Effects of epileptiform EEG discharges on cognitive function: is the concept of "transient cognitive impairment" still valid?

In this article we review the existing evidence on the cognitive impact of interictal epileptiform EEG discharges. Such cognitive impairment occurs exclusively in direct relation to episodes of epileptiform EEG discharges and must be distinguished from (post) ictal seizure effects and from the nonperiodic long-term "stable" interictal effects caused by the clinical syndrome or the underlying etiology. Especially in patients with short nonconvulsive seizures, characterized often by difficult-to-detect symptoms, the ictal or postictal effects may be overlooked and the resulting cognitive effects may be erroneously related to the epileptiform EEG discharges. The existing epidemiological data show that the prevalence of cognitive impairment during epileptiform EEG discharges is low. In one study 2.2% of the patients referred to a specialized epilepsy center for EEG recording showed a definite relationship between epileptiform EEG discharges and cognitive impairments ("transient cognitive impairment"). Several studies have sought to analyze to what extent cognitive impairment can be attributed to epileptiform EEG discharges among the other epilepsy factors (such as the effect of the clinical syndrome). These studies show that epileptiform EEG discharges have an additional and independent effect, but this effect is mild and limited to transient mechanistic cognitive processes (alertness, mental speed). This finding concurs with clinical studies that also reported only mild effects. In only exceptional cases are epileptiform EEG discharges the dominant factor explaining cognitive impairment. In addition, some studies have indicated that such mild effects may accumulate over time (when frequent epileptiform EEG discharges persist over years) and consequently result in effects on stable aspects of cognitive function such as educational achievement and intelligence. Hence, the clinical relevance is that early detection of cognitive effects of epileptiform EEG discharges and subsequent treatment may prevent a definite impact on cognitive and educational development. The disruptive effects of epileptiform EEG discharges on long-term potentiation, as established in animal experiments, may be one of the neurophysiological mechanisms underlying this accumulation. In conclusion the concept of "transient cognitive impairment" is still valid, but refinement of methodology has shown that a large proportion of presumed transient cognitive impairment can be attributed to subtle seizures, while interictal epileptic activity accounts for a much smaller part of the cognitive effects than previously thought. In particular cryptogenic partial epilepsies are associated with the risk of cognitive impairment. We hope that increased clinical awareness of this need for early detection will stimulate longitudinal and prospective research that eventually also will provide an answer to the questions of when and how epileptiform discharges that are not part of a seizure need to be treated.     

Therapeutically induced EEG burst-suppression pattern to treat refractory status epilepticus—what is the evidence?

Current guidelines advocate to treat refractory status epilepticus (RSE) with continuously administered anesthetics to induce an artificial coma if first- and second-line antiseizure drugs have failed to stop seizure activity. A common surrogate for monitoring the depth of the artificial coma is the appearance of a burst-suppression pattern (BS) in the EEG. This review summarizes the current knowledge on the origin and neurophysiology of the BS phenomenon as well as the evidence from the literature for the presumed benefit of BS as therapy in adult patients with RSE.

     

Naive theory impairment in schizophrenia: is it domain-specific?

The ability to represent mental states of self and others to account for behavior is called theory of mind (ToM). This study examined whether ToM deficit in schizophrenia patients is a specific deficit in the cognitive component of interpersonal skills or a more global deficit, involving impaired information processing skills. Schizophrenia inpatients (N = 41) were compared with a control group of healthy subjects (N = 22) and to nonschizophrenia psychiatric patients (24 with affective disorders, seven with other psychosis) over a range of ToM tasks and another naive theory (theory of biology; ToB). Psychiatric inpatients as a whole showed significant deficit compared with the control group of healthy subjects in ToM tasks. The schizophrenia patients showed significantly larger deficits compared with patients suffering from affective disorder, while the performance of patients with nonschizophrenia psychosis was intermediate. In contrast, no difference was observed in the performance of the different groups on the ToB tasks. The fact that a deficit was found in ToM but not in ToB suggests a specific deficit in a cognitive component of interpersonal skills in schizophrenia rather than a general deficit in information processing skills. Naive theories deficits in schizophrenia seem to be domain-dependent.     

Menopausal transition and depression: who is at risk and how to treat it?

