Clinical observations in acute neurology: A historical explanation of the present.

BACKGROUND: The history of the development of acute neurologic disease as a biologic mechanism is of interest. Equally important is how it translated to the bedside and how the clinical examination differentiated itself. METHODS: This paper reviews primary sources pertaining to acute neurologic conditions described mostly in the 19th and 20th century. A review of monographs, treatises, textbooks, and peer-reviewed articles was conducted. RESULTS: The evolution of clinical signs and syndromes associated with dynamic intracranial pathologies was predicated on the idea that animal studies informed clinicians, who then linked clinical signs to these observations. A dominant theme is that innovative technologies could trace acute processes through all their various stages, affording a complete picture of the disease process. Just as clinical descriptors of central nervous system processes evolved, the presentation of acute neuromuscular respiratory failure became better defined. Once practices incorporated these acute clinical signs, textbooks cemented their "gold standard" status with relative impunity. CONCLUSIONS: The practise of acute neurology and neurocritical care must find out what, historically, others were seeking but could not find. Patterns of clinical presentation in acute neurology are sufficiently recognizable to guide practise decisions. Although, the currently well-documented clinical syndromes of acute neurologic conditions (at presentation and during deterioration) have been taught for generations, practitioners have noted that they lack consistency and predictability. History also taught us that part of this improved knowledge came with designated units-a clear example of how protean systems (not always innovative neurologists or neuroscientists or technologies) shaped the history of neurology.

Improving Outcome in Severe Myasthenia Gravis and Guillain-Barré Syndrome.

When progressive and severe, myasthenia gravis and Guillain-Barré syndrome may have the potential for fatal and unfavorable clinical outcomes. Regardless of important differences in their clinical course, the development of weakness of oropharyngeal muscles and respiratory failure with requirement of mechanical ventilation is the main driver of poor prognosis in both conditions. The need for prolonged mechanical ventilation is particularly relevant because it immobilizes the patient and care becomes extraordinarily complex due to daily risks of systemic complications. Additionally, patients with myasthenia gravis often require long-term immunosuppressive treatments with associated toxicity and infectious risks. Unlike myasthenia gravis, the recovery period is prolonged in Guillain-Barré syndrome, but often favorable, even in the more severely affected patients. Outcome, for a large part, is determined by expert neurocritical care.

The Language of the UDDA is Sufficiently Precise and Pragmatic.

We have a reason to value the Uniform Determination of Death Act (UDDA). Since enactment, the UDDA has been of paramount importance to US citizens, families of comatose patients, and the health care professionals who care for them. The UDDA sets forth two standards for determining death and leaves to the medical community to elaborate criteria by which physicians can determine when those standards have been met. Neurologists and neurocritical care experts always have been center stage in this effort. Perfectly established, why change it? What ignited the recent review of the UDDA were lawsuits questioning medical (neurological) authority leading to the wording and accuracy of the UDDA being revisited. The major objections to the language of the UDDA by several groups led a committee appointed by the Uniform Law Commission to consider several substantial changes in the Act. After several years of discussion without reaching a consensus, the committee's chair suspended the effort. Upending the UDDA will lead to a legal crisis and confusion across the states. We present our main arguments against revising this statute and argue that the committee's failure to revise the UDDA should actually be seen as a necessary success.

Locked in from fulminant GBS after lumbar spine surgery.

Guillain-Barré syndrome (GBS) describes a neurological syndrome characterised by acute, areflexic paralysis, often preceded by an immune stimulating event such as infection or surgery. Spinal surgery as an inciting event is very uncommon with few reported cases. When paraparesis develops in close proximity of surgery, surgical complications should be considered, but if an asymptomatic clinical interval precedes a progressive ascending weakness this association weakens and may support an immunological mechanism. GBS after lumbar surgery is wholly unexpected and thus there are significant challenges in recognising and making the diagnosis. We report a case of fulminant GBS that progressed to loss of all motor function following elective lumbar spine surgery.

The Origin of the Burst-Suppression Paradigm in Treatment of Status Epilepticus.

