Dysbetalipoproteinaemia : clinical and laboratory aspects, changes in lipoprotein composition and remnant metabolism associated with lipid lowering drugs

Includes bibliographical references (p. 483-539).This thesis examines and reviews multiple aspects of dysbetalipoproteinaemia. Dysbetalipoproteinaemia is a severe, highly atherogenic mixed hyperlipidaernia characterized by the accumulation of remnants of triglyceride-rich lipoproteins. Genetic susceptibility is conferred by mutations in apolipoproteinE, but manifest hyperlipidaemia often only occurs in the presence of metabolic abnormalities that influence lipoprotein production or clearance. Normal lipid metabolism is briefly reviewed to enable a better understanding of the pathophysiology of dysbetalipoproteinaernia. Hepatic remnant clearance is reviewed in detail with particular emphasis on the roles of all hepatic lipoprotein receptors. The importance of differential hepatic lipoprotein receptor binding affinities according to apoE mutation is emphasized

Bleuler revisited:on persecutory delusions and their resistance to therapy

Stress and Psychopatholog

Severe Sleep Deprivation Causes Hallucinations and a Gradual Progression Toward Psychosis With Increasing Time Awake

Background: Going without sleep for long periods of time can produce a range of experiences, including perceptual distortions and hallucinations. Many questions, however, remain unanswered regarding the types of symptoms which are most reliably elicited, the time of symptom onset, and whether symptoms worsen over time toward psychotic decompensation. Since sleep deprivation exceeding 48 h is considered unethical today, an examination of historical studies with extreme sleep-loss duration is needed to obtain information about what happens during prolonged sleep loss.Methods: A systematic-review approach was used to identify experimental and observational studies of sleep deprivation in healthy people which describe the effects of prolonged sleep loss on psychopathological symptoms, without any date restriction.Results: A total of 476 articles were identified. Of these, 21 were eligible for inclusion. Duration of sleep loss ranged between 24 h and 11 nights (total 760 participants; average 72–92 h without sleep). All studies except one reported perceptual changes, including visual distortions (i.e., metamorphopsias), illusions, somatosensory changes and, in some cases, frank hallucinations. The visual modality was the most consistently affected (in 90% of the studies), followed by the somatosensory (52%) and auditory (33%) modalities. Symptoms rapidly developed after one night without sleep, progressing in an almost fixed time-dependent way. Perceptual distortions, anxiety, irritability, depersonalization, and temporal disorientation started within 24–48 h of sleep loss, followed by complex hallucinations and disordered thinking after 48–90 h, and delusions after 72 h, after which time the clinical picture resembled that of acute psychosis or toxic delirium. By the third day without sleep, hallucinations in all three sensory modalities were reported. A period of normal sleep served to resolve psychotic symptoms in many—although not all—cases.Conclusions: Psychotic symptoms develop with increasing time awake, from simple visual/somatosensory misperceptions to hallucinations and delusions, ending in a condition resembling acute psychosis. These experiences are likely to resolve after a period of sleep, although more information is required to identify factors which can contribute to the prevention of persistent symptoms

Alice in Wonderland Syndrome as a Presenting Manifestation of Creutzfeldt-Jakob Disease

Background: Alice in Wonderland syndrome (AIWS) is a rare neurological disorder characterized by distortions of visual perception (metamorphopsias), the body image, and the experience of time, along with derealization and depersonalization. Some 85% of patients present with perceptual distortions in a single sensory modality, e.g., only visual or only somesthetic in nature. Moreover, the majority experience only a single type of distortion, e.g., only micropsia or only macropsia. AIWS has many different etiologies, and hence an extensive differential diagnosis. Its amenability to treatment depends on the underlying pathological process, which in children is mostly encephalitis, and in adults, migraine. In the literature, no more than 180 “clinical” cases of AIWS have been described (i.e., cases in need of medical attention). Of them, some 50% showed a favorable prognosis. However, non-clinical cases (i.e., fleeting, transient cases of AIWS for which no professional help is needed) have been described in up to 30% of the general population. This indicates that AIWS is perhaps not as rare as traditionally assumed, and has led some authors to conclude that, prognostically, AIWS is usually harmless.Methods: From our own clinical practice, we describe the first known case of Creutzfeldt-Jakob Disease (CJD, Heidenhain variant) that presented with symptoms of AIWS.Results: In our patient, disease onset was sudden and rapidly progressive, starting with isolated visual symptoms. Symptoms of AIWS comprised akinetopsia, chloropsia, micropsia, macropsia, zoom vision, and time distortions (quick-motion phenomenon and protracted duration). Soon, these were complicated by paraesthesias, gait instability, aphasia, expressive amusia, cognitive decline, and behavioral changes in the form of agitation and emotional lability. The diagnosis of probable sporadic CJD was confirmed with the aid of a head MRI and cerebrospinal fluid (14-3-3 protein). In the absence of any treatment options, our patient was discharged home and died within 2 months after his visual symptoms had begun. Autopsy consent was not obtained.Conclusion: We conclude that AIWS is not always as harmless as sometimes suggested, and that CJD, although extremely rare, must be part of its extensive differential diagnosis, notably in the presence of rapid cognitive decline