The menopausal transition may impose a challenge to clinicians and health professionals who are invested in improving women's quality of life; after all, this period in life is commonly marked by significant hormone fluctuations accompanied by bothersome vasomotor symptoms (e.g., hot flushes and night sweats) and other somatic complaints. In addition, more recent epidemiologic data demonstrate that some women transitioning to menopause may be at higher risk for developing depression when compared with their risk during premenopausal years; this increased risk appears to be true even among those who had never experienced depression before. In this article, putative contributing factors for this window of vulnerability for depression during the menopausal transition are critically reviewed. Hormonal and nonhormonal factors that may contribute to the occurrence of physical and/or psychiatric complaints during the menopausal transition are discussed. Lastly, existing evidence-based treatment strategies are summarized.     

Can single pulse electrical stimulation provoke responses similar to spontaneous interictal epileptiform discharges?

ObjectiveTo estimate the proportion of patients where EEG responses to single pulse electrical stimulation (SPES) are similar to spontaneous interictal epileptiform discharges (IEDs) in the same patient, and whether such resemblance is related to seizure onset.MethodsWe have visually compared the morphology, topography and distribution of IEDs and of SPES responses in 36 patients with intracranial EEG recordings during presurgical evaluation.ResultsEach patient showed between 3 and 17 different IED patterns, located at seizure onset zone and elsewhere. Only 13 patients showed the highest incidence and amplitude of IEDs at the site of focal seizure onset. Twenty-eight patients showed early responses which were similar to at least one IED pattern. Thirty patients showed delayed responses which were always similar to at least one IED pattern and were always located at seizure onset or in its vicinity.ConclusionsEarly SPES responses often, and delayed responses always, were similar to at least one IED pattern in the same patient. The IEDs resembling delayed responses were those associated with seizure onset.SignificanceThe similarities between IEDs and SPES responses suggest that SPES can trigger the mechanisms responsible for generating IEDs, which may become a tool to study the pathophysiology of IEDs.     

Covert medication in psychiatric emergencies: is it ever ethically permissible?

Covert administration of medications to patients, defined as the administration of medication to patients without their knowledge, is a practice surrounded by clinical, legal, ethics-related, and cultural controversy. Many psychiatrists would be likely to advocate that the practice of covert medication in emergency psychiatry is not clinically, ethically, or legally acceptable. This article explores whether there may be exceptions to this stance that would be ethical. We first review the standard of emergency psychiatric care. Although we could identify no published empirical studies of covert administration of medicine in emergency departments, we review the prevalence of this practice in other clinical settings. While the courts have not ruled with respect to covert medication, we discuss the evolving legal landscape of informed consent, competency, and the right to refuse treatment. We discuss dilemmas regarding the ethics involved in this practice, including the tensions among autonomy, beneficence, and duty to protect. We explore how differences between cultures regarding the value placed on individual versus family autonomy may affect perspectives with regard to this practice. We investigate how consumers view this practice and their treatment preferences during a psychiatric emergency. Finally, we discuss psychiatric advance directives and explore how these contracts may affect the debate over the practice.     

What is the “Cognitive” in Cognitive Neuroscience?

This paper argues that the cognitive neuroscientific use of ordinary mental terms to report research results and draw implications can contribute to public confusion and misunderstanding regarding neuroscience results. This concern is raised at a time when cognitive neuroscientists are increasingly required by funding agencies to link their research to specific results of public benefit, and when neuroethicists have called for greater attention to public communication of neuroscience. The paper identifies an ethical dimension to the problem and presses for greater sensitivity and responsibility among neuroscientists regarding their use of such terms.     

Neonatal seizures: to treat or not to treat?

The immature brain is intrinsically hyperexcitable, a feature that, despite being crucial for learning, synaptogenesis and neuronal plasticity, predisposes the neonate to seizures. Seizures represent the most common neurologic manifestation of impaired brain function in this age group. Importantly, although seizure-induced neuronal injury is minimal in the "healthy" neonatal brain, the "metabolically-compromised" brain appears more vulnerable. Even in the "healthy" brain, however, seizures result in impaired learning, enhanced susceptibility to further seizures, and increased risk of brain injury with seizures later in life, as a result of altered hippocampal circuitry. Given these findings, an aggressive approach to neonatal seizures appears warranted. However, our current conventional therapies (including phenobarbital, phenytoin, and benzodiazepines), even when used in combination, are often ineffective in controlling seizures. Lidocaine may yield better efficacy but requires more study. Recent animal data suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonists such as topiramate may have a neuroprotective role. However, further work is needed to confirm the safety of excitatory amino acid antagonists in neonates because there remains a prevailing concern that such agents may impair normal neurodevelopmental processes.     

Mild cognitive impairment in the older population: Who is missed and does it matter?

