Long term video/EEG prevents unnecessary vagus nerve stimulator implantation in patients with psychogenic nonepileptic seizures

Results None of the patients had undergone prior long-term video/EEG monitoring to document the nature of their events. A total of 13 patients with an implanted VNS had exclusive PNES, 9 women and 4 men with a mean age of 38.2 ± 10.4 years. Mean age at seizure onset was 28.5 ± 15.4 years. Patients were taking two to four antiepileptic medications in addition to VNS at the time of video/EEG monitoring. The average latency from the time of VNS implantation to the confirmatory diagnosis was 2.8 years. One to ten (median = 3) of these patients’ typical seizures were recorded during video/EEG monitoring. All patients were subsequently discharged off antiepileptic medications, and five of these patients were discharged home with the VNS turned off. Conclusion A VNS may be implanted inappropriately in patients with PNES. As video/EEG monitoring may help in excluding the diagnosis of PNES and preventing unnecessary VNS implants, it should be a requirement before VNS implantation. Research highlights ► Patients with uncontrolled seizures are at times subjected to vagus nerve stimulator implantation to control their supposed seizures. ► The 13 patients implanted with vagus nerve stimulators had not undergone prior video/EEG monitoring to confirm epilepsy. ► All these patients were found to have psychogenic nonepileptic seizures and were subsequently discharged off antiepileptic medications. ► Video/EEG monitoring should be a requirement for vagus nerve stimulator implantation. Keywords Psychogenic seizures Nonepileptic seizures Pseudo-seizures Vagus nerve stimulator 1 Introduction Psychogenic nonepileptic seizures (PNES) mimic epileptic seizures and are commonly misdiagnosed as such. PNES account for 10 to 40% of all patients referred to epilepsy centers [1,2] . Patients with PNES often are refractory to antiepileptic drugs (AEDs), and PNES is one of the most common causes of refractory spells [2] . Patients with refractory spells are at times subjected to vagus nerve stimulator (VNS) implantation to control their spells. This is often done based on clinical impression and routine or extended outpatient EEGs without recording of typical spells. We report a series of such patients who were implanted with VNSs, but their spells remained refractory. These patients were referred to our center for evaluation with video/EEG monitoring, which confirmed PNES diagnosis without coexistent epilepsy. 2 Methods We reviewed the database from the Vanderbilt University epilepsy monitoring unit (EMU) from 2000 to 2009 and identified all patients who were diagnosed with PNES. Of this group of patients with PNES, we retrospectively identified patients who were previously implanted with a VNS by their primary neurologist. We included only patients whosd typical spells were recorded during their EMU stay. We excluded children younger than 10 years of age, patients with mental retardation, and patients with concomitant epileptic and nonepileptic seizures. Patients were referred for evaluation of seizures that remained refractory to VNS and multiple AED therapy. The presumed diagnosis of epilepsy was based primarily on abnormal routine EEG studies obtained by the primary neurologist. All patients were monitored in the EMU off AEDs to capture typical attacks. All except one patient, in whom the VNS had been turned off 15 months earlier, had their VNS turned off during EMU admission, and then, either the VNS remained off at discharge or was restarted at previous settings. Output current in these VNS ranged from 0.25 to 3.0 mA, and all patients were set at regular cycling mode with 30 seconds on and 5 minutes off. Continuous video/EEG recordings were obtained with scalp electrodes according to the 10–20 international system, with additional sphenoidal electrodes in some cases. In all patients almost all AEDs were discontinued on admission; carbamazepine, oxcarbazepine, and benzodiazepines were tapered over 24–48 hours to prevent severe withdrawal seizures. 3 Results A total of 13 patients with implanted VNSs had exclusive PNES. A total of 60 patients with VNS were studied in the EMU during this period. The patients were 9 females and 4 males with a mean age of 38.2 ± 10.4 years ( Table 1 ). The mean age at onset of spells was 28.5 ± 15.4 years. Spell frequency varied from 7/day to 5/year. A history of physical abuse was reported by 3 patients, and a history of sexual abuse by 2 patients. Two patients had an eighth grade education, 9 patients had a high school education, and 2 patients had a college education. All patients were taking AEDs when they were admitted to the EMU. Patients were taking two to four AEDs (mean = 2.46 ± 0.78) in addition to having the VNS at the time of EMU admission. The average latency from VNS implantation to the confirmatory diagnosis made in our EMU was 2.8 years. The EMU study for each patient recorded 1–10 attacks (mean = 2.6, median = 3), confirmed as typical by accompanying family members. All attacks were motor in nature. The interictal EEG was completely normal in all patients. None of the patients had undergone prior long term video/EEG monitoring to document the nature of their seizures. However, all patients had had an outpatient EEG done by their primary neurologist. The outside EEG recordings were not available for us to review. In four patients, the outside hospital EEG reports were available for review. The main EEG abnormalities reported were high-amplitude diffuse rhythmic sharp activity or sharply contoured waves in the