Antiepileptic drug effects on mood and behavior: Molecular targets

With almost 100 years of clinical experience, antiepileptic drugs (AEDs) remain the mainstay of epilepsy treatment. They suppress epileptic seizures by acting on a variety of mechanisms and molecular targets involved in the regulation of neuronal excitability. These include inhibitory-GABAergic and excitatory-glutamatergic neurotransmission, as well as ion (sodium and calcium) conductance through voltage-gated channels. On the other hand, accruing evidence indicates that these mechanisms and targets are also implicated in the regulation of mood and behavior, which may explain why each AED is associated with specific psychotropic effects. These effects, however, cannot be explained solely on the basis of the known mode of action of each AED, and other mechanisms or targets are likely to be implicated. In this article, we review positive and negative effects of AEDs on mood and behavior, discuss putative underlying mechanisms, and highlight knowledge gaps which should be addressed in future studies.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Hepatitis C virus infection and health-related quality of life

Hepatitis C virus (HCV) hepatitis and other diseases related to HCV, such as cryoglobulinemia, lymphoma and renal failure, impair health-related quality of life (HRQoL). In addition, HCV per se might directly influence HRQoL via colonization of microglia in the brain or, indirectly, via the effect of systemic inflammatory cytokines which, in turn, can trigger brain interleukin production. The treatment of HCV-related disorders with interferon (IFN) has an effect on HRQoL. Initially, IFN causes a transient deterioration of HRQoL, due to the induction of depression and other side effects of treatment. Subsequently, the subjects who obtain a sustained virologic response experience an improvement in HRQoL. Only rarely does interferon treatment causes permanent detrimental effects on HRQoL, due to residual psychiatric or neurologic side effects. Liver transplantation is the only treatment for end-stage HCV-related liver disease. HRQoL generally improves massively a few months after transplantation, except in the case of serious complications of the transplant procedure. Furthermore, high levels of anxiety and neuroticism pre-transplant are associated with lower HRQoL one year after transplant. Additionally, six months after transplant, patients with HCV who experience virologic recurrence show significantly greater depression, anxiety, phobic anxiety, and paranoid ideation than anti-HCV-negative patients. In conclusion, optimal care for the overall well-being of patients with HCV infection requires adequate knowledge of their neurological and psychological status.     

Simple tools for complex syndromes: A three-level difficulty test for hepatic encephalopathy

Background

Despite the impact of hepatic encephalopathy on quality of life and prognosis, easily administered tests for its diagnosis are still lacking.

Aim

To assess the usefulness of the Scan package, a three-level-difficulty computerised reaction time test, to diagnose varying degrees of hepatic encephalopathy.

Methods

Sixty-one cirrhotic patients underwent clinical evaluation, paper-and-pencil psychometry and the Scan package; 32 healthy controls served as reference.

Results

Twenty-nine patients were classified as unimpaired, 15 as having minimal and 17 as having overt hepatic encephalopathy. All healthy controls were able to complete the Scan package; in contrast, the number of patients who were able to complete three/two/one part decreased in parallel with the degree of encephalopathy (χ² = 17, p = 0.01). Reaction times in all three parts increased significantly with the severity of encephalopathy. However, the profile of increase was different [group: F(3,77) = 26, p < 0.0001; test: F(2,154) = 277, p < 0.0001; group × test: F(6,154) = 7, p < 0.0001], with different parts being more/less sensitive to varying degrees of encephalopathy.

Conclusions

The Scan package seems useful for the diagnosis of hepatic encephalopathy and covers a considerable portion of its spectrum of severity.     

Short-Term Outcomes of Laparoscopy Combined with Enhanced Recovery Pathway after Ileocecal Resection for Crohn’s Disease: a Case-Matched Analysis

Background

Laparoscopy combined with an enhanced recovery pathway (ERP) is widely considered to be the first-choice option for patients with colorectal cancer. However, no previous reports have focused on patients with Crohn’s disease (CD) treated by laparoscopy and ERP.

Methods

Twenty patients with CD underwent laparoscopic ileocecal resection with an ERP at two institutions. The ERP protocol included no bowel preparation nor fasting, no nasogastric tube, no abdominal drains, early removal of urinary catheter, early solid dietary intake and mobilization, opioid-sparing analgesia and restrictive fluid management. This group was compared with a matched historical control group of 70 CD patients who underwent laparoscopic ileocecal resection treated with conventional care.

Results

Compliance with the ERP was high (≥80 %) for all items except no drain placement. A significantly earlier return of bowel function (time to first flatus and stool) was observed in the ERP group. Mean postoperative and total length of stay were significantly shorter in the ERP group. Postoperative complications were similar in both groups.

Conclusions

This is the first reported experience of laparoscopy with ERP in CD patients and suggests that optimized perioperative care combined with minimally invasive techniques may lead to further improvements in surgical outcomes for CD patients.     

Effect of excessive methionine on the development of the cranial growth plate in newborn rats

ObjectiveMethionine is an essential amino acid and pivotal for normal growth and development. However, previous animal studies have shown that excessive maternal intake of methionine causes growth restrictions, organ damages, and abnormal growth of the mandible in newborn animals. However, the effect of excessive methionine on the development of the cranial growth plate is unknown. This study investigated histological alterations of the cranial growth plate induced by high methionine administration in newborn rats.DesignTwenty pregnant dams were divided into a control and an experimental group. The controls received a diet for rats and the experimental group was fed from the 18th gestational day with a special manufactured high methionine diet for rats. The high methionine diet was maintained until the end of the lactation phase (day 20). The offspring of both groups were killed at day 10 or 20 postnatally and their spheno-occipital synchondroses were collected for histological analysis.ResultsThe weight of the high-dose methionine treated experimental group was considerably reduced in comparison to the control group at day 10 and 20 postnatally. The cartilaginous area of the growth plate and the height of the proliferative zone were markedly reduced at postnatal day 10 in the experimental group.ConclusionsIn summary, the diet-induced hypermethioninemia in rat dams resulted in growth retardations and histomorphological changes of the spheno-occipital synchondrosis, an important craniofacial growth centre in newborns. This finding may elucidate facial dysmorphoses reported in patients suffering from hypermethioninemia.