A combination of biomarkers that might assist physicians in differentiating syncope from seizure; LiTT for intractable mesial temporal lobe epilepsy-these and other insights.
New research in epilepsy accounted for approximately 10% of the more than 3000 scientific presentations at the 71st American Academy of Neurology meeting in Philadelphia, PA, May 4 to 10, 2019. As a fellowship-trained epileptologist, I focused this brief review on research with clinical relevance to practitioners and people with epilepsy.
Syncope vs. seizure
Neurologists are frequently consulted to evaluate patients who may have had a syncopal event or epileptic seizure. Because there is rarely the opportunity to witness the clinical event, diagnosis must rely on the history, physical examination, laboratory studies, as well as electroencephalographic (EEG) and magnetic resonance imaging (MRI) results. Even after an extensive investigation, the diagnosis often remains unclear. Reliable biomarkers that discriminate between seizure and syncope would be extremely valuable.
Co-authors Kim and Kim1 evaluated 70 patients with syncope and 105 with epilepsy and developed an algorithm to differentiate the two conditions. They concluded that longer duration of loss of consciousness, increased neuron-specific enolase, prolactin, NH3, and myoglobin were more likely in seizure than syncope patients. The most powerful discriminator was NH3-a cut-off value of 45.5 umol/l offered a 71.23% specificity and 68.8% sensitivity. The authors suggest that a combination of biomarkers might assist physicians in differentiating syncope from seizure.
Laser ablation therapy for epilepsy
In patients with drug-resistant mesial temporal lobe epilepsy, surgical removal of the anterior temporal lobe is most likely to render patients seizure free. Magnetic resonance-guided laser interstitial thermal therapy (LiTT), which requires only a burr hole and not a craniotomy, has been proposed as a less invasive alternative. Although LiTT is less stressful for patients, it remains unclear whether long-term seizure control equals that of traditional temporal lobectomy.
Patel and colleagues2 performed a retrospective review of their experience with LiTT for intractable mesial temporal lobe epilepsy at the Mayo Clinic, Arizona, from 2013 to 2018. Of 25 patients followed for an average of 1.5 years, eight (33%) became seizure free. Post-operative neuropsychometric testing revealed cognitive decline in 8/10 (80%) patients. Visual field deficits were present in 5/11 (45%). Four patients required a second LiTT treatment or temporal lobectomy to improve seizure control.
The percentage of seizure-free patients (33%) was less than expected with anterior temporal lobectomy. Further, cognitive decline and visual field deficits were not uncommon. The authors concluded that more data is needed to identify patients most likely to benefit from LiTT rather than conventional epilepsy surgery.
LiTT is an exciting new minimally invasive therapy, but its role in treating patients with intractable epilepsy remains to be defined. Studies such as the one above reinforce the need to subject LiTT to more rigorous examination before it replaces traditional temporal lobectomy.
Diagnosis of psychogenic nonepileptic seizures
Psychogenic nonepileptic seizures (PNES) often clinically resemble epileptic seizures but do not respond to antiepileptic medications. Because these patients resemble those with drug-resistant epilepsy, physicians often refer them to an epilepsy center for video-EEG monitoring to determine seizure type.
Wolfe and colleagues3 performed a retrospective chart review of 480 adults (aged 18 to 92 years) referred to the Creighton University School of Medicine Epilepsy Center for diagnosis between January 2012 to January 2017. Of the 480 patients, 189 (39%) received the diagnosis of PNES followed by psychiatric treatment. Overall, 56.9% of patients with PNES who had follow-up data became seizure free. Older patients with PNES tended to have better outcomes; 69% of those 61 years or older improved vs. 47% of those aged 18 to 30 years. Although psychiatric diagnoses were common in all age groups, they were less likely in older patients (73%) than those between the ages of 18 to 30 (86%).
This is a nice study that provides insights into the characteristics and outcomes of a large population of PNES patients. Video-EEG has been an essential tool for PNES diagnosis for at least the last 30 years and will remain so into the foreseeable future.
Intranasal seizure treatment
Emergency medications for uncontrolled seizures are usually administered intravenously, intramuscularly, or per rectum. The intranasal route has been proposed as a more convenient method to treat breakthrough or acute repetitive seizures.
In this open-label study, Sperling and colleagues4 observed the efficacy and adverse effects of an experimental diazepam nasal spray (Valtoco) under investigation by Neurelis. Of the 109 patients who received at least one dose, a single dose controlled seizures in 92% of episodes. Overall, a total of 1585 episodes were treated with 1 to >40 doses. Adverse events occurred in 67/109 (61.5%) patients. Only 19 patients (17.4%) had adverse events that appeared drug-related. These included nasal discomfort (7 patients), epistaxis (4 patients), and headache (4 patients). There were no serious treatment-related side effects. The authors concluded that intranasal diazepam was safe and well-tolerated.