After electroencephalography (EEG) was introduced in hospitals, early literature recognized burst-suppression pattern (BSP) as a distinctive EEG pattern characterized by intermittent high-power oscillations alternating with isoelectric periods in coma and epileptic encephalopathies of childhood or the pattern could be induced by general anesthesia and hypothermia. The term was introduced by Swank and Watson in 1949 but was initially described by Derbyshire et al. in 1936 in their study about the anesthetic effects of tribromoethanol. Once the EEG/BSP pattern emerged in the literature as therapeutic goal in refractory status epilepticus, researchers began exploring whether the depth of EEG suppression correlated with improved seizure control and clinical outcomes. We can conclude that, from a historical perspective, the evidence to suppress the brain to a BSP when treating status epilepticus is inconclusive.

Identifying encephalopathies from acute metabolic derangements.

Metabolic derangements, when acute and severe, affect brain function. This presents mostly with a marked decline in the level of consciousness, resulting in impaired responsiveness, abnormal receptivity, impaired content, and loss of memory retention. The term metabolic encephalopathy has been used but is conjecture that can be challenged in the age of modern neuroimaging. We now recognize that many metabolic encephalopathies may involve structural lesions and at an early stage. Common clinical conundrums are the evaluation of the degree of brain injury and its recoverability. This review discusses the appropriate terminology for these conditions, the diagnostic approach, therapy recommendations, and prediction of recovery potential. In evaluating a presumed metabolic cause for encephalopathy, we must (1) search for and rule out structural injury to the brain despite an obvious explanatory metabolic derangement, (2) recognize that several confounding conditions often co-exist, and (3) acknowledge that resolution of brain dysfunction may be protracted despite normalization of laboratory values.

Cinema's Terrifying Realities: Pandemics, Zombification, and SARS-COV-2.

Contagion is a function of the properties of the pathogen, social interactions, and personal relationships in the society it attacks. Filmmakers in the horror genre were inspired by the idea of rabies as a virus that could mutate into something more dangerous. Fictional epidemics of scavenging undead were often attributed to encephalitis caused by rabies or a mutated rabies virus. During the early months of the SARS-COV-2 pandemic, there was a spike in streaming of Contagion that portrays a viral infectious disease modeled after a bat virus that spreads at an alarming rate, unleashing a global public panic and a clueless governmental response. We wanted to trace how filmmakers used rabies pathology as source material for their plots. We searched internet film databases and reviewed fictional films that utilized this plot device. Many dystopic, rabies-induced pandemic scenarios - mostly from the zombie genre - reveal parallels to the COVID-19 pandemic. Many zombie films, despite their absurd premise, anticipated the realities of future pandemics.

What is It Like to be Delirious?

The current terminology of delirium and encephalopathy is open to debate. As with any poorly understood disorder with an unknown mechanism, there is a range of opinions. Attention must be paid to a proliferation of new terms and the ease with which they were introduced. In this viewpoint article, the authors invite the readers to return to the patient and rethink linguistic usage. The meaning of terms will be determined by their use rather than by authoritative description. We conclude that the suggested terminology of delirium is subjective, unsatisfactory, and may seriously hamper scholarly work. Rather than expand the definitions of types of delirium and separate them from encephalopathy, we advocate a definition-encephalopathy with or without characteristics of delirium-with the understanding that agitated patients in a delirium are innately encephalopathic. We subscribe to the prevailing neurologic description of delirium. This would allow sufficient granularity for bedside use and prospective studies.

Status Myoclonus with Post-cardiac-arrest Syndrome: Implications for Prognostication.

