Localization value of ictal turning prone.

PURPOSE: Ictal semiology complements ictal EEG in identifying the likely epileptogenic zone. Ictal turning prone (ITP) with body turning of 90 ° or more can be seen with frontal lobe epilepsies. The aim of our study was to evaluate the localizing value of ITP in a general population of patients undergoing long term video-EEG monitoring. METHODS: We reviewed our epilepsy monitoring unit database for adult patients with recorded habitual seizures with ITP. All 16 patients identified had continuous video-EEG monitoring using standard scalp electrodes; eight patients also had intracranial EEG monitoring. We only included focal seizures without evolution to bilateral tonic-clonic activity. RESULTS: We identified 16 patients with ITP, mean age of 32.5 years (range 18-50). ITP was consistently seen in at least one focal impaired awareness seizure of all patients. Ictal onset zone on scalp EEG was left temporal in five, right temporal in three, left frontal convexity in two, right frontal convexity in two, probable right medial frontal in three and probable left medial frontal in one patient. Direction of ITP was uni-directional in 12 patients while 4 patients had ITP in opposite direction in different seizures. Nine patients underwent epilepsy surgery; five patients had Engel class I outcome and four patients had Engel class III outcome. CONCLUSIONS: Ictal turning prone does not have a consistent single localizing or lateralizing value and can be seen with various epileptogenic zones including medial frontal, lateral frontal or temporal. ITP direction can vary even with a single epileptogenic zone.

Lacosamide efficacy and tolerability in clinical practice - Post marketing analysis from a single dedicated epilepsy center.

OBJECTIVES: Post marketing analysis of anti-epileptic drug (AED) efficacy and tolerability is of great value to the clinician since it is more representative of clinical practice than clinical trial data. We analyzed our experience with lacosamide (LCM) in patients treated after marketing. PATIENTS AND METHODS: We identified all patients who were treated with LCM during the four year period after marketing, excluding patients who were in clinical trials. We recorded demographic data and analyzed efficacy and tolerability in patients who had at least one follow up visit or telephone call 3 months after the initiation of LCM. RESULTS: A total of 165 patients met our inclusion criteria. The mean age was 41 years. The majority of the cohort had focal epilepsy (146 patients) (88.4%). The mean duration of treatment was 31.2 months. Eighty one patients (49.1%) were continuing LCM at last follow up. Adverse effects (AEs) and discontinuation were significantly more common when LCM was added to one or more Na-channel blocking agents (NCB) (p = 0.0003 and 0.17). The 50% responder rate was 26% at 3 months and increased to 49% at 36 months. Patients were more likely to continue the drug and less likely to have AEs with slower titration over >4 weeks (p = 0.02 for each). Four or more previously failed AEDs predicted poorer response rate compared to three or less AEDs (p = 0.001). CONCLUSION: LCM use in clinical practice was associated with greater rate of seizure freedom than in clinical trials. Discontinuation and occurrence of AEs were significantly more likely with faster titration and adding LCM to NCB agents.

Characteristics of EEG Interpreters Associated With Higher Interrater Agreement.

PURPOSE: The goal of the project is to determine characteristics of academic neurophysiologist EEG interpreters (EEGers), which predict good interrater agreement (IRA) and to determine the number of EEGers needed to develop an ideal standardized testing and training data set for epileptiform transient (ET) detection algorithms. METHODS: A three-phase scoring method was used. In phase 1, 19 EEGers marked the location of ETs in two hundred 30-second segments of EEG from 200 different patients. In phase 2, EEG events marked by at least 2 EEGers were annotated by 18 EEGers on a 5-point scale to indicate whether they were ETs. In phase 3, a third opinion was obtained from EEGers on any inconsistencies between phase 1 and phase 2 scoring. RESULTS: The IRA for the 18 EEGers was only fair. A select group of the EEGers had good IRA and the other EEGers had low IRA. Board certification by the American Board of Clinical Neurophysiology was associated with better IRA performance but other board certifications, years of fellowship training, and years of practice were not. As the number of EEGers used for scoring is increased, the amount of change in the consensus opinion decreases steadily and is quite low as the group size approaches 10. CONCLUSIONS: The IRA among EEGers varies considerably. The EEGers must be tested before use as scorers for ET annotation research projects. The American Board of Clinical Neurophysiology certification is associated with improved performance. The optimal size for a group of experts scoring ETs in EEG is probably in the 6 to 10 range.

