Browsing by Author "Cerejeira, J"
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- An insulinoma presenting with hypochondriac delusions and food refusalPublication . Renca, S; Santos, G; Cerejeira, JABSTRACT The authors report a case of a 68-year-old man with an unrecognized insulinoma manifesting with neuropsychiatric symptoms. For two years, he presented with unspecified behavior changes, autonomic and neuroglycopenic symptoms, which led him to be misdiagnosed with a neurologic and psychiatric disorder before the insulinoma was recognized. Following neurological alterations in context of hypoglycemia, subsequent to longstanding food refusal, he was admitted in the psychiatric ward. Despite good global response and normal food intake, hypoglycemic episodes were still occurring and led to a careful evaluation which permitted the definitive diagnostic. This case highlights the diagnostic difficulties of medical disorders presenting with clinical features overlapping neurological and psychiatric syndromes. It also reflects the diagnostic difficulties in rare clinical entities, particularly in patients previously followed in psychiatry and underlines the need for a constant dialogue and updating of clinicians.
- Behavioral and psychological symptoms of dementiaPublication . Cerejeira, J; Lagarto, L; Mukaetova-Ladinska, EBBehavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric symptoms, represent a heterogeneous group of non-cognitive symptoms and behaviors occurring in subjects with dementia. BPSD constitute a major component of the dementia syndrome irrespective of its subtype. They are as clinically relevant as cognitive symptoms as they strongly correlate with the degree of functional and cognitive impairment. BPSD include agitation, aberrant motor behavior, anxiety, elation, irritability, depression, apathy, disinhibition, delusions, hallucinations, and sleep or appetite changes. It is estimated that BPSD affect up to 90% of all dementia subjects over the course of their illness, and is independently associated with poor outcomes, including distress among patients and caregivers, long-term hospitalization, misuse of medication, and increased health care costs. Although these symptoms can be present individually it is more common that various psychopathological features co-occur simultaneously in the same patient. Thus, categorization of BPSD in clusters taking into account their natural course, prognosis, and treatment response may be useful in the clinical practice. The pathogenesis of BPSD has not been clearly delineated but it is probably the result of a complex interplay of psychological, social, and biological factors. Recent studies have emphasized the role of neurochemical, neuropathological, and genetic factors underlying the clinical manifestations of BPSD. A high degree of clinical expertise is crucial to appropriately recognize and manage the neuropsychiatric symptoms in a patient with dementia. Combination of non-pharmacological and careful use of pharmacological interventions is the recommended therapeutic for managing BPSD. Given the modest efficacy of current strategies, there is an urgent need to identify novel pharmacological targets and develop new non-pharmacological approaches to improve the adverse outcomes associated with BPSD.
- A clinical Update on Delirium: from early recognition to effective managementPublication . Cerejeira, J; Mukaetova-Ladinska, EBDelirium is a neuropsychiatric syndrome characterized by altered consciousness and attention with cognitive, emotional and behavioural symptoms. It is particularly frequent in elderly people with medical or surgical conditions and is associated with adverse outcomes. Predisposing factors render the subject more vulnerable to a congregation of precipitating factors which potentially affect brain function and induce an imbalance in all the major neurotransmitter systems. Early diagnosis of delirium is crucial to improve the prognosis of patients requiring the identification of subtle and fluctuating signs. Increased awareness of clinical staff, particularly nurses, and routine screening of cognitive function with standardized instruments, can be decisive to increase detection rates of delirium. General measures to prevent delirium include the implementation of protocols to systematically identify and minimize all risk factors present in a particular clinical setting. As soon as delirium is recognized, prompt removal of precipitating factors is warranted together with environmental changes and early mobilization of patients. Low doses of haloperidol or olanzapine can be used for brief periods, for the behavioural control of delirium. All of these measures are a part of the multicomponent strategy for prevention and treatment of delirium, in which the nursing care plays a vital role.
