Efficacy, safety, and potential of extended-release lamotrigine in the treatment of epileptic patients

Epilepsy is a frequent, chronic disease demanding long-term medication with antiepileptic drugs (AEDs). When slow release formulations of AEDs are used the chance of compliance and control of seizures is increased. Lamotrigine (LTG) is a broad spectrum antiepileptic drug (AED), effective against both generalized and partial seizures. Its immediate-release formulation (LTG-IR) requires twice-daily dosing. In contrast, an extended-release formulation (LTG-XR) may be given once daily, providing a flatter dose-concentration curve with apparently lower maximum serum levels. Simplified dosing positively affects compliance and LTG-XR has a similar profile of efficacy and tolerability to LTG-IR. Rashes, including Stevens–Johnson syndrome, are the most serious adverse effect impacting 0.8% of pediatric patients. Thus, LTG-XR should be discontinued upon the appearance of rash

To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question

Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors – the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic drugs) is necessary to answer the title question

The Role of Gut Microbiota in an Ischemic Stroke

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke

Post-Ischemic Neurodegeneration of the Hippocampus Resembling Alzheimer’s Disease Proteinopathy

In this review, we summarize, inter alia, the protein and gene changes associated with Alzheimer’s disease and their role in post-ischemic hippocampal neurodegeneration. In the hippocampus, studies have revealed dysregulation of the genes for the amyloid protein precursor metabolism and tau protein that is identical in nature to Alzheimer’s disease. Data indicate that amyloid and tau protein, derived from brain tissue and blood due to increased permeability of the blood–brain barrier after ischemia, play a key role in post-ischemic neurodegeneration of the hippocampus, with concomitant development of full-blown dementia. Thus, the knowledge of new neurodegenerative mechanisms that cause neurodegeneration of the hippocampus after ischemia, resembling Alzheimer’s disease proteinopathy, will provide the most important therapeutic development goals to date

Neuroinflammation in Post-Ischemic Neurodegeneration of the Brain: Friend, Foe, or Both?

One of the leading causes of neurological mortality, disability, and dementia worldwide is cerebral ischemia. Among the many pathological phenomena, the immune system plays an important role in the development of post-ischemic degeneration of the brain, leading to the development of neuroinflammatory changes in the brain. After cerebral ischemia, the developing neuroinflammation causes additional damage to the brain cells, but on the other hand it also plays a beneficial role in repair activities. Inflammatory mediators are sources of signals that stimulate cells in the brain and promote penetration, e.g., T lymphocytes, monocytes, platelets, macrophages, leukocytes, and neutrophils from systemic circulation to the brain ischemic area, and this phenomenon contributes to further irreversible ischemic brain damage. In this review, we focus on the issues related to the neuroinflammation that occurs in the brain tissue after ischemia, with particular emphasis on ischemic stroke and its potential treatment strategies

Molecular Hydrogen Neuroprotection in Post-Ischemic Neurodegeneration in the Form of Alzheimer’s Disease Proteinopathy: Underlying Mechanisms and Potential for Clinical Implementation—Fantasy or Reality?

Currently, there is a lot of public interest in naturally occurring substances with medicinal properties that are minimally toxic, readily available and have an impact on health. Over the past decade, molecular hydrogen has gained the attention of both preclinical and clinical researchers. The death of pyramidal neurons in especially the CA1 area of the hippocampus, increased permeability of the blood-brain barrier, neuroinflammation, amyloid accumulation, tau protein dysfunction, brain atrophy, cognitive deficits and dementia are considered an integral part of the phenomena occurring during brain neurodegeneration after ischemia. This review focuses on assessing the current state of knowledge about the neuroprotective effects of molecular hydrogen following ischemic brain injury. Recent studies in animal models of focal or global cerebral ischemia and cerebral ischemia in humans suggest that hydrogen has pleiotropic neuroprotective properties. One potential mechanism explaining some of the general health benefits of using hydrogen is that it may prevent aging-related changes in cellular proteins such as amyloid and tau protein. We also present evidence that, following ischemia, hydrogen improves cognitive and neurological deficits and prevents or delays the onset of neurodegenerative changes in the brain. The available evidence suggests that molecular hydrogen has neuroprotective properties and may be a new therapeutic agent in the treatment of neurodegenerative diseases such as neurodegeneration following cerebral ischemia with progressive dementia. We also present the experimental and clinical evidence for the efficacy and safety of hydrogen use after cerebral ischemia. The therapeutic benefits of gas therapy open up new promising directions in breaking the translational barrier in the treatment of ischemic stroke

The Role of Gut Microbiota in an Ischemic Stroke

The intestinal microbiome, the largest reservoir of microorganisms in the human body, plays an important role in neurological development and aging as well as in brain disorders such as an ischemic stroke. Increasing knowledge about mediators and triggered pathways has contributed to a better understanding of the interaction between the gut-brain axis and the brain-gut axis. Intestinal bacteria produce neuroactive compounds and can modulate neuronal function, which affects behavior after an ischemic stroke. In addition, intestinal microorganisms affect host metabolism and immune status, which in turn affects the neuronal network in the ischemic brain. Here we discuss the latest results of animal and human research on two-way communication along the gut-brain axis in an ischemic stroke. Moreover, several reports have revealed the impact of an ischemic stroke on gut dysfunction and intestinal dysbiosis, highlighting the delicate play between the brain, intestines and microbiome after this acute brain injury. Despite our growing knowledge of intestinal microflora in shaping brain health, host metabolism, the immune system and disease progression, its therapeutic options in an ischemic stroke have not yet been fully utilized. This review shows the role of the gut microflora-brain axis in an ischemic stroke and assesses the potential role of intestinal microflora in the onset, progression and recovery post-stroke