Is Late-Onset Suicidal Behavior a Distinct Subtype?

This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.

[Recent studies about the underlying cerebral mechanism of the fearfull arousals from slow wave sleep].

We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful disorientation occurring in sleep terrors and hypermotor seizures, make them alike the acute stress-responses emerging from sleep; triggered by false alarms. An acute stress-response can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.

Patient perspectives of diabetes care in primary care networks in Singapore: a mixed-methods study.

BACKGROUND: Type 2 diabetes (T2D) remains an important chronic condition worldwide requiring integrated patient-centred care as advocated by the Chronic Care Model (CCM). The Primary Care Networks (PCNs) in Singapore organise general practitioners (GPs) with nurses and care coordinators to deliver team-based care for patients with chronic conditions. This study examined the quality of care in the PCNs as defined by the CCM from the patients' perspective. METHODS: This study followed a cross-sectional convergent mixed-method design with T2D patients across three PCN types (GP-led, Group, and Cluster). The Patient Assessment of Chronic Illness Care (PACIC, range 1-5) was completed by a convenience sample of 343 patients. Multivariate linear regression was performed to estimate the associations between patient and service characteristics and PACIC summary score. Twenty-four participants were purposively recruited for interviews on the experienced care until thematic saturation was reached. Quantitative and qualitative data were collected concurrently and independently. Integration occurred during study design and data analysis using the CCM as guidance. Quantitative and qualitative results were compared side-by-side in a joint comparison table to develop key concepts supported by themes, subthemes, and patients' quotes. RESULTS: The PACIC mean summary score of 3.21 for 343 patients evidenced that some have received CCM consistent care in the PCNs. Being younger and spending more time with the GP were associated with higher PACIC summary scores. PACIC summary scores did not differ across PCN types. The 24 patients interviewed in the qualitative study reported receiving team-based care, nurse services, good continuity of care, as well as patient-centred care, convenient access, and affordable care. Key concepts showed that integrated care consistent with the CCM was sometimes received by patients in the PCNs. Patient activation, delivery system design/decision support, goal setting/tailoring, and problem-solving/contextual counselling were sometimes received by patients, while follow-up/coordination was generally not received. CONCLUSIONS: Patients with T2D from the Singapore Primary Care Networks received integrated care consistent with the Chronic Care Model, particularly in patient activation, delivery system design/decision support, goal setting/tailoring, and problem-solving/contextual counselling. Follow-up/coordination needed improvement to ensure higher quality of diabetes care.

Derailment of Sleep Homeostatic Plasticity Affects the Most Plastic Brain Systems and Carries the Risk of Epilepsy.

Although a critical link between non-rapid eye movement (NREM) sleep and epilepsy has long been suspected, the interconnecting mechanisms have remained obscure. However, recent advances in sleep research have provided some clues. Sleep homeostatic plasticity is now recognized as an engine of the synaptic economy and a feature of the brain's ability to adapt to changing demands. This allows epilepsy to be understood as a cost of brain plasticity. On the one hand, plasticity is a force for development, but on the other it opens the possibility of epileptic derailment. Here, we provide a summary of the phenomena that link sleep and epilepsy. The concept of "system epilepsy", or epilepsy as a network disease, is introduced as a general approach to understanding the major epilepsy syndromes, i.e., epilepsies building upon functional brain networks. We discuss how epileptogenesis results in certain major epilepsies following the derailment of NREM sleep homeostatic plasticity. Post-traumatic epilepsy is presented as a general model for this kind of epileptogenesis.

Disorders of arousal and sleep-related hypermotor epilepsy - overview and challenges night is a battlefield of sleep and arousal promoting forces.

Arousability and reactivity to sensory stimuli are essential features of sleep, discriminating it from coma and keeping the sleeper in contact with the environment. Arousals and oscillations during sleep serve the reversibility of sleep and carry an alarm function awakening the sleeper in danger. In this review, we will explore mechanisms and circuits involved in arousal intrusions within the sleep texture, focusing on the significance of these phenomena in two sleep-related conditions: NREM sleep parasomnias and sleep-related hypermotor epilepsy. Knowledges and gaps in the field are discussed.

[How our view of epileptogenesis and mechanism of epilepsy changes? The system epilepsies' concept]. / Nézetváltozások az epilepszia keletkezésérol és mechanizmusáról. Rendszeralapú megközelítés.