Temporal lobe origin is common in patients who have undergone epilepsy surgery for hypermotor seizures.

RATIONALE: Hypermotor seizures are most often reported from the frontal lobe but may also have temporal, parietal, or insular origin. We noted a higher proportion of patients with temporal lobe epilepsy in our surgical cohort who had hypermotor seizures. We evaluated the anatomic localization and surgical outcome in patient with refractory hypermotor seizures who had epilepsy surgery in our center. METHODS: We identified twenty three patients with refractory hypermotor seizures from our epilepsy surgery database. We analyzed demographics, presurgical evaluation including semiology, MRI, PET scan, interictal/ictal scalp video-EEG, intracranial recording, and surgical outcomes. We evaluated preoperative variables as predictors of outcome. RESULTS: Most patients (65%) had normal brain MRI. Intracranial EEG was required in 20 patients (86.9%). Based on the presurgical evaluation, the resection was anterior temporal in fourteen patients, orbitofrontal in four patients, cingulate in four patients, and temporoparietal in one patient. The median duration of follow-up after surgery was 76.4months. Fourteen patients (60%) had been seizure free at the last follow up while 3 patients had rare disabling seizures. CONCLUSIONS: Hypermotor seizures often originated from the temporal lobe in this series of patients who had epilepsy surgery. This large proportion of temporal lobe epilepsy may be the result of a selection bias, due to easier localization and expected better outcome in temporal lobe epilepsy. With extensive presurgical evaluation, including intracranial EEG when needed, seizure freedom can be expected in the majority of patients.

Video-EEG results and clinical characteristics in patients with psychogenic nonepileptic spells: The effect of a coexistent epilepsy.

RATIONALE: Epilepsy and psychogenic nonepileptic spells (PNES) can coexist, often posing diagnostic and therapeutic challenges. We sought to identify clinical and historical characteristics of two groups of patients, those with coexisting epilepsy and PNES and those with PNES alone, and determine the prevalence of coexisting epilepsy/PNES with strict diagnostic criteria in a large group of epilepsy monitoring unit (EMU) patients. METHODS: We reviewed the medical records of all consecutive patients admitted to the Vanderbilt University Medical Center Adult EMU between July 1, 2007 and June 30, 2012. We identified patients with recorded PNES and classified them as having coexisting epilepsy/PNES or PNES alone and then systematically compared the clinical characteristics of these two groups. RESULTS: A total of 1567 patient medical records were reviewed. The prevalence rate of coexisting epilepsy/PNES was 5.2% among all EMU admissions (12.3% of all patients with epilepsy and 14.8% of all patients with PNES). These rates were lower when patients with interictal epileptiform activity (IEA) alone and no recorded ictal discharges were not included in the group with epilepsy (2.6%, 6.2%, and 7.4%, respectively). The accuracy of pre-EMU clinical suspicion was significantly higher in the group with PNES-only. Patients with epilepsy/PNES were significantly more likely to require more than one EMU admission for definitive diagnosis. The first PNES event preceded an epileptic seizure (ES) in 94.4% of patients with epilepsy/PNES. The group with PNES-only had significantly higher suggestibility, and the group with epilepsy/PNES had a significantly higher presence of epilepsy risk factors. Abnormal neurological examination and abnormal brain MRI were also significantly more common in the group with epilepsy/PNES. CONCLUSIONS: Our study defined the prevalence of coexisting epilepsy/PNES in a large cohort with strict diagnostic criteria and outlined specific clinical and historical characteristics differentiating the two groups of patients with coexisting epilepsy/PNES and PNES-only. These findings should help guide clinicians to reach the correct diagnosis faster and provide appropriate treatment earlier.

Communicating the diagnosis of psychogenic nonepileptic seizures: The patient perspective.

