COVID-19-induced acute loss of consciousness in Marchiafava-Bignami disease: a case report.

Among the various manifestations of COVID-19, the neurological implications of SARS-CoV-2 infection are of significant concern. Marchiafava-Bignami disease (MBD), a neurodegenerative disorder, exhibits a clinical spectrum ranging from mild progressive dementia in its chronic form to states of acute coma and varied mortality rates. Acute MBD primarily occurs in chronic alcoholics and malnourished individuals and is characterized by sudden loss of consciousness, seizures, confusion, and psychosis. We herein report a case of MBD presenting as acute loss of consciousness after the development of COVID-19. The patient presented with a history of fever and upper respiratory infection and was diagnosed with SARS-CoV-2 infection. He developed a neurological syndrome characterized by altered consciousness and convulsions, and brain magnetic resonance imaging revealed abnormal signals in the corpus callosum and frontoparietal lobes. Considering his alcohol intake history and the absence of other differential diagnoses, we diagnosed him with acute MBD triggered by COVID-19. After high-dose vitamin B1 and corticosteroid therapy, his clinical symptoms improved. In this case, we observed a temporal sequence between the development of COVID-19 and acute exacerbation of MBD. This case adds to the mounting evidence suggesting the potential effect of SARS-CoV-2 on the neurological system.

The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

[The effect of keratoconus-associated refractive errors on the results of tomographic methods of studying the posterior structures of the eye]. / Vliyanie opticheskikh narushenii pri keratokonuse na rezul'taty tomograficheskikh metodov issledovaniya struktur zadnego segmenta glaza.

PURPOSE: The study assesses the potential influence of refractive errors in keratoconus (KC) on the results of tomographic methods of studying the structures of the posterior eye segment. MATERIAL AND METHODS: The study included 30 patients with bilateral stabilized KC of stages I-IV in classification by M. Amsler. Spherical and cylindrical components of refractions were determined using automatic refractometry, keratometry measurements - based on scanning keratotopography with Scheimpflug analyzer. Aberrometry was performed to evaluate corneal wave front according to the following parameters: root mean square for lower order aberrations (RMS LOA), root mean square for higher order aberrations (RMS HOA), vertical trefoil, vertical coma, horizontal coma and spherical aberrations. Optical coherence tomography (OCT) and laser confocal scanning ophthalmoscopy (HRT 3) data was used in morphometric analysis of the optic nerve head and peripapillary retina. The following morphometric parameters were analyzed: optic nerve head (ONH) area, optic disc cup area, optic disc cup volume, ratio of optic disc cup area to ONH area, neuroretinal rim area, neuroretinal rim volume, peripapillary retinal nerve fiber layer (RNFL) thickness. All studies were performed first without correction, and 30 minutes after installing customized scleral hard contact lenses (SHCL). RESULTS: Compensation of the refractive errors characteristic for KC was achieved as expected with contact correction. OCT revealed a general trend for reduction in the area and volume of the optic disc cupping, ratio of area to volume of the optic disc cupping, as well as an increase in other parameters. As such, with correction the values for area and volume of the neuroretinal rim according to OCT were 2.2 and 13%, HRT 3 - 18 and 51.6%; comparable increase in mean RNFL thickness - 2.8 and 28.5%, respectively (p<0.001). According to HRT 3 data, the area and volume of optic disc cupping statistically significantly decreased (by 21 and 28%, respectively), while OCT showed statistically significant decrease only in cupping area (by 5.7%). The ratio of cupping to ONH area decreased by 6.6 and 23% relative to the initial data obtained with OCT and HRT 3, respectively. Significant decrease in ONH area amid SHCL correction was observed only with HRT 3. The revealed changes in morphometric parameters were analyzed using the fundamental principles of physiological optics. Changes in interference pattern and, consequently, morphometric parameters of structures of the eye fundus in KC are of multifactorial nature, and are mostly associated with refractive and wave artefacts occurring when the rays pass through the irregular corneal surface and cannot be optically compensated by the device. The use of SHCL as means for making the optic system relatively regular can significantly decrease the artefacts in morphometric measurements. CONCLUSION: The results obtained in this study demonstrate the practicality of tomographic examination in KC with contact correction. The optimal choice is custom-fit SHCL, which along with proper correction of refractive errors also ensures stable position of the lens on the cornea. In standard examination specialists should take into account the «false¼ decrease in parameters of the peripapillary retinal nerve fiber layer and increase in ONH cupping.

Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHP-score and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. CONCLUSIONS: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness.

OBJECTIVE: This study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. METHODS: We enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale-Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. RESULTS: Power spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. CONCLUSIONS: Auditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SIGNIFICANCE: Our findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

Hemiplegia resulting from acute carbon monoxide poisoning.

Carbon monoxide (CO) poisoning can cause neurological complications such as movement disorders and cognitive impairment through hypoxic brain damage. Although peripheral neuropathy of the lower extremities is a known complication of CO poisoning, hemiplegia is very rare. In our case, a patient who developed left hemiplegia due to acute CO poisoning received early hyperbaric oxygen treatment (HBOT). The patient had left hemiplegia and anisocoria at the beginning of HBOT. Her Glasgow coma score was 8. A total of five sessions of HBOT at 243.2 kPa for 120 minutes were provided. At the end of the 5th session, the patient's hemiplegia and anisocoria were completely resolved. Her Glasgow coma score was 15. After nine months of follow-up, she continues to live independently with no sequelae, including delayed neurological sequelae. Clinicians should be aware that CO poisoning can (rarely) present with hemiplegia.

Validation of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness With the Coma Recovery Scale-Revised.

OBJECTIVE: To examine (1) the concurrent validity of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC) with the criterion standard Coma Recovery Scale-Revised (CRS-R) for outcomes of awareness in patients with prolonged disorders of consciousness (PDoC), (2) the relationship between MATADOC items and CRS-R function subscales in similar domains, and (3) determine if items/function subscales measure different constructs. DESIGN: A prospective multicentric blinded study with repeated concurrent measures. SETTING: Three inpatient rehabilitation units. PARTICIPANTS: Convenience sample of 74 adults with PDoC (N=74). MAIN OUTCOME MEASURES: The MATADOC protocol elicits behavioral responsiveness using live music in 5 tasks. A total score ranges 0-10 scoring behaviors across 14-items. The CRS-R uses a language-based protocol and scores observed responses ranging from 0-23 in 6 function subscales. Both measures were delivered at 4 concurrent time points over 2 weeks. RESULTS: Fair (κ=0.238, P=.006) ranging to moderate (κ=0.419, P<.001) significant agreement was found between CRS-R and MATADOC diagnostic outcomes. Fair-borderline moderate significant agreement was found for overall diagnostic outcomes across all diagnostic categories (κ=0.397, P=.001). There was moderate significant agreement between measures for motor scores (0.551≤κ≤0.571, P<.001) and visual outcomes (0.192≤κ≤0.415, .001≤P<.005) but no agreement for item/function subscale outcomes assessing auditory responsiveness. Exploratory factor analysis of all items showed 2 factors, suggesting that MATADOC and CRS-R measure the same underlying latent variable (awareness) in different ways and could complement each other for diagnosis and intervention purposes. This was supported by scale analysis, which showed increased reliability when the 2 scales are used together rather than separately. CONCLUSIONS: Unlike the CRS-R, the music-based MATADOC scores auditory localization for complexity of response and categorizes these behaviors as conscious rather than reflexive. The MATADOC may supplement the CRS-R, having a particular role in interdisciplinary programming for providing a more robust assessment of auditory responsiveness because of using nonverbal musical stimuli.

From Mild Gait Difficulties to a Sudden Coma: A Rare Case of Marchiafava-Bignami Disease.