Background and purpose: To examine the ways of epileptogenesis closely linked to the system epilepsies' concept. Methods: We follow the ways of epileptic transformation in the declarative memory-system, in the sleep/arousal twin-systems, in the perisylvian neuronal network and in postinjury epilepsy, which we consider a general model of the epileptic transformation. Results: In the presented systems, epileptogenesis shares a similar mechanism in the form of augmentation and derailment of plasticity and sleep-related synaptic homeo-stasis. This highlights the central role of NREM sleep in those epilepsies. Conclusion: We try to characterize the concept of system epilepsies and suggest a shared mechanism of epileptogenesis.

REM sleep, REM parasomnias, REM sleep behaviour disorder.

We review the literature on REM parasomnias, and their the underlying mechanisms. Several REM parasomnias are consistent with sleep dissociations, where certain elements of the REM sleep pattern emerge in an inadequate time (sleep paralysis, hypnagogic hallucinations and cataplexy) or are absent/partial in their normal REM sleep time (REM sleep without atonia, underlying REM sleep behavior disorder). The rest of REM parasomnias (sleep related painful erection, catathrenia) may have other still unclear mechanisms. REM parasomnias deserve attention, because in addition to disturbing sleep and causing injuries, they may shed light on REM sleep functions as well as the heterogeneous etiologies of parasomnias. One of them, REM sleep behavior disorder has special importance as a warning sign of evolving neurodegenerative conditions mainly synucleinopathies (some cases synucleinopathies themselves) and it is a model parasomnia revealing that parasomnias may have by autoimmune, iatrogenic and even psychosomatic etiologies.

Fluoxetine use is associated with improved survival of patients with COVID-19 pneumonia: A retrospective case-control study.

BACKGROUND AND PURPOSE: We aimed to investigate the association between fluoxetine use and the survival of hospitalised coronavirus disease (COVID-19) pneumonia patients. METHODS: This retrospective case-control study used data extracted from the medical records of adult patients hospitalised with moderate or severe COVID-19 pneumonia at the Uzsoki Teaching Hospital of the Semmelweis University in Budapest, Hungary between 17 March and 22 April 2021. As a part of standard medical treatment, patients received anti-COVID-19 therapies as favipiravir, remdesivir, baricitinib or a combination of these drugs; and 110 of them received 20 mg fluoxetine capsules once daily as an adjuvant medication. Multivariable logistic regression was used to evaluate the association between fluoxetine use and mortality. For excluding a fluoxetine-selection bias potentially influencing our results, we compared baseline prognostic markers in the two groups treated versus not treated with fluoxetine. RESULTS: Out of the 269 participants, 205 (76.2%) survived and 64 (23.8%) died between days 2 and 28 after hospitalisation. Greater age (OR [95% CI] 1.08 [1.05-1.11], p<0.001), radiographic severity based on chest X-ray (OR [95% CI] 2.03 [1.27-3.25], p=0.003) and higher score of shortened National Early Warning Score (sNEWS) (OR [95% CI] 1.20 [1.01-1.43], p=0.04) were associated with higher mortality. Fluoxetine use was associated with an important (70%) decrease of mortality (OR [95% CI] 0.33 [0.16-0.68], p=0.002) compared to the non-fluoxetine group. Age, gender, LDH, CRP, and D-dimer levels, sNEWS, Chest X-ray score did not show statistical difference between the fluoxetine and non-fluoxetine groups supporting the reliability of our finding. CONCLUSION: Provisional to confirmation in randomised controlled studies, fluoxetine may be a potent treatment increasing the survival for COVID-19 pneumonia.

Personality of late- and early-onset elderly suicide attempters.

OBJECTIVES: While suicidal behavior often manifests in adolescence and early adulthood, some people first attempt suicide in late life, often with remarkable lethal intent and determination. Given these individuals' more adaptive functioning earlier in life, they may possess traits that hinder adjustment to aging, such as high conscientiousness, rather than impulsive-aggressive traits associated with suicidal behavior in younger adults. METHODS: A cross-sectional case-control study was conducted in older adults aged ≥50 (mean: 65), divided into early- and late-onset attempters (age at first attempt ≤ or >50, mean: 31 vs 61), suicide ideators as well as non-suicidal depressed and healthy controls. Personality was assessed in terms of the five-factor model (FFM, n = 200) and five DSM personality disorders analyzed on the trait level as continuous scores (PDs, n = 160). Given our starting hypothesis about late-onset attempters, the FFM dimension conscientiousness was further tested on the subcomponent level. RESULTS: All clinical groups displayed more maladaptive profiles than healthy subjects. Compared to depressed controls, higher neuroticism, and borderline traits characterized both suicide ideators and early-onset attempters, while only early-onset attempters further displayed lower extraversion and higher antisocial traits. Late-onset attempters were similar to depressed controls on most measures, but scored higher than them on orderliness, a conscientiousness subcomponent. CONCLUSIONS: While neuroticism, introversion, and cluster B traits are prominent in early-onset suicidal behavior, late-onset cases generally lack these features. In contrast, higher levels of orderliness in late-onset suicidal behavior are compatible with the age-selective maladjustment hypothesis. Key points Personality of elderly attempters differed between those with early- and late-onset first attempts. Early-onset attempters possessed personality traits generally found in younger suicidal populations (high neuroticism, low extraversion, antisocial, and borderline PD traits), supporting that constitutional suicide risk factors persist into late life in some individuals. Late-onset suicide attempters had higher levels of orderliness than non-suicidal depressed participants, suggesting that this generally adaptive trait may facilitate suicidal behavior in a subset of depressed elderly.