BACKGROUND: Status myoclonus (SM) after cardiac arrest (CA) may signify devastating brain injury. We hypothesized that SM correlates with severe neurologic and systemic post-cardiac-arrest syndrome (PCAS). METHODS: Charts of patients admitted with CA to Mayo Clinic Saint Marys Hospital between 2005 and 2019 were retrospectively reviewed. Data included the neurologic examination, ancillary neurologic tests, and systemic markers of PCAS. Nonsustained myoclonus was clinically differentiated from SM. The cerebral performance category score at discharge was assessed; poor outcome was a cerebral performance category score > 2 prior to withdrawal of life-sustaining therapies or death. RESULTS: Of 296 patients included, 276 (93.2%) had out-of-hospital arrest and 202 (68.5%) had a shockable rhythm; the mean time to return of spontaneous circulation was 32 ± 19 min. One hundred seventy-six (59.5%) patients had a poor outcome. One hundred one (34.1%) patients had myoclonus, and 74 (73.2%) had SM. Neurologic predictors of poor outcome were extensor or absent motor response to noxious stimulus (p = 0.02, odds ratio [OR] 3.8, confidence interval [CI] 1.2-12.4), SM (p = 0.01, OR 10.3, CI 1.5-205.4), and burst suppression on EEG (p = 0.01, OR 4.6, CI 1.4-17.4). Of 74 patients with SM, 73 (98.6%) had a poor outcome. A nonshockable rhythm (p < 0.001, OR 4.5, CI 2.6-7.9), respiratory arrest (p < 0.001, OR 3.5, CI 1.7-7.2), chronic kidney disease (p < 0.001, OR 3.1, CI 1.6-6.0), and a pressor requirement (p < 0.001, OR 4.4, CI 1.8-10.6) were associated with SM. No patients with SM, anoxic-ischemic magnetic resonance imaging findings, and absent electroencephalographic reactivity had a good outcome. CONCLUSIONS: Sustained status myoclonus after CPR is observed in patients with other reliable indicators of severe acute brain injury and systemic PCAS. These clinical determinants should be incorporated as part of a comprehensive approach to prognostication after CA.

Twitter Journal Club Impact on Engagement Metrics of the Neurocritical Care Journal.

BACKGROUND: Twitter journal clubs are a modern way of highlighting articles published in a scientific journal. The Neurocritical Care journal (NCC) initiated a bimonthly, Twitter-based, online journal club in 2015 to increase the outreach of its published articles. We hypothesize that articles included in the Neurocritical Care Society Twitter Journal Club (NCSTJC) had greater engagement than other articles published during the same time period. We also investigated the relationship between number of citations and Altmetric score to assess whether the enhanced online activity resulted in higher citations. METHODS: We gathered data in August 2020 on engagement metrics (number of downloads, Altmetric score, relative citation ratio, and number of citations) of all articles published in NCC between 2015 and 2018. Articles were analyzed into two groups: one featured in NCSTJC and the rest that were not (non-NCSTJC1), and the other comprised those that were not in NCSTJC but published under a similar category of articles as NCSTJC (non-NCSTJC2). Results were analyzed using descriptive statistics, and summary measures were used to report the spread. The groups were compared by using the Wilcoxon rank sum test, given that the data were not normally distributed. Spearman's rank correlation was used to assess correlation between Altmetric score and citations for the articles in the NCSTJC and non-NCSTJC groups. For comparison, the top ten cited articles in NCC were analyzed for similar correlations. RESULTS: Between 2015 and 2018, NCC published 529 articles, 24 of which were included in the Twitter journal club. A total of 406 articles were published in the same category as the category of articles selected for NCSTJC. The articles discussed as a part of NCSTJC had a statistically significant trend toward a higher number of downloads, Altmetric score, relative citation ratio, and number of citations than rest of the articles published in the journal during the same time period and the rest of the articles published in same categories. Three NCSTJC articles were among the ten most-cited articles published by NCC between 2015 and 2018. We did not find a correlation between Altmetric scores and number of citations in the NCSTJC or non-NCSTJC1 or non-NCSTJC2 group, but there was a strong correlation between these two variables in high performing articles when the top ten cited articles were analyzed. CONCLUSIONS: Scientific journals are evolving their social media strategies in attempt to increase the outreach of their articles to the medical community. Platforms such as Twitter journal clubs can enhance such engagement. The long-term influence of such strategies on the impact factor of a medical journal and traditional engagement metrics, such as citations, calls for further research.

Hospital to Hospital Transfers of Cerebral Hemorrhage: Characteristics of Early Withdrawal of Life-Sustaining Treatment.

