The role of neurosurgery in status epilepticus - Springer Link

Neurocrit Care (2007) 7:86–91 DOI 10.1007/s12028-007-0038-4

PRACTICAL PEARL

The role of neurosurgery in status epilepticus Yu-tze Ng Æ Ruth E. Bristol Æ Dewi V. Schrader Æ Kris A. Smith

Published online: 11 April 2007 Ó Humana Press Inc. 2007

Abstract Introduction Status epilepticus remains a life-threatening condition that afflicts both adults and children which although occurs in patients with epilepsy, often presents as new-onset seizure activity also. Refractory status epilepticus poses a management challenge for neurological and neurosurgical teams. Case report and methods Subdural grid electrodes were used to record cortical discharges and guide tumor resection involving eloquent cortex and multiple subpial transections in a 48-year-old man with left hemiparesis in status epilepticus. He had been refractory to multiple medical therapies in persistent epilepsia partialis continua for a prolonged period. As an alternative to higher-dose suppressive medical therapy, the patient elected to proceed with subdural grid mapping after seizure semiology (‘‘negative’’ scalp electroencephalogram) localized the seizure focus to the right hemisphere, motor cortex. Following tumor removal, multiple subpial transections were subsequently performed over large areas of the motor

and sensory strips and successfully resolved the status epilepticus. Results The patient made an excellent recovery, became seizure free, had improved left-sided strength and was discharged home shortly after. Conclusion This case illustrates a potentially life-saving technique for the treatment of refractory status epilepticus. Multiple subpial transections and other neurosurgical intervention should be considered for patients with status epilepticus. When localization with surface electrodes is poor, especially in eloquent cortex, subdural grid recording can be used to direct focal resection and/or multiple subpial transections to minimize neurological deficits. A review and summary of previously published neurosurgery cases for status epilepticus is discussed. Keywords Neurosurgery Multiple subpial transections Status epilepticus Epilepsia partialis continua

Introduction

Y.-t. Ng (&) Division of Pediatric Neurology, Barrow Neurological Institute/ St. Joseph’s Hospital and Medical Center, 500 West Thomas Road Suite 400, Phoenix, AZ 85013, USA e-mail: [email protected] Y.-t. Ng R. E. Bristol K. A. Smith Pediatric Neurology/Neurological Surgery, Barrow Neurological Institute/St. Joseph’s Hospital and Medical Center, 500 West Thomas Road Suite 400, Phoenix, AZ 85013, USA D. V. Schrader Division of Pediatric Neurology, British Columbia’s Children’s Hospital, University of British Columbia, Vancouver, BC, Canada

In terms of the duration of seizure activity, the definition of status epilepticus has recently become controversial [1]. It has been proposed that any one seizure or multiple seizures without full recovery of consciousness lasting more than 5 min (as opposed to the more traditional 20–30 min) should be classified as status epilepticus. Regardless of the strict definition, we present a case of status epilepticus refractory to medical treatment that was successfully treated neurosurgically and address this treatment option for such patients. The incidence of status epilepticus is estimated to be between 60,000 and 150,000 patients per year, highest in children less than one year of age (as high as 135–156/

Neurocrit Care (2007) 7:86–91

100,000/year) [2, 3]. Most cases occur in the pediatric population. About a quarter (24%) of children present with status epilepticus, as their first presentation of new onset seizure, although many of these children do well [3]. The overall mortality rates associated with status epilepticus during hospitalization or within 30 days of status epilepticus (short-term mortality) across all age groups is estimated at between 7.6 and 22% [3]. However there is a distinct subgroup of patients who have refractory status epilepticus who are extremely difficult to treat. In fact, the long-term mortality (mortality within 10 years following initial survival after 30 days) with status epilepticus is 43% [3]. In the Veteran Affairs Study, 65% of patients with subtle status epilepticus died within 30 days of status epilepticus, compared with 27% of patients with overt status epilepticus [4]. Of patients presenting with status epilepticus, almost 50% are newly diagnosed with epilepsy. Febrile seizures and infections of the nervous system are common predisposing factors in children, whereas cerebrovascular accidents are the most common cause in the elderly. An underlying structural lesion is more common in adults than in children. Death, however, is more likely to result from the underlying etiology than from the complications of status epilepticus itself. Irreversible changes occur in neurons after 20 min of seizure activity, and cell death begins after 60 min [5]. Patients also suffer stress on cardiac, respiratory, renal, and other metabolic systems. Status epilepticus that initially fails to respond to lorazepam or diazepam and subsequently fails to respond to second-line therapies such as phenytoin is defined as refractory [6]. Pharmacotherapy remains the first-line treatment for status, but patients with refractory status epilepticus and no underlying structural abnormality are a management challenge. Even when seizure activity can be controlled temporarily with medication, some patients experience recurrent status epilepticus with changes in medication or dose reductions. A randomized controlled trial comparing lorazepam alone, phenytoin alone, diazepam and phenytoin together, and phenobarbital demonstrated essentially equal effectiveness of these agents [4]. Despite the known difficulties with multiple medical therapies including high-dose suppressive therapies and persistently high mortality rates with refractory status epilepticus, other novel treatments, in particular neurosurgery is still rarely discussed. A recent detailed review of prolonged, refractory status epilepticus, included discussion of ‘‘less mainstream’’ treatments such as: very high dose phenobarbital, isoflurane, ketamine, ACTH, vigabatrin, the ketogenic diet, plasmaphoresis, intravenous immunoglobulin and steroid therapy [7]. Even within such a detailed discussion of unproven therapies, neurosurgery was only briefly raised which then actually included