Lamotrigine Induces Tremor among Epilepsy Patients Probably via Cerebellar Pathways.

Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.

Utilization of acute vascular imaging and neurointervention for acute ischaemic stroke patients in 20 Hungarian stroke centers.

BACKGROUND AND PURPOSE: Acute mortality rate of stroke in Hungary is significantly higher than in Western Europe, which is likely to be partially attributable to suboptimal treatment. METHODS: We examined the use of acute vascular imaging and mechanical thrombectomy for acute ischaemic stroke patients. We collected data on 20 consecutive patients from Hungarian stroke centers before 31st August 2016. RESULTS: Out of the reported 410 patients, 166 (40.4%) underwent CT angiography and 44 (10.7%) had mechanical thrombectomy. CONCLUSION: Only about 1/3 of acute ischaemic stroke patients eligible for thrombectomy actually had it. The underlying reasons include long onset-to-door time, low utilization of acute vessel imaging and a limited neuro-intervention capacity needing improvement.

[Psychiatric disorders in epilepsy: clinical phenomena]. / Pszichiátriai zavarok epilepsziában: klinikai jelenségek.

The frequent psychiatric comorbidity in epilepsy compromises the quality of life of those affected, further increasing their suicide risk and the high burden of stigmatisation. Out of adulthood epilepsies, mesio-temporal lobe epilepsy carries the highest cognitive and psychiatric risk, making mental health comorbidities its inherent features. The pathomechanism of the epilepsy-related mental health symptoms and conditions appears to be related to undetected subclinical seizures, postictal exhaustion and inhibition, and the non-REM sleep related interictal epileptic activity. In our work we try to present some of the typical psychiatric syndromes and conditions seen in epilepsy. We aim to highlight the difficulties of treatment on the borderline of neurology and psychiatry.

Epileptic Seizures in Alzheimer Disease: A Review.

Alzheimer disease (AD) is the most frequent cause of major neurocognitive disorders with a huge economical and medical burden. Several studies pointed out that AD is associated with a high risk for developing epileptic seizures. The aims of our review were to evaluate and to summarize the current literature (ending in September 2015) of animal and human studies in the relation of AD and epileptic seizures. It seems likely that epileptic hyperexcitation could be partially responsible for the progression of AD due to the increased rate of amyloid deposition. Pathologic changes in animal models of AD are similar to those seen in human temporal lobe epilepsy. Antiepileptic treatment had a positive effect on cognitive function in animal and human studies. Because the detection of seizures in patients with cognitive decline is extremely difficult because of methodological problems, the true prevalence of seizures has remained unclear. Nonconvulsive seizures with no overt clinical symptoms may be frequent seizure types in AD. These are difficult to detect by clinical observation and with standard scalp electroencephalogram (EEG) methods. We propose that long-term EEG recording and video-EEG monitoring is necessary to prove the presence of epileptiform activity in demented patients.

[Late life psychotic disorders : clinical aspects]. / Troubles psychotiques de l'âge avancé : aspects cliniques.

Old age is a vulnerable period of life for either the apparition or the exacerbation of psychiatric disorders. Among others, psychoses are relatively frequent in the elderly. Alas diagnoses of non-organic psychoses are still matters of debate, namely because of the important variability of symptoms and the lack of data in the elderly population. DSM-5 adds only little precision to this nosographic issue. These questions are however important in practice, since they influence prognostic aspects and treatment choices. Thus diagnostic criteria and care remain complex. The present article summarizes these clinical aspects for the most frequent forms of late life psychoses, namely early- and late-onset schizophrenia and delusional disorder.