BACKGROUND: Large intracerebral hemorrhages (ICHs) are associated with significant morbidity and mortality. Patient transfer to higher level centers is common, but care in these centers rarely demonstrably improves morbidity or reduces mortality. Patients may rapidly progress to brain death, but a large number die shortly after transferring because of withdrawal of life-sustaining treatment (WOLST). This outcome may result in poor resource use and unnecessary cost to patients, families, and institutions. We sought to determine clinical and radiographic predictors of early death or WOLST that may alter potential transfer. METHODS: We performed a retrospective review of patients admitted from outside medical centers to the neurosciences intensive care unit at Saint Marys Mayo Clinic Hospital in Rochester, MN, from January 2014 to December 2019. Patients ≥ 18 years old with a spontaneous ICH were included. Exclusion criteria included trauma, subarachnoid hemorrhage, and subdural hematoma. We identified patients who died or underwent WOLST within 24 h of transfer. Descriptive characteristics of patients and ICH were collected. Data were analyzed with univariable, multivariable, and logistic regression. Predictive modeling was performed. An additional case-matched study was completed to evaluate for characteristics further. RESULTS: A total of 317 consecutive patients were identified. Forty-two patients were found with early death or WOLST within 24 h of transfer. Do not resuscitate/do not intubate (DNR/DNI) code status (odds ratio [OR] 5.23, confidence interval [CI] 3.31-8.28), anticoagulation use (OR 2.11, CI 1.09-4.09), and lower level of consciousness at presentation based on Glasgow Coma Score (OR 1.41, CI 1.29-1.54) and Full Outline of Unresponsiveness (FOUR) score (OR 1.34, CI 1.26-1.46) were associated with WOLST. Associated characteristics on the computed tomography scan included midline shift (OR 4.64, CI 2.32-9.29), hydrocephalus (OR 9.30, CI 4.56-18.96), and intraventricular extension (OR 5.27, CI 2.60-10.68). Case matching restricted to midline shift demonstrated similarity between patients with aggressive care and WOLST. DNR/DNI code status, warfarin use, ICH score, and composite FOUR score were the best predictive characteristics (area under the curve 0.942). CONCLUSIONS: Early death or WOLST after ICH within 24 h of presentation was most associated with DNR/DNI code status, warfarin use, ICH score, and lower level of consciousness at presentation. These characteristics may be used by clinicians to guide conversations prior to transfer to tertiary care centers.

Repeat Catheter Angiography in Patients with Aneurysmal-Pattern Angiographically Negative Subarachnoid Hemorrhage.

BACKGROUND: A significant proportion of patients with subarachnoid hemorrhage have a normal cerebral angiogram. Patients with angiographically negative subarachnoid hemorrhage (anSAH) with either perimesencephalic- (panSAH) or aneurysmal-pattern hemorrhage (aanSAH, also known as diffuse anSAH) have an excellent prognosis, but only if underlying vascular abnormalities are completely excluded. The rate of occult aneurysms in patients with aanSAH varies widely across studies. The purpose of this study was to quantify the value of repeat DSA in these patients. METHODS: We reviewed the records of all patients initially diagnosed with aanSAH after a screening DSA at a single tertiary neurovascular referral center from January 2006-April 2018. Patients with panSAH and traumatic SAH were excluded. We also performed a systematic review and meta-analysis of positive second DSAs in previously published case series of patients with aanSAH who underwent two serial DSAs. For meta-analysis, PubMed Central, MEDLINE and Cochrane Library databases were searched for pertinent studies up to November 2019. The rate of aneurysm detection on repeat angiography was extracted from each study. Pooled rates for positive second angiogram were calculated as untransformed proportions in a binary random-effects model meta-analysis. Inter-study heterogeneity was calculated using an I2 statistic. RESULTS: Three of 27 patients (11.1%) with aanSAH and at least two DSAs were subsequently found to have a cerebral aneurysm in our institutional dataset. Twenty-six studies in our systematic review met inclusion criteria, and the pooled rate of positive second angiogram was 10.4% (95% CI 7.3%-13.5%, P < 0.001). Substantial inter-study heterogeneity was observed in the meta-analysis (I2 = 61.7%, P < 0.001). CONCLUSIONS: One in 10 patients with aanSAH has an occult ruptured aneurysm. A second-look DSA should be strongly considered in these cases.