- Low preoperative plasma cholinesterase activity as a risk marker of postoperative delirium in elderly patients.Publication . Cerejeira, J; Batista, P; Nogueira, V; Vaz-Serra, A; Mukaetova-Ladinska, EBBACKGROUND: delirium is a frequent neuropsychiatric syndrome affecting medical and surgical elderly patients. Cholinergic dysfunction has been implicated in delirium pathophysiology and plasmatic acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are suppressed in patients with delirium. In this cohort study, we investigated whether these changes emerge during delirium or whether they are present before its onset. METHODS: plasma activities of AChE and BuChE were measured pre- and postoperatively in consecutive patients ≥60 years old undergoing elective total hip replacement surgery. In addition to a comprehensive clinical and demographic baseline evaluation, venous blood samples were collected from each subject in the morning of hospital admission's day and in the morning of the first postoperative day. Delirium was screened daily with confusion assessment method (confirmed with diagnostic and statistical manual of mental disorders (DSM-IV)-TR). RESULTS: preoperatively, plasma esterase activity was significantly lower in patients who developed delirium compared with the remaining subjects. Following surgery BuChE activity was lower in the delirium group but this difference disappeared after controlling for preoperative values. Plasma cholinesterase activity correlated positively with calcium and haemoglobin and negatively with total bilirubin and international normalised ratio. CONCLUSION: plasma cholinesterase activity can be a useful candidate biomarker to identify subjects at greater risk of developing postoperative delirium.
- Screening instruments for delirium in older people with an acute medical illness.Publication . Yates, C; Stanley, N; Cerejeira, J; Jay, R; Mukaetova-Ladinska, EB
- The Cholinergic System and Inflammation: Common Pathways in Delirium PathophysiologyPublication . Cerejeira, J; Nogueira, V; Luís, P; Vaz-Serra, A; Mukaetova-Ladinska, EBOBJECTIVES: To investigate whether delirium is associated with an unbalanced inflammatory response or a dysfunctional interaction between the cholinergic and immune systems. DESIGN: Cohort observational study. SETTING: General hospital orthopedic ward. PARTICIPANTS: One hundred one individuals aged 60 and older with no previous cognitive impairment undergoing elective arthroplasty. MEASUREMENTS: Incidence of postoperative delirium, plasma cholinesterase activity (acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)) and inflammatory mediators (C-reactive protein (CRP), interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-6, IL-8, IL-10) before and after surgery. RESULTS: Thirty-seven participants developed postoperative delirium and had greater production of CRP and proinflammatory to anti-inflammatory ratio after surgery. In participants with delirium, but not in controls, preoperative levels of plasma cholinesterase activity correlated with ΔCRP (AChE: ρ = 0.428, P = .008 and BuChE: ρ = 0.423, P = .009), ΔIL-6 (AChE: ρ = 0.339, P = .04), and ΔP/A ratio (AChE: ρ = 0.346, P = .04). CONCLUSION: Delirium was associated not only with an unbalanced inflammatory response, but also with a dysfunctional interaction between the cholinergic and immune systems. Comprehensive understanding of the relationship between the cholinergic and immune systems is crucial to developing new insights into delirium pathophysiology and novel therapeutic interventions
- The Immunology of DeliriumPublication . Cerejeira, J; Lagarto, L; Mukaetova-Ladinska, EBDelirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs. Activated microglia is responsible for an acute neuroinflammatory reaction underlying the symptoms of sickness. In healthy conditions descending pathways from the paraventricular nucleus, locus coeruleus and dorsal motor nucleus organize a centralized response to influence the immune response at the periphery and restore homeostasis. In the context of ageing and chronic neurodegeneration, adaptive changes to acute insults are characterized by exaggerated production of pro-inflammatory cytokines by primed microglia coupled with dysfunction of brain-to-immune pathways. In animal models, these changes underlie a more severe manifestation of sickness behaviour with working memory deficits suggesting that inattention, a core feature of delirium, can be a clinical correlate of an increased neuroinflammatory reaction. In patients with delirium, higher levels of pro-inflammatory cytokines and cortisol were identified in plasma and cerebrospinal fluid. However, to date it has not been clarified how peripheral inflammatory or endocrine biomarkers can reflect the likelihood or severity of delirium symptoms. In the future, a better understanding of the interaction between the brain and peripheral organs and the exact mechanism by which systemic inflammation can lead to delirium, will allow the development of new therapeutic agents.