OBJECTIVES: Classifications of mild cognitive impairment (MCI) vary in the precision of the defining criteria. Their value in clinical settings is different from population settings. This difference depending on setting is to be expected, but must be well understood if population screening for dementia and pre-dementia states is to be considered. Of importance is the impact of missed diagnosis. The magnitude of missed 'at-risk' cases in the application of different MCI criteria in the population is unknown. METHODS: Data were from the Medical Research Council Cognitive Function and Ageing Study, a large population based study of older aged individuals in the UK. Prevalence and two-year progression to dementia in individuals whose impairment failed to fulfil published criteria for MCI was evaluated. RESULTS: Prevalence estimates of individuals not classified from current MCI definitions were extremely variable (range 2.5-41.0%). Rates of progression to dementia in these non-classified groups were also very variable (3.7-30.0%), reflecting heterogeneity in MCI classification requirements. CONCLUSIONS: Narrow definitions of MCI developed for clinical settings when applied in the population result in a large proportion of individuals who progress to dementia being excluded from MCI classifications. More broadly defined criteria would be better for selection of individuals at risk of dementia in population settings, but at the possibility of high false positive rates. While exclusion may be a good thing in the population since most people are presumably 'normal', over-inclusion is more likely to be harmful. Further work needs to investigate the best classification system for application in the population.     

Ethical issues involving the right hemisphere stroke patient: to treat or not to treat?

The management of patients with right hemisphere damage (RHD) presents a challenge to the allied health clinician. In addition to impairments in specific cognitive areas, some patients may not be aware of the presence or extent of their deficits or the impact of these deficits on everyday activities. This article briefly describes two related models of awareness/unawareness that may help guide the assessment and treatment process in patients with neurological damage including RHD. Then, some clinical care decisions regarding patients with decreased awareness are presented together with a framework for organizing and evaluating the various factors associated with a case.     

To treat or not to treat Alzheimer’s disease by the ketogenic diet? That is the question

Alzheimer’s disease (AD) and current treatments: AD is a serious neurological disorder worldwide that affects about 26 million people,and whose prevalence has been calculated to quadruple by 2050,thus reaching over 1% of the total population,with the highest prevalence occurring in both adults and elderly (Pluta et al.,2018).Neurodegenerative processes of the sporadic form of AD probably start 20 years before the clinical onset of the disorder (Pluta et al.,2018).This disease is the most important cause of dementia in world aged society (~75%).AD is a disorder that affects not only patients but also their caregivers.The social and economic burden associated with AD was calculated as an example in the United States alone;600 billion dollars annually is spent on caring for AD patients (Pluta et al.,2018).AD is the one of the great health-care challenges of the 21st century.The incidence of AD,a chronic and progressive neurodegenerative disorder,is increasing,as well as the need for efficient methods of diagnosis,prevention and treatment (Pluta et al.,2018).The characteristic clinical and neuropathological hallmarks of AD are: dementia as the main clinical symptom and in post-mortem neuropathological examination,the presence of amyloid plaques as well as neurofibrillary tangles and loss of neurons in the brain of AD patients.The role of amyloid and tau protein is questioned in the etiology of AD and other causes such as ischemic etiology are being considered (Pluta and U?amek-Kozio?,2019).There are several treatments that are not causal but symptomatic that are not effective,especially for advanced disease.To date,only a few drugs are approved,such as acetylcholinesterase inhibitors and memantine.Drugs that regulate partly the activity of neurotransmitters and partly alleviate behavioral symptoms.Other treatment options include active and passive immunization,anti-aggregation specifics,and secretase inhibitors.The road to clarity AD etiology,early final ante mortem diagnosis and treatment has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution.Research has recently been launched to identify new mechanisms underlying AD that could be the target of new prevention strategies (Pluta and U?amek-Kozio?,2019).Therefore,other treatment options can be recommended,and the ketogenic diet seems to be an interesting last resort solution at the moment (Rusek et al.,2019).The diet contains large amounts of fat and low carbohydrates with vitamin supplementation.New scientific articles suggest that a low-carbohydrate and high-fat ketogenic diet may help alleviate the brain damage in AD (Ota et al.,2019;Rusek et al.,2019).A ketogenic diet can alleviate the effects of impaired glucose metabolism in AD by providing ketones as an additional source of energy.Here,based on new data,we have presented that a ketogenic diet can be effective in preventing and treating AD,but both ketone bodies production and carbohydrate reduction are needed to achieve this.