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essentially only deep brain stimulation and the vagus nerve stimulator despite a growing awareness and literature on the successful use of neurosurgery in the treatment of status epilepticus. The use of multiple subpial transections (MSTs) was originally described by Morrel et al. as a ‘‘cortical-sparing’’ technique over eloquent cortex [8]. MSTs are performed by making vertical cuts in the cortex at 3–5-mm intervals to interrupt the epileptogenic spread along horizontal fibers, while sparing vertically oriented functional fibers. The theory behind this therapeutic technique is based upon maintaining the columnar organization of the cerebral cortex while disrupting the lateral communication of epileptogenic discharges [8]. We have previously advocated the use of neurosurgical focal resection in the treatment of various forms of status epilepticus, including status gelasticus, although our original series of patients did not include the (successful) use of MSTs [9–12]. There has only been a single case report of the use of isolated MSTs in epilepsia partialis continua secondary to focal cortical dysplasia [13]. There is a case report of complex partial status epilepticus in a 6-year-old boy who was treated initially unsuccessfully by MSTs. He then underwent ‘‘frontal lobe disconnection’’ and became seizure free, unfortunately complicated by moderate left hemiparesis with cognitive impairment [14]. We recently reported the only case as far as we are aware, of isolated MST procedure in the successful treatment of a patient in (non-convulsive) status epilepticus [15].

Case report A 48-year-old Hispanic man was with several hours of recurrent left upper limb and hand jerking without loss of awareness. He had a history of refractory, symptomatic, localization-related epilepsy secondary to a presumably low-grade glioma within the right superior, posterior frontal head region (Figs. 1 and 2). The tumor had been diagnosed 15 years previously and had been biopsied and treated with radiotherapy in another state. The patient was continuing to have daily partial seizures on both phenobarbital and phenytoin. He was also on temozolomide chemotherapy and ondansetron. The patient had been developing a progressive left hemiparesis over many months. There was no other significant medical history apart from a prosthetic left eye from a previous traumatic accident. His seizure activity quickly progressed to epilepsia partialis continua that was purely motor, consisting primarily of continuous twitching of all of the fingers in his left hand and also flexion of the wrist and to a lesser extent forearm. This persisted for several days intermittently and

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Fig. 1 Axial FLAIR sequence brain MRI scan showing the previously biopsied tumor with prominent edema


left upper limb motor cortex was involved. Four days after admission, the decision was made to place a large subdural grid on the right hemisphere over the tumor, for both better seizure localization and for cortical mapping. A craniotomy, extending over the superior fronto-parietal region was performed to place a large 6 by 8, 48-electrode subdural grid over the superior aspect of the middle of the central sulcus, across the motor and sensory strips (Fig. 3). The tumor underlay predominantly the superior, anterior quadrant of the grid. The patient was then transferred to our Epilepsy Monitoring Unit for intra-cranial, video-EEG monitoring. Near continuous seizure activity was seen over the most superior and anterior eight electrodes (33–36 and 41–44) although there was involvement of almost the entire grid (Figs. 3 and 4). Even during relatively quieter periods, periodic lateralizing epileptiform discharges (PLEDs) were seen arising from the superior, anterior electrodes (34, 42, and 43). Somewhat surprisingly, cortical mapping only localized motor involvement from the electrodes in the middle of the grid (26–28 and 18–21) which resulted in left hand and forearm contraction (Fig. 3). This area of eloquent cortex involved the border of the tumor and had very active epileptiform activity throughout. On day 10 of his admission, the patient then underwent removal of the subdural grid. Tumor resection was performed at the same time, which was guided by pial division and following of the sulci to reveal the motor strip, compressed behind the tumor. Fairly extensive MST was then performed over most of the exposed motor and sensory strips (as defined from the cortical mapping and also presumed areas of sensory and other motor cortex). Neuropathology of the tumor showed that the premotor lesion consisted of recurrent astrocytoma while the enhancing nodule was consistent with focal anaplastic progression. The patient made an excellent recovery and became seizure free. There was no residual deficit and in fact demonstrated some improvement in the strength of his left side, presumably due to relief of tumor compression and surrounding edema (Fig. 1).

