Moving Beyond Ruling Out Epilepsy: It Is PNES!
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1 Moving Beyond Ruling Out Epilepsy: It Is PNES! Current Literature In Clinical Science Minimum Requirements for the Diagnosis of Psychogenic Nonepileptic Seizures: A Staged Approach. A Report From the International League Against Epilepsy Nonepileptic Seizures Task Force. LaFrance WC Jr, Baker GA, Duncan R, Goldstein LH, Reuber M. Epilepsia 2013;Nov;54(11): An international consensus group of clinician-researchers in epilepsy, neurology, neuropsychology, and neuropsychiatry collaborated with the aim of developing clear guidance on standards for the diagnosis of psychogenic nonepileptic seizures (PNES). Because the gold standard of video electroencephalography (veeg) is not available worldwide, or for every patient, the group delineated a staged approach to PNES diagnosis. Using a consensus review of the literature, this group evaluated key diagnostic approaches. These included: history, EEG, ambulatory EEG, veeg/monitoring, neurophysiologic, neurohumoral, neuroimaging, neuropsychological testing, hypnosis, and conversation analysis. Levels of diagnostic certainty were developed including possible, probable, clinically established, and documented diagnosis, based on the availability of history, witnessed event, and investigations, including veeg. The aim and hope of this report is to provide greater clarity about the process and certainty of the diagnosis of PNES, with the intent to improve the care for people with epilepsy and nonepileptic seizures. Commentary Patients with psychogenic nonepileptic seizures (PNES) have historically lived in the borderland between neurologists and psychiatrists, with neither group taking ownership of patient care. Past approaches to the diagnosis of PNES have largely focused on removing the diagnosis of epilepsy and sending the patient for psychiatric but not necessarily neurologic follow-up. Making the diagnosis is a critical first step for proper clinical management. It prevents further iatrogenic complications (i.e., removing unnecessary anti-epileptic drugs [AEDs]) and creates an opportunity for patients to receive the psychiatric care they need. Typically, patients with PNES come to diagnosis after 7 to 10 years of treatment for epilepsy. There is a high cost associated with this diagnostic delay (1). Proper diagnosis is also critical for research trials, which can move treatments forward and allow for the comparability of various study findings. The incidence of PNES has been estimated at 3 to 5 per 100,000 patients per year or about 20 to 30% of referrals to epilepsy centers (2). The prevalence and burden are probably much higher though, owing to a lack of identification of patients with infrequent events, presentation to nonspecialists, evaluation refusals, and inability to capture events during video-eeg monitoring. While there are multiple studies describing semiologic differences and the sensitivity and specificity of certain signs that help to distinguish PNES from epileptic seizures, epilepsy monitoring units (EMUs) vary with regard to the percentage of patients admitted for spell Epilepsy Currents, Vol. 14, No. 3 (May/June) 2014 pp American Epilepsy Society clarification that eventually are diagnosed with not having epilepsy. In any EMU, rendering this diagnosis is something that must be handled adeptly. For the approximately 16% of cases discharged from the EMU without a clear diagnosis, guidelines on how to proceed for further diagnostic clarification and management are lacking (3). Those within this undefined group who have PNES will likely be even more difficult to control when they are eventually clarified as psychogenic. The past 10 years have seen a marked increase in research in PNES and other functional neurologic symptom disorders (aka conversion disorders) as well as the emergence of a growing number of specialists who practice at the intersection of neurology and psychiatry (4,5). More focus on the biologic underpinnings and novel treatment approaches are emerging, and it will be increasingly important to correctly characterize patients. Many may not be able to be diagnosed in EMUs owing to lack of proper insurance, lack of appropriate referral, and patient unwillingness for the monitoring. The article Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: A staged approach. A report from the International League against Epilepsy Nonepileptic Seizures Task Force by LaFrance and colleagues (6) addresses the level of certainty of the diagnosis of PNES with the hope of broadening the ability to identify and ultimately treat PNES patients without requiring the use of the usual gold standard video-eeg technology. There are multiple articles on the semiologic differences between PNES and epileptic seizures, and some of the most discriminating signs for PNES including eye closure during an event, prolonged event duration, ictal crying, and event recall are highly specific though not robustly sensitive. The studies acknowledge that findings from a combination of diagnostic modalities (history, EEG, neuropsychologic and psychiatric 131
2 Moving Beyond Ruling Out Epilepsy assessments) need to converge in order to have greater diagnostic confidence. Improving diagnostic confidence in PNES is paramount for removal of the anticonvulsants and getting patients to the correct treatments and providers. The diagnostic suggestions in this article will aid in the ability to compare the various published studies in PNES by utilizing agreed-upon criteria for certainty of diagnosis (Table 1) (6). Epileptologists have recognized that it is not always possible to definitively diagnose PNES even after EMU admission. Having agreed-upon levels of certainty from this internationally gathered group of experts is very helpful to accommodate the reality of this complex clinical area of practice. Recognizing the importance of excluding events consistent with simple partial seizures from research studies was a stated goal. In addition, this article emphasizes the importance of knowing whether the data reported are derived from history or from captured events with associated video and EEG. Despite these strengths, this consensus statement