Psychogenic nonepileptic seizures (PNES) are a common cause of refractory seizures. Video-electroencephalographic (EEG) monitoring has allowed PNES to be effectively distinguished from epileptic seizures. Once the diagnosis of PNES is established, neurologists face the challenge of explaining it to patients. Patients may not always receive the diagnosis well. The aim of this study is to evaluate how effectively patients receive and perceive the diagnosis of PNES. This prospective study was conducted in an eight-bed epilepsy monitoring unit (EMU). Adult patients with newly confirmed PNES were included. After receiving written consent, a self-administered questionnaire was given to patients after the attending physician had communicated the diagnosis of PNES. A total of 75 patients were recruited. All patients had their typical seizures recorded on video-EEG (range 1-12, mean 2.18). Seventy patients were satisfied with the diagnosis of PNES. Nine patients did not agree that PNES has a psychological cause. Nineteen patients thought that the EMU doctors had no clue as to the cause of their seizures and 20 thought that there was no hope for a cure of their seizures. A significant number of patients with PNES feel that there is no hope for cure of their seizures. Thorough education about PNES, properly preparing patients before discussing the diagnosis of PNES, and preferably earlier diagnosis may prevent this miscommunication and result in better outcomes. A comprehensive approach including psychological counseling and psychiatric input, evaluation and treatment, in order to bring the illness from the subconscious to the conscious level, and effective follow-up may be helpful.

Revisiting the laterality of wicket spikes with continuous EEG.

PURPOSE: Wicket spikes (WS) are a benign EEG variant classically defined to be bilateral independent temporal in localization. The authors observed that the majority of WS are exclusively unilateral temporal. The aim was to identify the laterality and clinical significance of the WS. METHODS: Epilepsy monitoring unit reports of adult patients were searched for keywords "wicket" or "wickets" and examined for WS lateralization dividing it into three groups: bilateral, left, and right temporal. The age, sex, hand dominance, admission duration, epilepsy risk factors, cerebral microvascular disease, and final diagnosis were also collected. RESULTS: Wicket spikes were present in 133 studies and were significantly more prevalent in the left temporal region (69%, P < 0.05). Cerebral microvascular disease was more prevalent in patients with left temporal WS (64%, P < 0.05). There were no differences in the remaining studied variables among the three groups. Wicket spikes were not associated with epilepsy. CONCLUSIONS: The authors' findings demonstrate that the majority of WS are strictly left temporal. Despite their predominant unilaterality, WS are not associated with epilepsy but may be associated with cerebral microvascular disease. The authors propose redefining the WS lateralization to be mostly unilateral rather than bilateral. This may prevent misinterpretation of this challenging yet benign EEG variant.

Acute pancreatitis and elevated liver transaminases after rapid titration of oral levetiracetam.

We report a 25-year-old woman with new onset convulsive episodes. The patient initially failed to respond to phenytoin and was switched to levetiracetam (LEV) which was rapidly titrated to 3000 mg daily over 1 week. At initiation of LEV therapy, she developed mild nausea and decrease in appetite. This was rapidly followed by severe digestive symptoms consistent with acute pancreatitis. She was also found to have elevated liver transaminases. An extensive work-up failed to reveal an organic cause for her symptoms, suggesting a direct relationship to LEV. Clinical symptoms and laboratory abnormalities normalized after LEV discontinuation, along with supportive therapy.

Leptomeningeal metastasis from occult signet-ring cell colon adenocarcinoma presenting with isolated headache.

We report a patient with a rare primary signet-ring cell carcinoma of the transverse colon with secondary leptomeningeal carcinomatosis. The only presenting and persistent symptom was worsening headache for 6 weeks until death. There were no other neurological, constitutional, or gastrointestinal symptoms. The primary tumor was detected by CT scan and confirmed by endoscopy, and the final diagnosis was eventually made from cerebrospinal fluid and tissue cytology. This report confirms the dismal prognosis of leptomeningeal carcinomatosis, especially when the primary malignancy is asymptomatic.

Tiagabine-induced stupor in patients with psychogenic nonepileptic seizures: nonconvulsive status epilepticus or encephalopathy?

BACKGROUND: Nonconvulsive status epilepticus has been rarely reported with tiagabine (TGB) use. METHODS: We report findings from continuous video-EEG monitoring and serial neurological examinations during prolonged episodes of stupor associated with TGB use in three patients who did not have epilepsy. RESULTS: All three patients had emergence of new type of events after starting TGB treatment. All three patients had gradual decline in responsiveness to verbal stimuli, intermittent twitching of the upper extremities, and urinary incontinence. The corresponding EEG showed gradual build-up of generalized bisynchronous delta-wave activity with subsequent intermingled sharp transients. Two patients did not respond to IV lorazepam, one of whom also did not respond to IV phenytoin. The EEG slowly normalized in conjunction with associated clinical improvement. Habitual seizures were found to be psychogenic, with no interictal evidence for epilepsy. CONCLUSION: Tiagabine-related stupor may represent a form of toxic encephalopathy in some cases rather than nonconvulsive status epilepticus.

