Dopamine/BDNF loss underscores narcosis cognitive impairment in divers: a proof of concept in a dry condition.

PURPOSE: Divers can experience cognitive impairment due to inert gas narcosis (IGN) at depth. Brain-derived neurotrophic factor (BDNF) rules neuronal connectivity/metabolism to maintain cognitive function and protect tissues against oxidative stress (OxS). Dopamine and glutamate enhance BDNF bioavailability. Thus, we hypothesized that lower circulating BDNF levels (via lessened dopamine and/or glutamate release) underpin IGN in divers, while testing if BDNF loss is associated with increased OxS. METHODS: To mimic IGN, we administered a deep narcosis test via a dry dive test (DDT) at 48 msw in a multiplace hyperbaric chamber to six well-trained divers. We collected: (1) saliva samples before DDT (T0), 25 msw (descending, T1), 48 msw (depth, T2), 25 msw (ascending, T3), 10 min after decompression (T4) to dopamine and/or reactive oxygen species (ROS) levels; (2) blood and urine samples at T0 and T4 for OxS too. We administered cognitive tests at T0, T2, and re-evaluated the divers at T4. RESULTS: At 48 msw, all subjects experienced IGN, as revealed by the cognitive test failure. Dopamine and total antioxidant capacity (TAC) reached a nadir at T2 when ROS emission was maximal. At decompression (T4), a marked drop of BDNF/glutamate content was evidenced, coinciding with a persisting decline in dopamine and cognitive capacity. CONCLUSIONS: Divers encounter IGN at - 48 msw, exhibiting a marked loss in circulating dopamine levels, likely accounting for BDNF-dependent impairment of mental capacity and heightened OxS. The decline in dopamine and BDNF appears to persist at decompression; thus, boosting dopamine/BDNF signaling via pharmacological or other intervention types might attenuate IGN in deep dives.

Thalamic strokes that severely impair arousal extend into the brainstem.

In this study, we evaluate the role of the thalamus in the neural circuitry of arousal. Level of consciousness within the first 12 hours of a thalamic stroke is assessed with lesion symptom mapping. Impaired arousal correlates with lesions in the paramedian posterior thalamus near the centromedian and parafascicular nuclei, posterior hypothalamus, and midbrain tegmentum. All patients with severely impaired arousal (coma, stupor) had lesion extension into the midbrain and/or pontine tegmentum, whereas purely thalamic lesions did not severely impair arousal. These results are consistent with growing evidence that pathways most critical for human arousal lie outside the thalamus. Ann Neurol 2018;84:926-930.

Cerebellar Hippocampal and Basal Nuclei Transient Edema with Restricted diffusion (CHANTER) Syndrome.

BACKGROUND: Abnormal restricted diffusion on magnetic resonance imaging is often associated with ischemic stroke or anoxic injury, but other conditions can present similarly. We present six cases of an unusual but consistent pattern of restricted diffusion in bilateral hippocampi and cerebellar cortices. This pattern of injury is distinct from typical imaging findings in ischemic, anoxic, or toxic injury, suggesting it may represent an under-recognized clinicoradiographic syndrome. Despite initial presentation with stupor or coma in the context of obstructive hydrocephalus, patients may have acceptable outcomes if offered early intervention. METHODS: We identified an ad hoc series of patients at our two institutions between years 2014 and 2017 who presented to the neurocritical care unit with severe, otherwise unexplained cerebellar edema and retrospectively identified several commonalities in history, presentation, and imaging. RESULTS: Between two institutions, we identified six patients-ages 33-59 years, four male-with similar presentations of decreased level of consciousness in the context of intoxicant exposure, with acute cytotoxic edema of the cerebellar cortex, hippocampi, and aspects of the basal nuclei. All patients presented with severe cerebellar edema which led to obstructive hydrocephalus requiring aggressive medical and/or surgical management. The five patients who survived to discharge demonstrated variable degrees of physical and memory impairment on discharge and at follow-up. CONCLUSIONS: We present findings of a potentially novel syndrome involving a distinct pattern of cerebellar and hippocampal restricted diffusion, with imaging and clinical characteristics distinct from ischemic stroke, hypoxic injury, and known toxidromes and leukoencephalopathies. Given the potential for favorable outcome despite early obstructive hydrocephalus, early identification and treatment of this syndrome are critical.