Mycotic aneurysm.

Angioinvasive fungal infections of the cerebral vasculature often lead to significant morbidity and mortality. High clinical suspicion and early antifungal therapy could improve outcomes. We describe the fatal case of a patient with a rapidly enlarging cavernous carotid aneurysm due to angioinvasive fungus. This case highlights the challenges in diagnosis and management of this condition.

Preadmission Antiplatelet Use and Associated Outcomes and Costs Among ICU Patients With Intracranial Hemorrhage.

INTRODUCTION: Patients with intracranial hemorrhage (including intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic hemorrhage) are commonly admitted to the intensive care unit (ICU). Although indications for oral antiplatelet agents are increasing, the impact of preadmission use on outcomes in patients with intracranial hemorrhage admitted to the ICU is unknown. We sought to evaluate the association between preadmission oral antiplatelet use, in-hospital mortality, resource utilization, and costs among ICU patients with intracranial hemorrhage. METHODS: We retrospectively analyzed a prospectively collected registry (2011-2016) and included consecutive adult patients from 2 hospitals admitted to ICU with intracranial hemorrhage. Patients were categorized on the basis of preadmission oral antiplatelet use. We excluded patients with preadmission anticoagulant use. The primary outcome was in-hospital mortality and was analyzed using a multivariable logistic regression model. Contributors to total hospital cost were analyzed using a generalized linear model with log link and gamma distribution. RESULTS: Of 720 included patients with intracranial hemorrhage, 107 (14.9%) had been using an oral antiplatelet agent at the time of ICU admission. Oral antiplatelet use was not associated with in-hospital mortality (adjusted odds ratio: 1.31 [95% confidence interval [CI]: 0.93-2.22]). Evaluation of total costs also revealed no association with oral antiplatelet use (adjusted ratio of means [aROM]: 0.92 [95% CI: 0.82-1.02, P = .10]). Total cost among patients with intracranial hemorrhage was driven by illness severity (aROM: 1.96 [95% CI: 1.94-1.98], P < .001), increasing ICU length of stay (aROM: 1.05 [95% CI: 1.05-1.06], P < .001), and use of invasive mechanical ventilation (aROM: 1.76 [95% CI: 1.68-1.86], P < .001). CONCLUSIONS: Among ICU patients admitted with intracranial hemorrhage, preadmission oral antiplatelet use was not associated with increased in-hospital mortality or hospital costs. These findings have important prognostic implications for clinicians who care for patients with intracranial hemorrhage.

HIT in the head: a systematic review of cerebral venous sinus thrombosis in classical and autoimmune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) causes thrombosis and thrombocytopenia, usually due to prior heparin exposure, so-called classical HIT. However, in the autoimmune form, the signs and symptoms of HIT occur without prior heparin exposure. Development of cerebral venous sinus thrombosis (CVST) secondary to HIT is a rare occurrence, with relatively few reports in the literature. There is a need to better understand the clinical presentation and treatment paradigms in these rare cases. Therefore, we present the first systematic review of CVST occurring in classical and autoimmune HIT. Cases of HIT-induced CVST were identified through a systematic search of Pubmed from the date of inception to March 2021. Literature search revealed 21 cases of HIT and associated CVST with six cases (28.6%) of autoimmune HIT. Patients presented with signs and symptoms consistent with increased intracranial pressure, intracerebral hemorrhage (ICH), and/or focal neurologic deficits. Headache was the most common symptom with 12 patients (60.0%) presenting as such. 10 patients (47.6%) included in the study developed ICH. Non-heparin anticoagulants, especially direct thrombin inhibitors, were the first-line treatment for the majority of patients (55.6%). Intravenous immunoglobulin (IVIG) was used as treatment for select patients (16.7%) with autoimmune HIT. Few patients received surgical intervention for CVST (14.3%) or ICH (30.0%). Four patients had a full recovery, four patients had residual deficits, and seven patients ultimately expired. Symptoms of HIT-induced CVST are often related to CNS dysfunction. Non-heparin anticoagulants are important to treat CVST, even when patients have concomitant ICH, and may be supplemented with IVIG if treating autoimmune HIT. Rapid identification and treatment of HIT-induced CVST is imperative in order to prevent morbidity and mortality.

