Raoul Sutter

Electroencephalographic criteria for nonconvulsive status epilepticus: Synopsis and comprehensive survey

There have been many attempts at defining the electroencephalography (EEG) characteristics of nonconvulsive status epilepticus (NCSE) without a universally accepted definition. This lack of consensus arises because the EEG expression of NCSE does not exist in isolation, but reflects status epilepticus under the variety of pathologic conditions that occur with age, cerebral development, encephalopathy, and epilepsy syndrome. Current NCSE definitions include “boundary conditions,” in which electroencephalographic seizure activity occurs without apparent clinical seizures. Furthermore, what appears to one interpreter as status epilepticus, is not to another reader, reflecting the “art” of EEG interpretation. Seizures and epilepsy syndromes have undergone an evolution that has moved beyond a classification of focal or generalized conditions into a syndromic approach. It seems appropriate to make similar changes in the EEG analysis of the syndromes of NCSE. In effect, the literature on epilepsy classification has progressed to incorporate the different NCSE types with clinical descriptions, but the specific EEG evidence for these types is found largely in individual reports, and often by description only. NCSE classification of EEG patterns should derive from the aggregate of published EEG patterns in the respective clinical subtype, supported by an analysis of these EEG studies. The analysis that follows presents clinical descriptions and EEG patterns of NCSE in the neonatal period, infancy, childhood, adulthood, and late adulthood from a syndromic perspective based on age, encephalopathy, cerebral development, etiology, and syndrome. Proceeding from the proposed classification of status epilepticus syndromes in “Status epilepticus: its clinical features and treatment in children and adults” (published in 1994 by Cambridge University Press, New York), we have performed a systematic search for reports presenting EEG patterns of NCSE using the online medical search engine PubMed for 22 different search strategies. EEG patterns were reviewed by two board‐certified epileptologists who reached consensus regarding presence of NCSE. From a total of 4,328 search results, 123 cases with corresponding EEG patterns could be allocated to underlying epilepsy syndromes. Typical characteristic, prominent electrographic patterns, and sequential arrangements are elucidated for the different NCSE syndromes. This compendium of patterns by NCSE syndrome classification with illustration of EEGs, and delineation of electroencephalographic features helps define the characteristics and semiologic borderlines among the types of NCSE.

Mortality and recovery from refractory status epilepticus in the intensive care unit: A 7‐year observational study

Refractory status epilepticus (RSE) is a life‐threatening neurologic emergency with high mortality and morbidity. The aim of this study was to identify and quantify associations between clinical characteristics of adult RSE patients and outcome.

Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU

Purpose:  Status epilepticus (SE) is an important neurologic emergency requiring treatment on an intensive care unit (ICU). Although convulsive SE is self‐evident, the diagnosis of nonconvulsive SE (NCSE) depends on electroencephalography (EEG) confirmation. Previous work showed that 82% of patients with SE had NCSE in our ICU. We hypothesize that continuous video‐EEG monitoring (CVEM) may increase the diagnostic yield in patients with SE, especially NCSE, and leave fewer patients undiagnosed.

Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS.

Objective: To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab. Results: Polyomavirus JC (JCV)–specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities. Conclusions: This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution.

Associations between infections and clinical outcome parameters in status epilepticus: A retrospective 5-year cohort study

Purpose:  Status epilepticus (SE) represents a life‐threatening condition, requiring pharmacologic therapy and neurointensive care. Infectious complications in SE are suspected to be frequent and worsen outcome. However, little is known about their incidence during SE and their impact on course and outcome. The aim of this study was to determine the incidence and time of onset of infections during SE, as well as their association with particular SE courses, length of hospitalization, intensive care unit (ICU) stay, and outcome.

Significance of triphasic waves in patients with acute encephalopathy: a nine-year cohort study.