Electro-Radiological Observations of Grade III/IV Hepatic Encephalopathy Patients with Seizures.

BACKGROUND: Neurological complications in liver failure are common. Often under-recognized neurological complications are seizures and status epilepticus. These may go unrecognized without continuous electroencephalography (CEEG). We highlight the observed electro-radiological changes in patients with grade III/IV hepatic encephalopathy (HE) found to have seizures and/or status epilepticus on CEEG and the associated neuroimaging. METHODS: This study was a retrospective review of patients with West Haven grade III/IV HE and seizures/status epilepticus on CEEG. RESULTS: Eleven patients were included. Alcohol was the most common cause of HE (54.5%). All patients were either stuporous/comatose. The most common CEEG pattern was diffuse slowing (100%) followed by generalized periodic discharges (GPDs; 36.4%) and lateralized periodic discharges (LPDs, 36.4%). The subtype of GPDs with triphasic morphology was only seen in 27.3%. All seizures and/or status epilepticus were without clinical signs. Magnetic resonance imaging (MRI) was available in six patients. Cortical hyperintensities on diffusion weighted imaging sequence were seen in all six patients. One patient had CEEG seizure concomitantly with the MRI. Seven patients died prior to discharge. CONCLUSION: Seizures or status epilepticus in the setting of HE were without clinical findings and could go unrecognized without CEEG. The finding of cortical hyperintensity on MRI should lead to further evaluation for unrecognized seizure or status epilepticus.

Relationship of time to presentation after onset of upper GI bleeding with patient characteristics and outcomes: a prospective study.

BACKGROUND AND AIMS: We performed a prospective multi-national study of patients presenting to the emergency department with upper GI bleeding (UGIB) and assessed the relationship of time to presentation after onset of UGIB symptoms with patient characteristics and outcomes. METHODS: Consecutive patients presenting with overt UGIB (red-blood emesis, coffee-ground emesis, and/or melena) from March 2014 to March 2015 at 6 hospitals were included. Multiple predefined patient characteristics and outcomes were collected. Rapid presentation was defined as ≤6 hours. RESULTS: Among 2944 patients, 1068 (36%) presented within 6 hours and 576 (20%) beyond 48 hours. Significant independent factors associated with presentation ≤6 hours versus >6 hours on logistic regression included melena (odds ratio [OR], 0.22; 95% CI, 0.18-0.28), hemoglobin ≤80 g/L (OR, 0.47; 95% CI, 0.36-0.61), altered mental status (OR, 2.06; 95% CI, 1.55-2.73), albumin ≤30 g/L (OR, 1.43; 95% CI, 1.14-1.78), and red-blood emesis (OR, 1.29; 95% CI, 1.06-1.59). Patients presenting ≤6 hours versus >6 hours required transfusion less often (286 [27%] vs 791 [42%]; difference, -15%; 95% CI, -19% to -12%) because of a smaller proportion with low hemoglobin levels, but were similar with regard to hemostatic intervention (189 [18%] vs 371 [20%]), 30-day mortality (80 [7%] vs 121 [6%]), and hospital days (5.0 ± 0.2 vs 5.0 ± 0.2). CONCLUSIONS: Patients with melena alone delay their presentation to the hospital. A delayed presentation is associated with a decreased hemoglobin level and increases the likelihood of transfusion. Other outcomes are similar with rapid versus delayed presentation. Time to presentation should not be used as an indicator for poor outcome. Patients with delayed presentation should be managed with the same degree of care as those with rapid presentation.

Steak and Stupor: seizures and E. coli O157 infection.