Rescue medication for seizures are generally limited to intravenous and intramuscular preparations that must be administered by qualified medical personnel. One FDA-approved exception is diazepam rectal gel (Diastat). Because of the awkward route of administration, Diastat use has been severely limited. Research into a more convenient alternative, such as an intranasal spray, has been ongoing for a number of years and finally appears to have borne fruit. If the Neurelis drug receives FDA approval, it may be available before the end of 2019.
Incomplete seizure control due to intractable epilepsy or nonadherence may result in life-threatening status epilepticus. Early readmissions indicate poor seizure control after hospital discharge. The Center for Medicare and Medicaid Services (CMS) imposes financial penalties on hospitals for early readmissions for a number of conditions such as myocardial infarction and pneumonia. Although epilepsy is not yet one of the diagnoses subject to these CMS penalties, the 30-day period without readmission has become a performance benchmark for hospitals.
Rahwan and colleagues5 addressed the problem of hospital readmissions for status epilepticus in their presentation, “How often and what predicts…30-day hospital readmissions after generalized convulsive status epilepticus?” From a total population of 14,562 adults with generalized convulsive status epilepticus in the 2014 Nationwide Readmission Database, the authors identified 2520 (17.3%) patients who were readmitted within 30 days of discharge. On multivariate logistic analysis, risk factors for readmission included leaving against medical advice (OR: 1.45), length of stay greater than six days (OR: 1.42), discharge to a short-term hospital (OR: 1.39), and the presence of comorbidities (OR: 1.12). Conversely, patients aged 45 years or older and those in high-income households were less likely to suffer early readmission.
In a similar retrospective study utilizing the Nationwide Readmission database, Savani and colleagues6 expanded the study duration to 2010-2014 and examined all patients with epilepsy who were readmitted, not just those with status epilepticus. Their analysis included 622,467 patients with hospitalization for epilepsy using the primary diagnostic ICD-9CM code 345.xx. Of these, 76,911 (12.4%) were readmitted within 30 days. Risk factors for readmission included discharge to another facility (OR: 1.22), higher comorbidity index (1.10), and longer length of stay (OR: 1.01).
Relevant comorbidities included chronic kidney disease (OR: 1.35); opioid abuse (OR: 1.30); chronic liver disease (OR: 1.26); psychiatric illness (OR: 1.22); heart failure (OR: 1.19); chronic lung disease (OR: 1.17); cocaine (OR: 1.14); diabetes (OR: 1.10); hypertension (OR: 1.07) and hypothyroidism (OR 1.06). Conversely, the following variables decreased readmissions: elective admission (OR: 0.42); self-payment vs. Medicare/Medicaid (OR: 0.67); private insurance vs. Medicare/Medicaid (OR: 0.75); and teaching hospital admission (OR:0.96). The authors suggest that proactively addressing risk factors for readmission may improve patient outcomes.
In my experience in several hospitals, physicians suffer undue pressure to discharge patients at the earliest possible moment. Data such as those provided by Savani and colleagues may help bolster physician decisions to retain patients in hospital until they are truly ready to return home.
This short sample of the 2019 American Academy of Neurology’s epilepsy presentations revealed laboratory measures that may help differentiate syncope from seizure; the effect of laser ablation on intractable epilepsy; the importance of video-EEG for the diagnosis and management of PNES; the potential for intranasal diazepam to safely stop seizures; and patient characteristics associated with early hospital readmission. This research all has the potential to improve the care of people with epilepsy.
About the author
Andrew Wilner, MD, is a neurologist who blogs at www.andrewwilner.com/blog. His latest book is The Locum Life: A Physician’s Guide to Locum Tenens.
1. Kim H, Kim JB. Differential diagnosis of epileptic seizure and syncope using machine learning algorithms. American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (P2.5-031).
2. Patel A, Dawit S, Mastorakos G et al. Long-term outcomes in patients with intractable mesial temporal lobe epilepsy who undergo laser ablation. American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (P5.5-019).
3. Wolfe M, Singh S, Sankaraneni RM. Profile and outcome of psychogenic nonepileptic seizures patients undergoing video-EEG monitoring. American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (P4.5-032).
4. Sperling M, Hogan R, Biton V, et al. A 12-month, open-label, repeat-dose safety study of Valtoco (NRL-1, diazepam nasal spray) in patients with epilepsy: Interim report. American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (P2.5-029).
5. Rahwan M, Looti AL, Bishu K, Ovbiagele B. How often and what predicts…30-day hospital readmissions after generalized convulsive status epilepticus? American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (S36.006).
6. Savani C, Kumar V, Richardson C et al. Predictors of 30-day readmission after index hospitalization for epilepsy: a 5-year national estimate using the Nationwide Readmission (NRD) database. American Academy of Neurology Annual Meeting, Philadelphia, PA, May 4-10, 2019 (P2.5-029).