they further increase in occurrence after HT. A reduction of the deep peroneal nerve CMAP amplitude after HT may help to identify patients who need a more detailed neurophysiological evaluation. The diagnosis of neuromuscular disorders before and after HT may contribute to the development of more accurate therapeutic and rehabilitative strategies for these patients.

Background: Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease (AD). Although the mechanisms that lead to AD after a TBI are unclear, we hypothesize that changes in amyloid-β (Aβ) metabolism and abnormal tau phosphorylation are reasonable candidates.Objective: To investigate Aβ and tau dynamics in the chronic phase of TBI.Methods: We evaluated Aβ1-42, total tau (t-tau), and phosphorylated tau (p-tau) levels in the cerebrospinal fluid (CSF) of 15 patients who developed a prolonged disorder of consciousness after a severe TBI (mean time from TBI 271.6 ± 176.5 days).Results: Reduced Aβ1-42 levels (median 258 pg/ml, range 90–833.6) were observed in 14/15 patients (93.3%) with severe post-TBI disorders of consciousness. These CSF analysis data did not correlate with time since TBI or with the patients’ level of consciousness as determined by the Coma Recovery Scale Revised. Normal t-tau levels (median 95.2 pg/ml, range 52–256.9) were found in all patients. Normal p-tau levels (...

Objective: Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage. Methods: a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain. Results: FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment. Conclusion: In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.

Diagnostic accuracy and reliable assessment of prognosis are challenging in patients in vegetative state (VS) and in minimally conscious state (MCS). This longitudinal multi-centric study aims to identify neurophysiological patterns with diagnostic and prognostic value. 59 patients in VS and 63 in MCS underwent clinical assessment by Coma Recovery Scale-Revised3 and neurophysiological evaluations of EEG background activity and reactivity, somatosensory evoked potential (SEP) and event related potential (ERP) at 63 months after brain-injury. Clinical outcome was evaluated at 6 months post-injury. EEG background activity and reactivity significantly differed between VS and MCS patients (p < .001), whereas the presence of cortical component N20 on SEP and P300 on ERP did not differ between the two groups. Good outcome was significantly more frequent in patients with moderately abnormal to normal EEG background activity than in patients with poor EEG background organization (p = .001), in patients showing EEG reactivity (p < .001) and in patients showing P300 (p = .016). The presence of SEP did not differ significantly between the two prognostic groups. Multimodal clinical and neurophysiological assessment could provide useful diagnostic and prognostic information for disorder of consciousness. This multicentric project calls for international standardization of diagnostic and prognostic procedures

Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. Recent studies suggest that amyloid-beta (Aβ) deposit can be detected several years after TBI. However, it is unknown whether post-TBI Aβ deposits arise from short-term changes in Aβ metabolism or reflect a long-term sequela. To answer this question, we evaluated the cerebrospinal levels of Aβ several months after a severe TBI. The participants of this study were eight consecutive patients who developed a disorder of consciousness after a TBI, including seven in a minimally conscious state and one with unresponsive wakefulness syndrome (mean age: 35.4±14.2 years, mean time since brain injury 297.9±189.8 days). Cerebrospinal Aβ1-42 peptide was measured using a commercially available Aβ enzyme-linked immunoassay kit. Reduced Aβ1-42 levels were observed in seven of eight (87.5%) patients with severe post-TBI disorders of consciousness, with the magnitude of reduction among these seven patients ranging from 27 to 75.1% of the lower normal limit. These results point to prolonged changes in Aβ metabolism after a TBI and they suggest a potential mechanism of long-term neurotoxicity.

Discrimination between patients in vegetative (VS) and minimally conscious state (MCS) is currently based upon the behavioral gold standard. Behavioral assessment remains equivocal and difficult to interpret as evidence for the presence or absence of consciousness, resulting in possible clinical misdiagnosis in such patients. Application of an operational architectonics (OA) strategy to electroencephalogram (EEG) analysis reveals that absence of consciousness in patients in VS is paralleled by significant impairment in overall EEG operational architecture compared to patients in MCS: neuronal assemblies become smaller, their life span shortened, and they became highly unstable and functionally disconnected (desynchronized). However, in a previous study, patients with different brain damage etiologies were intermixed. Therefore, the goal of the present study was to investigate whether the application of OA methodology to EEG could reliably dissociate patients in VS and MCS independent of brain damage etiology. We conclude that the observed EEG OA structure impairment in patients in VS and partial preservation in patients in MCS is a marker of consciousness/unconsciousness rather than physiological damage. Results of this study may have neuroscientific, clinical, and ethical implications.