Discussion Fig. 2 Sagittal T1–weighted brain MRI scan with contrast showing slight enhancement of the tumor

was refractory to maximal levels of intravenous phenytoin and phenobarbital. Levetiracetam was added and titrated rapidly orally to a total daily dose of 2,000 mg with no improvement. In addition, the patient developed complications of hypotension and fever. As was fairly typical for epilepsia partialis continua, scalp EEG recordings did not show ictal discharges, although it was fairly clear that the

For patients who continue to have status epilepticus despite receiving multiple medications, including barbiturate anesthesia, surgical intervention is another option. Although previously thought of as a ‘‘final’’ option, this should not necessarily be the case. As our case illustrates, tumor resection and MSTs over eloquent cortex turned out to be a curative epilepsy surgical procedure with good outcome. There was some crowding and posterior displacement of the motor strip likely secondary to the tumor itself as well as surrounding tissue edema. Subdural cortical


Fig. 3 Schematic diagram of where the subdural grid was placed. The maximal seizure activity was seen over the superior, anterior quadrant (overlying most of the tumor, shown by circle) and the only motor area found was in the center of the grid, with left forearm and hand flexion

grid mapping gave our neurosurgeon the confidence to fully resect the tumor and perform generous MSTs, knowing that the areas of underlying cortex should not lose function. Surface electrodes are useful in localizing seizure foci in many patients, but intracranial depth electrodes and implantable grids provide more definitive localization [16]. When multiple subpial transections are performed, the increased specificity for localization greatly decreases risk to eloquent cortex. Intraoperative electrocorticography (ECoG) can also be used to guide resection, although the amount of tissue that needs to be removed may be

Fig. 4 Subdural grid EEG recording showing near continuous epileptiform discharges, maximal over the superior, anterior electrodes

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overestimated [17]. Furthermore, the use of ECoG is limited in patients acutely suffering from status epilepticus. We favor the use of subdural grids for the ability to record for an extended period. Rather than restricting the recording session to the length of surgery, grids can be left in place while medications are adjusted and patients undergo provocative testing. Grid mapping also helps to identify eloquent motor regions that can be preserved. In our case, early surgical intervention was performed, bearing in mind that many other institutions may have performed more conventional treatments such as high-dose suppressive therapy and inhalational anesthesia first. The fact that there was a clear causative lesion (of the epilepsia partialis continua) and the patient’s interest in neurosurgical resection prompted our clinical decision. Many centers do not favor MSTs as much and possibly the outcome would have been the same in this patient simply from isolated focal corticectomy and tumor removal; however we have had success even with MSTs performed in isolation. We recently described the successful cessation of nonconvulsive status epilepticus in a 29-year-old woman who had failed high-dose prolonged, suppressive barbiturate therapy [15]. Following subdural grid monitoring (withdrawal of care had previously been discussed with her family who refused) which localized the seizure focus as over left-hemispheric, eloquent cortex centered around the Rolandic fissure, MSTs without resection were the only option. The patient underwent MSTs in the angular gyrus, superior temporal gyrus and suprasylvian frontal lobe and

FMSE, focal motor status epilepticus; CPSE, complex partial status epilepticus; RE, Rasmussen encephalitis; HD, hemicortical dysplasia; IS, infantile spasms, FCD, focal cortical dysplasia; EPC, epilepsia partialis continua; MSTs, multiple subpial transections; NCSE, non-convulsive status epilepticus; GCSE, generalized convulsive status epilepticus; VNS, vagus nerve stimulation

Winston et al. [29] Patwardhan et al. [30] VNS CPSE GCSE 13 yrs, 30 yrs 2

Non-lesional

Xa et al. [23]

Ng et al. [9] Lesionectomy

Corpus callosotomy GCSE

EPC 2 yrs 1

Cavernous malformation

25 yrs 1

Non-lesional

Ng et al. [9, 12] Transcallosal, endoscopic resection 30 mo 1

Hypothalamic hamartoma

Status gelasticus

Molyneux et al. [13] Bristol et al. [15] Isolated MSTs EPC NCSE 19 yrs, 29 yrs 2

FCD Non-lesional

Desbiens et al. [25] Ng et al. [10] Costello et al. [26] D’Giano et al. [14] Xa et al. [23] Focal (cortical) resection MSTs FMSE EPC CPSE 3 mo–36 yrs 8

