Prevalence of autoimmune diseases in functional neurological disorder: influence of psychiatric comorbidities and biological sex.

BACKGROUND: Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition, which disproportionally affects women compared with men. While the etiopathogenesis of this disorder remains elusive, immune dysregulation is emerging as one potential mechanism. To begin to understand the role of immune dysfunctions in FND, we assessed the prevalence of several common autoimmune diseases (ADs) in a large cohort of patients with FND and examined the influence of psychiatric comorbidities and biological sex. METHODS: Using a large biorepository database (Mass General Brigham Biobank), we obtained demographic and clinical data of a cohort of 643 patients diagnosed with FND between January 2015 and December 2021. The proportion of ADs was calculated overall, by sex and by the presence of psychiatric comorbidities. RESULTS: The overall prevalence of ADs in our sample was 41.9%, with connective tissue and autoimmune endocrine diseases being the most commonly observed ADs. Among patients with FND and ADs, 27.7% had ≥2 ADs and 8% met criteria for multiple autoimmune syndrome. Rates of ADs were significantly higher in subjects with comorbid major depressive disorder and post-traumatic stress disorder (p= 0.02). Women represented the largest proportion of patients with concurrent ADs, both in the overall sample and in the subgroups of interest (p's < 0.05). CONCLUSIONS: This study is unique in providing evidence of an association between FND and ADs. Future studies are needed to investigate the mechanisms underlying this association and to understand whether FND is characterised by distinct dysregulations in immune response.

Postictal psychiatric symptoms: A neurophysiological study.

OBJECTIVE: Postictal psychiatric symptoms (PPS) are a relatively common but understudied phenomenon in epilepsy. The mechanisms by which seizures contribute to worsening in psychiatric symptoms are unclear. We aimed to identify PPS prospectively during and after admission to the epilepsy monitoring unit (EMU) in order to characterize the postictal physiologic changes leading to PPS. METHODS: We prospectively enrolled patients admitted to the EMU and administered repeat psychometric questionnaires during and after their hospital stay in order to assess for postictal exacerbations in four symptom complexes: anger/hostility, anxiety, depression, and paranoia. Electroclinical and electrographic seizures were identified from the EEG recordings, and seizure durations were measured. The severity of postictal slowing was calculated as the proportion of postictal theta/delta activity in the postictal EEG relative to the preictal EEG using the Hilbert transform. RESULTS: Among 33 participants, 8 demonstrated significant increases in at least one of the four symptoms (the PPS+ group) within three days following the first seizure. The most common PPS was anger/hostility, experienced by 7/8 participants with PPS. Among the 8 PPS+ participants, four experienced more than one PPS. As compared to those without PPS (the PPS- group), the PPS+ group demonstrated a greater degree of postictal EEG slowing at 10 min (p = 0.022) and 20 min (p = 0.05) following seizure termination. They also experienced significantly more seizures during the study period (p = 0.005). There was no difference in seizure duration between groups. SIGNIFICANCE: Postictal psychiatric symptoms including anger/hostility, anxiety, depression, and paranoia may be more common than recognized. In particular, postictal increases in anger and irritability may be particularly common. We provide physiological evidence of a biological mechanism as well as a demonstration of the use of quantitative electroencephalography toward a better understanding of postictal neurophysiology.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Initial case series of a novel sensing deep brain stimulation device in drug-resistant epilepsy and consistent identification of alpha/beta oscillatory activity: A feasibility study.

OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.

Sustained improvement with mindfulness-based therapy for psychogenic nonepileptic seizures.

BACKGROUND: We previously reported on the efficacy of a manualized 12-session mindfulness-based therapy (MBT) for psychogenic nonepileptic seizures (PNES). Completion of MBT provided improvements in weekly PNES frequency and self-rated intensity. OBJECTIVES: In this study, we aimed to determine sustainability of improvement of seizure-related measures at 3- to 6-month follow-up after treatment completion. We also examined changes at treatment end and at follow-up on therapeutic targets of the MBT program. METHODS: Patients with documented PNES were recruited from 2014 to 2018. Baseline measures were collected at time of diagnosis (T0) and at first follow-up post-diagnosis (T1). Outcomes are reported at MBT treatment completion (T3) and 3- to 6-month follow-up (T4). The Wilcoxon signed-rank test was used for pair-wise comparisons of PNES frequency; linear mixed models were used for other outcomes. RESULTS: Fourteen of the 26 MBT completers (54%) attended follow-up (median 147.5 days between T3 and T4). PNES frequency, intensity, and number of days/week with PNES remained reduced at T4 (p < 0.01 for all; median frequency reduction 1.3/week from T1). Illness perception and feeling understood remained improved at T4 (p < 0.001 for both) as did worry about PNES (p < 0.05). Illness attribution (physical, mental or both) changed from T0 to T3 (p < 0.01), but not to T4. Psychological flexibility did not change over time. CONCLUSION: Previously reported improvements in seizure-related measures with MBT at treatment conclusion were maintained at 3- to 6-month follow-up. There were sustained improvements in some underlying processes (illness perception, feeling understood, and symptom worry) over the course of treatment and at follow-up. Long-term benefits of MBT need to be established with randomized controlled trials.