OBJECTIVE Triphasic waves (TWs) are a frequent electroencephalography (EEG) finding in encephalopathy, yet their origin and prognostic significance are not well understood. The aim of this study was to determine the clinical and EEG characteristics in encephalopathic patients with TWs. We hypothesized that specific EEG characteristics are predictive of outcome. METHODS Consecutive adult encephalopathic patients with TWs on EEG and neuroimaging were included. EEG analysis included semiquantitative evaluation of TWs, background activity, and EEG reactivity. The study endpoint was death. RESULTS Over a nine-year period, 105 patients with TWs were included. Common abnormalities on neuroimaging were white matter lesions (60%) and cerebral atrophy (59%). Pathologic conditions included infections (56%), renal (50%) and liver insufficiency (12%), and respiratory failure (20%). Mortality was 20%. Absent EEG background reactivity and respiratory failure were independently associated with death (OR 3.73, 95%CI 1.08-12.80, p=0.037 and OR 6.47, 95%CI 1.98-21.12, p=0.02). CONCLUSIONS These results suggest that TWs are a marker of structural brain disease coupled with toxic-metabolic perturbations, and that etiologies or underlying pathologies were not predictive for outcome while non-reactive EEG was independently associated with death. SIGNIFICANCE In contrast to clinical, EEG and neuroimaging findings, non-reactive EEG patterns predicted death in encephalopathic patients with TWs.

Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study.

AbstractBackground: Refractory status epilepticus (RSE) is the most severe manifestation of status epilepticus (SE), often requiring intensive care and therapeutic coma. It is associated with prolonged intensive care unit (ICU) and hospital stays, as well as increased morbidity and mortality. Treatment involves both intravenous anaesthetics and antiepileptic drugs (AEDs) that can be administrated intravenously, by nasogastric tube or by percutaneous endoscopic gastrostomy. Experience with some of the newer AEDs for the treatment of RSE is restricted and higher-class evidence regarding tolerability and efficacy is lacking.Topiramate is a potent broad-spectrum AED with several modes of action, including blockade of the ionotropic glutamatergic AMPA receptor, which is likely to be an important mechanism for the treatment of SE. While there is no commercially available intravenous formulation, topiramate can be administered enterally, which may make it suitable for the treatment of RSE. Objective: The objective of this study was to evaluate the tolerability, safety profile and efficacy of adjunctive and enterally administered topiramate in patients with RSE. Methods: A medical chart review was performed of all consecutive patients treated for RSE between August 2004 and December 2011 at the ICU of the University Hospital Basel (Basel, Switzerland). Results: 113 (43%) of all consecutive 268 patients with SE developed RSE. Of those, 35 (31%) were treated with topiramate. Median age was 60.5 years. Topiramate was used as an add-on treatment after 1–6 (median 4) prior administered AEDs had failed. It was introduced after a median of 2 (range 2–23) days for a duration of 1–24 (median 3) days. The response rate after topiramate administration as the third AED was 86% (6/7 patients), and remained stable at 67% after administration as the fourth, fifth, sixth or seventh AED when the groups of successfully and probably successfully treated patients were pooled. Overall, RSE was terminated in 71% of patients within 72 hours after first administration of topiramate, in 9% of patients, within 24 hours (none in the 800 mg/day group; 9% in the 400–799 mg/day group; and 11% in the <400 mg/day group). Mortality was 31% and was not strictly dependent on failure to terminate RSE, but also on the underlying aetiology of RSE. There were no serious or fatal adverse events directly attributable to topiramate. Adverse effects included slight hyperchloremic acidosis and hyperammonemia (all associated with co-medication with valproic acid). Conclusion: Treatment with enterally administered topiramate was feasible, well tolerated and had a good safety profile in patients with RSE in this observational, single-centre, cohort study. Refractory SE was terminated in the majority of patients within 3 days after initiation of topiramate. Prospective studies are warranted to further evaluate topiramate for the treatment of RSE.