- The neuroinflammatory hypothesis of deliriumPublication . Cerejeira, J; Firmino, H; Vaz-Serra, A; Mukaetova-Ladinska, EBDelirium is a neuropsychiatric syndrome characterized by a sudden and global impairment in consciousness, attention and cognition. It is particularly frequent in elderly subjects with medical or surgical conditions and is associated with short- and long-term adverse outcomes. The pathophysiology of delirium remains poorly understood as it involves complex multi-factorial dynamic interactions between a diversity of risk factors. Several conditions associated with delirium are characterized by activation of the inflammatory cascade with acute release of inflammatory mediators into the bloodstream. There is compelling evidence that acute peripheral inflammatory stimulation induces activation of brain parenchymal cells, expression of proinflammatory cytokines and inflammatory mediators in the central nervous system. These neuroinflammatory changes induce neuronal and synaptic dysfunction and subsequent neurobehavioural and cognitive symptoms. Furthermore, ageing and neurodegenerative disorders exaggerate microglial responses following stimulation by systemic immune stimuli such as peripheral inflammation and/or infection. In this review we explore the neuroinflammatory hypothesis of delirium based on recent evidence derived from animal and human studies.
- The Portuguese version of Mini-Tinnitus Questionnaire: brief screening test for assessment of tinnitus-induced stress.Publication . Cerejeira, R; Cerejeira, J; Paiva, S; Gonçalves, P; Firmino, H; Quartilho, MJ; Vaz-Serra, A; Paiva, AHYPOTHESIS: The Portuguese version of Mini-Tinnitus Questionnaire (Mini-TQ) is as valid as the English version to assess tinnitus-associated distress in the Portuguese-speaking population. BACKGROUND: Tinnitus is a major symptom in ENT practice affecting subjects in all demographic groups. Our objective is to validate a Portuguese version of Mini-TQ (Mini-TQ-pv) to be used in clinical practice and research. METHODS: Mini-TQ-pv was administered to 51 patients with chronic tinnitus. Statistical analysis was done to determine the psychometric properties of the instrument. RESULTS: After double translation, face and content validity were confirmed by high internal consistency (Cronbach alpha = 0.861) and significant correlation between individual items and total score. The questionnaire was easy and quick to administer (2.57 min). CONCLUSION: We provide a suitable Mini-TQ-pv to be used in the assessment of Portuguese-speaking patients with tinnitus
- The Stress Response to Surgery and Postoperative Delirium: Evidence of Hypothalamic—Pituitary—Adrenal Axis Hyperresponsiveness and Decreased Suppression of the GH/IGF-1 AxisPublication . Cerejeira, J; Batista, P; Nogueira, V; Vaz-Serra, A; Mukaetova-Ladinska, EBIntroduction: The aim of this study is to determine whether postoperative delirium is associated with dysregulation of hypothalamic—pituitary—adrenal and growth hormone/insulin-like growth factor 1 (GH/IGF-1) responses following acute systemic inflammation. Methods: Plasma levels of cortisol, IGF-1, C-reactive protein, interleukin (IL)-6, IL-8, and IL-10 were measured before and after surgery in 101 patients 60 years without dementia undergoing elective hip arthroplasty. Participants were assessed with confusion assessment method and Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR) postoperatively and 37 patients fulfilled the DSM-IV-TR criteria for delirium. Results: Preoperative plasma cortisol levels were similar in delirium and nondelirium groups (405.37+189.04 vs 461.83+219.39; P ¼ .22). Participants with delirium had higher postoperative cortisol levels (821.67 + 367.17 vs 599.58 + 214.94; P ¼ .002) with enhanced postoperative elevation in relation to baseline (1.9- vs 1.5-fold; P ¼ .004). The plasma levels of IGF1 did not differ in delirium and nondelirium groups before (18.12 + 7.58 vs 16.8 + 7.86; P ¼ .477) and following surgery (13.39 + 5.94 vs 11.12 + 6.2; P ¼ .639), but the levels increased in relation to baseline more frequently in patients who developed delirium (24.3% vs 7.8%; P ¼ .034). The magnitude of postoperative cortisol elevation correlated with DIL-6 (P ¼ .485; P ¼ .002), DIL-8 (P ¼ .429; P ¼ .008), and DIL-10 (P ¼ .544; P < .001) only in patients with delirium. Conclusions: Hypothalamic—pituitary—adrenal axis hyperresponsiveness and a less frequent suppression of the GH/IGF-1 axis in response to acute stress are possibly involved in delirium pathophysiology.