Homonymous hemianopia in nonketotic hyperglycemia is an ictal phenomenon.

Extended video-EEG or 18F-fluorodeoxyglucose PET (FDG-PET) was obtained in 3 adult patients with hemianopia secondary to nonketotic hyperglycemia. Two male patients presented with left hemianopia and episodic left gaze deviation and one male patient presented with right hemianopia and visual hallucinations. None of the 3 patients had a history of seizures or known epilepsy risk factors. All 3 patients were found to have elevated serum glucose (267 mg/dL, 320 mg/dL, and 487 mg/dL) without acidosis or urine ketones. In all 3 patients, video-EEG recorded recurrent ictal discharges originating from the posterior quadrant contralateral to their hemianopia. In 2 patients, FDG-PET demonstrated corresponding focal areas of hypermetabolism. Resolution of visual symptoms was achieved with antiepileptic drugs, hydration, and tight glycemic control.

Marked Seizure Reduction after MCT Supplementation.

We report the case of a 43-year-old man with history of nonsurgical partial epilepsy who previously failed multiple trials of antiepileptic drugs. Medium-chain triglycerides (MCT) were added to his regular diet in the form of pure oil. Subsequently, his seizure frequency was markedly reduced from multiple daily seizures to one seizure every four days. His seizures recurred after transient discontinuation of MCT over a period of ten days. His seizure improvement was achieved at a dose of four tablespoons of MCT twice daily with no reported side effects. He developed significant diarrhea and flatulence at higher doses. We conclude that MCT oil supplementation to regular diet may provide better seizure control in some patients. MCT oil supplementation may be a more tolerable alternative to the standard ketogenic diet.

Severe new seizures after initiation of vagus nerve stimulation therapy.

Vagus nerve stimulation is considered to be a safe and effective adjunctive therapy for patients with drug-resistant epilepsy. Contrary to some antiepileptic drugs, vagus nerve stimulation is not known to precipitate or aggravate new or preexisting seizures. We describe the emergence of a new type of disabling, recurrent partial seizure immediately after initiation of vagus nerve stimulation in a 51-year-old man with a known history of refractory partial epilepsy. Discontinuation of vagus nerve stimulation therapy and multiple antiepileptic drug interventions were required to abort these unexpected new seizures. We conclude that vagus nerve stimulation may induce paradoxical seizures, similarly to some antiepileptic drugs.

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

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common paroxysmal events that mimic and can often be misdiagnosed as epileptic seizures. PNES account for 10 to 40% of patients referred to epilepsy centers. Patients with uncontrolled PNES are at times subjected to vagus nerve stimulator (VNS) implantation. We report a series of such referred patients studied with video/EEG monitoring at our institution. METHODS: We evaluated patients who were implanted with a VNS by their primary neurologist for refractory seizures and who were referred to the Vanderbilt University epilepsy monitoring unit for a second opinion. The presumed diagnosis of epilepsy was based on abnormal routine EEG studies obtained by their primary neurologist. We evaluated these patients and recorded their typical spells between 2005 and 2009. We describe the results of 13 patients with VNS who were found to have PNES. The total number of patients with a VNS studied during this time was 60. 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.

Predictors of a nondiagnostic epilepsy monitoring study and yield of repeat study.

OBJECTIVE: Failure to record typical events during long-term video/EEG monitoring (LTM) leaves the diagnosis uncertain. The purpose of this study was to analyze predictors of an initial nondiagnostic LTM study and to evaluate the yield of a repeat study. METHODS: We reviewed all adult LTM studies performed at Vanderbilt University from January 2004 to June 2008. We identified 150 patients with no typical events on LTM and matched them with consecutive controls with typical events. We compared patient demographics, epilepsy risk factors, history of antiepileptic use/failures, and prior EEG and MRI results. RESULTS: Of 2397 LTM studies, 380 (15.8%) failed to record typical events. Absence of epilepsy risk factors and normal outpatient EEG predicted this outcome. A repeat LTM study was successful in 18 of 45 patients (42%). CONCLUSION: The prediction of a nondiagnostic LTM can help to reduce the cost of investigating spells of unknown nature.