Neurological complications of haemolytic uraemic syndrome (HUS) include altered states of consciousness, seizures, ischaemic stroke and encephalopathy. Adult-onset HUS is uncommon, and there is only a limited literature reporting neurological complications in this population. We report an adult with Shiga toxin-associated HUS complicated by focal-onset non-convulsive status epilepticus, who made a full neurological recovery.

[Unconsciousness and clouded awareness]. / Bewusstseinsstörung oder -trübung.

Stupor and coma are clinical states in which patients have impaired responsiveness or are unresponsive to external stimulation and are either difficult to arouse or are unarousable. The term stupor refer to states between alertness and coma. An alteration in arousal represents an acute life-threatening emergency, requiring prompt intervention for preservation of life and brain function.

Wax on, wax off: a rare case of catatonia.

Catatonia was first described by a German psychiatrist, Karl Kahlbaum, in 1874. It is a behavioral syndrome marked by an inability to move normally, which can occur in the context of many underlying general medical and psychiatric disorders. A wide variety of neurologic, metabolic, drug-induced, and psychiatric causes of catatonia have been reported. We present a unique case of late onset catatonia in a 56-year-old man with no prior medical or psychiatric history initially presenting with stroke-like symptoms. The patient was awake and alert, with spontaneous eye opening, but completely nonverbal and not following any commands. Specifically, the patient demonstrated stupor, catalepsy, mutism, and negativism. After extensive emergency department testing, including negative computed tomography head, negative magnetic resonance imaging brain, negative electroencephalogram, and normal laboratory results, the patient was diagnosed with new-onset bipolar disorder with depressive features presenting as catatonia. Recognizing catatonia is important because it may be caused or exacerbated by treatment of the underlying disorder. Failure to institute treatment early in the course of catatonia is associated with a poor prognosis.

Evaluation of obstetrical factors related to Sheehan syndrome.

AIM: To evaluate factors related to the occurrence of Sheehan syndrome. METHODS: The obstetrical disseminated intravascular coagulation score, total volume of hemorrhage, shock index, level of consciousness at the time of shock occurrence and pituitary magnetic resonance imaging findings were evaluated in nine women who showed massive hemorrhage during delivery. These clinical outcomes were analyzed in all these patients who were prospectively followed-up to identify any possible occurrence of Sheehan syndrome. RESULTS: Compared to six women with non-Sheehan syndrome, three women who were diagnosed with Sheehan syndrome showed significant elevation of the obstetrical disseminated intravascular coagulation score, decrease in the level of consciousness during shock and remarkable pituitary gland atrophic change with an empty sella turcica detected by pituitary magnetic resonance imaging. The volume of hemorrhage during delivery and shock index were not significantly different between these two groups of women. CONCLUSION: Careful attention and follow-up should be paid to women with post-partum massive hemorrhage for early detection and management of women with Sheehan syndrome.

[Endovascular coiling of a «true¼ posterior communicating artery aneurysm]. / Tratamiento endovascular de un aneurisma «verdadero¼ de la arteria comunicante posterior.

True posterior communicating artery aneurysms originate exclusively from the wall of this artery and should be differentiated from aneurysms of the posterior communicating segment of the distal carotid artery. As these lesions are rare, their anatomical relationships have been poorly described; likewise, reports concerning their endovascular treatment are extremely rare and the technical aspects poorly detailed. A case of a patient with a true aneurysm of the left posterior communicating artery treated by endovascular coiling is presented. A literature review was also conducted to illustrate the anatomical and technical details relevant to achieving its successful treatment.

Predictors of five days mortality in diabetic ketoacidosis patients: a prospective cohort study.

