Comorbidities in newly diagnosed epilepsy: Pre-existing health conditions are common and complex across age groups.

OBJECTIVES: People with epilepsy have a higher prevalence of medical and psychiatric comorbidities compared to the general population. Comorbidities are associated with poor epilepsy outcomes, and there have been recommendations for screening and early identification to improve clinical management. Data from 'First Seizure Clinics' (FSCs) with expert epileptological review can inform about disorders already present at the point of diagnosis of epilepsy or unprovoked seizures. Here, we aimed to describe pre-existing conditions with a focus on psychiatric, substance use, cardiac, neurological, and cancer health domains. METHODS: We included 1383 adults who received a new diagnosis of epilepsy or unprovoked seizures at Austin Hospital (AH) or Royal Melbourne Hospital (RMH) (Australia) FSCs from 2000 to 2010. Data were audited from FSC records, primarily detailed interviews undertaken by epileptologists. Logistic regression examined age distribution and other risk factors. RESULTS: The median age at FSC presentation was 37 years (IQR 26-53, range 18-94). Pre-existing conditions were reported by 40 %; from 32 % in the youngest group (18-30 years) to 53 % in the oldest (65+ years). Psychiatric (18 %) and substance use (16 %) disorders were most common, with higher prevalence among patients 18 to 65 years of age compared to those older than 65 years (p < 0.001). Cardiac, neurological, or cancer conditions were reported by 3-6 %, most often amongst those older than 65 years (p < 0.01). Eight percent (n = 112) reported disorders in >1 health domain. The commonest combination was a psychiatric condition with substance use disorder. Of the sixty-two patients reporting this combination, 61 were ≤65 years of age. CONCLUSIONS: Pre-existing health conditions are present in a substantial proportion of patients diagnosed with epilepsy or unprovoked seizures. Disorders are highest amongst elders, but one-third of younger adults also reported positive histories. These are predominantly psychiatric and/or substance use disorders, conditions strongly associated with poor outcomes in the general population. These findings inform post-diagnosis planning and management, as well as research examining post-diagnostic outcomes and associations between comorbidities and epilepsy.

Newly diagnosed seizures assessed at two established first seizure clinics: Clinic characteristics, investigations, and findings over 11 years.

Objective: 'First seizure' clinics (FSCs) aim to achieve early expert assessment for individuals with possible new-onset epilepsy. These clinics also have substantial potential for research into epilepsy evolution, outcomes, and costs. However, a paucity of FSCs details has implications for interpretation and utilization of this research. Methods: We reviewed investigation findings over 11 years (2000-2010) from two established independent FSCs at Austin Health (AH) and Royal Melbourne Hospital (RMH), Australia. These adult clinics are in major public hospitals and operate with similar levels of expertise. Organizational differences include screening and dedicated administration at AH. Included were N = 1555 patients diagnosed with new-onset unprovoked seizures/epilepsy (AH n = 901, RMH n = 654). Protocol-driven interviews and investigations had been recorded prospectively and were extracted from medical records for study. Results: Median patient age was 37 (IQR 26-52, range 18-94) years (AH 34 vs RMH 42 years; P < .001). Eighty-six percent of patients attended FSC within three weeks postindex seizure (median AH 12 vs RMH 25 days; P < .01). By their first appointment, 42% had experienced ≥2 seizures. An EEG was obtained within three weeks postindex seizure in 73% of patients, demonstrating epileptiform discharges in 25% (AH 33% vs RMH 15%). Seventy-six percent of patients had an MRI within 6 weeks. Of those with imaging (n = 1500), 19% had potentially epileptogenic abnormalities (RMH 28% vs AH 12%; P < .01). At both sites, changes due to previous stroke/hemorrhage were the commonest lesions, followed by traumatic brain injury. ≥WHO level 1 brain tumors diagnosed at presentation comprised a very small proportion (<1%) at each clinic. At both sites, epilepsy type could be determined in 60% of patients; RMH had more focal and AH more generalized epilepsy diagnoses. Significance: Differences between the clinics' administrative and screening practices may contribute to differences in investigation findings. Insight into these differences will facilitate interpretation and utilization, and planning of future research.

Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress.

This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress.

AIMS: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. METHODS: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. RESULTS: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. CONCLUSIONS: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.