Which EEG patterns in coma are nonconvulsive status epilepticus?

Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma.Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary.The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future.This article is part of a Special Issue entitled “Status Epilepticus”.     

What can we learn from animal models of convulsive status epilepticus?

Animal models of convulsive status epilepticus (SE) are essential tools for studying human SE and developing novel therapies. Although they do not exhibit the prolonged“silent period” that is characteristic of the typical mesial temporal lobe epilepsy (mTLE) patient, they have proven invaluable for investigating the pathophysiology of seizure-induced brain damage. Recurrent spontaneous seizures also make them useful for antiepileptic drug screening, albeit only for a subset of patients who experience frequent, convulsive seizures. Chemoconvulsant-based models are particularly relevant to those patients that have survived prolonged SE and exhibit severe brain damage and epilepsy with no apparent latent period. Although promising results have been obtained from SE animal models, translating them into human trials has proven difficult. This may be due to several important differences to the human disease, including etiology, neuropathology, and seizure manifestation. Provided their limitations are acknowledged and respected, animal models of SE will continue to produce useful data for years to come.     

Mixed split cord malformation: are we missing something?

Background

The new classification for split cord malformation, based on the unified theory of embryogenesis includes two types Type I and II defined on the basis of the nature of the medium septum and the state of the dural tube. According to this, these are the only two essential features needed for typing and there is never an overlap between the two main forms. We have described two cases that defy this theory.

Case report

We present two patients with split cord malformation who appear to have a combination of features specific to Type I and Type II. Both patients had a partial bony spur within a single dural sac.

Conclusion

An overlap between the two forms of split cord malformation does exist. The role of meninx primitiva in the formation of median bony septum is debatable.     

Outcome of status epilepticus. What do we learn from animal data?

Status Epilepticus (SE) is a life‐threatening neurologic disorder defined as 5 minutes or more of a continuous seizure. SE can represent an exacerbation of a preexisting seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder. In humans, there are several differences between SE that occurs in adults and children. In adult patients, the mortality is high but the incidence is lower than in childhood. Experimental studies have been essential in helping clinicians describe SE, and since these early initial studies, further experimental studies have helped us to better understand the consequences of SE. Animal models of SE support the notion that SE induces brain damage and contribute to epileptogenesis. Laboratory models of SE in developing animals demonstrate age‐ and model‐dependent propensity for brain injury and for epileptogenesis. The use of models with a double hit including a clinical relevant component to seizures provides data that allows us to further understand the contribution of early‐life events in the future development of epilepsy. Using this approach, it has been shown that inflammation or a preexisting brain lesion enhance epileptogenesis in the developing brain. The use of models of SE also permits to establish that treatment to stop the seizure and/or the duration of the SE results in a decrease of SE induced cell injury. Preventing epileptogenesis remains an important goal to modify the development of comorbidities, and it still represents an area of research in need of much progress.     

Klüver-Bucy syndrome following status epilepticus associated with hepatic encephalopathy

Described here is the case of a patient with liver cirrhosis who developed bilateral temporo-occipital lobe lesions on MRI and Klüver-Bucy syndrome following status epilepticus. Herpes encephalitis, paraneoplastic syndrome, Hashimoto's encephalopathy, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episode syndrome were judged not to be involved on the basis of laboratory results. The possible cause of the temporo-occipital lesions on MRI in this patient was cortical damage related mainly to status epilepticus and partially to coexisting hepatic encephalopathy.     

Systemic complications of status epilepticus — An update

Systemic complications occur at every stage of status epilepticus, involve every organ system, and may worsen outcome. Initially, there is a massive catecholamine release and hyperadrenergic state that may result in neurocardiogenic, pulmonary, and, sometimes, musculoskeletal or renal injury. Further medical complications accompany the various treatments used to abort the seizures including the use of nonanesthetic antiseizure drugs and high-dose anesthetic infusions. Later, sequelae of prolonged immobility and critical illness occur and add to the cumulative morbidity of these patients. Clinicians should follow a protocol to guide screening for early markers of systemic injury, complications of specific pharmacologic and adjunctive treatments, and periodic surveillance for complications related to prolonged immobility.This article is part of a Special Issue entitled “Status Epilepticus”.     

What are the most important nonmotor symptoms in patients with Parkinson's disease and are we missing them?

Nonmotor symptoms (NMS) are increasingly recognized as important and neglected aspects of Parkinson's disease (PD). We evaluated their relative frequency and comparative impact on health‐related quality of life (Hr‐QoL) using validated questionnaires. In addition, we assessed the rate of reporting of NMS in neurology clinics compared with their subjective impact on patients. We used a range of validated clinimetric scales of motor and nonmotor symptoms and Hr‐QoL to assess consecutive patients with PD. Reporting of NMS was assessed by comparison with case note documentation. A mean of 11 of 30 NMS per patient were elicited on the NMS questionnaire of which on average 4.8 were reported in the clinical notes (44%). The most common NMS were autonomic (particularly urinary). The Hr‐QoL scores correlated most strongly with autonomic dysfunction (r = 0.84; particularly urinary and gastrointestinal symptoms), mood (r = 0.74), fatigue (r = 0.74), sleep problems (nocturnal r = 0.55; daytime somnolence r = 0.65), pain (r = 0.56), and psychosis (r = 0.55, all p < 0.0001) followed by UPDRS motor score (r = 0.48, p < 0.0001). Greater motor fluctuations (r = 0.57) and dyskinesia (r = 0.43, both p < 0.0001) were also associated with worse Hr‐QoL. In multivariate analysis, depression had the strongest association with Hr‐QoL (adjusted R² = 0.53, p = 0.005) followed by fatigue, thermoregulatory, gastrointestinal, and cardiovascular autonomic function (especially orthostatic hypotension), daytime somnolence, and urinary problems. This study demonstrates that a autonomic dysfunction, psychiatric complications, pain, fatigue, and sleep problems are major correlates of poor Hr‐QoL. However, whilst psychiatric problems are increasingly documented, many symptoms (particularly those possibly perceived as embarrassing or unrelated) remain under‐reported. © 2010 Movement Disorder Society     

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.