The probability of sudden unexpected death in epilepsy given postictal prone position.

Sudden Unexpected Death in Epilepsy (SUDEP) is strongly linked to prone position in the immediate aftermath of a generalized tonic-clonic seizure (GTCS). The risk of SUDEP after a GTCS resulting in prone position has not yet been estimated. We calculated the probability of SUDEP given prone position after a GTCS using Bayesian analysis with inputs obtained from known risk of SUDEP and probability of prone position after a GTCS. The risk for SUDEP given the prone position is estimated to be 0.41% (95% Credible Interval 0.13-0.69%). The relative risk of SUDEP in prone vs. non-prone position following a GTCS is estimated to be 63 (95% Credible Interval 30-96). Sudden Unexpected Death in Epilepsy might be prevented by repositioning the patient after a seizure to avoid the prone position.

Racial and Ethnic Disparities in Postcardiac Arrest Targeted Temperature Management Outcomes.

OBJECTIVES: To evaluate racial and ethnic disparities in postcardiac arrest outcomes in patients undergoing targeted temperature management. DESIGN: Retrospective study. SETTING: ICUs in a single tertiary care hospital. PATIENTS: Three-hundred sixty-seven patients undergoing postcardiac arrest targeted temperature management, including continuous electroencephalogram monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical variables examined in our clinical cohort included race/ethnicity, age, time to return of spontaneous circulation, cardiac rhythm at time of arrest, insurance status, Charlson Comorbidity Index, and time to withdrawal of life-sustaining therapy. CT at admission and continuous electroencephalogram monitoring during the first 24 hours were used as markers of early injury. Outcome was assessed as good (Cerebral Performance Category 1-2) versus poor (Cerebral Performance Category 3-5) at hospital discharge. White non-Hispanic ("White") patients were more likely to have good outcomes than white Hispanic/nonwhite ("Non-white") patients (34.4 vs 21.7%; p = 0.015). In a multivariate model that included age, time to return of spontaneous circulation, initial rhythm, combined electroencephalogram/CT findings, Charlson Comorbidity Index, and insurance status, race/ethnicity was still independently associated with poor outcome (odds ratio, 3.32; p = 0.003). Comorbidities were lower in white patients but did not fully explain outcomes differences. Nonwhite patients were more likely to exhibit signs of early severe anoxic changes on CT or electroencephalogram, higher creatinine levels and receive dialysis, but had longer duration to withdrawal of lifesustaining therapy. There was no significant difference in catheterizations or MRI scans. Subgroup analysis performed with patients without early electroencephalogram or CT changes still revealed better outcome in white patients. CONCLUSIONS: Racial/ethnic disparity in outcome persists despite a strictly protocoled targeted temperature management. Nonwhite patients are more likely to arrive with more severe anoxic brain injury, but this does not account for all the disparity.

Motivational Interviewing Techniques to Improve Psychotherapy Adherence and Outcomes for Patients With Psychogenic Nonepileptic Seizures.

Psychogenic nonepileptic seizures (PNES) are a highly disabling disorder frequently encountered by neurologists, psychiatrists, and emergency medicine physicians. There is accumulating evidence for the efficacy of psychological therapies, yet the majority of patients do not complete treatment. A range of health care system-based, clinician-based, and patient-based barriers to treatment exists, including stigma, poor clinician-patient communication, and patient ambivalence about the diagnosis and treatment of PNES. These barriers frequently lead to treatment nonadherence. Motivational interviewing (MI) is a patient-centered counseling style targeting ambivalence about behavior change, which has been shown to be effective in improving psychotherapy adherence and outcomes among patients with PNES. The authors review MI processes and techniques that may be useful to health care providers helping patients with PNES and other functional neurological disorders to engage in psychotherapy. The authors examine common challenges arising during MI for patients with PNES, including somatic symptoms distracting from clinician-patient communication, ambivalence about making concrete plans for treatment, and psychiatric comorbidities. Strategies for overcoming these obstacles are reviewed, including the use of complex reflections to enhance patient engagement; the use of an ask-tell-ask format and specific, measurable, achievable, relevant, and time-limited (SMART) goals to facilitate treatment planning; and close collaboration between the neurology and psychotherapy teams.

