Primary Lateral Sclerosis: Clinical,radiological and molecular features

Primary Lateral Sclerosis (PLS) is an uncommon motor neuron disorder. Despite the well-recognisable constellation of clinical manifestations, the initial diagnosis can be challenging and therapeutic options are currently limited. There have been no recent clinical trials of disease-modifying therapies dedicated to this patient cohort and awareness of recent research developments is limited. The recent consensus diagnostic criteria introduced the category ‘probable’ PLS which is likely to curtail the diagnostic journey of patients. Extra-motor clinical manifestations are increasingly recognised, challenging the view of PLS as a 'pure' upper motor neuron condition. The post mortem literature of PLS has been expanded by seminal TDP-43 reports and recent PLS studies increasingly avail of meticulous genetic profiling. Research in PLS has gained unprecedented momentum in recent years generating novel academic insights, which may have important clinical ramifications.     

Clinical failure of natalizumab in multiple sclerosis: Specific causes and strategy

BackgroundNatalizumab is a very effective treatment of multiple sclerosis (MS). Failure is rare and should lead to consider some specific etiologies. The purpose of our study was to describe causes of subacute neurological events under natalizumab.MethodsObservational single-center retrospective study in the MS expert center of Lyon, France. Inclusion criteria: any patient with definite MS who received at least three infusions of natalizumab between April 2007 and February 2017. Clinical data were extracted from the Lyon EDMUS/OFSEP database. Events of interest: occurrence of a subacute neurological deficit, characterized by new clinical symptoms. We excluded pseudo-relapses and progression.FindingsA subacute neurological deficit occurred in 35 cases, for 607 patients treated with natalizumab. Ten patients presented natalizumab antibodies, nine had progressive multifocal leukoencephalopathy (PML), five presented an isolated subacute neurological deficit and two had AQP4 antibodies. No myelin oligodendrocyte glycoprotein (MOG) antibodies were found.InterpretationThe occurrence of an acute or subacute neurological deficit with natalizumab is rarely a MS relapse and should lead systematically to explore some important alternate etiologies, eliminating PML first.     

Denial of Cerebrovascular Events in a National Clinical Quality Registry for Stroke: A Retrospective Cohort Study

ObjectivesTo investigate cerebrovascular event (CVE) denials reported by registered patients to the Australian Stroke Clinical Registry, and to examine the factors associated with CVE denial.Material and methodsCVE denials reported from January 1, 2017 to June 30, 2018 were followed up with hospitals to verify their discharge diagnosis. CVE denials were compared with all non-CVE denial registrants and a 5% random sub-sample of non-CVE deniers according to patient and clinical characteristics, quality of care indicators and health outcomes. Multilevel, multivariable logistic regression models were used. Factors explored were age, sex, stroke severity, type of stroke, treatment in a stroke unit, length of stay and discharge destination. Level was defined as hospital.ResultsOverall, 339/23,830 (<2%) CVE denials were reported during the 18-month period. Hospitals confirmed 117 (61%) of CVE denials as a verified diagnosis of stroke or transient ischaemic attack (TIA). Compared to non-CVE deniers, CVE deniers were younger, had a shorter median length of stay (four days versus one day) and were more likely to be diagnosed with a TIA (64%) compared to the other types of stroke (11% intracerebral haemorrhage; 20% ischaemic; 5% undetermined).ConclusionVery few patients denied their CVE, with the majority of denials subsequently confirmed as eligible for registry inclusion. Diagnosis of a TIA and shorter length of stay were associated with CVE denial. These findings provide evidence that very few cases are incorrectly entered into a national registry, and highlight the characteristics of those unlikely to accept their clinical diagnosis where further education of diagnosis may be needed.     

Bariatric surgery related proximal myopathy: A partially reversible complication

Deficiency neuropathies and rhabdomyolysis have previously been reported after bariatric surgery (BS) but never myopathies. We report cases of five patients with morbid obesity who developed within 2 to 4 months of a BS, proximal myopathy following significant and rapid weight loss worsened by postoperative gastrointestinal complications. Muscle weakness concerned lower limbs in particular in quadriceps and less frequently in upper limbs and diaphragm, sometimes mimicked a Guillain–Barré syndrome. Muscle biopsy performed in 1 patient, revealed selective atrophy of type 2 fibers. Weakness slowly decreased with refeeding with vitamins supplementation. We enlarge here the clinical pattern of post-BS complications.     

