Jeffrey W. Britton

Low-Grade Glial Neoplasms and Intractable Partial Epilepsy: Efficacy of Surgical Treatment

Summary: We performed a retrospective study of 51 consecutive patients who underwent operation for intractable partial epilepsy related to low‐grade intracerebral neoplasms between 1984 and 1990. All patients had medically refractory partial seizures and a mass lesion identified on neuroimaging studies. Lesionectomy was performed on 17 patients, and 34 had lesion resection and corticectomy. Mean postoperative follow‐up was 4.4 years (range 2–8 years). Sixty‐six percent of patients were seizure‐free, and 88% experienced a significant reduction in seizure frequency. In 16 patients (31%), antiepileptic drugs (AEDs) were successfully discontinued. Twenty‐five of 31 (81%) eligible patients obtained a drivers license after successful operation. Patients with complete tumor resection and no interictal epileptiform activity on postoperative EEG studies had the best operative outcome. Epilepsy surgery can result in long‐term improvement in seizure control and quality of life (QOL) in selected patients with intractable tumor‐related epilepsy. Our results should be useful to clinicians considering treatment options for patients with intractable seizures related to low‐grade intracerebral neoplasms.

Continuous EEG in therapeutic hypothermia after cardiac arrest: Prognostic and clinical value

Objectives: To determine the prognostic value of an EEG grading scale and clinical outcome of treated seizures detected with continuous EEG (cEEG) during therapeutic hypothermia (TH) and rewarming post cardiac arrest (CA). Methods: Our cohort study retrospectively reviewed the electronic medical records and cEEGs of all patients undergoing TH after CA under protocol over 2 years. cEEG was initiated during TH and continued until restoration of normothermia (NT). EEGs were graded 1–3 (3 = most severe) using a departmentally developed EEG severity grading scale by 2 authors blinded to clinical outcome. Outcome was measured using the Cerebral Performance Category scale; grades 1–2 were considered a “good” outcome, 3–5 “poor.” Results: Fifty-four patients were included; 51 remained on cEEG through NT. Nineteen died. EEG severity grading during both TH and NT statistically correlated with outcome (grade 1 = good, grade 3 = poor). Other EEG features correlating with poor outcome included seizures, nonreactive background, and epileptiform discharges. Changes in EEG grade during monitoring did not statistically correlate with outcome. Five patients had seizures; all occurred in patients with grade 3 EEG backgrounds and all had a poor outcome. Conclusion: Grades 1 and 3 on our EEG severity grading scale during TH and NT correlated with outcome. Treating seizures did not improve outcome in our cohort.

Predictors of Outcome in Refractory Status Epilepticus

OBJECTIVE To further characterize the demographics, outcomes, and prognostic factors for refractory status epilepticus (RSE). DESIGN Retrospective analysis of all the episodes of RSE treated between January 1, 1999, and August 30, 2011. SETTING Neurointensive care unit within a tertiary referral center, Mayo Clinic, Rochester, Minnesota. PATIENTS Refractory status epilepticus was defined as generalized convulsive or nonconvulsive status epilepticus (SE) that continued despite initial first- and second-line therapies. Exclusion criteria were aged younger than 18 years, anoxic/myoclonic SE, psychogenic SE, simple partial SE, and absence SE. MAIN OUTCOME MEASURES Functional outcome was defined by modified Rankin scale (mRS) dichotomized into good (mRS, 0-3) and poor (mRS, 4-6). Functional decline was defined as a change in mRS greater than 1 from hospital admission to discharge. RESULTS We identified 63 consecutive episodes of non-anoxic RSE in 54 patients. Anesthetic agents were used in 55 episodes (87.30%), and duration of drug-induced coma was (mean [SD]) 11.0 (17.9) days. In-hospital mortality was 31.75% (20 of 63 episodes). Poor functional outcome at discharge occurred in 48 of 63 episodes (76.19%). Hospital length of stay was (mean [SD]) 27.7 (37.3) days. Duration of drug-induced coma (P=.03), arrhythmias requiring intervention (P=.01), and pneumonia (P=.01) were associated with poor functional outcome. Prolonged mechanical ventilation was associated with mortality (P=.04). Seizure control without suppression-burst or isoelectric electroencephalogram predicted good functional recovery (P=.01). Age, history of epilepsy, previous SE, type of SE, and anesthetic drug used were not associated with functional outcome. CONCLUSIONS Three-quarters of patients with RSE have a poor outcome. Achieving control of the SE without requiring prolonged drug-induced coma or severe electroencephalographic suppression portends better prognosis.

