Depression is a multicausal disorder and has been associated with the risk to develop cancer, dementia, diabetes, epilepsy and stroke. As a metabolic disorder depression has been associated with obesity, diabetes, insulin sensitivity, neuropeptide Y, glucose regulation, poor glycemic control, glucagone-like peptide-1, cholezystokinin, ghrelin, leptin, the endocannabinoid system, insulin-like growth factor and gastrin-releasing peptide. As a cardiovascular disease a close relationship exists between depression and blood pressure, heart rate, norepinephrine, sympathetic tone, vascular resistance, blood viscosity, plasma volume, intima thickness and atherosclerosis. Additionally blood coagulation, fibrinolysis, D-dimers, plasminogen activator inhibitor-1 protein, platelet activation, VEGF, plasma nitric oxide and its synthase are changed in depressed patients. As an endocrinological and stress disorder depression has been connected with the concentration of free T4, TSH, CRH, arginine vasopressin, corticotrophin, corticosteroid release and ACTH. Depression as an inflammatory disorder is mediated by pro-inflammatory cytokines, interleukin-1, interleukin-6, TNF-alpha, soluble interleukin-2 receptors, interferon-alpha, interleukin 8, interleukin-10, hs-CRP, acute phase proteins, haptoglobin, toll like receptor 4, interleukin-1beta, mammalian target of rapamycin pathway, substance P, cyclooxygenase-2, prostaglandin-E2, lipid peroxidation levels and acid sphingomyelinase. Nutritional factors might influence depression risk, i.e. the consumption of folate, omega-3 fatty acids, monounsaturated fatty acids, olive oil, fish, fruits, vegetables, nuts, legumes, vitamin B6 and vitamin B12. The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone. In this context, a fast neuroprotective and antidepressant effect has also been observed by ketamine, which acts via the glutamatergic system. Hence, GABA, AMPA, EAAT, NMDA- and metabotropic glutamate receptors (mGluR1 to mGluR8) have gained interest in depression recently. Alternative, causative or also easy available treatment strategies beyond serotonin and noradrenaline reuptake inhibition might be a major topic of future psychiatric care. In this review, an attempt is made to overview concepts of the disease and search for perspectives on antidepressant treatment strategies beyond approved medications.

/pdf/molecular-mechanisms-of-depression-perspectives-on-new-51kg9254ke.pdf

Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies

/pdf/practice-guideline-for-the-treatment-of-patients-with-major-ofberaz3o1.pdf

PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder

Status epilepticus (SE) treatment strategies vary substantially from one institution to another due to the lack of data to support one treatment over another. To provide guidance for the acute treatment of SE in critically ill patients, the Neurocritical Care Society organized a writing committee to evaluate the literature and develop an evidence-based and expert consensus practice guideline. Literature searches were conducted using PubMed and studies meeting the criteria established by the writing committee were evaluated. Recommendations were developed based on the literature using standardized assessment methods from the American Heart Association and Grading of Recommendations Assessment, Develop- ment, and Evaluation systems, as well as expert opinion when sufficient data were lacking.

/pdf/guidelines-for-the-evaluation-and-management-of-status-3h3cqurhgk.pdf

Guidelines for the Evaluation and Management of Status Epilepticus

Mood disorders in the medically ill: scientific review and recommendations.

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2011.03121.x

Standards for epidemiologic studies and surveillance of epilepsy

We tested the hypothesis that major depression meeting DSM-III-R criteria or medical therapies for depression increase the risk for unprovoked seizures. Major depression was associated with a sixfold increased risk for unprovoked seizures (95% CI, 1.56-22). The risk remained increased even when controlling for age, sex, length of medical follow-up, and medical therapies for depression. In the absence of known prior neurological insult, major depression is associated with an increased risk for unprovoked seizures.

Major depression is a risk factor for seizures in older adults

Summary: Purpose: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE.



Methods: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1,1965 and December 31, 1984, we studied all first episodes of a febrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996).



Results: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with non febrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2–0.9). No effect of duration or seizure type was shown after adjusting for other risk factors.



Conclusions: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1157.1997.tb00073.x

Short-Term Mortality After a First Episode of Status Epilepticus

We asked whether acute symptomatic status epilepticus (SE) increases the risk for subsequent unprovoked seizure compared with less prolonged acute symptomatic seizure. We also explored whether the risk of unprovoked seizure differs by cause. We ascertained all first episodes of acute symptomatic seizure among residents of Rochester, Minnesota, through the Rochester Project's records-linkage system. Information was collected on seizure duration, age, sex, cause, and subsequent unprovoked seizure. At 10 years of follow-up, the risk of unprovoked seizure was 41% for those with acute symptomatic seizure with SE and 13% for those without SE. Controlling for age, sex, and cause, SE increased the risk for subsequent unprovoked seizure 3.3-fold (95% confidence interval, 1.8-6.1) compared with brief acute symptomatic seizures. Among patients with SE, the risk of unprovoked seizure was increased 18.8-fold for patients with anoxic encephalopathy, 7.1-fold for patients with a structural cause, 3.6-fold for patients with a metabolic cause. The increased risk for unprovoked seizure after SE compared with shorter seizures may be due to SE being a marker for severity of injury, damage caused by SE, or a biological substrate associated with the tendency to experience SE.

Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus

SUMMARY Objective: Whether magnetic resonance imaging (MRI) is informative in febrile seizures (FS) is unknown. We undertook a study to determine the frequency of MRI-detected brain abnormalities and to evaluate their association with FS type and with specific features of complex FS. Methods: A prospective cohort study, from 1999 to 2004, included children with first FS from one Pediatric Emergency Department. MRI of the brain was performed within 1 week of the seizure. FS type was categorized by experts blind to the prior clinical history and MRI results. MRI examinations were read blind to the child’s clinical history and FS type, and interviewers were blind to MRI results. Results: In 159 children with a first FS, imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.). Compared to children with simple FS, children with both focal and prolonged FS (N = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2–15.0), even after adjustment for abnormal neurological examination. Imaging abnormalities included those known to be associated with seizures (e.g., focal cortical dysplasia) and those not typically associated with seizures (e.g., subcortical focal hyperintensities ≥ 5 mm).

FULL-LENGTH ORIGINAL RESEARCH Are MRI-detected brain abnormalities associated with febrile seizure type?

Purpose:No previous population-based study has addressed the contribution of activation procedures to the yield of epileptiform abnormalities on serial EEGs. We assessed yield of activation-related epileptiform abnormalities and predictors of finding an activation-related abnormality with multiple E

Dale C. Hesdorffer

Papers

Major depression is a risk factor for seizures in older adults

Short-Term Mortality After a First Episode of Status Epilepticus

Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus

FULL-LENGTH ORIGINAL RESEARCH Are MRI-detected brain abnormalities associated with febrile seizure type?

Utility of EEG Activation Procedures in Epilepsy: A Population-Based Study.