Non-lesional MRI scan ± FCD (pathology)

Alexopoulos et al. [22] Ng et al. [9] Ng et al. [11] Xa et al. [20] Gorman et al. [27] Krsek et al. [28] Focal (cortical) resection CPSE FMSE Tonic 2 mo–31 yrs 8

FCD (lesional on MRI), Tuberous sclerosis - Multiple tubers

Alexopoulos et al. [22] Duane et al. [10] Hemi-spherectomy FMSE CPSE IS 5 mo-6.5 yrs 7

Hemimegencephaly Encephalomalacia, RE, HD

Surgical procedure Seizure type Diagnosis Age(s) Number of cases

Table 1 Summary of previously published neurosurgery performed for different forms and etiologies of status epilepticus

was subsequently weaned from barbiturates and discharged home, seeking employment [15]. She did extremely well, particularly in a patient with subtle status epilepticus which has been shown to have a poorer prognosis than overt convulsive status epilepticus [4]. Resection of seizure foci and hemispherectomy are options for focal abnormalities or for patients with a damaged hemisphere with less functional significance as we have previously reported [10]. However, corpus callosotomy and multiple subpial transections should be considered for patients without a discrete underlying lesion, especially when the epileptiform discharges localize to eloquent cortex. The use of MSTs as a major treatment in refractory status epilepticus had essentially never been described. Its use in the treatment of refractory epilepsy, although highly effective is difficult to evaluate in isolation as among the majority of reported cases, MSTs were performed with focal resection [8, 18]. In a meta-analysis on the efficacy of MSTs on patients with intractable epilepsy, in the group where MST was preformed with focal resection, the >95% reduction in seizure rate was between 68 and 87% of patients, whereas among patients who underwent MST without resection, the rate was between 62 and 71% [18]. Marked seizure reduction is of course still very different to complete seizure freedom in terms of final outcome. We have previously reported the case of a non-lesional, 4-yearold girl in life-threatening complex partial status epilepticus who failed MSTs and subsequently had successful focal resection who has now been seizure-free without any deficit for over 4 years [11]. Hence although MSTs can be highly effective, it should probably remain a second choice option to focal resection unless eloquent cortex is involved. As our two discussed cases highlight, MSTs should be considered as a different neurosurgical surgical option over the epileptogenic zone, either in isolation if only eloquent cortex is involved or in conjunction with focal cortical resection when the epileptogenic zone involves both areas of eloquent and non-eloquent cortex. Epilepsia partialis continua remains a subject of much speculation, at times a diagnostic and therapeutic challenge with persistently poor prognosis. It has been argued that epilepsia partialis continua is a form of focal cortical myoclonus, although subcortical mechanisms have also been proposed [19, 20]. As in our case, the scalp EEG often does not show correlating ictal patterns or epileptiform discharges even during the seizure. Two comprehensive studies on epilepsia partialis continua found abnormal ictal EEG patterns only in six of 16 and nine of 11 patients, respectively, during the patients’ clinical seizures [19, 21]. Even then, many of the abnormalities recorded were not spike and slow wave discharges. Certainly a normal or ‘‘negative’’ EEG does not exclude epilepsia partialis continua. The vast majority of these patients do not of


Author

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course undergo invasive monitoring. It is interesting to note that our patient showed PLEDs on the invasive grid EEG even though his scalp EEG was ‘‘negative.’’ It is possible that the majority or even all patients with epilepsia partialis continua on invasive EEG monitoring would show similar PLEDs over the focal motor area of origin, thus ending any persistent debate as to their cortical origin. Several authors have discussed factors that determine the timing of surgical intervention for status epilepticus, and although probably not yet a mainstream consideration in the treatment of refractory status epilepticus, there certainly is a growing awareness and literature for consideration of this ‘‘new,’’ highly effective treatment option [9, 16, 19–27]. Table 1 summarizes the previously published 30 cases of different neurosurgical procedures performed, including vagus nerve stimulation (in two patients) for various forms of status epilepticus and different etiologies. The ages of the patients included several infants through to a 36-year-old adult. There were varying degrees of success but with 21 of these 30 (70%) refractory seizure patients becoming seizure-free. Prolonged medical management is associated with other complications, such as hypotension, myocardial and respiratory depression, development of deep venous thrombosis and pulmonary emboli and increased risks of infection and poikilothermia. Delaying surgery may be an option for patients whose status epilepticus is controlled with medication. However, we believe that surgical intervention should be considered earlier in the course of refractory status epilepticus. In our patient, the natural progressive option of high-dose suppressive medical therapy with its complications was avoided and at least a shortterm cure of his epilepsy was the outcome.

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