[Premenstrual syndrome and premenstrual dysphoric disorder-Overview on pathophysiology, diagnostics and treatment]. / Prämenstruelles Syndrom und prämenstruelle dysphorische Störung ­ Übersicht zu Pathophysiologie, Diagnostik und Therapie.

Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as a differential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From a pathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by a complex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.

[Analysis of the prevalence of anticoagulant therapy in patients with cognitive disorders and cerebral amyloid angiopathy (CAA)]. / Analyse zur Häufigkeit einer gerinnungshemmenden Medikation bei Patientinnen mit kognitiven Störungen und zerebraler Amyloidangiopathie (CAA).

OBJECTIVES: To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. MATERIALS AND METHODS: Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. RESULTS: Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9 years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. A total of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). CONCLUSION: CAA is a frequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with a higher number of cortical and subcortical microbleeds.

[Delirium in the context of intensive care medicine-Part 2: diagnosis, prevention and treatment]. / Delirante Syndrome im intensivmedizinischen Kontext ­ Teil 2: Diagnose, Prävention und Therapie.

Despite the high prevalence and the enormous medical and health economic impact, delirium syndromes are often underdiagnosed, which is mainly attributable to the high frequency of hypoactive delirium and to the frequently subtle and fluctuating psychopathology in the initial phase of delirium. These aspects also justify the need for a consequent and continuous application of standardized screening tools to detect delirium as early as possible. A multidimensional, nonpharmacological prevention of delirium is effective and still underutilized in the clinical practice. So far, there are no consensus recommendations regarding the pharmacological prevention of delirium. From a therapeutic perspective a causal approach is prioritized. Pharmacological treatment of delirium can only be considered under strict observance of specific indicators. When treating non-withdrawal-related delirium benzodiazepines should be avoided.

[Delirium in the context of intensive care medicine-Part 1: epidemiology, definitions, pathophysiology]. / Delirante Syndrome im intensivmedizinischen Kontext ­ Teil 1: Epidemiologie, Definitionen, Pathophysiologie.

The prevalence of delirium syndromes is high, they are often underdiagnosed and therefore medically as well as economically highly relevant syndromes due to the long-term sequelae. In the majority of cases, delirium has a multifactorial etiology, which is why a comprehensive search for the cause is of highest priority. Surgery, administration of potentially proinflammatory drugs as well as the intensive care environment, including the underlying disease and drugs used, represent relevant etiological factors. Pathophysiology and psychopathology are complex and vary depending on the etiological factors present. Prominent impairment of attention and consciousness are central symptoms of delirium allowing the differentiation from important differential diagnoses, such as encephalopathy, depression, psychosis and dementia.

[Prognostic and diagnostic value of cerebrospinal fluid analysis in neurodegenerative dementia diseases]. / Prognostischer und differenzialdiagnostischer Stellenwert der Liquordiagnostik bei neurodegenerativen Demenzerkrankungen.

Cerebrospinal fluid (CSF) analysis is an important diagnostic tool in the assessment of dementia. For the differentiation of Alzheimer's disease from other etiologies of dementia syndromes, established biological markers could be helpful to confirm a distinctive neuropathology. Whereas negative CSF findings can rule out the majority of primarily neurodegenerative disorders, overlapping biomarker profiles remain a diagnostic challenge. Therefore, it is important to interpret CSF results within a specific clinical context. Furthermore, atypical CSF data can be challenging and require profound knowledge of preanalytics, biomarker profiles and the broad spectrum of diseases associated with cognitive decline. Beyond the Alzheimer's disease clinical spectrum, current studies aim at investigating CSF biomarkers to better differentiate tauopathies, TDP43(Transactive response DNA binding protein 43 kDa)-proteinopathies and synucleinopathies.

[Criminal behavior in frontotemporal dementia and Alzheimer's disease]. / Delinquentes Verhalten im Rahmen frontotemporaler Demenzen und der Alzheimer-Erkrankung.

Criminal behavior in older people represents a rare phenomenon. Among older criminals there are many first offenders and 75% are men. Dementia poses one possible origin of delinquency in advanced age. It is unclear how often dementia is the actual cause of delinquency in older age. In studies with older criminals the prevalence of dementia was heterogeneous due to methodological study issues. In the course of the disease 50% of patients with frontotemporal dementia and 10% of patients with Alzheimer's disease commit crimes. The neurobiological origin of delinquency in dementia is poorly understood. On the basis of current study results first delinquency in older age can be explained by impairment of social cognition, difficulties in making appropriate emotional contributions and disturbed control of behavior. Affection of frontal and anterior temporal brain structures seem to be of high relevance. As dementia impairs criminal responsibility psychiatrists are confronted with a forensic evaluation of legal culpability of older criminals. Regarding different etiologies of dementia, specific peculiarities need to be considered in a forensic psychiatric assessment. Especially frontotemporal dementia predisposes towards a wide spectrum of criminal behavior whereas patients with Alzheimer's disease predominantly commit crimes due to cognitive impairment. The review summarizes the present knowledge about criminal behavior in the context of dementia.