The ictal bradycardia syndrome : Localization and lateralization

Summary:  Purpose: Previous studies have established the importance of the insular cortex and temporal lobe in cardiovascular autonomic modulation. Some investigators, based on the results of cortical stimulation response, functional imaging, EEG recordings of seizures, and lesional studies, have suggested that cardiac sympathetic and parasympathetic function may be lateralized, with sympathetic representation lateralized to the right insula, and parasympathetic, to the left. These studies have suggested that ictal bradycardia is most commonly a manifestation of activation of the left temporal and insular cortex. However, the evidence for this is inconsistent. We sought to assess critically the predictable value of ictal bradycardia for seizure localization and lateralization.

Intracranial electroencephalography seizure onset patterns and surgical outcomes in nonlesional extratemporal epilepsy

OBJECT Patients with normal MR imaging (nonlesional) findings and medically refractory extratemporal epilepsy make up a disproportionate number of nonexcellent outcomes after epilepsy surgery. In this paper, the authors investigated the usefulness of intracranial electroencephalography (iEEG) in the identification of surgical candidates. METHODS Between 1992 and 2002, 51 consecutive patients with normal MR imaging findings and extratemporal epilepsy underwent intracranial electrode monitoring. The implantation of intracranial electrodes was determined by seizure semiology, interictal and ictal scalp EEG, SPECT, and in some patients PET studies. The demographics of patients at the time of surgery, lobar localization of electrode implantation, duration of follow-up, and Engel outcome score were abstracted from the Mayo Rochester Epilepsy Surgery Database. A blinded independent review of the iEEG records was conducted for this study. RESULTS Thirty-one (61%) of the 51 patients who underwent iEEG ultimately underwent resection for their epilepsy. For 28 (90.3%) of the 31 patients who had epilepsy surgery, adequate information regarding follow-up (> 1 year), seizure frequency, and iEEG recordings was available. Twenty-six (92.9%) of 28 patients had frontal lobe resections, and 2 had parietal lobe resections. The most common iEEG pattern at seizure onset in the surgically treated group was a focal high-frequency discharge (in 15 [53.6%] of 28 patients). Ten (35.7%) of the 28 surgically treated patients were seizure free. Fourteen (50%) had Engel Class I outcomes, and overall, 17 (60.7%) had significant improvement (Engel Class I and IIAB with > or =80% seizure reduction). Focal high-frequency oscillation at seizure onset was associated with Engel Class I surgical outcome (12 [85.7%] of 14 patients, p = 0.02), and it was uncommon in the nonexcellent outcome group (3 [21.4%] of 14 patients). CONCLUSIONS A focal high-frequency oscillation (> 20 Hz) at seizure onset on iEEG may identify patients with nonlesional extratemporal epilepsy who are likely to have an Engel Class I outcome after epilepsy surgery. The prospect of excellent outcome in nonlesional extratemporal lobe epilepsy prior to intracranial monitoring is poor (14 [27.5%] of 51 patients). However, iEEG can further stratify patients and help identify those with a greater likelihood of Engel Class I outcome after surgery.

Autoimmune Dementia: Clinical Course and Predictors of Immunotherapy Response

OBJECTIVE To define the diagnostic characteristics and predictors of treatment response in patients with suspected autoimmune dementia. PATIENTS AND METHODS Between January 1, 2002, and January 1, 2009, 72 consecutive patients received immunotherapy for suspected autoimmune dementia. Their baseline clinical, radiologic, and serologic characteristics were reviewed and compared between patients who were responsive to immunotherapy and those who were not. Patients were classified as responders if the treating physician had reported improvement after immunotherapy (documented in 80% by the Kokmen Short Test of Mental Status, neuropsychological testing, or both). RESULTS Initial immunotherapeutic regimens included methylprednisolone in 56 patients (78%), prednisone in 12 patients (17%), dexamethasone in 2 patients (3%), intravenous immune globulin in 1 patient (1%), and plasma exchange in 1 patient (1%). Forty-six patients (64%) improved, most in the first week of treatment. Thirty-five percent of these immunotherapy responders were initially diagnosed as having a neurodegenerative or prion disorder. Pretreatment and posttreatment neuropsychological score comparisons revealed improvement in almost all cognitive domains, most notably learning and memory. Radiologic or electroencephalographic improvements were reported in 22 (56%) of 39 patients. Immunotherapy responsiveness was predicted by a subacute onset (P<.001), fluctuating course (P<.001), tremor (P=.007), shorter delay to treatment (P=.005), seropositivity for a cation channel complex autoantibody (P=.01; neuronal voltage-gated potassium channel more than calcium channel or neuronal acetylcholine receptor), and elevated cerebrospinal fluid protein (>100 mg/dL) or pleocytosis (P=.02). Of 26 immunotherapy-responsive patients followed up for more than 1 year, 20 (77%) relapsed after discontinuing immunotherapy. CONCLUSION Identification of clinical and serologic clues to an autoimmune dementia allows early initiation of immunotherapy, and maintenance if needed, thus favoring an optimal outcome.