Nutrient Status in Patients with Frequent Episodic Tension-Type Headache: A Case-Control Study

ObjectiveTo investigate the relationship between frequent episodic tension-type headache (FE-TTH) and 25-hydroxyvitamin-D (25(OH)D), folate, vitamin B12, and magnesium.Design-MethodsA prospective case-control study involving adults with FETTH and age-sex matched healthy controls (HC) was performed. Individuals under the responsibility of the three provincial Health Centres of the prefecture of Trikala (Central Greece) were recruited during their regular check-up visits. The relationship between FETTH and serum levels of 25(OH)D, vitamin B12, folate, and magnesium was investigated (primary outcomes). Demographics, daily habits, somatometrics, psychometric and sleep quality measurements, laboratory indices, cardiovascular comorbidities and medications taken were also recorded and compared (secondary outcomes). Potential associations of the above-listed parameters with headache parameters (headache frequency, severity and analgesic consumption) were also examined (secondary outcomes).ResultsBetween September and December 2020, 30 patients with FETTH and 30 HC were successfully recruited. Demographics, comorbidities, regular medications, smoking habits, alcohol and coffee consumption, body mass index measurements, markers of systemic inflammation, folate and vitamin B12 levels were similar between the two groups (P > 0.05). Lower serum 25(OH)D was both univariately (P < 0.001) and multivariately [OR= 0.72, 95%CI = (0.55, 0.94) per 1 ng/ml increase] associated with FETTH, while serum magnesium was found lower in FETTH only according to the univariate approach (P = 0.036). Higher levels of depression (P = 0.050) and anxiety (P = 0.020), as well as poor quality of sleep (P = 0.008), were univariately associated with FETTH. Only the effect of anxiety remained significant following the multivariate logistic regression [OR= 7.90, 95%CI = (1.00, 62.47)]. Headache parameters were not associated with any one of the assessed variables.DiscussionLower serum 25(OH)D was related to the presence of FETTH. This finding could imply a potential role for vitamin D in the pathophysiology of TTH.     

Review of synthetic MRI in pediatric brains: Basic principle of MR quantification,its features,clinical applications,and limitations

Quantitative magnetic resonance imaging (MRI) with multislice, multi-echo, and multi-delay acquisition enables simultaneous quantification of R₁ and R₂ relaxation rates, proton density, and the B₁ field in a single acquisition, and requires only about 6 minutes for full-head coverage. Using dedicated SyMRI software, radiologists can generate any contrast-weighted image by manipulating the acquisition parameters, including repetition time, echo time, and inversion time. Moreover, automatic brain tissue segmentation, volumetry, and myelin measurement can also be performed. Using the SyMRI approach, a shorter scan time, an objective examination, and personalized MR imaging parameters can be obtained in daily clinical pediatric imaging. Here we summarize and review the use of SyMRI in imaging of the pediatric brain, including the basic principles of MR quantification along with its features, clinical applications, and limitations.     

Clinical features and prognostic factors in patients with cancer-associated multiple ischemic stroke: A retrospective observational study

ObjectivesTo investigate the patient demographics, survival after diagnosis, and prognostic factors among patients with multiple-territory cerebral infarctions due to cancer-associated ischemic stroke (multiple CAIS).Materials and methodsWe performed a retrospective review of the medical records from a 10-year period of consecutive patients with multiple CAIS, defined as (1) newly developed multiple cerebral infarctions involving two or more cerebrovascular territories, (2) association with active cancer diagnosed or treated <6 months before or after stroke, and (3) exclusion of obvious etiologies other than cancer-associated coagulopathy in routine screening. We extracted demographic features, stroke severity and characteristics, cancer characteristics, comorbidities, and laboratory data. Univariable Cox proportional hazards regression was used to idenify the prognostic factors.ResultsThe median age was 74 years (interquartile range, 68.3–80.5), and the median survival after diagnosis was 44.5 (27.3–76.8) days in 26 patients with complete follow-up. The median National Institutes of Health Stroke Scale was 5.5 (2.0–9.0). Twenty (76.9%) patients had received a cancer diagnosis prior to the diagnosis of multiple CAIS, and most patients (25 patients, 96.2%) had stage IV cancer. Univariate analysis showed that high serum albumin (hazard ratio, 0.31; 95% confidence interval, 0.11–0.88) was significantly associated with prolonged survival, whereas stroke severity and comorbidities were not associated with survival.ConclusionMultiple CAIS predominantly occurred in elderly patients with advanced cancer, and their survival was short. Serum albumin levels were significantly associated with prognosis, indicating the poor general condition associated with cancers may affect prognosis.     

Signal changes in enhanced T1-weighted images related to gadolinium retention: A three-time-point imaging study

Background and PurposeConcern has grown about the finding of gadolinium deposits in the brain after administering gadolinium-based contrast agents (GBCAs). The mechanism is unclear, and related questions remain unanswered, including the stability over time. Therefore, we conducted a three-time-point study to explore T1-weighted (W) signal changes in the dentate nucleus (DN) and globus pallidus (GP), after the first, fifth, and tenth injections of either a macrocyclic agent (gadoterate meglumine) or a linear agent (gadobenate dimeglumine).Materials and methodsFor this retrospective, multicenter, longitudinal study, two groups of 18 (gadoterate meglumine) and 19 (gadobenate dimeglumine) patients were identified. The evolution of the signal over time was analyzed using DN/pons (DN/P) and GP/thalamus (GP/T) ratios.ResultsDN/P and GP/T ratios tended to increase after the fifth administration of gadobenate dimeglumine, following by a downward trend. A trend in a decrease in DN/P and GP/T ratios were found after the fifth and tenth administrations of gadoterate meglumine.ConclusionAfter exposure to gadobenate dimeglumine, the signal intensity (SI) tended to increase after the fifth injection owing to gadolinium accumulation, however, a SI increase was not found after the tenth administration supporting the hypothesis of a slow elimination of the previously retained gadolinium (wash-out effect) from the brain or of a change in form (by dechelation), causing the signal to fade. No increasing SI was found in the DN and GP after exclusive exposure to gadoterate meglumine, thus confirming its stability. We found, instead, a trend for a significative gadolinium elimination over time.     

Cognitive deficits and rehabilitation mechanisms in mild traumatic brain injury patients revealed by EEG connectivity markers

ObjectiveTo explore the multiple specific biomarkers and cognitive compensatory mechanisms of mild traumatic brain injury (mTBI) patients at recovery stage.MethodsThe experiment was performed in two sections. In Section I, using event-related potential, event-related oscillation and spatial phase-synchronization, we explored neural dynamics in 24 volunteered healthy controls (HC) and 38 patients at least 6 months post-mTBI (19 with epidural hematoma, EDH; 19 with subdural hematoma, SDH) during a Go/NoGo task. In Section II, according to the neuropsychological scales, patients were divided into sub-groups to assess these electroencephalography (EEG) indicators in identifying different rehabilitation outcomes of mTBI.ResultsIn Section I, mean amplitudes of NoGo-P3 and P3d were decreased in mTBI patients relative to HC, and NoGo-theta power in the non-injured hemisphere was decreased in SDH patients only. In Section II, patients with chronic neuropsychological defects exhibited more serious impairments of intra-hemispheric connectivity, whereas inter-hemispheric centro-parietal and frontal connectivity were enhanced in response to lesions.ConclusionsEEG distinguished mTBI patients from healthy controls, and estimated different rehabilitation outcomes of mTBI. The centro-parietal and frontal connectivity are the main compensatory mechanism for the recovery of mTBI patients.SignificanceEEG measurements and network connectivity can track recovery process and mechanism of mTBI.     