[Current findings on the coincidence of cerebral amyloid angiopathy and Alzheimer's disease]. / Aktuelle Befunde zur Koinzidenz von zerebraler Amyloidangiopathie und Alzheimer-Erkrankung.

Cerebral amyloid angiopathy (CAA) is closely related to Alzheimer's disease (AD) despite having distinct pathomechanisms. The CAA modulates cognitive impairment within AD by synergistic effects. The pathophysiologic relations are complex and incompletely understood, possibly due to the heterogeneous nature of CAA with its different subtypes. Both diseases are characterized by a pathologic amyloid metabolism but the pathologic processing of amyloid precursor proteins is distinct. The manifestation of vascular and parenchymal amyloid deposits can either overlap or occur independently and isolated. The investigation of the specific contribution of co-occurring CAA within AD to cognitive deficits requires diagnostic methods that sufficiently identify CAA severity and complexity as well as detailed neuropsychological testing to precisely characterize the cognitive deficits and to draw conclusions regarding their etiology.

[Intracerebral hemorrhage under platelet inhibition and oral anticoagulation in patients with cerebral amyloid angiopathy]. / Intrazerebrale Blutungen unter Plättchenaggregationshemmung und oraler Antikoagulation bei Patienten mit zerebraler Amyloidangiopathie.

Oral anticoagulation in patients with cerebral amyloid angiopathy is a therapeutic challenge. The association of cerebral amyloid angiopathy with intracerebral hemorrhage, a high mortality of intracerebral hemorrhage especially under oral anticoagulation and the high risk of recurrent bleeding require a multidisciplinary approach and a thorough risk-benefit analysis. Vitamin K antagonists increase the risk of intracerebral bleeding and the accompanying mortality by 60% and should be avoided if possible or reserved for special clinical situations (e.g. mechanical aortic valve replacement). Treatment with novel oral anticoagulants and antiplatelet drugs also increases the risk of cerebral bleeding and therefore needs a thorough risk-benefit evaluation. An interventional left atrial appendage closure is a promising therapeutic option especially in patients with an absolute arrythmia with atrial fibrillation. Furthermore, other clinical implications in patients with cerebral amyloid angiopathy are the subject of this review of the literature, such as special characteristics after acute ischemic stroke and the necessary secondary prophylaxis, with previous intracerebral hemorrhage and in patients with cognitive deficits.

Direct Correlation Function of a Crystalline Solid.

Direct correlation functions (DCFs), linked to the second functional derivative of the free energy with respect to the one-particle density, play a fundamental role in a statistical mechanics description of matter. This holds, in particular, for the ordered phases: DCFs contain information about the local structure including defects and encode the thermodynamic properties of crystalline solids; they open a route to the elastic constants beyond low temperature expansions. Via a demanding numerical approach, we have explicitly calculated for the first time the DCF of a solid: based on the fundamental measure concept, we provide results for the DCF of a hard sphere crystal. We demonstrate that this function differs at coexistence significantly from its liquid counterpart-both in shape as well as in its order of magnitude-because it is dominated by vacancies. We provide evidence that the traditional use of liquid DCFs in functional Taylor expansions of the free energy is conceptually wrong and show that the emergent elastic constants are in good agreement with simulation-based results.

[Cognitive deficits following brain tumor radiation therapy]. / Kognitive Defizite nach Strahlentherapie von Hirntumoren.

Brain radiation is an important treatment option for malignant and benign brain diseases. The possible acute or chronic impact of radiation therapy on cognitive performance is important for daily functioning and quality of life. A detailed evaluation of cognitive impairment is important in the context of how to control disease progression. The susceptibility of the hippocampus to radiation-induced neuronal damage and its important role in memory highlight that therapeutic strategies require precision medicine.

[Correct treatment of mood disorders with lithium]. / Sachgerechte Behandlung affektiver Störungen mit Lithium.

Due to their unique therapeutic effects and high efficacy, lithium salts are recommended in guidelines, particularly for the treatment of mood disorders; however, despite the therapeutic efficacy lithium treatment is underutilized in the treatment of these disorders. The therapeutic efficacy of lithium is contrasted by a narrow therapeutic range and a potential risk of intoxication, which is why close drug monitoring is necessary during lithium treatment. Furthermore, lithium therapy requires well-founded knowledge about patient selection with respect to approved areas of administration and indications. This review article summarizes clinically relevant knowledge of lithium treatment to improve treatment of patients with mood disorders and to increase patient safety when using lithium.

[Alzheimer's disease and epilepsy]. / Alzheimer-Demenz und Epilepsie.