Seizures as adverse events of antibiotic drugs: A systematic review

Objective: Antibiotic drugs are commonly associated with seizures. Tailoring antibiotics to the individual risk for seizures is challenged as avoidance of certain antibiotic classes may no longer be possible due to the emergence of resistant bacteria. We performed a systematic review regarding the current evidence for seizures associated with all antibiotic classes, their underlying mechanisms, and predisposing factors. Methods: The medical search engine PubMed was systematically screened to identify articles in English published between 1960 and 2013. All study designs were considered and evidence was assessed. Results: We included 143 articles involving 25,712 patients and 25 different antibiotics. Evidence for antibiotic-related symptomatic seizures is low to very low, mainly deriving from studies regarding β-lactams, especially unsubstituted penicillins and fourth-generation cephalosporins, as well as carbapenems, mainly imipenem, all administered in high doses or in patients with renal dysfunction, brain lesions, or known epilepsy. Evidence regarding symptomatic seizures from fluoroquinolones only relies on case reports and case series with most reports for ciprofloxacin in patients with renal dysfunction, mental disorders, prior seizures, or coadministered theophylline. Conclusions: Evidence for an association between antibiotic drugs and symptomatic seizures is low to very low (evidence Class III–IV). Despite this, numerous reports point to an increased risk for symptomatic seizures especially of unsubstituted penicillins, fourth-generation cephalosporins, imipenem, and ciprofloxacin in combination with renal dysfunction, brain lesions, and epilepsy. During administration of such antibiotics in patients with particular predispositions, close monitoring of serum levels is advocated. As most seizures associated with cephalosporins are nonconvulsive, continuous EEG should be considered in patients with altered levels of consciousness.

High prevalence of nonconvulsive and subtle status epilepticus in an ICU of a tertiary care center: A three-year observational cohort study

BACKGROUND Status epilepticus is one of the most important neurological emergencies and requires immediate therapy and admission to the intensive care unit. We hypothesized that nonconvulsive and subtle status epilepticus are more frequent than reported. METHODS This observational cohort study describes types, courses, duration, length of hospital stay, outcome and case fatality rate of status epilepticus in adults in relation to demographic and clinical variables. It was conducted in an intensive care unit of a tertiary care center over three years. RESULTS 111 status epilepticus episodes had a median duration of 48h. Hospitalization length was 18±15.3 days. 81% of the status epilepticus episodes were nonconvulsive and subtle. Case fatality rate was 17%. Age over 70 years had independent positive influence on status epilepticus course (OR: 5.135; p=0.0029). Hospital stay increased by 1.13h with each additional hour of status epilepticus (p=0.02). Subtle status epilepticus was a risk factor for refractoriness (p=0.0065). CONCLUSIONS Prevalence of nonconvulsive and subtle status epilepticus was higher than reported, emphasising the importance of clinical awareness. Older age was associated with more favorable course. This unexpected and contradictory result has to be taken into account during therapeutic interventions in the elderly and should warn from early resignation regarding treatment.

Electroencephalography for diagnosis and prognosis of acute encephalitis

OBJECTIVES To confirm the previously identified EEG characteristics for HSV encephalitis and to determine the diagnostic and predictive value of electroencephalography (EEG) features for etiology and outcome of acute encephalitis in adults. In addition, we sought to investigate their independence from possible clinical confounders. METHODS This study was performed in the Intensive Care Units of two academic tertiary care centers. From 1997 to 2011, all consecutive patients with acute encephalitis who received one or more EEGs were included. Examination of the diagnostic and predictive value of EEG patterns regarding etiology, clinical conditions, and survival was performed. The main outcome measure was in-hospital death. RESULTS Of 103 patients with encephalitis, EEGs were performed in 76 within a median of 1 day (inter quartile range 0.5-3) after admission. Mortality was 19.7%. Higher proportions of periodic discharges (PDs) (p=0.029) and focal slowing (p=0.017) were detected in Herpes Simplex virus (HSV) encephalitis as compared to non-HSV encephalitis, while clinical characteristics did not differ. Normal EEG remained the strongest association with a low relative risk for death in multivariable analyses (RR<0.001, p<0.001) adjusting for confounders as coma, global cerebral edema and mechanical ventilation. None of the patients with a normal EEG had a GCS of 15. CONCLUSIONS Normal EEG predicted survival independently from possible confounders, highlighting the prognostic value of EEG in evaluating patients with encephalitis. EEG revealed higher proportions of PDs along with focal slowing in HSV encephalitis as compared to other etiologies. SIGNIFICANCE EEG significantly adds to clinical, diagnostic and prognostic information in patients with acute encephalitis.