     

Epileptic prodromes: Are they nonconvulsive status epilepticus?

PurposeThe aim of this study was to assess how frequently prodromes occur in an adult patient group from a tertiary referral epilepsy centre and to investigate the EEG changes during the prodromes.Methods578 consecutive patients were interviewed on subjective phenomena, experiences heralding the seizures, for at least 30 min before the start of the seizure. EEGs were recorded during the prodromes.ResultsTen out of 490 included patients had prodromes (2%). We were able to record EEG during prodromes in 6 patients. Three patients had EEG changes corresponding to nonconvulsive status epilepticus. Three patients had unrevealing EEG recordings during prodromes.ConclusionOur results suggest that at least in a part of the patients, the prodromes are actually ictal phenomena, and should be treated as nonconvulsive status epilepticus.     

Can anesthetic treatment worsen outcome in status epilepticus?

Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms.In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated.This article is part of a Special Issue entitled “Status Epilepticus”.     

What are we missing? The costs versus benefits of skip rule designs

Many research diagnostic interviews employ skip rules, such that some questions are only asked based on answers to prior questions. In the context of large‐scale epidemiological studies, skip rules are important to study feasibility by reducing the time, money, and participant burden required for assessment. However, less is understood about information lost when questions are skipped. This study examines the relative prevalence, clinical significance, and additional time required to assess eating disorder symptom patterns skipped in the Structured Clinical Interview for DSM‐IV Axis I Disorders (SCID‐I) to understand the costs and benefits of following skip rules. Data come from the second stage of a two‐stage cohort sample (N = 400) in which the SCID‐I eating disorders module was administered without following skip rules. Results were weighted to correct for the sampling framework. Over a third of subjects endorsed symptoms that would have been missed had skip rules been followed. Uncaptured symptom patterns were associated with increased psychosocial impairment, and the additional time required to assess all symptoms averaged 1.8 minutes per participant. Clinically significant symptom patterns are missed by the SCID‐I and similar diagnostic tools, suggesting that epidemiologic studies using such instruments under‐estimate the prevalence and public health impact of mental disorders. Copyright © 2013 John Wiley & Sons, Ltd.     

The genetics of dementia with lewy bodies: what are we missing?

Dementia with Lewy bodies is a complex brain disorder and a key member of the Lewy body disease spectrum. Its genetic etiology is unclear, and information is scattered. However, the results of molecular genetic studies imply a genetic and mechanistic overlap with Alzheimer disease, Parkinson disease with dementia, and Parkinson disease. In this review, we provide a comprehensive overview of the current studies on dementia with Lewy bodies heritability, genetic etiology, and genetic heterogeneity. We conclude with a critical discussion of the missing heritability in dementia with Lewy bodies and encourage scientists to further explore the underlying mechanisms of this disease.     

Will MRI replace the EEG for the diagnosis of nonconvulsive status epilepticus,especially focal?

Magnetic resonance imaging (MRI) can now be used to diagnose or to provide confirmation of focal nonconvulsive status epilepticus (NCSE). Approximately half of patients with status epilepticus (SE) have signal changes. MRI can also aid in the differential diagnosis with generalized NCSE when there is a clinical or EEG doubt, e.g. with metabolic/toxic encephalopathies or Creutzfeldt-Jakob disease. With the development of stroke centers, MRI is available 24 h/24 in most hospitals. MRI has a higher spatial resolution than electroencephalography (EEG). MRI with hyperintense lesions on FLAIR and DWI provides information related to brain activity over a longer period of time than a standard EEG where only controversial patterns like lateralized periodic discharges (LPDs) may be recorded. MRI may help identify the ictal nature of LPDs. The interpretation of EEG tracings is not easy, with numerous pitfalls and artifacts. Continuous video-EEGs require a specialized neurophysiology unit. The learning curve for MRI is better than for EEG. It is now easy to transfer MRI to a platform with expertise. MRI is more accessible than single photon emission computed tomography (SPECT) or positron emission tomography (PET). For the future, it is more interesting to develop a strategy with MRI than SPECT or PET for the diagnosis of NCSE. With the development of artificial intelligence, MRI has the potential to transform the diagnosis of SE. Additional MRI criteria beyond the classical clinical/EEG criteria of NCSE (rhythmic versus periodic, spatiotemporal evolution of the pattern…) should now be systematically added. However, it is more complicated to move patients to MRI than to perform an EEG in the intensive care unit, and at this time, we do not know how long the signal changes persist after the end of the SE. Studies with MRI at fixed intervals and after SE cessation are necessary.     

The nature of neonatal status epilepticus — a clinician's perspective

Neonatal status epilepticus occurs within the substrate of the hyperexcitable newborn brain and is usually provoked by acute CNS derangements, although status can also be the presentation of early-life epilepsy. Provoked neonatal status usually resolves within a few days, with or without treatment, but new data suggests that status is associated with adverse outcomes, even after controlling for underlying disease severity and MRI structural brain injury. Novel treatments may be needed to improve seizure control and outcome, given the characteristics of neurotransmission in the newborn brain.This article is part of a Special Issue entitled “Status Epilepticus”.