Mindfulness-based therapy for psychogenic nonepileptic seizures.

BACKGROUND: Mindfulness-based therapies (MBTs) are effective in many neuropsychiatric disorders, and represent a potential therapeutic strategy for psychogenic nonepileptic seizures (PNES). OBJECTIVE: The objective of this study was to investigate the clinical effect of a manualized 12-session MBT for PNES in an uncontrolled trial. We hypothesized reductions in PNES frequency, intensity, and duration, and improvements in quality of life and psychiatric symptom severity at treatment completion. METHODS: Between August 2014 and February 2018, 49 patients with documented PNES (with video electroencephalography [EEG]) were recruited at Brigham and Women's Hospital to participate in the MBT for PNES treatment study. Baseline demographic and clinical information and self-rating scales were obtained during the diagnostic evaluation (T0). Baseline PNES frequency, intensity, and duration were collected at the first follow-up postdiagnosis (T1). Frequency was obtained at each subsequent MBT session and analyzed over time with median regression analysis. Outcomes for other measures were collected at the last MBT session (T3), and compared to baseline measures using linear mixed models. RESULTS: Twenty-six patients completed the 12-session MBT program and were included in the analysis. Median PNES frequency decreased by 0.12 events/week on average with each successive MBT session (p = 0.002). At session 12, 70% of participants endorsed a reduction in PNES frequency of at least 50%. Freedom from PNES was reported by 50% of participants by treatment conclusion. Seventy percent reported a 50% reduction in frequency from baseline and 50% reported remission at session 12. By treatment end, PNES intensity decreased (p = 0.012) and quality of life improved (p = 0.002). Event duration and psychiatric symptom severity were lower after treatment, but reductions were not statistically significant. CONCLUSIONS: Completion of a manualized 12-session MBT for PNES provides improvement in PNES frequency, intensity, and quality of life. The high dropout rate is consistent with adherence studies in PNES. Possible reasons for dropout are discussed. Randomized controlled trials and longer-term outcomes are needed to demonstrate the efficacy of MBT in PNES.

Randomized controlled trial of motivational interviewing for psychogenic nonepileptic seizures.

OBJECTIVE: We conducted a randomized controlled trial of motivational interviewing (MI) as an intervention to improve psychotherapy adherence and outcomes, including frequency of psychogenic nonepileptic seizures (PNES), quality of life, and emergency department utilization, among participants with PNES. METHODS: Sixty participants were randomized to receive either psychotherapy alone or MI plus psychotherapy. Participants and therapists were contacted at 16-week follow-up. Participants were considered adherent with psychotherapy if they attended at least eight sessions within 16 weeks following referral. RESULTS: Among control participants, 31.0% were adherent, whereas among MI participants, 65.4% were adherent (P = 0.015, absolute risk reduction = 34.4%, number needed to treat = 2.9). In the control arm, PNES frequency decreased by 34.8% (standard deviation [SD] = 89.7%), whereas in the MI arm, PNES frequency decreased by 76.2% (SD = 39.2%; P = 0.034, Cohen's d = 0.59). Among control participants, 10.7% achieved PNES freedom versus 30.8% of MI participants (P = 0.095). Quality of Life in Epilepsy-10 scores (a 40-point scale) improved by an average of 1.8 (SD = 7.9) points among control participants, and by 7.2 (SD = 10.0) points among MI participants (P = 0.047, Cohen's d = 0.60). Monthly emergency department visits increased by 0.06 (SD = 0.47) visits per month among control participants versus a decrease of 0.15 (SD = 0.76) among MI participants (P = 0.23). SIGNIFICANCE: Motivational interviewing improved treatment adherence, PNES frequency, and quality of life among our participants with PNES. Our study is limited in that it was conducted at a single quaternary care medical center, and MI was provided by a single neurologist, which may limit generalization of results.

Hiding in Plain Sight: Functional Neurological Disorders in the News.

