Ten-year diagnostic consistency of bipolar disorder in a first-admission sample

Ruggero CJ, Carlson GA, Kotov R, Bromet EJ. Ten-year diagnostic consistency of bipolar disorder in a first-admission sample.
Bipolar Disord 2010: 12: 21–31. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S.
Objectives:  A number of reports have examined the stability of the diagnosis of schizophrenia, but fewer studies have considered the long-term consistency of a bipolar diagnosis or factors that influence the likelihood of a diagnostic change. The present study sought to estimate how consistently a bipolar diagnosis was made across a 10-year period and factors associated with consistency, particularly demographic and clinical characteristics, childhood-related factors, and illness course.
Methods:  The sample included 195 first-admission patients presenting with psychosis who were assessed soon after hospitalization and at 6-month, 2-year, and 10-year follow-up and diagnosed with bipolar disorder on at least one of these assessments. Diagnoses were made using best-estimate procedures and were blind to all previous consensus diagnoses. Respondents who were consistently diagnosed with bipolar disorder were compared to those whose diagnosis shifted across assessments.
Results:  Overall, 50.3% (n = 98) of the 195 respondents were diagnosed with bipolar disorder at every available assessment, but 49.7% (n = 97) had a diagnostic shift to a non-bipolar disorder at least once over the course of the 10-year study. Childhood psychopathology and poorer illness course were among the few variables associated with increased odds of a change in diagnosis.
Conclusions:  Even with optimal assessment practices, misdiagnosis of bipolar disorder is common, with complex clinical presentations often making it difficult to consistently diagnose the disorder over the long term.     

Chimaeric anti-CD4 monoclonal antibody cross-linked by monocyte Fcγ receptor mediates apoptosis of human CD4 lymphocytes

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apoptosis of murine CD4⁺ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti-CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4⁺ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross-linked by rabbit anti-mouse immunoglobulin. The chimeric anti-CD4 monoclonal antibody, cM-T412 whose Fc fragment is human, was able to cause apoptosis without cross-linking by a second antibody. Similarly, abolition of PPD-induced proliferation of peripheral blood mononuclear cells by cM-T412 did not require cross-linking with rabbit anti-human immunoglobulin. Inhibition of proliferation by cM-T412 could be reduced by pre-treating monocytes with heat-aggregated human IgG. This suggested that monocyte Fcγ receptors might be cross-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4⁺ lymphocytes. It is proposed that during treatment with cM-T412 in autoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fey receptor-positive cells within the joint.     

Postpartum psychological distress after emergency team response during childbirth

Purpose: To evaluate the feasibility and acceptability of a protocol determining the relationship between emergency team response (ETR) during childbirth and acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) symptoms.

Methods: In a prospective, observational, cohort design, women experiencing ETR during childbirth were approached and recruited on postpartum day-1 and followed for six weeks. Demographics, obstetric and birth characteristics, ASD scores and PTSD scores (by Impact of Events Scale, IES and PCL-civilian) were recorded. Recruitment and retention rates were recorded, and scores were compared to women who did not experience ETR.

Results: Three hundred sixty-nine were approached and 249 were enrolled (67.5% recruitment rate). One hundred twenty-five completed all procedures (50.2% retention). Twenty experienced ETR (3.5% event rate), 12 enrolled (60.0% recruitment rate) and 8 completed the study (66.7% retention). The ETR group had higher PCL and IES scores (PCL: ETR median 12, non-ETR median 2, p?=?.08; IES: ETR median 22.5, non-ETR median 20, p?=?.08). ASD scores were similar between groups.

Conclusions: Methodology investigating the link between ETR and postpartum psychological distress is feasible and acceptable. A relationship between ETR and PTSD symptoms appears to exist, with ETR being associated with higher PTSD scores compared to non-ETR childbirths. Methods that incorporate awareness of the unique concerns of vulnerable populations are needed.     