ABSTRACT: In this case report we describe the case of a 66-year old man with subacute gait difficulties, with a progression to confusion coma with multiple generalised epileptic seizures during the following days. Biochemical analysis showed hyperglycaemia, cerebrospinal fluid (CSF) testing showed a mild lymphocytic pleocytosis and an elevated protein and lactate. Broad-spectrum antibiotics and antiviral therapy where initiated. However, all other CSF testing remained negative. Magnetic resonance imaging of the brain showed remarkably symmetric hyperintense T2 white matter lesions most noticable in the corpus callosum. The lesion pattern was suggestive of a metabolic or toxic encephalopathy, the preponderance for the corpus callosum was furthermore suggestive for Marchiafava-Bignami disease (MDB), as was the clinical course since admission of the patient. A high dose IV substitution of vitamin B1, B6 and B12 was started and antibiotic and antiviral therapy was discontinued. After one day the patient showed progressive regaining of consciousness and he returned to premorbid functioning in a matter of 1-2 weeks. MRI of the brain after 1 week showed notable improvement of the white matter lesions. At routine follow-up two weeks later he presented with icterus and a diagnosis of Epstein-Barr virus (EBV) hepatitis was made, lymph node biopsies showed an EBV positive diffuse large cell B-cell lymphoma (DLCBL). MDB is mostly associated with severe alcoholism, with malnourishment being the second leading cause, however there are case reports describing MDB in patients with chronically poorly controlled diabetes mellitus. We hypothesize that his condition may have been precipitated by his poorly controlled diabetes mellitus. However it is also possible that weight loss (probably related to the DLCBL diagnosis) might have contributed to a state of malnourishment and therefore played a role in the aetiology as well.

Auditory stimulation and deep learning predict awakening from coma after cardiac arrest.

Assessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a 'grey zone', with uncertain prognosis. Quantitative analysis of EEG responses to auditory stimuli can provide a window into neural functions in coma and information about patients' chances of awakening. However, responses to standardized auditory stimulation are far from being used in a clinical routine due to heterogeneous and cumbersome protocols. Here, we hypothesize that convolutional neural networks can assist in extracting interpretable patterns of EEG responses to auditory stimuli during the first day of coma that are predictive of patients' chances of awakening and survival at 3 months. We used convolutional neural networks (CNNs) to model single-trial EEG responses to auditory stimuli in the first day of coma, under standardized sedation and targeted temperature management, in a multicentre and multiprotocol patient cohort and predict outcome at 3 months. The use of CNNs resulted in a positive predictive power for predicting awakening of 0.83 ± 0.04 and 0.81 ± 0.06 and an area under the curve in predicting outcome of 0.69 ± 0.05 and 0.70 ± 0.05, for patients undergoing therapeutic hypothermia and normothermia, respectively. These results also persisted in a subset of patients that were in a clinical 'grey zone'. The network's confidence in predicting outcome was based on interpretable features: it strongly correlated to the neural synchrony and complexity of EEG responses and was modulated by independent clinical evaluations, such as the EEG reactivity, background burst-suppression or motor responses. Our results highlight the strong potential of interpretable deep learning algorithms in combination with auditory stimulation to improve prognostication of coma outcome.

Clinical Characteristics, Imaging Findings, and Outcomes of Cerebral Air Embolism.

BACKGROUND: Arterial cerebral air embolism (CAE) is an uncommon but potentially catastrophic event. Patients can present with focal neurologic deficits, seizures, or coma. They may be treated with hyperbaric oxygen therapy. We review the causes, radiographic and clinical characteristics, and outcomes of patients with CAE. METHODS: We performed a retrospective chart review via an existing institutional database at Mayo Clinic to identify patients with arterial CAE. Demographic data, clinical characteristics, and diagnostic studies were extracted and classified on predefined criteria of diagnostic confidence, and descriptive and univariate analysis was completed. RESULTS: Fifteen patients met criteria for inclusion in our study. Most presented with focal deficits (80%) and/or coma (53%). Seven patients (47%) had seizures, including status epilepticus in one (7%). Five presented with increased muscle tone at the time of the event (33%). Computed tomography (CT) imaging was insensitive for the detection of CAE, only identifying free air in 4 of 13 who underwent this study. When obtained, magnetic resonance imaging typically showed multifocal areas of restricted diffusion. Six patients (40%) were treated with hyperbaric oxygen therapy. Age, Glasgow Coma Scale score at nadir, and use of hyperbaric oxygen therapy were not associated with functional outcome at 1 year in our cohort. Twenty-six percent of patients had a modified Rankin scale score of 0 one year after the event, and functional improvement over time was common after discharge. CONCLUSIONS: A high index of clinical suspicion is needed to identify patients with CAE because of low sensitivity of free air on CT imaging and nonspecific clinical presentation. Acute alteration of consciousness, seizures, and focal signs occur frequently. Because improvement over time is possible even among patients with severe presentation, early prognostication should be approached with caution.

Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Effect of Low Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Combined with Hyperbaric Oxygen (HBO) on Awakening of Coma Patients with Traumatic Brain Injury.

Coma caused by craniocerebral injury is a common condition of neurosurgical acute injury. There is no specific method to promote awakening in a clinic. Early comprehensive treatment may be helpful to patients. The common methods are hyperbaric oxygen (HBO) and low-frequency repetitive transcranial magnetic stimulation (rTMS). However, the application effect and mechanism of rTMS combined with HBO on coma patients with traumatic brain injury need to be further studied. The brain stem auditory evoked potential (BAEP) is examined by the Kennedy coma recovery scale (CRS-R), the recovery of brain function and the state of consciousness are evaluated, and the therapeutic effect is evaluated by the Glasgow Coma Scale (GCS). Cerebrospinal fluid NE level, MCA blood flow velocity, and left brainstem and right brainstem auditory evoked potential are used to evaluate brain rehabilitation. RTMS combined with HBO could shorten the wake-up time, improve the wake-up rate, improve the GCS score and CRS-R score, shorten the brain wave latency time of the left and right brainstem, increase the NE level of cerebrospinal fluid, and decrease the blood flow velocity of MCA. RTMS combines with HBO can improve the nerve excitability of brain cells, reduce the disturbance of consciousness, promote the functional recovery of brain injury, and has a certain role in promoting the awakening of patients with traumatic brain injury coma.

Marchiafava-Bignami disease presenting as reversible coma.

Marchiafava-Bignami disease (MBD) is a rare demyelinating condition of the corpus callosum and subcortical white matter that is most commonly seen in alcoholic patients. The course of the disease varies with symptoms that range from dementia to complete coma; severe intermittent sympathetic storming with abnormal posturing is often reported in literature. It is presumably secondary to a deficiency of B complex vitamins, specifically thiamine and many patients have clinical improvement after repletion of B vitamins. We present a case of a 35-year-old man who developed MBD secondary to polysubstance misuse without history of alcohol use. His clinical course was complicated by persistent comatose state with autonomic dysfunction. After the administration of high-dose thiamine and vitamin C and E, the patient regained consciousness and was able to follow commands within 48 hours. Furthermore, this case showed recognising brain MRI findings for MBD is a crucial step in disease identification.

Fatal Wernicke's Encephalopathy with Cardiovascular Involvement in a Young Psychiatric Patient.

Wernicke's encephalopathy (WE) is an acute neurological disorder caused by thiamine deficiency that is frequently missed in non-alcoholic patients. Coma and cardiomyopathy are uncommon presentations of WE that have been rarely reported in the literature. We report the case of a 36-year-old male with a known history of schizophrenia who presented with coma and vasopressor refractory hypotension. Initial computed tomography (CT) of the head at admission was unremarkable. Transthoracic echocardiogram showed diffuse myocardial hypokinesia with a left ventricular ejection fraction of 40-45%. Due to persistent encephalopathy, a repeat non-enhanced CT head was obtained on the second day of hospital admission followed by magnetic resonance imaging (MRI) of brain that showed findings suggestive of WE. The patient was immediately started on high-dose intravenous (IV) thiamine therapy. Although his hemodynamic parameters significantly improved following thiamine replacement, he did not show signs of neurological recovery and resulted in a dismal outcome. This case illustrates the importance of early recognition of thiamine deficiency in critically ill patients to prevent fatal outcomes. Immediate parenteral thiamine administration should be considered in all patients presenting with coma, cardiomyopathy, and refractory hypotension regardless of their body mass index, and alcohol use status.

Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

Complementary roles of neural synchrony and complexity for indexing consciousness and chances of surviving in acute coma.