does not provide an evidence-based pathway needed to navigate which patients may not require monitoring and which patients may need further monitoring. Limitations of resources such as cuts to reimbursements and distance from an epilepsy center may dictate what approach is most appropriate or affordable to take. Clinicians need to be prepared to diagnose PNES in the absence of captured events to move clinical care forward. Some subgroups of PNES patients, such as those who present with nonepileptic psychogenic status, may present additional challenges when establishing the diagnosis given the nature of their acute presentation. Anticipating these clinical variants can be quite helpful for practical management of this heterogenous group. This consensus statement does inform when it is acceptable or not acceptable to remove anti-convulsants and when a repeat video EEG is necessary. It may also guide more universal diagnostic standards for research trials in PNES. For example, patients with only possible PNES should potentially be excluded from treatment trials. Also, perhaps there is a cohort of patients who remain highly symptomatic after an initial diagnosis of probable PNES that require a more definitive diagnostic evaluation. Different levels of diagnostic certainty may require different thresholds for initiating empirical treatment, so that diagnosis does not continue to be delayed and hence impact prognosis. Perhaps there is a cohort of patients where after an initial probable diagnosis does not lead to improvement, they are then sent for definitive study. By utilizing these certainty criteria (Table 1) (6), it may be possible to look for subgroups of patients with PNES that require fewer resources to receive appropriate treatment. There are a number of patients who refuse to come to a center, or who leave the EMU against medical advice shortly after arrival, perhaps ambivalent about finding out if they have epilepsy or not. The certainty criteria would be particularly helpful here. Neurologists need to become more comfortable with utilizing a set of criteria for rendering a positive diagnosis of PNES that involves stages of certainty before leading up to the gold standard of video-eeg. This would likely also require a paradigm shift in the educational approach of residents and fellows. The diagnosis of clinically establishedpnes may be adequate for removing medications obviating the need for admission, reserving a lower percentage of cases for the gold-standard monitoring after initial attempts to wean medications fail or are too dangerous in the outpatient setting. Table 1. Overview of Proposed Diagnostic Levels of Certainty for Psychogenic Nonepileptic Seizures* History Witnessed Event EEG Diagnostic Level Possible + By witness or self-report/description No epileptiform activity in routine or sleepdeprived interictal EEG Probable + By clinician who reviewed video recording or in person, showing semiology typical of PNES Clinically established + By clinician experienced in diagnosis of seizure disorders (on video or in person), showing semiology typical of PNES, while not on EEG Documented + By clinician experienced in diagnosis of seizure disorders, showing semiology typical of PNES, while on video-eeg No epileptiform activity in routine or sleepdeprived interictal EEG No epileptiform activity in routine or ambulatory ictal EEG during a typical ictus/event in which the semiology would make ictal epileptiform EEG activity expectable during equivalent epileptic seizures No epileptiform activity immediately before, during, or after ictus captured on ictal video-eeg with typical PNES semiology +, history characteristics consistent with PNES; EEG, electroencephalography (as noted in the text, additional tests may affect the certainty of the diagnosis for instance, self-protective maneuvers or forced eye closure during unresponsiveness or normal postictal prolactin levels with convulsive seizures). *Reproduced with permission from Wiley and Sons. 132
3 Moving Beyond Ruling Out Epilepsy For patients who have both PNES and and active epileptic seizures, video-eeg will likely be a critical tool due to the higher complexity in management. Future research will be important to further our understanding of PNES diagnosis and potentially aid prognostic and treatment determinations. The use of biomarkers such as heart rate variability or neuroimaging may prove important along with understanding cross-cultural differences. Screening for risk factors using self-administered questionnaires may be increasingly utilized and may solidify a positive etiologic explanation for patients and aid in prevention (7). Patients need to know what they have; not just what they do not have. Creating a narrative that is based on individualized risk factors, while not broadly specific for all PNES patients, may improve treatment retention in this difficult-to-engage population. by Barbara Dworetzky, MD References 1. Reuber M, Fernandez G, Bauer J, Helmstaedter C, Elger CE. Diagnostic delay in psychogenic nonepileptic seizures. Neurology 2002;58: Duncan R, Razvi S, Mulhern S. Newly presenting psychogenic nonepileptic seizures: Incidence, population characteristics, and early outcome from a perspective audit of a first seizure clinic. Epilepsy Behav 2011;20: Robinson AA, Pitiyanuvath N, Abou-Khalil BW, Wang L, Shi Y, Azar NJ. Predictors of a nondiagnostic epilepsy monitoring study and yield of repeat study. Epilepsy Behav 2011;21: Driver-Dunckley E, Stonnington CM, Locke DE, Noe K. Comparison of psychogenic movement disorders and psychogenic nonepileptic seizures: Is phenotype clinically important? Psychosomatics 2011;52: Hopp JL, Anderson KE, Krumholz A, Gruber-Baldini AL, Shulman LM. Psychogenic seizures and psychogenic movement disorders: Are they the same patients? Epilepsy Behav 2012;25: LaFrance WC Jr, Baker GA, Duncan R, Goldstein LH, Reuber M. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia 2013; Nov;54(11): Syed TU, Arozullah AM, Loparo KL, Jamasebi R, Suciu GP, Griffin C, Mani R, Syed I, Loddenkemper T, Alexopoulos AV. A self-administered screening instrument for psychogenic nonepileptic seizures. Neurology 2009;72:
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