Relationship between circadian typology and risk-taking behaviors in adolescents: A cross-sectional study

ObjectiveThis study examined the relationship between circadian typology and risk-taking behavior.MethodsA cross-sectional study was conducted, involving 755 primary and junior school students aged 11–16 years. The Adolescent Risk-Taking Questionnaire and Morningness-Eveningness Questionnaire were administered to assess risk-taking behavior and circadian typology, respectively. Multiple linear regression analyses were performed to analyze the factors influencing risk-taking behavior.ResultsCircadian typology was negatively correlated with risk-taking behavior, with age and sex controlled for (Model 1). When family and class circumstances were added in Model 2, the significance of the association persisted (β = −1.67, 95% CI: [−2.93, −0.42], P = .009). However, the association between circadian typology and risk-taking behavior showed no significance (P = 0.050) when personality characteristics were controlled for in Model 3.ConclusionsThese results provide evidence indicating a relationship between circadian typology and risk-taking behavior, suggesting that evening circadian type is a risk factor for risk-taking behavior in adolescents.     

Associations of carotid artery flow parameters with MRI markers of cerebral small vessel disease and patterns of brain atrophy

ObjectivesA growing body of evidence links age related brain pathologies to systemic vascular processes. We aimed to study the prevalence and interrelations between magnetic resonance imaging (MRI) markers of cerebral small vessel disease and patterns of brain atrophy, and their association to carotid duplex ultrasound flow parameters.Materials and methodsWe investigated a population based randomised cohort of older adults (n=391) aged 70-87, part of the Swedish Good Aging in Skåne Study. Peak systolic and end diastolic velocities of the carotid arteries were measured by ultrasound, and resistivity- and pulsatility indexes were calculated. Subjects with increased peak systolic velocity indicating carotid stenosis were excluded from analysis. Nine MRI findings were rated by visual scales: white matter changes, pontine white matter changes, microbleeds, lacunar infarctions, medial temporal lobe atrophy, global cortical atrophy, parietal atrophy, precuneus atrophy and central atrophy.ResultsMRI pathologies were found in 80% of subjects. Mean end diastolic velocity in common carotid arteries was inversely associated with white matter hyperintensities (OR=0.92; p=0.004), parietal lobe atrophy (OR=0.94; p=0.039), global cortical atrophy (OR=0.90; p=0.013), precuneus atrophy (OR=0.94; p=0.022), “number of CSV pathologies” (β=-0.07; p<0.001) and “MRI-burden score” (β=-0.11; p<0.001), after adjustment for age and sex. The latter three were also associated with pulsatility and resistivity indexes.ConclusionsLow carotid end diastolic velocity, as well as increased carotid resistivity and pulsatility, were associated with signs of cerebral small vessel disease and patterns of brain atrophy, indicating a vascular component in the process of brain aging.     

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients

BackgroundAtrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk.MethodsThe present study followed a cross-sectional design. 70 patients with a history of AF and CHADS₂ score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany.Results45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99–23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment.ConclusionsBMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.     

Pre-surgical embolization of intracranial meningioma with Onyx: A safety and efficacy study

Background and purposePre-surgical embolization of large intracranial meningioma has been demonstrated to decrease blood loss and to improve the resectability of the tumor. Few reports have evaluated the risk and benefits of using Onyx in this indication. The objective of our study was to assess the efficiency and safety of pre-surgical embolization in a consecutive series of intracranial meningioma using Onyx.Materials and methodsWe conducted a retrospective study of consecutive patients treated from 2010 to 2018 with pre-surgical embolization with Onyx for intracranial histologically-proven meningioma. Safety was evaluated by a report of the complications related to the procedure while efficacy was assessed on angiographic and histopathologic criteria.ResultsForty-four meningioma in 44 patients treated with pre-surgical embolization were included in this study. Proximal artery occlusion was obtained in 97.6% (41/42) of the cases and good intra-tumoral penetration was achieved in 75.6% (31/41). Embolic agent inside blood vessels was identified in 63.5% (28/44) of cases. Embolization-induced necrosis was present in 79.6% (35/44) of cases. Six complications have been encountered (13.6%); 3 were stated as minor complications (6.8%) and 3 as major occurring in case of trans-ophthalmic route (6.8%).ConclusionsThe present work is to date the largest study to evaluate intracranial meningioma embolization using Onyx. Onyx's allowed good intra-tumoral penetration and proximal artery occlusion in most cases but carries a higher risk of complication in case of ophthalmic supply.     

Difference in acute and chronic stage ischemic stroke metabolic markers with controls

BackgroundAcute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls.MethodsThrough the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations.ResultsThe sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls.ConclusionOur pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.     