OBJECTIVE: Functional movement and seizure disorders are still widely misunderstood and receive little public and academic attention. This is in stark contrast to their high prevalence and levels of associated disability. In an exploratory observational study, the authors examined whether the relative lack of media coverage of functional neurological disorders is in part due to misidentification in "human interest" news stories. METHODS: Thirteen recent news stories from high-impact English-language media outlets that portrayed patients with complex symptoms either attributed to other diagnoses or presented as medical mysteries were identified using online keyword searches. All selected news stories contained video or still images displaying relevant symptoms. Cases were categorized into movement disorders or seizure disorders and were then independently assessed by 10 respective expert raters. For each category, one story of a patient whose symptoms were due to a well-recognized neurological disease was also included. Both the diagnostic category and the respective confidence level were reported by each rater for each case. The interrater agreement was calculated for each group of disorders. RESULTS: The raters confirmed almost unanimously that all presented news stories except the negative control cases portrayed misidentified functional movement or seizure disorders. The interrater agreement and average diagnostic confidence were high. CONCLUSIONS: Functional neurological disorders are often wrongly considered a rare medical curiosity of the past. However, these findings suggest that, while they are largely absent from public discourse, they often appear in the news incognito, hiding in plain sight.

Long-term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures.

We conducted a prospective cohort study, examining long-term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures (PNES). Subjects diagnosed with documented PNES were scheduled for 4 psychiatric visits. Survival analysis was performed, and covariates were assessed for association with time to nonadherence using Cox proportional hazard regression analysis. One hundred twenty-three subjects were recruited and followed for up to 17 months. Eighty percent of subjects attended the first outpatient visit, 42% attended the second, 24% attended the third, and only 14% remained adherent through the fourth visit. Two covariates were associated with nonadherence: (1) a prior diagnosis of PNES (hazard ratio 1.57, P-value .046); (2) a lower score on the Brief Illness Perception Questionnaire (BIPQ), signifying lower concern about one's illness (hazard ratio 0.77 for every 10-point increment on the 80-point scale, P-value .008). Adherence with psychiatric treatment among patients with PNES is initially reasonably good but worsens rapidly over visits 2-4. Risk factors for nonadherence include a history of a prior diagnosis of PNES, and a lower level of concern about the illness as assessed by a lower score on the BIPQ.

Sleep in psychogenic nonepileptic seizures: Time to raise a red flag.

Poor sleep is a frequent complaint in patients with psychogenic nonepileptic seizures (PNES). However, few studies have examined sleep problems in this population. We aimed to compare sleep complaints in patients with PNES with those with epilepsy. Subjects diagnosed as having PNES by experts using video-electroencephalography (vEEG) were recruited through the Brigham and Women's Hospital epilepsy monitoring unit (EMU) between 3/25/2013 and 3/29/2018. Controls were patients with epilepsy recruited through the EMU and subspecialty clinics. All subjects were given the Beck Depression Inventory, 2nd Edition (BDI-II) and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). Subjective sleep problems were identified from item 16 (changes in sleep patterns) of the BDI-II. Independent sample t-test, chi-square test, and Spearman correlation were used. A total of 149 patients with PNES and 82 patients with epilepsy completed the BDI-II and QOLIE-10. Compared with control subjects with epilepsy, patients with PNES more frequently reported moderate-severe changes in sleep patterns, notably sleeping less than usual, waking up 1-2 h too early, and having trouble returning to sleep. These changes in sleep patterns were associated with worse quality of life. Our findings suggest that sleep is more commonly reported as a problem in PNES compared with epilepsy. Because sleep plays a major role in good health, understanding the specific sleep problem in PNES may provide insight for improving quality of life for this challenging disorder.

Nocturnal seizures are associated with more severe hypoxemia and increased risk of postictal generalized EEG suppression.

Patients with epilepsy have 20-fold risk of sudden death when compared to the general population. Uncontrolled seizures is the most consistent risk factor, and death often occurs at night or in relation to sleep. We examined seizure-related respiratory disturbances in sleep versus wakefulness, focusing on periictal oxygen saturation. Respiratory measures were examined in 48 recorded seizures (sleep, n = 23, wake, n = 25) from 20 adult patients with epilepsy. Seizures from sleep were associated with lower saturation, as compared to seizures from wakefulness, both during ictal (sleep median = 90.8, wake median = 95.5; p < 0.01) and postictal periods (sleep median = 94.3, wake median = 96.9; p = 0.05). Compared to wake-related seizures, seizures from sleep were also associated with a larger desaturation drop (sleep median = -4.2, wake median = -1.2; p = 0.01). Postictal generalized electroencephalography (EEG) suppression (PGES) occurred more frequently after seizures from sleep (39%), as compared to wake-related seizures (8%, p = 0.01). Our findings suggest that nocturnal seizures may entail a higher sudden unexpected death in epilepsy (SUDEP) severity burden, as they are associated with more severe and longer hypoxemia events, and more frequently followed by PGES, both factors implicated in sudden death.

Psychogenic Nonepileptic Seizures in Women.