An open challenge in consciousness research is understanding how neural functions are altered by pathological loss of consciousness. To maintain consciousness, the brain needs synchronized communication of information across brain regions, and sufficient complexity in neural activity. Coordination of brain activity, typically indexed through measures of neural synchrony, has been shown to decrease when consciousness is lost and to reflect the clinical state of patients with disorders of consciousness. Moreover, when consciousness is lost, neural activity loses complexity, while the levels of neural noise, indexed by the slope of the electroencephalography (EEG) spectral exponent decrease. Although these properties have been well investigated in resting state activity, it remains unknown whether the sensory processing network, which has been shown to be preserved in coma, suffers from a loss of synchronization or information content. Here, we focused on acute coma and hypothesized that neural synchrony in response to auditory stimuli would reflect coma severity, while complexity, or neural noise, would reflect the presence or loss of consciousness. Results showed that neural synchrony of EEG signals was stronger for survivors than non-survivors and predictive of patients' outcome, but indistinguishable between survivors and healthy controls. Measures of neural complexity and neural noise were not informative of patients' outcome and had high or low values for patients compared to controls. Our results suggest different roles for neural synchrony and complexity in acute coma. Synchrony represents a precondition for consciousness, while complexity needs an equilibrium between high or low values to support conscious cognition.

A novel metabolic disorder in the degradation pathway of endogenous methanol due to a mutation in the gene of alcohol dehydrogenase.

BACKGROUND: A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. RESULTS: This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1-4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and appeared healthy. Organ evaluations and his laboratory tests were normal. Toxicological evaluation of his blood showed a high methanol level [12.2 mg/dL (3.8 mmol/L), normal range up to 3.5 mg/dL (1.09 mmol/L) while the formaldehyde level was undetectable. The finding of liver function tests that were within normal limits, coupled with a normal eye examination and size of the liver, elevated blood methanol levels and an undetectable formaldehyde level, suggested ADH insufficiency. Adding zinc to the drug regimen 15 mg/daily dramatically reduced the patient's methanol level and alleviated the abnormal symptoms. When zinc supplementation was discontinued, the patient relapsed into a coma and hemodialysis was once again required. A homozygous mutation in ADH1C gene located at exon 3 was found, and both parents were heterozygous for this mutation. CONCLUSION: Accumulation of methanol due to mutation in ADH1C gene may result in drunkenness and ataxia, and leads to coma. This condition can be successfully treated with zinc supplementation as the cofactor of ADH.

Disseminated Nocardia infection with a lesion occupying the intracranial space complicated with coma: a case report.

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.

The time course of acute Percheron artery ischemic coma on imaging: A retrospective cohort study.

We were to investigate the time course of lesions for awakening in acute Percheron artery ischemic coma (PAIC), which was previously unknown. Patients who had newly identified acute PAIC events in 2012-2015 and had not received thrombolytic therapy were enrolled retrospectively. The time course of lesions in PAIC was investigated by diffusion-weighted imaging (DWI). Ninety-three patients met the inclusion criteria, of whom 63 and 30 had transient PAIC and persistent PAIC, respectively. The time course of awakening events in persistent PAIC decreased over time, with large lesions in the bilateral paramedian thalamus/ rostral midbrain on DWI almost in all patients who was either plus or minus a "top of basilar artery" strokes. Whereas awakening events in transient PAIC increased over time, with small or lacunar lesions in the unilateral or bilateral thalamus/rostral midbrain about in 30.2 % cases, and the rest in naturally recanalization of infarcts or TIA. Lesion volumes were larger for persistent PAIC than for transient PAIC (median, 2.4 cm3 vs. 0.03 cm3, P < 0.0001). In Cox hazards ratio (HR) analysis, a lower GCS score was associated with mortality (HR, 5.5; 95 % confidence interval [CI],1.427-21.45). Multivaliate analysis shown that the predictors of higher risk of persistent PAIC were only increased NIHSS scores (HR,1.3; 95 % CI,1.109-1.640) and large lesions in bilateral thalamus/rostral midbrain (HR,15.0; 95 % CI,1.440-58.13). The time course of acute PAIC included transient and persistent. Most persistent PAIC was associated with large lesions in bilateral paramedian thalamus/ rostral midbrain, and with high mortality.