Data regarding the incidence and prevalence of epileptic seizures in Alzheimer's disease show great variability and are clinically underestimated due to their atypical symptomatology. Considering their considerable negative effects on cognition and activities of daily living, epileptic seizures need to be correctly treated. Hypotheses with respect to the pathogenetic mechanisms and associations between Alzheimer's disease and epilepsy are mostly derived from animal experiments. The causal connections are so far insufficiently understood. Data on risk factors are inconsistent due to methodological limitations in studies. Clinical data for these indications show good response to therapy with anticonvulsants and good tolerability in the case of new active substances. When treating epileptic seizures in this patient collective using anticonvulsants, potential adverse effects and possible drug interactions need to be closely monitored.

[Assessment of ability to drive in patients with MCI and dementia]. / Beurteilung der Fahrtauglichkeit bei Patienten mit MCI und demenziellen Syndromen.

People with mild cognitive impairment and dementia are a frequent and continuously increasing patient group in practically all fields of medicine. The associated challenges involve nearly all areas of life in addition to the direct medical treatment. Assessment of the ability to drive in patients with cognitive deficits is becoming increasingly more important. What are the options available to physicians in order to make a valid assessment? Which legal aspects must be taken into consideration? Which rights and obligations arise from the framework conditions? These questions nowadays give rise to great uncertainty for many medical personnel; however, the increasing importance of these problems necessitates a clear procedure, which allows difficult decisions to be made with utmost sovereignty and legal certainty and to be able to give patients and relatives a plausible explanation. Because age is a substantial risk factor for the development of cognitive disorders, the question of the ability to drive is affected not only by neuropsychiatric diseases, such as mild cognitive disorders or dementia but also the frequently occurring somatic comorbidities. Estimation of the ability to drive is therefore a complex approach, which should be standardized in order to appreciate all relevant aspects. It would be desirable to have a practice-oriented algorithm, the formulation of which is the aim of this article. Additionally, we would like to make a contribution to road safety and make medical personnel fully aware of this topic.

[Memantine as add-on medication to acetylcholinesterase inhibitor therapy for Alzheimer dementia]. / Memantin als Add-on-Medikation zur Acetylcholinesteraseinhibitor-Therapie bei Alzheimer-Demenz.

Currently available data indicate superior therapeutic effects of combination treatment for Alzheimer dementia with memantine and acetylcholine esterase inhibitors in certain clinical contexts. Out of five randomized, placebo-controlled, double-blind trials two showed superior therapeutic effects in comparison to monotherapy with acetylcholinesterase inhibitors regarding various domains. Recently published meta-analyses and cost-benefit analyses also showed positive results. Recently published German guidelines for dementia treatment also take these new data into account and recommend combination treatment in patients with severe dementia on stable donepezil medication. This article gives an overview of current evidence for combination therapy.

[Psychopharmaceuticals for treatment of suicidal patients and for suicide prevention]. / Psychopharmaka zur Behandlung suizidaler Patienten und zur Suizidprävention.

Suicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term "suicidality" seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.

[Non-withdrawal-related delirium : Evidence on prevention and therapy]. / Das nichtentzugsbedingte Delir : Evidenz zu Prävention und Therapie.

Delirium is a severe and common yet under-diagnosed disorder in the clinical routine. Multiple factors may contribute to the development of delirium, which is associated with increased mortality and high healthcare costs. Treatment of delirium is often provided with delay and limited to pharmacological interventions. This article summarizes the key symptoms for delirium as well as risk factors and highlights the pharmacological and non-pharmacological options for treatment and prevention.

[Evidence-based treatment of psychosis associated with Parkinson's disease]. / Evidenz zur Behandlung der Parkinson-assoziierten Psychose.

Psychotic symptoms in Parkinson's disease are frequent phenomena and are often associated with an immense burden for caregivers, increased risk of nursing home placement and mortality. Treatment of psychotic disorders associated with Parkinson's disease often poses a therapeutic dilemma and necessitates a differentiated risk-benefit assessment as both the reduction of antiparkinsonian drugs and use of antipsychotic drugs can result in deterioration of motor functions. This article gives an overview of relevant clinical aspects and highlights the pharmacological evidence-based treatment options.

Treatment of lithium intoxication: facing the need for evidence.

Lithium has been used as the gold standard in the treatment of major depressive and bipolar disorders for decades. Due to its narrow therapeutic index, lithium toxicity is a common clinical problem. Although risk factors for lithium intoxication seem to be well-described, lacking patient education and inexperience of treatment are assumed to contribute to the probability of lithium intoxication. A review of literature shows that the treatment of lithium intoxication has not been adequately studied or standardized. The aim of this literature review is to compile and present current evidence on the treatment of lithium intoxication and contribute to a standardization regarding general treatment recommendations as well as evidence on indication for extracorporeal methods. Against the background of this common and potentially life-threatening condition, the standardization of the treatment of lithium intoxication is definitely a task for the future.

Does lithium reduce acute suicidal ideation and behavior? A protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode.

BACKGROUND: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE. METHODS/DESIGN: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome. DISCUSSION: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02039479.