INTRODUCTION
The diagnosis of an epileptic encephalopathy like Lennox Gestaut syndrome (LGS) was once considered a final verdict which could not be improved on through surgical procedures. The role of focal resective surgeries in the management of a multifocal symptomatic epilepsy, or rather epileptic encephalopathy, like LGS, is underrecognized and underutilized. The underlying pathomechanism of a symptomatic LGS is the widespread electrographic expression of a focal pathology developing early in life through the rich anatomical networks of a developing brain1. By expelling the culprit substrate, the brain gets the opportunity to effectuate a functional reorganization, resulting in reduction or abolition of seizures as well as improvements in cognitive functions. This exceptional and exciting clinical scenario is elaborated in this narrative of a 20-year-old male diagnosed with LGS and consequent pharmaco- resistant epilepsy. This is the first such report from India wherein unequivocal success has been achieved after focal resective surgery in patients with LGS.
CASE REPORT
The patient is a 20-year-old man, born to unrelated parents by normal vaginal delivery with a birth weight of 3.0 kg, with no perinatal issues and timely attainment of developmental milestones. He performed well in comparison to his peers in terms of activity, interaction and schooling until 7 years of age, when he started experiencing seizures at a frequency of 1-5 per day which ever since have not abated in frequency or intensity. The primary seizure pattern was that of a tonic seizure, characterized by posturing of all four limbs with head drop and loss of awareness. The second most common semiology was that of brief and at times prolonged periods of behavioural arrest and unresponsiveness reminiscent of atypical /complex absences. There was no history of myoclonic jerks, although occasional generalized tonic clonic seizures were seen. He also had intermittent versive seizures, which could manifest in conjunction with other seizure types. With the advent of the seizures, his mother noticed a slow and progressive decline in his scholastic function, ability to take care of himself, and verbal and non- verbal forms of communication. When he was first seen at our facility, he had 3 episodes of seizures per day while on four anti-seizure medications.
The patient was uncooperative, poorly interactive and shy on examination, with preserved motor, cranial nerve and sensory functions. Verbal expression was only a few words. His gait was normal. Visual field assessment and cognitive assessment was attempted, but failed on multiple occasions due to poor patient co-operation. He was subjected to a 24-hour period of epilepsy monitoring which revealed a 2-2.5 Hz spike and wave discharges occupying almost the entire record, with a multifocal albeit predominant posterior distribution. The sleep record showed an accentuation of spikes, generalized paroxysmal fast activity (GPFA) and markedly reduced stage II sleep architecture. Clinical events were recorded, with both the clinical and electrographic patterns being consis-tent with tonic and atypical absence seizures. An electroclinical diagnosis of epileptic encephalopathy / LGS was made (Fig. 1).
A MRI of the brain conducted following an epilepsy protocol revealed ulegyria involving the precuneus and cuneus on the left side. Thinning and hyperintensity involving the left occipital white matter also was noted. There was no evidence of grey matter heterotopias or cortical dysplasia (Fig. 2). The rest of the parenchyma appeared normal. An 18F-FDG PET–CT scan demonstrated asymmetrical hypometabolism of the left hippocampus, left precuneus and left visual cortex (Fig. 3).
Left occipital craniotomy was per formed under general anaesthesia with electroencephalogram (EEG) recording. Upon dural opening, the region of interest showed focal scarring and thickening. An intra operative ultrasonogram was used to visualize the ulegyria and the sulcus within. On visual evaluation, the left occipital lobe showed the area of ulegyria extending from the depth of the sulcus towards the ventricle, which was bordered by thickened greyish firm cortical gyri, was ill-defined and appeared to be merging with normal looking surrounding gyri and white matter. Intraoperative neuronavigation was utilized to draw out the margins for resection. Electrocorticography (ECOG) monitoring with a 4-contact surface strip electrode was performed to identify the region over the lesion which showed spikes in electrical activity. The ulegyric area, which was relatively non-suckable firm and avascular, was resected to the depth at which it was observed to merge with deep white matter under neuronavigation. Post-resection, the walls of the cavity and surrounding margins revealed no spikes, with occasional spikes from distant sites. A post-operative CT scan showed no hematoma or increase in edema. The histopathology of the resected specimen was consistent with ulegyria (gliosis).