Levetiracetam Extended Release as Adjuvant Therapy for the Control of Partial-onset Seizures.

Extended release (XR) formulation of levetiracetam (LEV) is approved by the Food and Drug Administration as an add-on to other antiepileptic drugs (AEDs) for adults with partial onset seizures. This is based on class-I evidence demonstrating significant seizure reduction in once daily dosing. Keppra-XR is marketed with the brand name of Keppra XR since 2008 (UCB Pharma). Its original immediate release (IR) formulation has been in the market since 2000. LEV has a unique molecular structure which is chemically unrelated to existing AEDs. The precise mechanism of action is unknown. Animal studies showed binding to synaptic vesicle protein SV2A, thought to be involved in modulating synaptic neurotransmitter release. LEV-IR is proven effective as adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures and myoclonic seizures. It was shown to be equivalent to carbamazepine as first-line treatment for partial-onset seizures. The extended release formulation added advantages such as better tolerance and increased compliance.

A structured questionnaire predicts if convulsions are epileptic or nonepileptic.

OBJECTIVE: Therapy for convulsive seizures is usually initiated on the basis of clinical assessment, without video/EEG confirmation, but a nonepileptic origin may eventually be demonstrated. This study evaluates the diagnostic value of a witness-questionnaire in distinguishing between convulsive epileptic seizures (CES) and convulsive nonepileptic seizures (CNES). METHODS: We prospectively identified all adult patients admitted for video/EEG evaluation of convulsive attacks and interviewed the "best" witness using 12 questions on ictal and postictal features. RESULTS: Video/EEG diagnosed CES in 19 and CNES in 26 patients. The predictive accuracy of the questionnaire was 84.4%. Six features were strong predictors of CNES diagnosis: ictal eye closure, presence of side-to-side movements, prolonged seizure duration, and three postictal breathing features (not loud, shallow, no snoring). CONCLUSION: A structured witness questionnaire distinguishes CES and CNES and will help in selecting patients for early video/EEG evaluation and rapid initiation of appropriate therapy.

Transient improvement after brief antiepileptic drug withdrawal in the epilepsy monitoring unit--possible relationship to AED tolerance.

PURPOSE: A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance. METHODS: We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission. RESULTS: A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days). DISCUSSION: SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Ictal flatulence: seizure onset in the nondominant hemisphere.

We describe the case of a 45-year-old woman with frequent simple partial seizures consisting mainly of autonomic manifestations including flatulence. The ictal onset and interictal EEG epileptiform abnormalities were localized to the right frontotemporal region. This localization was supported by structural brain imaging showing recurrence of a right frontotemporal oligodendroglioma with involvement of the insula. We therefore suggest that ictal flatulence is one of several autonomic and gastrointestinal symptoms and signs that may be used clinically in lateralizing to the nondominant hemisphere.

Transitional sharp waves at ictal onset--a neocortical ictal pattern.

OBJECTIVE: Some seizures are characterized by a transitional sharp wave (TShW) at ictal onset. We evaluated the clinical significance and localizing value of TShW in partial-onset seizures. METHODS: We identified and analyzed all scalp ictal recordings with a TShW at ictal onset in the Vanderbilt Epilepsy Monitoring Unit over a period of 12 months. RESULTS: A total of 52 ictal discharges in 13 patients started with a TShW. The center of TShW field was concordant with the final localization/lateralization, while that of the subsequent ictal discharge was concordant in only 6 patients. The subsequent rhythmic ictal discharge was non-localizing in 4 patients and misleading in the remaining 3 patients. The final localization was neocortical temporal or frontal in 11 patients, occipito-parietal in one, and undetermined in 1 patient. None of 61 ictal discharges in 15 patients with mesial temporal lobe epilepsy studied in the same time period started with a TShW. CONCLUSION: In this patient series, the TShW was a marker of neocortical seizure onset. The TShW field provided more accurate localization or lateralization of the ictal focus than the following rhythmic ictal discharge. SIGNIFICANCE: TShW at seizure onset should suggest a neocortical rather than hippocampal seizure onset.