Positron Emission Tomography–Computed Tomography in Paraneoplastic Neurologic Disorders: Systematic Analysis and Review

OBJECTIVE To evaluate the cancer detection rate of whole-body positron emission tomography-computed tomography (PET-CT) in a paraneoplastic neurologic context. DESIGN Retrospective medical record review. SETTING Mayo Clinic, Rochester, Minnesota. PATIENTS Fifty-six consecutive patients with clinically suspected paraneoplastic neurologic disorders who underwent PET-CT after negative standard evaluations, including CT. MAIN OUTCOME MEASURE Rate of cancer detection. RESULTS Abnormalities suggestive of cancer were detected using PET-CT in 22 patients (39%); 10 patients (18%) had cancer confirmed histologically. Cancers detected (limited stage in 9 of 10 patients and extratruncal in 4) were as follows: 2 thyroid papillary cell carcinomas, 3 solitary lymph nodes with unknown primary (2 adenocarcinomas and 1 small cell carcinoma), 1 tonsil squamous cell carcinoma, 3 lung carcinomas (1 adenocarcinoma, 1 small cell, and 1 squamous cell), and 1 colon adenocarcinoma. Detection of a well-characterized neuronal nuclear or cytoplasmic paraneoplastic autoantibody was associated with a successful PET-CT-directed cancer search (P < .001). Detection of limited-stage cancer facilitated early initiation of oncologic treatments and immunotherapy; cancer remission was reported in 7 patients, and sustained improvements in neurologic symptoms were reported in 5 (median follow-up, 11 months; range, 2-48 months). Combined data from 2 previous studies using conventional PET alone (123 patients) revealed that 28% of patients had a PET abnormality suggestive of cancer and that 12% had a cancer diagnosis. CONCLUSION In a paraneoplastic neurologic context, PET-CT improves the detection of cancers when other screening test results are negative, particularly in the setting of seropositivity for a neuronal nuclear or cytoplasmic autoantibody marker of cancer.

Functional and Cognitive Outcome in Prolonged Refractory Status Epilepticus

OBJECTIVE To determine the functional and cognitive outcomes of patients with prolonged refractory status epilepticus (PRSE) lasting 7 or more days despite the use of anesthetic agents for seizure suppression. DESIGN Retrospective analysis. SETTING St Marys Hospital, Mayo Clinic, Rochester, Minnesota. PARTICIPANTS Fourteen patients with PRSE. INTERVENTION Hospital follow-up interview. MAIN OUTCOME MEASURES Survival rate of PRSE and functional and cognitive outcome of surviving patients based on the modified Rankin Scale (mRS) and Telephone Interview for Cognitive Status (TICS). RESULTS Forty-three percent of patients (6 of 14) died during hospitalization for PRSE, and 57% (8 of 14) had died by the last follow-up. Of the 6 surviving patients, 4 showed improvement and 2 showed no change in mRS score (median mRS change, -1; range, 0 to -3). Owing to preexisting cognitive deficits, 1 patient could not complete the TICS. The 5 remaining patients scored a median of 34 on the TICS (range, 30-37; reference TICS score, >or=31; maximum TICS score, 41). Age, sex, PRSE duration, and etiology were not associated with chance of survival. CONCLUSIONS Despite the high mortality rate, survival with meaningful functional and cognitive recovery is possible after PRSE. Prolonged duration of status epilepticus alone should not be considered a reason to discontinue treatment.

Utility of an immunotherapy trial in evaluating patients with presumed autoimmune epilepsy.

Objective: To evaluate a trial of immunotherapy as an aid to diagnosis in suspected autoimmune epilepsy. Method: We reviewed the charts of 110 patients seen at our autoimmune neurology clinic with seizures as a chief complaint. Twenty-nine patients met the following inclusion criteria: (1) autoimmune epilepsy suspected based on the presence of ≥1 neural autoantibody (n = 23), personal or family history or physical stigmata of autoimmunity, and frequent or medically intractable seizures; and (2) initiated a 6- to 12-week trial of IV methylprednisolone (IVMP), IV immune globulin (IVIg), or both. Patients were defined as responders if there was a 50% or greater reduction in seizure frequency. Results: Eighteen patients (62%) responded, of whom 10 (34%) became seizure-free; 52% improved with the first agent. Of those receiving a second agent after not responding to the first, 43% improved. A favorable response correlated with shorter interval between symptom onset and treatment initiation (median 9.5 vs 22 months; p = 0.048). Responders included 14/16 (87.5%) patients with antibodies to plasma membrane antigens, 2/6 (33%) patients seropositive for glutamic acid decarboxylase 65 antibodies, and 2/6 (33%) patients without detectable antibodies. Of 13 responders followed for more than 6 months after initiating long-term oral immunosuppression, response was sustained in 11 (85%). Conclusions: These retrospective findings justify consideration of a trial of immunotherapy in patients with suspected autoimmune epilepsy. Classification of evidence: This study provides Class IV evidence that in patients with suspected autoimmune epilepsy, IVMP, IVIg, or both improve seizure control.

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.