Risk factors associated with venous thromboembolism in 49,028 mastectomy patients

Venous thromboembolism (VTE) is a potentially preventable disease that carries significant morbidity and mortality. Although malignancy is associated with increased risk for VTE, it varies according to cancer type. Despite the fact that breast cancer is the most common form of cancer in women, the incidence and risk factors associated with VTE in patients undergoing mastectomy have not been well characterized. To address this we utilized the ACS-NSQIP database to identify and characterize independent risk factors for VTE in 49,028 mastectomy patients. We identified 116 cases of VTE in the 49,028 cases analyzed (0.23%). Obesity (BMI > 30, OR = 1.91, p < 0.001), inpatient status (OR = 3.75, p < 0.001), venous catheterization (OR = 2.67, p = 0.012), prolonged operative time >3 h (OR = 4.36, p < 0.001), and immediate reconstruction (OR = 3.23, p < 0.001) were found to be independent risk factors for VTE. While the incidence of VTE is rare in mastectomy patients, the heightened awareness and increased VTE prophylaxis should be considered in high risk groups.     

Variation in opioid utilization among neonates with gastroschisis

PurposeRepetitive painful stimuli and early exposure to opioids places neonates at risk for neurocognitive delays. We aimed to understand opioid utilization for neonates with gastroschisis.MethodsWe performed a retrospective review of infants with gastroschisis at a tertiary children's hospital (2017–2019). Multivariate linear regression was performed to analyze variations in opioid use.ResultsAmong 30 patients with gastroschisis, 33% were managed by primary suture-less closure, 7% by primary sutured closure, 40% by spring silo, and 20% by handsewn silo. The proportion of pain medication used was: morphine (89%), acetaminophen (8%), and fentanyl (3%). Opioids were used for a median of 6.5 days (range 0–20) per patient. Median total opioid administered across all patients was 2.2 morphine milligram equivalents (MME)/kg (IQR 0.7–3.3). Following definitive closure, median opioid use was 0.2 MME/kg (IQR 0.1–0.8). With multivariate regression, 45% of the variation in MME use was associated with the type of surgery after adjusting for weight, gestational age, and gender, p = 0.02. After definitive fascial closure, there was no significant variations in opioid use.ConclusionThere is a significant variation in the utilization of opioid, primarily prior to fascial closure. Understanding pain needs and standardization may improve opioid stewardship in infants with gastroschisis. 197/200Level of EvidenceLevel III     

Fluctuations in EEG band power at subject‐specific timescales over minutes to days explain changes in seizure evolutions

Epilepsy is recognised as a dynamic disease, where both seizure susceptibility and seizure characteristics themselves change over time. Specifically, we recently quantified the variable electrographic spatio‐temporal seizure evolutions that exist within individual patients. This variability appears to follow subject‐specific circadian, or longer, timescale modulations. It is therefore important to know whether continuously recorded interictaliEEG features can capture signatures of these modulations over different timescales. In this study, we analyse continuous intracranial electroencephalographic (iEEG) recordings from video‐telemetry units and find fluctuations in iEEG band power over timescales ranging from minutes up to 12 days. As expected and in agreement with previous studies, we find that all subjects show a circadian fluctuation in their iEEG band power. We additionally detect other fluctuations of similar magnitude on subject‐specific timescales. Importantly, we find that a combination of these fluctuations on different timescales can explain changes in seizure evolutions in most subjects above chance level. These results suggest that subject‐specific fluctuations in iEEG band power over timescales of minutes to days may serve as markers of seizure modulating processes. We hope that future study can link these detected fluctuations to their biological driver(s). There is a critical need to better understand seizure modulating processes, as this will enable the development of novel treatment strategies that could minimise the seizure spread, duration or severity and therefore the clinical impact of seizures.     