Communicating Neurocritical Illness: The Anatomy of Misunderstanding.

We talk, text, email all day. Do we perceive things correctly? Do we need to improve the way we communicate? It is a truism that providing insufficient information about a patient results in delays and errors in management. How can we best communicate urgent triage or urgent changes in the patient condition? There is no substitute for a face-to-face conversation but what would the receiving end want to know? One starting point for those practicing acute neurology and neurocritical care is a new mnemonic TELL ME (Time course, Essence, Laboratory, Life-sustaining interventions, Management, Expectation), which will assist physicians in standardizing their communication skills before they start a conversation or pick up a phone. These include knowing the time course (new and "out of the blue" or ongoing for some time); extracting the essentials (eliminating all irrelevancies); communicating what tests are known and pending (computerized tomography and laboratory); relaying how much critical support will be needed (secretion burden, intubation, vasopressors); knowing fully which emergency drugs have been administered (e.g., mannitol, antiepileptics, tranexamic acid), when transport is anticipated, and what can be expected in the following hours. Perfect orchestration in communication may be too much to ask, but we neurointensivists strive to convey information accurately and completely. Communication must be taught, learned, and practiced. This article provides guiding principles for a number of scenarios involving communication inside and outside the hospital.

Predicting Coma Trajectories: The Impact of Bias and Noise on Shared Decisions.

Coma trajectories are characterized by quick awakening or protracted awakening. Outcome is bookended by restored functionality or permanent cognitively and physically debilitated states. Given the stakes, prognostication cannot be easily questioned as a judgment call, and a scientific underpinning is elemental. Conventional wisdom in determining coma-outcome trajectories posits that (1) predictive models are better than personal experiences, (2) self-fulfilling prophesy is unchecked and driven by nihilism, with little regard for prior probability outcomes, and (3) recovery is impacted by patients' prior wishes and preexisting medical conditions-but also by what families are told about the patient's state and anticipated clinical course. Moreover, a predicted good outcome can be offset by a major subsequent complication, or a predicted poor outcome can be offset by aggressive care. This article examines some of these concepts, including how we decide on aggressiveness of care, how we judge quality of life, and the impact on outcome. Most patients who awaken quickly do well and can resume their pretrauma injury lives. In worse off, slow-to-awaken patients, outcomes are a mixed bag of limited innate resilience, depleted cognitive and physical reserves, and adjusted quality of life. Bias and noise are factors not easily measured in outcome prediction, but their influence on recovery trajectories raises some troubling issues.

Worth Their Salt: One Hundred Years of Hyperosmolar Therapy.

In this article, we commemorate the centenary of the discovery and clinical implementation of hyperosmolar therapy for the treatment of increased intracranial pressure (ICP). Following the pioneering work of anatomists Weed and McKibben in 1919, the use of hypertonic solutions was soon adopted into clinical practice, even though the preferred hypertonic agent, route of administration, and ideas regarding the physiological mechanism by which it reduced ICP diverged. These divergent conceptions and practices have continued to surround the use of hyperosmolar therapy into present times.

Taking a History in Neurocritically Ill Patients.

A clinical history leads to an examination, tests and a diagnosis. This time-honored sequence in medicine remains valid in critical illness, but in the heat of the moment there is a quickly appearing inevitable sketchiness. Intensivists should never be too unquestioning, too comfortable with incomplete information, or too unwilling to start over if information is muddled or contradictory. No scale in neurology looks at history. There is no tool or requirement to provide a standard system of communication. I review the essentials of history taking in a neurocritically ill patient. Examples of the value of a good medical history are shown but also the familiar biases when asking questions. There are obstacles, errors of commission and omission, and the importance of recognition of a clinical trajectory.