DISCUSSION
Lennox Gestaut Syndrome is a severe form of epileptic encephalopathy, the typical phenotype consisting of polymorphic seizures, characteristic EEG features and poor cognitive outcome. The seizure semiology most characteristic of this entity is the tonic seizure which can result in drop attacks, leading to frequent injuries. The severity and burden of seizures along with the dismal cognitive outlook can create an atmosphere of hopelessness and despair in families. A diagnosis can be easily made using an interictal record, along with a recording of clinical events over a period of 24 hours. The presence of atypical slow spike and wave activity in the range of 2-2.5 Hz during wakefulness and marked activation and generalization of spikes and emergence of generalized paroxysmal fast activity during sleep are the cardinal interictal features. The electrography and semiology of the seizures, especially the electrodecrement and fast activity typical of tonic seizures, confirms the diagnosis of this electro-clinical syndrome [2].
The scientific world was for a long time totally averse to even the consideration of a definitive form of epilepsy surgery for remedying this type of malignant epileptic encephalopathy. The presence of widespread electrographic abnormalities in such epilepsies was equated to the presence of a multifocal epileptogenic zone. However, focal electrographic abnormalities are found in about one quarter of patients. Furthermore, focal pathologies are also revealed by neuroimaging in patients with bi-hemispheric and multifocal EEG abnormalities [1]. Al- leviation of falls through interrupting the bi-hemispheric spread of electrical activity by corpus callosotomy was formerly the only surgical option offered to these patients. This mindset and rigid thinking were finally put to rest by the revolutionary concept of focal resections in LGS, advocated first by Wiley and colleagues, with many others following this new path of treatment for seizure freedom[1,3]. The excellent outcomes achieved by these investiga-tors have created a new paradigm for treatment of patients with epileptic encephalopathies; The presence of a focallesion in a patient with LGS,either congenital or acquired early in life,has to be treated by focal resection or disconnection. Their contribution to the “generalized” seizure phenomenology and cognitive impairment has its roots in the rich connectivity of the developing brain serving as a conduit for a widespread representation of a focal process. So, although these pathologies are acquired quite early in life or even antenatally, the clinical presentation may be delayed for several years.
One such focal lesion is ulegyria, which is often the result of perinatal ischemic injury, that is defined upon MRI visualization of a poorly demarcated lesion with a thinned and atrophied cortex, especially towards the deeper parts of the convolution sparing the apical part, along with white matter abnormalities in T2/FLAIR sequences. The lesion gives the gyri a supposedly mushroom like appearance. In 1899 Bresler described this cortical abnormality and named it ulegyria from the Greek word “ule” meaning “scar” [4].
The evolution of this new concept is interesting, as many of the authors even after buying into this new theory chose to base their decisions on electrographic clues, which indeed was the right approach for all refractory epilepsies. This is true of Lee et al and Liu et al, who in their series of patients with a tendency for more lateralized electrographic findings found a formidable benefit from resective surgeries, with approximately 70 percent of patients achieving an Engel class I or II outcome. Also, Usui et al, who studied the role of focal resection inulegyric patients, achieved an Engel class I outcome in 7 out of 10 patients and suggests not to exclude even bilaterallesions from are section[5,6,7]. The procedures performed, namely hemispherectomy, multi lobarresection and lesionectomies, and accordingly the results, varied from patient to patient. The best results were seen with functional hemispherotomy.
In the first steps towards surgical remediation of LGS, only those with predominantly lateralized discharges were accepted as candidates. Later on, it became apparent that an early insult had the potential to generate a large domain of interictal representation in the form of spikes and GPFA. So, an imaging-based approach to patient selection came into place. Nevertheless, the idea of focal resective surgery for epileptic encephalopathies still remains foreign to some and unacceptable to others. The arrival of network-based approaches into the epileptic arena can further enable the epileptologist to identify primary foci in patients with diffuse encephalopathies [7,8,9].
The above case report is intended to reaffirm the role of surgery in treating epileptic encephalopathies, with an emphasis on the remarkable improvement in quality of life and seizure burden after such procedures. The reversal of electrographic abnormalities validates the hypothesis of the electrographic dissemination from a focal pathology being responsible for the condition. Another major revelation is the utility of this approach in patients as old as 20 years of age which opposes the general belief that paediatric patients are the only ones that can benefit. Finally,this case report, we believe will serve to address the closed thinking that is prevalent when it comes to the question of “treatable” or “curable” epilepsies . Many times, vital breakthroughs in the lives of patients are prevented by a disinclination of clinicians to explore all potential treatment options. Every patient with refractory epilepsy needs to be treated with a positive outlook and a collective effort taken at every step to ensure that they are on the path to seizure freedom.
References
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