Background. Patients in a vegetative state pose problems in diagnosis, prognosis, and treatment. Currently, no prognostic markers predict the chance of recovery, which has serious consequences, especially in end-of-life decision making. Objective. We aimed to assess an objective measurement of prognosis using advanced electroencephalography (EEG). Methods. EEG data (19 channels) were collected in 14 patients who were diagnosed to be persistently vegetative based on repeated clinical evaluations at 3 months following brain damage. EEG structure parameters (amplitude, duration, and variability within quasi-stationary segments, as well as the spatial synchrony between such segments and the strength of this synchrony) were used to predict recovery of consciousness 3 months later. Results. The number and strength of cortical functional connections between EEG segments were higher in patients who recovered consciousness ( P < .05 to P < .001) compared with those who did not recover. Linear regression analysis confirms that EEG structure parameters are capable of predicting ( P = .0025) recovery of consciousness 6 months postinjury, whereas the same analysis failed to significantly predict patient outcome based on aspects of their clinical history alone ( P = .629) or conventional EEG spectrum power ( P = .473). Conclusions. The result of this preliminary study demonstrates that structural strategy of EEG analysis is better suited for providing prognosis of consciousness recovery than existing methods of clinical assessment and of conventional EEG. Our results may be a starting point for developing reliable prognosticators in patients who are in a vegetative state, with the potential to improve their day-to-day management, quality of life, and access to early interventions.

Electroencephalogram (EEG) recordings are increasingly used to evaluate patients with disorders of consciousness (DOC) or assess their prognosis outcome in the short-term perspective. However, there is a lack of information concerning the effectiveness of EEG in classifying long-term (many years) outcome in chronic DOC patients. Here we tested whether EEG operational architectonics parameters (geared towards consciousness phenomenon detection rather than neurophysiological processes) could be useful for distinguishing a very long-term (6 years) clinical outcome of DOC patients whose EEGs were registered within 3 months post-injury. The obtained results suggest that EEG recorded at third month after sustaining brain damage, may contain useful information on the long-term outcome of patients in vegetative state: it could discriminate patients who remain in a persistent vegetative state from patients who reach a minimally conscious state or even recover a full consciousness in a long-term perspective (6 years) post-injury. These findings, if confirmed in further studies, may be pivotal for long-term planning of clinical care, rehabilitative programs, medical-legal decisions concerning the patients, and policy makers.

The default mode network (DMN) has been consistently activated across a wide variety of self-related tasks, leading to a proposal of the DMN’s role in self-related processing. Indeed, there is limited fMRI evidence that the functional connectivity within the DMN may underlie a phenomenon referred to as self-awareness. At the same time, none of the known studies have explicitly investigated neuronal functional interactions among brain areas that comprise the DMN as a function of self-consciousness loss. To fill this gap, EEG operational synchrony analysis [1, 2] was performed in patients with severe brain injuries in vegetative and minimally conscious states to study the strength of DMN operational synchrony as a function of self-consciousness expression. We demonstrated that the strength of DMN EEG operational synchrony was smallest or even absent in patients in vegetative state, intermediate in patients in minimally conscious state and highest in healthy fully self-conscious subjects. At the same time the process of ecoupling of operations performed by neuronal assemblies that comprise the DMN was highest in patients in vegetative state, intermediate in patients in minimally conscious state and minimal in healthy fully self-conscious subjects. The DMN’s frontal EEG operational module had the strongest decrease in operational synchrony strength as a function of selfconsciousness loss, when compared with the DMN’s posterior modules. Based on these results it is suggested that the strength of DMN functional connectivity could mediate the strength of self-consciousness expression. The observed alterations similarly occurred across EEG alpha, beta1 and beta2 frequency oscillations. Presented results suggest that the EEG operational synchrony within DMN may provide an objective and accurate measure for the assessment of signs of self-(un)consciousness in these challenging patient populations. This method therefore, may complement the current diagnostic procedures for patients with severe brain injuries and, hence, the planning of a rational rehabilitation intervention.

The value of resting electroencephalogram (EEG) in revealing neural constitutes of consciousness (NCC) was examined. We quantified the dynamic repertoire, duration and oscillatory type of EEG microstates in eyes-closed rest in relation to the degree of expression of clinical self-consciousness. For NCC a model was suggested that contrasted normal, severely disturbed state of consciousness and state without consciousness. Patients with disorders of consciousness were used. Results suggested that the repertoire, duration and oscillatory type of EEG microstates in resting condition quantitatively related to the level of consciousness expression in brain-damaged patients and healthy-conscious subjects. Specifically, results demonstrated that (a) decreased number of EEG microstate types was associated with altered states of consciousness, (b) unawareness was associated with the lack of diversity in EEG alpha-rhythmic microstates, and (c) the probability for the occurrence and duration of delta-, theta- and slow-alpha-rhythmic microstates were associated with unawareness, whereas the probability for the occurrence and duration of fast-alpha-rhythmic microstates were associated with consciousness. In conclusion, resting EEG has a potential value in revealing NCC. This work may have implications for clinical care and medical-legal decisions in patients with disorders of consciousness.