AIM: to determine the role of serum lactate and diabetic ketoacidosis (DKA) severity as predictors for five-days mortality in DKA patients. METHODS: a prospective cohort study was conducted in DKA patients admitted to emergency department (ED) at Cipto Mangunkusumo Hospital, Jakarta, Indonesia, during 2007-2008 periods. Predictors for 5 days mortality in DKA patients in this study including serum lactate and DKA severity (plasma glucose, arterial blood pH, serum bicarbonate, osmolality, anion gap, and alteration in sensorium) at admission. Cox's Proportional Hazard Regression Analysis was used to determine independent predictors for 5-days mortality among study population. RESULTS: sixty patients with diabetic ketoacidosis were enrolled in the study; in which 24 (40%) patients were died within 5 days after admission. In the multivariate analysis, the lactate level 4 mmol/L (HR, 3.09; 95% CI, 1.36-7.05) and altered in sensorium stuporous/comatose (HR, 3.38; 95% CI, 1.45-7.87) were identified as independent predictors for 5-days mortality in DKA adult patients. CONCLUSION: lactate level 4 mmol/L and altered in sensorium stuporous/comatose can be used to predict 5-days mortality in adult patients with DKA.

Case Report of Retarded Catatonia: Always Consider Catatonia as a Differential Diagnosis of Altered Mental Status.

BACKGROUND: Catatonia is a rare neuropsychiatric condition; it is estimated that around 10% of patients with mood disorders present signs and symptoms of catatonia. A catatonic syndrome is characterised by mutism, negativism, rigidity, and stupor. CASE REPORT: We report the case of a 59-year-old patient with a medical history of bipolar disorder who was admitted to the internal medicine service due to a seizure episode. During hospitalisation, the patient presented significant worsening of her clinical condition, showing marked symptoms of stupor and catatonia. Once the neurological and metabolic etiologies of altered mental status had been ruled out, pharmacological treatment with high doses of lorazepam was started. The patient had a complete clinical remission, and her evolution was favourable without any complications. Electroconvulsive therapy was recommended as a definitive treatment. CONCLUSIONS: The diagnosis of catatonia is a challenge for both hospitalists and psychiatrists due to the clinical presentation of catatonia. In reporting this clinical case, we want to emphasise the importance of taking into account the catatonic syndrome in our differential diagnoses in patients with altered mental status.

Outcomes of patients admitted for hanging injuries with decreased consciousness but without cardiac arrest.

OBJECTIVE: The objective of this study is to provide appropriate treatment of patients who showed decreased mentality but did not suffer cardiac arrest (CA) from hanging injury, from reviewing the characteristics and analyzing the outcomes in such patients. METHODS: A retrospective review of victims with decreased mentality but without CA due to hanging presenting to 2 tertiary general hospitals between January 2005 and August 2011 was performed. Treatments and examinations were evaluated, and the outcomes were assessed by cerebral performance category at hospital discharge. RESULTS: A total of 21 patients were included, and their initial Glasgow Coma Scale scores were between 3 and 11. No one received therapeutic hypothermia, but all regained consciousness spontaneously and were discharged with cerebral performance category 1. They received only conservative treatment such as respiratory care, fever control, and inotropic use. Computed tomography and magnetic resonance imaging studies revealed no definite abnormality if the patient did not show abnormal symptom and sign. CONCLUSION: Unconscious patients without CA from hanging could recover consciousness through conservative treatment.

Physical and physicochemical factors effecting transport of chlorohydrocarbon gases from lung alveolar air to blood as measured by the causation of narcosis.