La vieillesse est une phase de la vie vulnérable à l'apparition ou à l'exacerbation de troubles psychiatriques, dont les psychoses, relativement fréquentes chez l'âgé. Le diagnostic des psychoses non organiques continue hélas à faire l'objet de controverses en raison notamment de l'importante variabilité des symptômes et d'un manque de données chez l'âgé. Le DSM-5 n'a apporté que peu de réponses par rapport à ces difficultés nosographiques. Cette détermination reste néanmoins importante en pratique, influençant le pronostic et les choix thérapeutiques. Les critères diagnostiques et la prise en charge restent donc complexes. Le présent article résume les aspects cliniques des psychoses de l'âge avancé les plus courantes : les schizophrénies à débuts précoce et tardif, ainsi que le trouble délirant.

[Individual differences in sleep macrostructure: effects of anxiety, depression, aging and gender]. / Egyéni különbségek az alvási makrostruktúrában: a szorongás, a depresszió, az öregedés és a nem hatása.

OBJECTIVE: Anxiety is one of the most common psychiatric symptoms frequently associated with sleep disorders. Despite the intensive research, the role of sleep in the patomechanism of anxiety has remained unclear. The aim of the study was to investigate the anxiety-related changes in the sleep macrostructure and the impact of ageing, gender and the presence of depression. METHODS: 1083 patients with sleep symptoms were enrolled in the study. All patients have all night polysomnographies. The effect of anxiety, depression, aging and gender on the sleep initiation, maintenance and sleep stages respectively; were analysed in 4 different statistical approaches. RESULTS: Anxiety increased the latency of sleep and REM sleep; and decreased the length of REM sleep and slow-wave sleep; while depressive symptoms were associated with reduced REM latency, slow-wave sleep and increased REM duration. The length of slow-wave sleep, REM phase decreased with ageing and the sleep was fragmented. Women had more slow-wave sleep and less REM sleep than men. CONCLUSION: Normal order of sleep stages is essential in the cognitive processing of the brain. Changes in sleep macrostructure may have an impact in the impairment of cognitive functions of patients suffering from anxiety or depression.

[The efficacy of lacosamide in relation to antiepileptic drug history. Clinical experiences in adult partial epilepsy]. / A lacosamid hatékonysága a gyógyszeres kezelési elozmények tükrében. Klinikai tapasztalatok felnottkori parciális epilepsziában.

OBJECTIVE: A retrospective study in adult partial epilepsy on the efficacy of lacosamide in relation to previous antiepileptic drug experiences. METHOD: We analysed 3-65 months' data on epilepsy-care of 43 pharmacoresistant partial epilepsy patients treated with lacosamide. Further analysis of antiepileptic drug history was carried out in strictly selected subgroups of patients with good and poor therapeutic response to lacosamide (10 and 9 patients, respectively) for 2-10 years long retrospective follow up. PATIENTS: Adult patients with partial-onset seizures had been treated previously with three or more lifetime antiepileptic drugs without permanent success. RESULTS: Six patients (14%) were seizure free, eleven patients (25%) have experienced important improvement (their seizure-frequency decreased by at least 50%) for more than 12 months. Fourteen patients (32%) improved for less than 6 months and then have relapsed; and add-on lacosamide proved ineffective in 12 patients (28%). Those selected 10 patients successfully treated with lacosamide (seizure free for at least six months) favourably responded to carbamazepine or oxcarbazepine earlier and levetiracetam was ineffective or even caused worsening. The selected lacosamide-unresponsive nine patients responded unfavourably to carbamazepine or oxcarbazepine earlier. Fifteen patients (35%) suffered side effects as dizziness or sleepiness, in 11 of them lacosamide was combined with a "traditional" sodium-channal blocker antiepileptic drug. CONCLUSION: Lacosamide is an effective add-on antiepileptic drug in difficult-to treat adult partial epilepsy patients. Our data suggest that good lacosamide response may be expected in those patients who reacted favourably to "traditional" sodium-channel blocker carbamazepine or oxcarbazepine earlier.

Anti glutamate-decarboxylase antibodies: a liaison between localisation related epilepsy, stiff-person syndrome and type-1 diabetes mellitus.

We present two patients with partial epilepsy, type-1 diabetes and stiff person syndrome associated with high serum auto-antibody levels to glutamate-decarboxylase (anti-GAD). Both patients were or have suffered from additional autoimmune conditions. The presence of stiff person syndrome and elevated anti-GAD levels have to make clinicians look for additional autoimmune conditions including type-1 diabetes. On the other hand, the co-morbidity of partial epilepsy with autoimmune conditions in patients with elevated serum anti-GAD suggests an autoimmune mechanism of partial epilepsy in these cases.

LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders.

Celiac disease--in its typical form--is a chronic immune-mediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.