Effect of the proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab on glycemia, body weight, and new-onset diabetes mellitus

Statin therapy modestly increases new-onset diabetes risk. The effect of proprotein convertase subtilisin/kexin type 9 inhibition on new-onset diabetes, glycemia, and weight remains unclear. We studied the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab on fasting plasma glucose, glycated hemoglobin, weight, and new-onset diabetes mellitus. We pooled 1-year (48-week) data for participants who had completed an evolocumab parent study before entering an open-label extension (OLE) trial. Data were available for 4,802 participants (1,602 on standard of care [SOC]; 3,200 on evolocumab plus SOC) in 2 OLE trials. Evolocumab lowered low-density lipoprotein cholesterol by approximately 60% compared with SOC alone. Over the first year of the OLE trials, there was no difference in median (Q1, Q3) change in glycated hemoglobin (0.1% [-0.1, 0.2] for both SOC and evolocumab plus SOC) and fasting plasma glucose (0.06 mmol/L [-0.28, 0.38 mmol/L] for SOC and 0.06 mmol/L [-0.28, 0.44 mmol/L] for evolocumab plus SOC). Mean weight change (standard error) at 1 year was -0.1 kg (0.2) on SOC compared with 0.3 kg (0.1) on evolocumab plus SOC. The exposure-adjusted incidence rate (95% confidence intervals) for new-onset diabetes per 100 patient years was 3.7 (2.9 to 4.7) on control/SOC alone and 3.9 (3.2 to 4.6) on evolocumab/evolocumab plus SOC treatment. Glycemic changes observed in 6,430 participants at week 12 in the parent studies were comparable with OLE trial findings. In conclusion, evolocumab therapy has no effect on glucose homeostasis over 1 year of open-label treatment

Sexual Hallucinations in Schizophrenia Spectrum Disorders and Their Relation With Childhood Trauma

Background : Sexual hallucinations are probably the most neglected types of hallucination, even in psychiatric settings. They are often multimodal in nature, and their prevalence rate is unknown. For other types of hallucination, notably auditory hallucinations, childhood trauma is an important risk factor. However, whether this also applies to sexual hallucinations is unexplored. Objective : To establish the prevalence rate of sexual hallucinations in a clinical sample of patients diagnosed with a schizophrenia spectrum disorder, to describe their phenomenological characteristics, and to estimate their relationship with childhood trauma. Methods : After screening 778 patients diagnosed with a schizophrenia spectrum disorder, 42 were considered eligible for inclusion by their treating physician or psychiatrist. Thirty of these patients were interviewed to assess the presence of sexual hallucinations, using a tailor-made questionnaire and the short form of the Childhood Trauma Questionnaire. Results : Of the 30 patients interviewed, 13 reported sexual hallucinations, yielding a 1-year prevalence rate of 0.017 in this clinical sample. Of the hallucinating patients, 46.2% reported multimodal hallucinations, with involvement of up to five sensory modalities. All patients who experienced sexual hallucinations reported a history of childhood trauma, of which 76.9% involved sexual trauma (OR 8.7). In addition, 61.5% of the patients reported high levels of distress. Conclusion : In patients diagnosed with a schizophrenia spectrum disorder, sexual hallucinations warrant appropriate medical attention. They are not as rare as traditionally thought, and their relationship with childhood trauma is overwhelming. Therefore, we recommend that clinical attention be paid to the psychotic and traumatic symptoms of these patients, as well as to the somatic conditions that may underlie them. For clinical and research purposes, we propose a classification of sexual hallucinations in accordance with the sensory modalities involved. As sexual hallucinations are also experienced in the context of temporal lobe epilepsy, narcolepsy, persistent genital arousal disorder, intoxications and other somatic conditions, further research in transdiagnostic populations seems warranted. In line with the current practice of providing trauma-focused treatment for trauma-related auditory hallucinations, we recommend that future studies explore the effectiveness of this type of treatment for sexual hallucinations