Psychogenic nonepileptic seizures (PNES) are the most common type of functional neurological symptom disorders and are frequently diagnosed in tertiary care epilepsy monitoring units. These are associated with significant decline in social functioning and quality of life. The majority of patients with PNES are women, outnumbering men by a ratio of 3:1. Female sex preponderance occurs after puberty and usually before the age of 55 years. Many of the psychiatric risk factors in PNES (depression, anxiety, history of traumatic experiences, other somatic symptom disorders) are more common in women and may partially account for the difference in sex prevalence. Neurobiological and neurohumoral mechanisms may also play a role, but our understanding is limited at this point. In this review, we present information on epidemiology and risk factors, neurobiological and psychological mechanisms, clinical approach to diagnosis, evidence-based treatment, and long-term outcomes. We highlight findings related to differences between women and men in PNES. Most of these data are not decisive and require further corroboration. While the disorder may be more frequently suspected in women, all patients with suspected PNES deserve an objective and thorough investigation of their symptoms. Early and accurate identification of this disorder should be a priority, especially as evidence-based treatments, which may lead to improved outcomes, are increasingly available.

Preliminary Predictors of Initial Attendance, Symptom Burden, and Motor Subtype in a US Functional Neurological Disorders Clinic Population.

BACKGROUND AND OBJECTIVE: Although many patients present with functional neurological symptoms (FNS), few US clinics offer specialized FNS care, and data on clinic attendees remain limited. We determined predictors of initial attendance, symptom burden, and FNS subtype in the first patients referred to our Functional Neurological Disorders Clinic for suspected FNS. METHODS: We reviewed the charts of 62 consecutive patients (46 women, 16 men). Regression analyses investigated predictors of keeping the first scheduled clinic appointment. For the 49 patients who did keep that appointment, regression analyses examined neuropsychiatric factors associated with symptom burden and motor FNS subtypes. RESULTS: The odds of not keeping the first appointment were 10.4 times greater for patients referred from the emergency department than from other sources. The patients who kept their appointment reported a symptom burden that was significantly associated with a past FNS-related emergency department visit and a diagnosis of another medically unexplained somatic syndrome. The number of FNS findings on neurological examination also correlated with a history of an FNS-related emergency department visit. Patients with psychogenic non-epileptic seizures reported cognitive complaints and prior psychiatric hospitalizations significantly more often than did patients with other FNS. One fourth of all patients had two or more motor FNS. CONCLUSIONS: In our FNS cohort, patients were less likely to keep an initial clinic appointment if they were referred from the emergency department than from other sources. Patients with psychogenic non-epileptic seizures were more likely to report cognitive symptoms and past psychiatric hospitalizations than patients with other FNS.

Characteristics and role in outcome prediction of continuous EEG after status epilepticus: A prospective observational cohort.

OBJECTIVE: Continuous electroencephalography (cEEG) is important for treatment guidance in status epilepticus (SE) management, but its role in clinical outcome prediction is unclear. Our aim is to determine which cEEG features give independent outcome information after correction for clinical predictor. METHODS: cEEG data of 120 consecutive adult patients with SE were prospectively collected in three academic medical centers using the 2012 American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. Association between cEEG features and two clinical outcome measures (mortality and complete recovery) was assessed. RESULTS: In the first 24 h of EEG recording, 49 patients (40.8%) showed no periodic or rhythmic pattern, 45 (37.5%) had periodic discharges, 20 (16.7%) had rhythmic delta activity, and 6 (5%) had spike-and-wave discharges. Seizures were recorded in 68.3% of patients. After adjusting for known clinical predictive factors for mortality including the STatus Epilepticus Severity Score (STESS) and the presence of a potentially fatal etiology, the only EEG features (among rhythmic and periodic patterns, seizures, and background activity) that remained significantly associated with outcome were the absence of a posterior dominant rhythm (odds ratio [OR] 9.8; p = 0.033) for mortality and changes in stage II sleep pattern characteristics (OR 2.59 for each step up among these categories: absent, present and abnormal, present and normal; p = 0.002) for complete recovery. SIGNIFICANCE: After adjustment for relevant clinical findings, including SE severity and etiology, cEEG background information (posterior dominant rhythm and sleep patterns) is more predictive for clinical outcome after SE than are rhythmic and periodic patterns or seizures.

Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison.

OBJECTIVE: Benzodiazepines (BZD) are recommended as first-line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date. METHODS: We identified all patients treated with CLZ, LZP, or MDZ as a first-line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE. RESULTS: Among 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66-15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8-10.49). SIGNIFICANCE: CLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice.