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.

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.

The Origin of Intracranial Pressure Causing Brainstem Hemorrhages.

The origin of secondary brainstem hemorrhages following an acute expansive hemispheric lesion has been attributed to Henri Duret, who proposed that hemorrhaging was caused by a shock wave through the cerebral spinal fluid. However, other experiments have shown important findings correlating brainstem hemorrhages to arterial hemorrhages. Animal studies found that the rapidity of expansion of a lesion would be crucial in producing these lesions, but there was no consistent correlation with paratentorial grooving so commonly seen with increased intracranial pressure. This historical perspective studies the different experimentalists who paved the way for the discovery of these secondary brainstem hemorrhages-often named after Duret-and now known not to be invariably associated with poor outcome.

Treatment of Movement Disorder Emergencies in Autoimmune Encephalitis in the Neurosciences ICU.

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes.

BACKGROUND: Guillain-Barré syndrome (GBS), when severe, involves the autonomic nervous system; our objective was to assess the spectrum and predictors of dysautonomia, and how it may impact functional outcomes. METHODS: A retrospective review of patients admitted to the Mayo Clinic in Rochester, MN between January 1, 2000, and December 31, 2017, with GBS and dysautonomia was performed. Demographics, comorbidities, parameters of dysautonomia, clinical course, GBS disability score, and Erasmus GBS Outcome Score (EGOS) at discharge were recorded. RESULTS: One hundred eighty seven patients were included with 71 (38%) noted to have at least one manifestation of dysautonomia. There are 72% of patients with a demyelinating form of GBS and 36% of patients with demyelination had dysautonomia. Ileus (42%), hypertension (39%), hypotension (37%), fever (29%), tachycardia or bradycardia (27%), and urinary retention (24%) were the most common features. Quadriparesis, bulbar and neck flexor weakness, and mechanical ventilation were associated with autonomic dysfunction. Patients with dysautonomia more commonly had cardiogenic complications, syndrome of inappropriate antidiuretic hormone, posterior reversible encephalopathy syndrome, and higher GBS disability score and EGOS. Mortality was 6% in patients with dysautonomia versus 2% in the entire cohort (P = 0.02). CONCLUSIONS: Dysautonomia in GBS is a manifestation of more severe involvement of the peripheral nervous system. Accordingly, mortality and functional outcomes are worse. There is a need to investigate if more aggressive treatment is warranted in this category of GBS.