Katherine H. Noe

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Frequency of seizures in patients with newly diagnosed brain tumors: A retrospective review

Brain tumors may lead to symptomatic epilepsy. A retrospective analysis was undertaken to evaluate the frequency of seizure as the presenting symptom leading to brain tumor diagnosis in adults. One hundred and forty-seven consecutive patients with newly diagnosed brain tumors were analyzed regarding the frequency of seizures as the initial presenting symptoms and those subsequently developing seizures. One hundred twelve patients had primary central nervous system tumors (CNS) and 35 had metastatic lesions. Statistical evaluation was carried out using the Chi-square test with p values of <0.05 considered to be statistically significant. Astrocytomas and meningiomas were the most common primary CNS tumors in this study. Of these, oligodendrogliomas and grade 2 astrocytomas were significantly more likely to present with seizures (p<0.001). Seizures were a frequent presenting symptom, occurring in over 38% of those with primary brain neoplasms and 20% of those with cerebral metastases. Primary location of tumor also correlated amongst primary CNS tumors and was associated with a trend in seizure risk: parietal (80%); temporal (74%); frontal (62%); and occipital (0%) (p<0.5). The findings highlight the importance of obtaining appropriate evaluation for underlying malignancy in adults with new-onset seizures as well as provide more information to the patient for prognosis and counseling.

Safety of Long-term Video-Electroencephalographic Monitoring for Evaluation of Epilepsy

OBJECTIVE To determine the rate of medical complications from long-term video-electroencephalographic (EEG) monitoring for epilepsy. PATIENTS AND METHODS We reviewed the medical records of 428 consecutive adult patients with epilepsy who were admitted for diagnostic scalp video-EEG monitoring at Mayo Clinics site in Arizona from January 1, 2005, to December 31, 2006; 149 met inclusion criteria for the study. Seizure number and type as well as timing and presence of seizure-related adverse outcomes were noted. RESULTS Of the 149 adult patients included in the study, seizure clusters occurred in 35 (23%); 752 seizures were recorded. The mean time to first seizure was 2 days, with a mean length of stay of 5 days. Among these patients, there was 1 episode of status epilepticus, 3 potentially serious electrocardiographic abnormalities, 2 cases of postictal psychosis, and 4 vertebral compression fractures during a generalized convulsion, representing 11% of patients with a recorded generalized tonic-clonic seizure. No deaths, transfers to the intensive care unit, falls, dental injuries, or pulmonary complications were recorded. An adverse event requiring intervention or interfering with normal activity occurred in 21% of these patients. Length of stay was not affected by occurrence of adverse events. CONCLUSION Prolonged video-EEG monitoring is an acceptably safe procedure. Adverse events occur but need not result in substantial morbidity or increase length of hospitalization. Appropriate precautions must be in place to prevent falls and promptly detect and treat seizure clusters, status epilepticus, serious electrocardiographic abnormalities, psychosis, and fractures.