Intravascular T‐cell lymphoma: A rare,poorly characterized entity with cytotoxic phenotype

Intravascular T‐cell lymphomas are rare, poorly characterized lesions. We discuss the clinical, radiologic and especially the laboratory characteristics of a lesion which presented in a 62‐year‐old woman with a history of progressive CNS abnormalities. Throughout the course of the disease, radiologic findings consisted mainly of multifocal mixed areas of ischemia and vasogenic edema involving cortical and subcortical regions. A brain biopsy identified an abnormal T‐cell population confined to lumens of vessels. These T‐cells were abnormal cytotoxic cells, positive for CD3, CD8, and negative for CD2, CD4, CD5, CD7 and CD30. While flow cytometry and immunohistochemistry failed to identify a similar population in the blood or bone marrow, molecular studies showed a clonal T‐cell population in both the brain and the bone marrow. No other organs were involved. In spite of aggressive treatment, the patient's medical condition continued to progress and she passed away. In conclusion, this abnormal population of cytotoxic T‐cells with intravascular localization probably represents a specific type of T‐cell lymphoma with specific clinical, radiologic, molecular and immunophenotypic characteristics.     

Idiopathic focal epilepsies: the “lost tribe”

The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010 ), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many “treats” for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age‐related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow‐wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro‐temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau‐Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro‐clinical features warranting inclusion. In addition, a number of less well‐defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The term “benign” is often used in connection with the IFEs and is increasingly being challenged. Certainly most of these disorders are not associated with the devastating cognitive and behavioural problems seen with early childhood epileptic encephalopathies, such as West or Dravet syndromes. However, it is clear that specific, and sometimes persistent, neuropsychological deficits in attention, language and literacy accompany many of the IFEs that, when multiplied by the large numbers affected, make up a significant public health problem. Understanding the nature, distribution, evolution, risk and management of these is an important area of current research. A corollary to such questions regarding comorbidities is the role of focal interictal spikes and their enduring impact on cognitive functioning. What explains the paradox that epilepsies characterised by abundant interictal epileptiform abnormalities are often associated with very few clinical seizures? This is an exciting area in both clinical and experimental arenas and will eventually have important implications for clinical management of the whole child, taking into account not just seizures, but also adaptive functioning and quality of life. For several decades, we have accepted an evidence‐free approach to using or not using antiepileptic drugs in IFEs. There is huge international variation and only a handful of studies examining neurocognitive outcomes. Clearly, this is a situation ready for an overhaul in practice. Fundamental to understanding treatment is knowledge of aetiology. In recent years, there have been several significant discoveries in IFEs from studies of copy number variation, exome sequencing, and linkage that prompt reconsideration of the “unknown cause” classification and strongly suggest a genetic aetiology. The IFE are strongly age‐related, both with regards to age of seizure onset and remission. Does this time window solely relate to a similar age‐related gene expression, or are there epigenetic factors involved that might also explain low observed twin concordance? The genetic (and epigenetic) models for different IFEs, their comorbidities, and their similarities to other neurodevelopmental disorders deserve investigation in the coming years. In so doing, we will probably learn much about normal brain functioning. This is because these disorders, perhaps more than any other human brain disease, are disorders of functional brain systems (even though these functional networks may not yet be fully defined). In June 2012, an international group of clinical and basic science researchers met in London under the auspices of the Waterloo Foundation to discuss and debate these issues in relation to IFEs. This Waterloo Foundation Symposium on the Idiopathic Focal Epilepsies: Phenotype to Genotype witnessed presentations that explored the clinical phenomenology, phenotypes and endophenotypes, and genetic approaches to investigation of these disorders. In parallel, the impact of these epilepsies on children and their families was reviewed. The papers in this supplement are based upon these presentations. They represent an updated state‐of‐the‐art thinking on the topics explored. The symposium led to the formation of international working groups under the umbrella of “Luke's Idiopathic Focal Epilepsy Project” to investigate various aspects of the idiopathic focal epilepsies including: semiology and classification, genetics, cognition, sleep, high‐frequency oscillations, and parental resources (see www.childhood-epilepsy.org ). The next sponsored international workshop, in June 2014, was on randomised controlled trials in IFEs and overnight learning outcome measures.