Hypothermia due to Antipsychotic Medication:A Systematic Review

Background: Hypothermia is a rare, but potentially fatal adverse effect of antipsychotic drug (APD) use. Although the opposite condition, hyperthermia, has been researched extensively in the context of the malignant antipsychotic syndrome, little is known about hypothermia due to APDs. Objective: This study aimed to review the literature on hypothermia in the context of APD use, and formulate implications for research and clinical care. Methods: A systematic search was made in PubMed and Ovid Medline. Results: The literature search yielded 433 articles, including 57 original case descriptions of hypothermia developed during APD use with non-toxic plasma levels. All cases together indicate that the risk of developing hypothermia is highest during the 7 days following initiation, or increase in dosage, of APDs, especially in the presence of additional predisposing factors, such as advanced age, exposure to cold, adjuvant use of benzodiazepines, and (subclinical) hypothyroidism. In addition, data derived from drug-monitoring agencies suggest that the prevalence of APD-related hypothermia is at least 10 times higher than suggested by the literature. Conclusion: We conclude that health-care professionals need to monitor the body temperature of patients starting with (an increased dose of) APDs for a duration of 7-10 days to prevent hypothermia, especially in the presence of multiple risk factors. Moreover, systematic studies are needed to establish the actual prevalence of APD-related hypothermia as well as the relative risk for individual APDs

On Perception and Consciousness in HPPD:A Systematic Review

Hallucinogen-persisting perception disorder (HPPD) features as a diagnostic category in the DSM-5, ICD-11, and other major classifications, but our knowledge of the phenomenology of the perceptual symptoms involved and the changes in consciousness during the characteristic “flashbacks” is limited. We systematically evaluated original case reports and case series on HPPD to define its phenomenology, associated (psycho)pathology, and course. Our search of PubMed and Embase yielded 66 relevant publications that described 97 people who, together, experienced 64 unique symptoms of HPPD. Of these, 76% concerned symptoms characteristic of Alice in Wonderland syndrome, over 50% non-visual symptoms, and 38% perceptual symptoms not clearly linked to prior intoxication states. This is in contrast with the DSM-5 diagnostic criteria for HPPD. Even though less than half of the patients showed a protracted disease course of over a year, a third achieved remission. However, in patients with co-occurring depression (with or without anxiety) HPPD symptoms persisted longer and treatment outcomes were more often negative. Thus, unlike the acute stages of psychedelic drug intoxication, which may be accompanied by altered states of consciousness, HPPD is rather characterized by changes in the content of consciousness and an attentional shift from exogenous to endogenous phenomena. Since HPPD is a more encompassing nosological entity than suggested in the DSM-5, we recommend expanding its diagnostic criteria. In addition, we make recommendations for clinical practice and future research

Musical hallucinations, secondary delusions, and lack of insight: results from a cohort study

IntroductionAlthough musical hallucinations do not tend to be accompanied by delusions, occasionally patients persistently accuse others of being responsible for causing the music they perceive, sometimes with severe social consequences such as frequently calling the police or moving house. In this study we seek to broaden our understanding of this rare type of musical hallucination that comes with secondary delusions and lack of insight, and to explore associations, underlying mechanisms, and treatment possibilities.MethodsThe present study is part of a cohort study on musical hallucinations carried out in the Netherlands from 2010 through 2023. Participants underwent testing with the aid of the MuHa Questionnaire, Launay-Slade Hallucinations Scale (LSHS), Schizotypal Personality Questionnaire (SPQ), Hamilton Depression Rating Scale (HDRS), and Mini Mental State Examination (MMSE). Additionally, they underwent a brain MRI, electroencephalogram, and audiological testing.ResultsFive patients out of a group of N = 81 (6%) lacked insight and presented with secondary delusions regarding the perceived music. They were all female, of advanced age, and hearing-impaired, and were diagnosed with cognitive impairment. In three patients (60%), risperidone was started. This had a positive effect on the hallucinations and secondary delusions.ConclusionThe pathophysiological process underlying musical hallucinations is multifactorial in nature. We consider cognitive impairment the most likely contributing factor of the secondary delusions and lack of insight encountered in our patients, and antipsychotics the most beneficial treatment. On the basis of these small numbers, no definite conclusions can be drawn, so further research is needed to elucidate the underlying mechanisms and to develop evidence-based treatment methods for people experiencing this rare and debilitating combination of symptoms. Since the black box warning of risperidone cautions against the use of this drug in elderly persons with dementia, a proper comparison with the efficacy and safety of other antipsychotics for this group is paramount