New advances in Amyotrophic Lateral Sclerosis genetics: Towards gene therapy opportunities for familial and young cases

Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.     

Epilepsy and pregnancy: What should the neurologists do?

Epilepsy is one of the most common chronic disorders affecting women of childbearing age. Unfortunately, many women with epilepsy (WWE) still report not receiving key information about pregnancy. They obviously need information about epilepsy and pregnancy prior to conception with a particular emphasis on effective birth control (i.e. contraception), necessity to plan pregnancy, antiepileptic drugs optimization, and folate supplementation. The risks associated with use of antiepileptic drugs during pregnancy have to be balanced against fetal and maternal risks associated with uncontrolled seizures. This report reviews evidence-based counseling and management strategies concerning maternal and fetal risks associated with seizures, teratogenic risks associated with antiepileptic drug exposure with a special emphasis on developmental and behavioural outcomes of children exposed to intra utero antiepileptic drugs.     

Multinodular and Vacuolating Neuronal Tumor of the Cerebrum (MVNT): A case series and review of the literature

Background and purposeMultinodular and Vacuolating Neuronal Tumor of the cerebrum (MVNT) is a benign –seizure associated– lesion affecting mostly adults. This new entity has been included in the 2016 World Health Organization classification of tumors of the central nervous system.Its pathologic hallmark consist of a subcortical cluster of nodular lesions located on the subcortical white matter.We aim to report a series of cases of presumed MVNT observed in our institution and review the literature.Materials and methodsIn this retrospective study, a search was performed on our hospital information system. Sixteen cases were included. Demographic, clinical and radiological features were detailed in a table.All patients had an MRI acquired either on a 1.5 or a 3 Tesla scanner. Sequences performed included T1, T2, GRE/SWI, T2 FLAIR and DWI. Gadolinium enhanced T1-WI wer available in 11 patients and follow-up MRI were available in 7 patients.ResultsPatient ages ranged from 16 to 77 years (mean 42 years). Seizure and non-focal headache were by far the most common neurological complaints for which MRI was requested. All lesions consisted of clusters of multiple, discrete, round or ovoid, intra-axial, FLAIR and T2-WI hyperintense nodules. Follow-up MRI scans showed no changes between studies.ConclusionsMVNT is a benign, stable lesion that exhibits a typical radiological pattern that most of the times sufficed to arrive to a diagnosis, without the need of pathological confirmation. We confirm that our demographic, clinical and radiological findings are in accordance with those published in international literature.     

Mechanism of action of s1p receptor modulators in multiple sclerosis: The double requirement

The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS.     

Quantitative evaluation of WEB shape modification: A five-year follow-up study

Background and purposeWeb shape modification (WSM) has previously been associated with aneurysm recurrence. We report here our five-year experience of WEB device use with a quantitative approach of the WSM phenomenon.MethodsFrom July 2012 to July 2017, 50 patients with 51 unruptured aneurysms treated with the WEB device have been prospectively enrolled in our data base and retrospectively analyzed. An independent “core lab” evaluated anatomical results and potential WSM in DSA follow-up. We defined the WSM ratio (WSMr) as a relative index between the height and the width of the device in working projections which gave an evaluation of the device deformation over the time.ResultsDuring the total follow-up period, WSM was observed in 35/48 aneurysms (72.9%). Adequate occlusion rates were 87.0% and 92.6% with and without WSM respectively (P = 0.65). 30 out the 35 (85.7%) shape modifications were already noticed at short-term follow-up (6-month DSA). 33 patients had 2 DSA controls and WSMr measurements were available in 24 patients: 18 (75%) with WSM and 6 (25%) without WSM. In the group with WSM, WSMr values were 0.80 in post-embolization, 0.52 at the first DSA angiogram and 0.42 at the second DSA angiogram.ConclusionWEB shape modification was observed in more than half of cases but with no influence regarding adequate occlusion rate. This quantitative approach of WSM highlights that this phenomenon appears to be early and progressive over time. This supports the hypothesis that WSM could be more probably related to aneurysm healing rather than external compression.     

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group

The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of both consolidated and investigational electrophysiological techniques for the prognostic and diagnostic assessment of DoC. We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats. The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.