Long-term Outcomes After Nonlesional Extratemporal Lobe Epilepsy Surgery

IMPORTANCE A focal lesion detected by use of magnetic resonance imaging (MRI) is a favorable prognostic finding for epilepsy surgery. Patients with normal MRI findings and extratemporal lobe epilepsy have less favorable outcomes. Most studies investigating the outcomes of patients with normal MRI findings who underwent (nonlesional) extratemporal epilepsy surgery are confined to a highly select group of patients with limited follow-up. OBJECTIVE To evaluate noninvasive diagnostic test results and their association with excellent surgical outcomes (defined using Engel classes I-IIA of surgical outcomes) in a group of patients with medically resistant nonlesional extratemporal epilepsy. DESIGN A retrospective study. SETTING Mayo Clinic, Rochester, Minnesota. PARTICIPANTS From 1997 through 2002, we identified 85 patients with medically resistant extratemporal lobe epilepsy who had normal MRI findings. Based on a standardized presurgical evaluation and review at a multidisciplinary epilepsy surgery conference, some of these patients were selected for intracranial electroencephalographic (EEG) monitoring and epilepsy surgery. EXPOSURE Nonlesional extratemporal lobe epilepsy surgery. MAIN OUTCOMES AND MEASURES The results of noninvasive diagnostic tests and the clinical variables potentially associated with excellent surgical outcome were examined in patients with a minimum follow-up of 1 year (mean follow-up, 9 years). RESULTS Based on the noninvasive diagnostic test results, a clear hypothesis for seizure origin was possible for 47 of the 85 patients (55%), and 31 of these 47 patients (66%) proceeded to intracranial EEG monitoring. For 24 of these 31 patients undergoing long-term intracranial EEG (77%), a seizure focus was identified and surgically resected. Of these 24 patients, 9 (38%) had an excellent outcome after resective epilepsy surgery. All patients with an excellent surgical outcome had at least 10 years of follow-up. Univariate analysis showed that localized interictal epileptiform discharges on scalp EEGs were associated with an excellent surgical outcome. CONCLUSIONS AND RELEVANCE Scalp EEG was the most useful test for identifying patients with normal MRI findings and extratemporal lobe epilepsy who were likely to have excellent outcomes after epilepsy surgery. Extending outcome analysis beyond the resective surgery group to the entire group of patients who were evaluated further highlights the challenge that these patients pose. Although 9 of 24 patients undergoing resective surgery (38%) had excellent outcomes, only 9 of 31 patients undergoing intracranial EEG (29%) and only 9 of 85 patient with nonlesional extratemporal lobe epilepsy (11%) had long-term excellent outcomes.

Cardiac pathology in status epilepticus

Massive catecholamine release resulting in the formation of cardiac contraction bands may represent the cause of death in status epilepticus (SE). We reviewed the cardiac pathology of patients who died during SE to asses for contraction bands. Eight of 11 patients who died during SE had identifiable myocardial contraction bands compared with 5 of 22 control patients (p < 0.05, Fishers exact t test). These findings delineate a pathological substrate and provide compelling evidence that excessive catecholamine release is the mechanism responsible for death in SE. Ann Neurol 2005

Treatment of Depression in Patients with Epilepsy

Opinion statementIn this article, we review the current best evidence for the treatment of depression in patients with epilepsy. Depression is a common epilepsy comorbidity, but it is often unrecognized. The most important step in appropriately managing mood disorders in this population is making the diagnosis. Clinical vigilance and routine use of a validated screening tool can improve detection and quality of care. As is increasingly the case for the general population, persons with epilepsy are often interested in exploring alternative therapies for chronic conditions, including depression. Unfortunately, the benefit of complementary and alternative therapies for depression currently is largely unproven for persons with a seizure history, although an early study of exercise for mild depression has shown some benefit. Concerns about drug interactions, side effects, and expense may be barriers to the prescription of antidepressant medications for people requiring chronic antiepileptic drug (AED) therapy. For this reason, use of an AED with mood-stabilizing properties has appeal and may be appropriate for selected individuals with mild depressive symptoms. Undue fear of lowering seizure threshold should not preclude the prescription of an antidepressant medication, as the perceived risks are often overestimated and rarely outweigh the risk of leaving depression untreated. At present, the best evidence for efficacy and safety support the use of citalopram, sertraline, or mirtazapine as initial pharmacotherapy, whereas bupropion should be avoided. Start low, go slow, and use the lowest effective dose. Cognitive behavioral therapy is a valuable adjunct to antidepressant therapy in this population. For people with refractory partial epilepsy and refractory depression, vagus nerve stimulation has some appeal, in that it may be beneficial for both conditions, but the efficacy of vagus nerve stimulation in improving mood in patients with epilepsy remains unclear.

Comparison of Psychogenic Movement Disorders and Psychogenic Nonepileptic Seizures: Is Phenotype Clinically Important?

