Undiagnosed and Rare Diseases in Critical Care: The Role of Diagnostic Access.

Critically ill patients with undiagnosed and rare diseases are at high risk for cognitive diagnostic errors as well as delays in diagnosis that are the result of impaired diagnostic access. Local evaluation teams dedicated to undiagnosed and rare diseases can address both the risk and actuality of diagnostic error, as well as shortfalls in diagnostic access, particularly for patients whose diminished access is a result of critical illness. Features of successful teams are discussed.

Diagnostic Time-Outs to Improve Diagnosis.

Diagnostic errors harm patients. While the underlying causes of diagnostic error and the settings in which they occur are diverse, the use of a cognitive forcing function in the form of a diagnostic time-out can mitigate the risk of diagnostic error. Barriers to the implementation of diagnostic time-outs remain. In our survey of neonatal intensive care unit (NICU) providers, perceived time constraints were universally cited as a barrier. Attending neonatologists and neonatology nurse practitioners reported decreased perception of the risk of diagnostic error impacting patient outcomes, relative to the perception among neonatology fellowship trainees. Future directions include addressing concerns over the perceived time investment required for a diagnostic time-out and increasing provider appreciation of the nature and impact of diagnostic error on patient outcomes.

A pause in pediatrics: implementation of a pediatric diagnostic time-out.

OBJECTIVES: Diagnostic errors are frequently the product of cognitive biases that arise when heuristic-based approaches fail. The efficiency-thoroughness tradeoff (ETTO) principle states sacrificing thoroughness for efficiency is normal and occurs frequently in medicine. The goal of a diagnostic timeout was to provide an actionable template for when providers transition to an analytical mindset and to help incorporate the ETTO principle during the diagnostic process. METHODS: A diagnostic time-out was adapted for use in pediatric hospital medicine (PHM). In this prospective study, a group of eight PHM providers piloted the time-out in the hospitalized setting. Data was collected over 12 months and descriptive statistics were used for analysis. RESULTS: Cases were most frequently chosen for time-out use due to clinician intuition. In more than half the cases the time-out didn't confirm the initial diagnosis and alternate diagnoses for the wrong diagnosis were pursued. There was only one case of the time-out being burdensome from a time perspective. Learners participated in all cases. As a result of the diagnostic time-out, new actions were taken in all cases. CONCLUSIONS: Implementation of a diagnostic time out provides an actionable template for providers to actively change their mindset to an analytical thinking process to counteract cognitive biases and potentially reduce diagnostic errors in the pediatric inpatient setting.

Overmedicalization in Children with Medical Complexity.

Children with medical complexity (CMC) are a unique pediatric patient population with increased exposure and interactions with the health care system and reliance on family caregivers. These attributes place CMC at high risk of overmedicalization (OM). This article reviews the risk factors for OM in CMC and presents an algorithm that primary providers can use to recognize and address this issue. Involvement of a broad multidisciplinary team, including child advocacy when needed, is recommended. The article also focuses on challenges and additional considerations that arise when medical child abuse as the cause of OM is suspected in this population. [Pediatr Ann. 2020;49(11):e478-e485.].

Undiagnosed and Rare Diseases in Perinatal Medicine: Lessons in Context and Cognitive Diagnostic Error.

Critically ill neonates experience high rates of morbidity and mortality. Major diagnostic errors are identified in up to 20% of autopsied neonatal intensive care unit deaths. Neonates with undiagnosed or rare congenital disorders may mimic critically ill neonates with more common acquired conditions. The context of the diagnostic evaluation can introduce unique biases that increase the likelihood of diagnostic error. Herein is presented a framework for understanding diagnostic errors in perinatal medicine, and individual, team, and systems-based solutions for improving diagnosis learned through the implementation and administration of an undiagnosed and rare disease program.

How Doctors Think: Common Diagnostic Errors in Clinical Judgment-Lessons from an Undiagnosed and Rare Disease Program.

The scientific process of analysis and deduction is frequently, often subconsciously, used by physicians to develop a differential diagnosis based on patients' symptoms. Common disorders are most frequently diagnosed in general practice. Rare diseases are uncommon and frequently remain undiagnosed for many years. Cognitive errors in clinical judgment delay definitive diagnosis. Whole-exome sequencing has helped identify the cause of undiagnosed or rare diseases in up to 40% of children. This article provides experiences with an undiagnosed or rare disease program, where detailed data accumulation and a multifaceted analytical approach assisted in diagnosing atypical presentations of common disorders.

Differentiating Familial Neuropathies from Guillain-Barré Syndrome.

Differentiating Guillain-Barré syndrome (GBS) from inherited neuropathies and other acquired peripheral neuropathies requires understanding the atypical presentations of GBS and its variant forms, as well as historical and physical features suggestive of inherited neuropathies. GBS is typically characterized by the acute onset of ascending flaccid paralysis, areflexia, and dysesthesia secondary to peripheral nerve fiber demyelination. The disorder usually arises following a benign gastrointestinal or respiratory illness, is monophasic, reaches a nadir with several weeks, and responds to immunomodulatory therapy. Inherited neuropathies with onset before adulthood, whose presentation may mimic Guillain-Barré syndrome, are reviewed.

Immune-Mediated Diseases of the Central Nervous System: A Specificity-Focused Diagnostic Paradigm.

Immune-mediated diseases of the central nervous system show wide variability both symptomatically and with respect to underlying pathophysiology. Recognizing aberrant immunologic activity as the cause of neurologic dysfunction requires establishing as precise a neuroanatomic and functional phenotype as possible, and a diagnostic and therapeutic strategy that stabilizes the patient, excludes broad categories of disease via rapidly available diagnostic assays, and maintains a broad differential diagnosis that includes immune-mediated conditions. This process is aided by recognizing the appropriate clinical circumstances under which immune-mediated disease should be suspected, and how to differentiate these conditions from other causes of similar neurologic dysfunction.

BAG3 myofibrillar myopathy presenting with cardiomyopathy.

Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy.

Neuropsychological effects of bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

OBJECTIVE: Although a relatively new technique, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the treatment of advanced cases of Parkinson's disease (PD) shows considerable promise. While the benefits of the STN stimulation for the treatment of motor symptoms of PD are well established, some studies have reported negative neuropsychological outcomes, especially in elderly patients. The objective of the present study was to investigate the neuropsychological effects of bilateral STN-DBS in a small sample of elderly patients with PD. METHODS: Six patients with PD (mean age 73.0 +/- 10.45 years) were assessed both before and approximately 6 months after DBS surgery in six neuropsychological domains. These domains included orientation, estimated IQ, attention/working memory, language, memory, and visual-spatial functioning. Additionally, depressive symptoms were assessed using the Geriatric Depression Scale. Daily doses of antiparkinsonian medications, in levodopa equivalents, were also compared pre- and postoperatively. RESULTS: Antiparkinsonian medications were reduced postoperatively by a mean of 65%, from a mean levodopa equivalent dosage of 987 mg/day to 346 mg/day. Category fluency, a word generation task within the language domain, was the only test in which participants demonstrated a statistically significant decline in performance. Participants demonstrated a mean score decrease of 41% (p < 0.05) in category fluency. CONCLUSIONS: The pathophysiology of the observed deficit remains ill defined. However, despite a small sample size, the study provides further evidence that bilateral STN-DBS in PD patients can be associated with negative neuropsychological outcome in word fluency, especially in elderly patients. Implications regarding patient selection for bilateral STN-DBS and recommendations for future research are further discussed.