temporal regions (possibly overread wicket spikes or sharply contoured waves or both). There was no mention of recording attacks during these EEG studies. After their EMU study, all patients were discharged off AEDs. Five were discharged home with the VNS turned off. In one other patient, the VNS had been turned off 18 months prior to EMU admission. Seven patients requested that their VNSs be restarted at the previous settings ( Table 1 ), and their request was accepted as they felt comfortable with keeping the VNS functional. However, these patients did not mention any benefit on mood from the VNS. Interestingly, the duration of spells was significantly longer in patients who requested that the VNS not be turned off ( P = 0.05, Wilcoxon exact rank sum test). In patients in whom the VNS was stopped, other variables were not statistically significant ( Table 2 ). 4 Discussion We report a series of patients with PNES in whom a VNS had been implanted on the presumed diagnosis of epilepsy based on routine EEG. The VNS has been reported to have some beneficial effect on depression [3,4] . However, it has no established role in PNES, and was of no benefit for PNES in the current patient series. Misdiagnosis of epilepsy is a common problem, and about 30% of patients referred to epilepsy centers do not have epilepsy [1] . One of the major reasons for misdiagnosis is overreading of normal EEG patterns as epileptiform. Overreading of EEGs is a common problem, and often normal variants such as temporal sharp rhythms and wicket spikes are overread as epileptiform, as was the case with four patients in our cohort [5–7] . This misreading of EEG results has enormous consequences, including unnecessary exposure to AEDs, invasive interventions such as intubation, and invasive therapeutic modalities such as VNS implantation. PNES often are refractory to AEDs and remain uncontrolled, affecting the quality of life of these patients and resulting in frequent emergency room visits. Although the VNS is an established treatment for epilepsy [8] , it is not free of risks. VNS therapy may be associated with possible complications including dysarthria, vomiting, cardiac arrhythmia, electrode fracture, dislocation, and generator malfunction. The VNS also may be an obstacle to MRI studies that may be medically indicated. Patients with PNES in whom a VNS has been implanted based on the erroneous diagnosis of epilepsy face these long-term consequences. Interestingly, seven patients in our cohort, despite being correctly diagnosed with PNES, requested that their VNSs be kept functional. This may reflect the comfort patients may have felt with the VNS (a security zone) or may be a “teddy bear sign” indicating a transitional object from dependency on spells to independence [9] . This may also represent an underlying dysfunctional personality style that predisposes to PNES. According to psychoanalytic theory, the conversion reaction is caused by regression of unconscious intrapsychic conflict and conversion of anxiety into PNES. The patients who declined to turn off the VNS were probably receiving some relief from their anxiety and depressive signs and symptoms from the VNS. This conflict is between instinctual impulse and prohibition of its expression, which results in depression and anxiety symptoms, and turned their personalities into the histrionic (5–21% of cases) or passive dependent (9–40% of cases) type [10] . Vagus nerve stimulation therapy results in a significant cost. VNS therapy currently costs approximately $50,956, which includes the implant and surgical procedure, and there has been a significant increase in the cost of VNS therapy [11] . Patients also require regular appointments at their neurologist to check the device. This high cost of therapy results in a significant burden not only for the patient, but also for society from the public health perspective. For this reason there is a general consensus among epileptologists that a VNS be implanted only if there is convincing evidence of epilepsy [11,12] . However, we still see, from time to time, that patients with PNES are implanted with a VNS. Our study fortunately involved a small cohort, but has certain limitations such as the retrospective nature of the trial and the unavailability of prior EEG recordings from their neurologists’ offices. These EEGs could have revealed the specific findings on the EEGs that were considered abnormal and led to VNS implantation. There are very few reports of VNS implantation in patients with PNES. Attarian et al. described four patients who were erroneously implanted with VNSs. Two had PNES, and the other two had lesional epilepsy that could have benefited the most from resective epilepsy surgery. One had epilepsy secondary to oligoastrocytoma and another had epilepsy from left hippocampal sclerosis [13] . We agree with Attarian et al. that VNSs should be implanted only in patients who have an unequivocal diagnosis of epilepsy. A definitive diagnosis of epilepsy should be made by recording typical spells with video/EEG before VNS implantation. Video/EEG recording may help in excluding the diagnosis of PNES and thus preventing the unnecessary surgical procedure of VNS implantation. Ethical approval We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest statement None of the authors has any conflict of interest to disclose. References [1] S.R. Benbadis E. O'Neill W.O. Tatum L. Heriaud Outcome of prolonged video-EEG monitoring at a typical referral epilepsy center Epilepsia 45 2004 1150 1153 [2] A.M. Arain A.M. Hamadani S. Islam B.W. 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