BACKGROUND Psychogenic non-epileptic seizures (PNES) and psychogenic movement disorders (PMDs) are common in neurology practice, yet it is not established whether clinically relevant differences between these two groups exist. METHODS In this retrospective chart review 172 patients were identified (PNES n = 116, PMD n = 56). RESULTS The whole group was characterized by female gender (82%), abuse history (45%), chronic pain (70%), depression (42%), subjective fatigue (47%), subjective cognitive complaints (55%), and referral for psychiatric evaluation (54%). Statistically significant differences (P <. 01) were found for age, education, frequency of symptoms, altered consciousness, developmental abuse, and coexisting anxiety. Clinical practice also differed for the two groups in history-taking and referrals for neuropsychological testing and/or psychiatric evaluation. CONCLUSIONS This retrospective study revealed more similarities than differences suggesting these are manifestations of the same psychopathology, with age and co-morbid anxiety potentially being important factors in predicting the symptomatic presentation. Prospective studies are needed to confirm our results. Future studies focusing more globally on somatoform disorders, rather than each phenotypic presentation, are likely needed to improve clinical care and outcomes.

Clinical predictors of psychogenic nonepileptic seizures: a critically appraised topic.

Background:Psychogenic nonepileptic seizures (PNES) are often disabling and usually associated with psychiatric disorders and reduced quality of life. Although often suspected based on historical and clinical features, the gold standard for diagnosis of PNES is video electroencephalography. Identification of clinical features that reliably distinguish PNES from ES would be valuable in acute care settings, for patients that have coexisting disorders, and those with multiple event types. Objective:To determine the diagnostic value of putative clinical symptoms or signs of PNES against the gold standard of video electroencephalography. Methods:We addressed the objective through development of a structured critically appraised topic that included a clinical scenario, structured question, search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of epileptology. Results:There were wide variations in the rates of coexisting PNES and epilepsy and study methodology. Ictal stuttering and the “teddy bear” sign were associated with moderate specificity for PNES. However, the presence of pelvic thrusting or ictal eye closure did not accurately distinguish PNES from ES. Conclusions:The presence of either ictal stuttering or the teddy bear sign is moderately specific but poorly sensitive for PNES. Pelvic thrusting and ictal eye closure are not reliable indicators of PNES. Future studies should establish more precise and reliable definitions of clinical signs and evaluate combinations of such signs in a broad spectrum of patients with PNES and ES spell phenotypes that may be difficult to distinguish, such as spells of unresponsiveness with motor manifestations. Because PNES and ES may coexist, analysis of diagnostic accuracy of clinical features should be performed for individual spells.

Antiepileptic Drugs 2012: Recent Advances and Trends

There are now 24 antiepileptic drugs (AEDs) approved for use in epilepsy in the United States by the Food and Drug Administration. A literature search was conducted using PubMed, MEDLINE, and Google for all English-language articles that discuss newly approved AEDs and the use of AEDs in epilepsy in the United States from January 1, 2008, through December 31, 2011. Five new agents were identified that have come onto the market within the past 2 years. Moreover, 3 trends involving AEDs have become clinically important and must be considered by all who treat patients with epilepsy. These trends include issues of generic substitution of AEDs, pharmacogenomics predicting serious adverse events in certain ethnic populations, and the issue of the suicide risk involving the entire class of AEDs. This article discusses the most recent AEDs approved for use in the United States and the 3 important trends shaping the modern medical management of epilepsy.

A consensus-based approach to patient safety in epilepsy monitoring units: Recommendations for preferred practices

Patients in an epilepsy monitoring unit (EMU) with video-EEG telemetry have a risk for seizure emergencies, injuries and adverse events, which emphasizes the need for strategies to prevent avoidable harm. An expert consensus process was used to establish recommendations for patient safety in EMUs. Workgroups analyzed literature and expert opinion regarding seizure observation, seizure provocation, acute seizures, and activity/environment. A Delphi methodology was used to establish consensus for items submitted by these workgroups. Fifty-three items reached consensus and were organized into 30 recommendations. High levels of agreement were noted for items pertaining to orientation, training, communication, seizure precautions, individualized plans, and patient/family education. It was agreed that seizure observation should include direct observation or use of closed-circuit camera. The use of continuous observation was strongest in patients with invasive electrodes, at high risk for injury, or undergoing AED withdrawal. This process provides a first step in establishing EMU safety practices.