This systematic investigation examines gas transport in the lung for two sets of chlorohydrocarbons (CHCs): the chloromethanes (C1) and chloroethanes (C2). The C1 series includes chloromethane, methylene chloride, chloroform, and carbon tetrachloride, and the C2 series includes chloroethane, 1,2-dichloroethane, 1, 1, 2-trichloroethane, and 1, 1, 2, 2-tetrachloroethane. Most CHC gases cause narcosis. The comprehensive narcosis work of Lehmann and colleagues on CHCs was used as a basis for the narcosis endpoint in the present examination. The sites for narcosis are located in the brain (midline cortex and posterior parietal area), the spine, and at many peripheral nerve sites. Central nervous system (CNS) exposure executes a multisite, neural transmission set of inhibitions that promotes rapid loss of consciousness, sensory feeling, and current and stored memory while providing temporary amnesia. Absorption into the system requires dissolution into many lipid membranes and binding to lipoproteins. Lipophilicity is a CHC property shared with many anesthetics according to the Meyer-Overton Rule. Many structurally different lipid chemicals produce the narcosis response when the lipid concentration exceeds -67 mM. This suggests narcotic or anesthetic dissolution into CNS membranes until the lipid organization is disrupted or perturbed. This perturbation includes loading of Na(+)- and K(+)-channel transmembrane lipoprotein complexes and disrupting their respective channel functional organizations. The channel functions become attenuated or abrogated until the CHC exposure ceases and CHC loading reverses. This investigation demonstrates how the CHC physical and chemical properties influence the absorption of these CHCs via the lung and the alveolar system on route to the blood. Narcosis in test animals was used here as an objective biological endpoint to study the effects of the physical factors Bp, Vp, Kd (oil: gas) partition, Henry's constant (HK), and water solubility (S%) on gas transport. Narcosis is immediate after gas exposure and requires no chemical activation only absorption into the blood and circulation to CNS narcotic sites. The three physical factors Bp, K(d) (oil: air), and S% vary directly with unitary narcosis (UN) whereas Vp and HK vary inversely with UN in linear log-log relationships for the C2 series but not for the C1 series. Physicochemical properties of C1 series gases indicate why they depart from what is usually assumed to be an Ideal Gas. An essential discriminating process in the distal lung is the limiting alveolar film layer (AFL) and the membrane layer of the alveolar acini. The AFL step influences gas uptake by physically limiting the absorption process. Interaction with and dissolution into aqueous solvent of the AFL is required for transport and narcotic activity. Narcotics or anesthetics must engage the aqueous AFL with sufficient strength to allow transport and absorption for downstream CNS binding. CHCs that do not engage well with the AFL are not narcotic. Lipophilicity and amphipathicity are also essential solvency properties driving narcotics' transport through the alveolar layer, delivery to the blood fats and lipoproteins, and into critical CNS lipids, lipoproteins, and receptor sites that actuate narcosis. AFL disruption is thought to be strongly related to a number of serious pulmonary diseases such acute respiratory distress syndrome, infant respiratory distress syndrome, emphysema, chronic obstructive pulmonary disease, asthma, chronic bronchitis, pneumonia, pulmonary infections, and idiopathic pulmonary fibrosis. The physical factors (Bp, Vp, Kd [oil: gas] partition, Henry's constant, and water solubility [S%]) combine to affect a specific transport through the AFL if lung C > C(0) (threshold concentration for narcosis). The degree of blood CHC absorption depends on dose, lipophilicity, and lung residence time. AFL passage can be manipulated by physical factors of increased pressure (kPa) or increased gas exposure (moles). Molecular lipophilicity facilitates narcosis but lipophilicity alone does not explain narcosis. Vapor pressure is also required for narcosis. Narcotic activity apparently requires stereospecific processing in the AFL and/or down-stream inhibition at stereospecific lipoproteins at CNS inhibitory sites. It is proposed that CHCs likely cannot proceed through the AFL without perturbation or disruption of the integrity of the AFL at the alveoli. CHC physicochemical properties are not expected to allow their transport through the AFL as physiological CO(2) and O(2) naturally do in respiration. This work considers CHC inspiration and systemic absorption into the blood with special emphasis on the CHC potential perturbation effects on the lipid, protein liquid layer supra to the alveolar membrane (AFL). A heuristic gas transport model for the CHCs is presented as guidance for this examination. The gas transport model can be used to study absorption for other gas delivery endpoints of environmental concern such as carcinogens.

Cognitive outcome of cerebral fat embolism.

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory.

High altitude induced bilateral non-traumatic subdural hematoma.

