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Clinical Crossroads | Clinician's Corner

A 24-Year-Old Woman With Intractable Seizures:  Review of Surgery for Epilepsy

Donald L. Schomer, MD; Peter M. Black, MD, PhD
JAMA. 2008;300(21):2527-2538. doi:10.1001/jama.2008.709.
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Epilepsy, a recurrent seizure disorder affecting 1% of the population, can be genetic in origin and thereby affect multiple members in a family, or it can be sporadic. Many sporadic seizures come from a specific “focus” in the cortex. Focal-onset seizures account for 60% of all cases of epilepsy. Among patients with partial seizures, 35% respond poorly to available medication and may benefit from neurosurgical excisional surgery. In cases in which epilepsy is localized through different modes (electroencephalogram, magnetic resonance imaging, etc) to a specific area of the brain where there is an associated lesion, more than half of patients can expect a successful surgical outcome. In patients with consistent seizure-associated behavior but without a lesion, surgical treatment is less successful. Ms H, a young woman with a history of medically intractable partial epilepsy, does not have an anatomical lesion but wants to know if a surgical approach is a good option for her.

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Figure 1. Ms H's Routine Electroencephalograms (EEGs)
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A, Slow-wave activity (theta and delta) in the left temporal and central and right central areas is suggestive of localized cortical injury. The rare left temporal interictal epileptiform discharges are suggestive of an area of cortical irritability. B, Herald spike is the first physiological sign that a seizure is coming (appeared before every seizure); seizure onset is noted by reviewing the video recording linked to the EEG; pushbutton is an electrical artifact put on the EEG recording that marks the moment noted either by the patient or a family member that a clinical seizure has started.

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Figure 2. High-Resolution T1-Weighted, Coronal Magnetic Resonance Imaging of Ms H's Brain
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A, Slightly enlarged right temporal horn (arrowhead), normal hippocampal volumes bilaterally. B, Mild cerebellar atrophy (arrowheads). No evidence of congenital or developmental anomalies.

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Figure 3. Positron Emission Tomography Scan of Ms H's Brain When She Was Not Having Symptoms
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Decreased fluorodeoxyglucose (FDG) use (circled areas) in the right temporal lobe is suggestive of decreased metabolic activity in that region.

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Figure 4. Anatomical Regions Involved in Frontal Lobe Seizures
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Three-dimensional cortical reconstruction from high resolution T1-weighted magnetic resonance imaging scans of Ms H identifying regions of interest (boldface) involved in frontal lobe seizures (note: insula is not shown).

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Surgical Management of Medically Intractable Epilepsy
Posted on November 26, 2008
Chandan G. Reddy, MD
Neurosurgery Resident and Epilepsy Fellow, Department of Neurosurgery, University of Iowa
Conflict of Interest: None Declared
Ms. H has medically intractable epilepsy [1]. She has been unable to enjoy outdoor activities and has been unable to work as a preschool teacher. Uncontrolled seizures have been associated with reduced quality of life, diminished psychosocial functioning, lower rates of employment, delay in neurocognitive development, and increased rates of depression. There is also an increased risk of accidental death or disability [2].
Her seizure disorder is consistent with a complex partial seizure disorder with secondary generalization. Traditionally, many neurologists would try carbamazepine as a first-line treatment, although there is considerable variability, especially given the advent of newer generation anticonvulsants, and considering numerous factors including age, gender, regional preferences, and comorbid conditions such as HIV, depression, anxiety, renal disorders and hepatic failure [3]. In a young woman of child-bearing age, some neurologists prefer lamotrigine, given its presumed safer profile during pregnancy. Failing carbamazepine or lamotrigine, numerous alternatives exist, each with its own unique profile and particular side effects [4, 5]. Common class-wide side effects include oversedation, teratogenicity, exacerbation of depression, anxiety, and weight fluctuation. Newer anticonvulsants tend to have fewer enzyme- inducing hepatic interactions. Rare but serious long-term side effects of carbamazepine include agranulocytosis, aplastic anemia, and Stevens- Johnson Syndrome [6].
There is Class I Evidence suggesting that resective surgery in patients with medically refractory temporal lobe epilepsy leads to higher rates of seizure freedom and better quality of life when compared to best medical management. In one Canadian study [2], 80 patients with temporal lobe epilepsy were randomized, with 40 randomized to surgery and 40 to best medical management. Seizure free rates at 1 year were 58% in the surgical group, compared to 8% in the medical group (p < 0.001), with significant differences in improvement of quality of life (p < 0.001). Adverse effects of surgery rated at 10% and included one thalamic infarct (2.5%), two patients with a decline in verbal memory (5%) and one wound infection (2.5%). Asymptomatic superior subquadrantic visual-field defects occurred in 22 patients (55%). Rates of depression were comparable between the two groups (18-20%).
Meta-analyses of epilepsy surgery generally quote between 60-70% seizure-freedom rate for temporal lobe epilepsy, with lower rates of long- term success quoted for extratemporal foci (on the order of 20-40%) [7, 8].
Ms. H's preoperative evaluation has led to a mixed picture. Her semiology is consistent with left frontal lobe origin (noctural seizures, short duration, arm tonicity, partial awareness) with consistent exam findings (reduced right arm swing despite being right-handed), but there is insufficient consistency among her preoperative investigations to proceed with a straightforward left frontal or mesial-temporal resection [9].
Invasive monitoring, in the manner of left greater than right coverage, with left fronto-temporal cortical as well as bilateral invasive medial-temporal coverage (either with depth electrodes or subtemporal strips) would be indicated. It is possible she has left mesial temporal onset with rapid generalization. If her invasive monitoring suggests a unified location of seizure onset, resection surgery might be indicated in the form of either left anterior temporal lobectomy or selective amygdalo- hippocampectomy. Preoperative WADA testing, in addition to electrophysiologic motor and language mapping, would aid in surgical decision making [10].
The author has no relevant financial interests.
References:
1) Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000; 342(5): 314-319.
2) Wiebe S, Blume WT, Girvin JP, Eliasziw M. A Randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001; 345(5): 311-318.
3) Karceski S, Morrell MJ, Carpenter D. Treatment of epilepsy in adults: expert opinion, 2005. Epilepsy & Behavior. 2005; 7: S1-S64.
4) Glauser T, Ben-Menachem E, et al. ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes. Epilepsia. 2006; 47(7): 1094-1120.
5) Semah F, Picot MC, et al. The choice of antiepileptic drugs in newly diagnosed epilepsy: A national French survery. Epileptic Disord. 2004; 6(4): 255-265.
6) Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press: 1997, 61-74.
7) Tellez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis. Brain: 2005; 128: 1188-1198.
8) Tonini C, Beghi E, et al. Predictors of epilepsy surgery outcome: a meta-analysis. Epilepsy Research: 2004; 62: 75-87.
9) Jan MMS, Girvin JP. Seizure Semiology: Value in Identifying Seizure Origin. Can J Neurol. Sci: 2008; 35: 22-30.
10) Schramm J. Temporal lobe epilepsy surgery and the quest for optimal extent of resection: A review. Epilepsia: 2008; 49(8): 1296-1307.
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