BACKGROUND: Minor clinical complaints such as headache and drowsiness after a disco party with alcohol abuse may be an unlikely cause for neurological consultation, but, rarely, they may hide a challenging diagnosis. CASE REPORT: A young male patient admitted to our Neurosurgical Department for progressive headache showed a sudden clinical deterioration of consciousness; head CT scan was promptly obtained and thick bilateral subdural hematomas requiring urgent craniotomies and drainage were detected. While his anamnesis was surprisingly negative for head trauma, coagulopathies, or other common causes of subdural hematoma, he reported a curious history of 10-d onset of symptoms after a farewell disco party on a high-altitude location, almost 9000 ft (>2700 m) above mean sea level, followed by an intercontinental flight back to his seaside hometown. Following surgery the patient eventually experienced a rapid recovery from this frightening experience. DISCUSSION: Due to its uniqueness, the case is reported and the influence of possible provoking causes relevant in the pathogenesis of subdural hematomas is carefully outlined.

Modified electroconvulsive therapy for recurrent major depressive disorder in a meningioma patient: a case report of clinical experience.

Electroconvulsive therapy (ECT) is primarily indicated for mood disorders and schizophrenia. Clinicians may encounter cases in which ECT is administered to patients with various kinds of complications. However, to our knowledge, no detailed medical guideline is available about the indications for ECT in psychiatric illness complicated with a concomitant brain tumor, which is one of the most likely physical complications that can directly affect ECT. We report a case in which 3 courses of modified ECT (m-ECT) were successfully administered without any neurological deterioration to a patient, who was frequently hospitalized for recurrent depressive disorder with stupor. We did not undertake any additional measures for reducing adverse events derived from the meningioma during m-ECT. In this report, we discuss the relation between brain tumor and depression.

Common Carotid Artery Occlusion in a Young Patient: Can Large-Vessel Stroke Be the Initial Clinical Manifestation of Coronavirus Disease 2019?

BACKGROUND: The occurrence of large-vessel occlusion in young patients with coronavirus disease 2019 (COVID-19) infection has been exceedingly rare. An extensive review of reported studies revealed a few reported cases. In the present report, we have described the clinical presentation, radiological findings, and outcome of large-vessel occlusion in a young patient with COVID-19 and reviewed the pertinent reported data on this condition. CASE DESCRIPTION: A 31-year-old woman was in her usual state of health until she had presented with a 3-day history of right-sided weakness, slurred speech, and decreased vision. The patient had been taken to several hospitals where she had been treated conservatively with analgesics and discharged. Shortly thereafter, her weakness had become progressive. She had become severely dysarthric and unresponsive. On arrival to the emergency department, her physical examination revealed that she was stuporous, with a Glasgow coma scale of 10 (eye response, 3; verbal response, 2; motor response, 5). The National Institutes of Health Stroke Scale score was 19 on presentation. Brain computed tomography and computed tomography venography revealed an occluded left internal carotid artery and left middle cerebral artery with subacute left middle cerebral artery territory infarction and midline shift. Computed tomography angiography revealed complete occlusion of the left common carotid artery. An emergent decompressive craniectomy was successfully performed. The patient was shifted to the intensive care unit. She was later found to be positive for COVID-19. CONCLUSIONS: Although rare, patients with COVID-19 can present with large-vessel occlusion. Prompt identification of COVID-19-related coagulopathy is essential to assess young patients with clinical manifestations of infarction.

Delayed Diagnosis of Postintubation Tracheal Stenosis due to the Coronavirus Disease 2019 Pandemic: A Case Report.

Tracheal stenosis is an uncommon but severe problem after long-term intubation. Here, we report a patient who came from a containment zone of coronavirus disease 2019 (COVID-19) and presented with complaints of breathlessness and cough. She was suspected to have an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Later, she developed type 2 respiratory failure and carbon dioxide narcosis because of delay in diagnosis of severe, near-complete postintubation tracheal stenosis due to over suspicion of COVID-19 during the current pandemic.