MRI-negative frontal lobe epilepsy with ipsilateral akinesia and reflex activation

ARTICLE

Auteur(s) : Stephen Malone¹, Ian Miller¹, Prasanna Jakayar¹, Trevor Resnick^1,2, Sanjiv Bhatia^1,3, Michael Duchowny^1,2

¹Brain Institute and Comprehensive Epilepsy Program, Miami Children’s Hospital
²Department of Neurology, University of Miami Miller School of Medicine
³Department of Neurosurgery, University of Miami Miller School of Medicine, Miami Florida, USA

Article reçu le 23 Mai 2008, accepté le 28 Septembre 2008

A 17-year-old, right-handed male presented for management of intractable, partial epilepsy. Seizures had begun at age six years and were characterized by brief periods of unresponsiveness and fumbling hand movements, preceded by an aura of vague cephalic sensations or more rarely, an ill-defined sensation in both hands that began minutes or hours before motor seizure-onset. At onset, he complained of an inability to use his right hand. Awareness was preserved during his seizures, which typically lasted 10-20 seconds, and he was mute throughout. Head turning to the right, with accompanying clonic jerking of the left arm accompanied some seizures. Secondary generalized events occurred infrequently, but ictal falls and injuries were common. Seizure frequency was at least weekly. His longest seizure-free interval was two years. Failed medications included carbamazepine and oxcarbazepine, both maintained at high doses, at the time of surgical intervention. Compliance was demonstrated by therapeutic plasma levels of anticonvulsants. Drug side effects included diplopia and severe fatigue.

The patient had been born at term, by elective C-section, after an unremarkable maternal pregnancy. He had borderline hypothyroidism as a younger child. Developmental milestones were normal and he was an above-average student. There was no family history of seizures. His sister has neurofibromatosis type 1. Neurological examination revealed two, small, “café au lait” patches, but no other stigmata of neurofibromatosis. There were no focal neurological abnormalities.

Pre-surgical investigations

His seizures were induced by alternating rapid movements of the hands on two separate occasions, and he consistently described an inability to initiate movement in his right hand at seizure-onset. The earliest observable clinical change was a sudden head tilt/gaze to the right, at times accompanied by atonia of the upper limbs. Longer events evolved into clonic motor activity of the left arm and versive, left, head turning. Secondary generalized tonic-clonic activity accompanied a minority of seizures after drug withdrawal. Speech arrest occurred at seizure-onset, but fluency returned soon after seizure-offset. He remained fully conscious and remembered words spoken during the seizures. Electrographic ictal onset localized to the right frontal and midline regions (figure 2), with later involvement of the contralateral hemisphere during longer events.

Anatomical and functional neuroimaging

PET imaging (FDG/flumazanil) revealed focal hypometabolism in the left mesial temporal and inferior frontal regions. A cluster of seizures had occurred immediately prior to scanning (figure 4). A repeat PET in the interictal state revealed bi-parietal hypometabolism.

Neuropsychological assessment

Pre-surgical case conference discussion

The presence of bilateral upper limb atonia during some seizures suggested possible bilateral involvement of both motor cortices or unilateral involvement of the supplementary sensorimotor area (SSMA).

The epileptogenic region was hypothesized to involve right premotor cortex and ipsilateral SSMA with secondary involvement of the right motor cortex. Left hemisphere involvement was a concern, given the early, negative, right-hand motor phenomenon, PET findings, and dominant hemisphere dysfunction as suggested by neuropsychological evaluation. However, the hyperperfusion in the right frontal region on ictal SPECT reliably co-localized seizure origin to the region of maximal EEG abnormality.

Surgical plan and procedure, and outcome

Subdural monitoring revealed continuous epileptiform discharges over the right frontal lobe, with a consistent lead from area 6 on the convexity (figure 6), just anterior to the hand motor cortex identified via electro-cortical stimulation mapping. Epileptiform discharges recorded from the right interhemispheric SSMA region were synchronous, but usually less prominent than those recorded over the convexity. Infrequent, independent epileptiform activity was noted in the left interhemispheric and perirolandic regions (figure 7).

Clinical seizures were accompanied by ictal onset from area 6 over the right frontal convexity and spread to the interhemispheric region (figure 8). Electrical stimulation during mapping over area 6 on the convexity induced his habitual seizures but none were induced upon stimulation of the SSMA region. Independent ictal sequences were recorded from the left frontal convexity contacts, and correlated with episodes of bilateral, tonic, limb stiffening lasting seconds and occurring in clusters.

A corticectomy was performed involving the right frontal premotor region. The resection plane included the regions of early, subdural, ictal involvement and the SPECT abnormality (figure 9). The interhemispheric region was not resected and motor cortex was spared.

Immediately post-operatively, the patient was emotionally blunted and exhibited a resting tremor of the upper limb that was exacerbated by movement. The emotional blunting disappeared over the subsequent week, although subtle, bilateral, upper extremity tremor has remained. The patient had a cluster of non-typical seizures, following a brief reduction of anticonvulsant medication on the third and fourth post-operative days. He has been seizure-free for nine months following surgery, and is taking fewer anticonvulsant medications. Quality of life has subjectively improved. Neuropathology of the tissue revealed Palmini type 2b cortical dysplasia.

Discussion

It is of interest that our patient’s seizures were at times provoked by sequenced motor tasks, suggesting an intermittent reflex ictal component. Subdural recording revealed ictal involvement of cortical regions known to subserve the planning and sequencing of ipsilateral and bilateral motor movements (Krakauer and Ghez 2000). In animal studies, the lateral prefrontal area and SSMA participate in the learning phase of coordinated movements; the lateral prefrontal area being preferentially involved (Krakauer and Ghez 2000). In our patient, seizures may have been triggered by prefrontal and SSMA activation during the fine motor tasks offered. Lateral frontal and premotor seizures with a reflex component have been reported previously, usually as a response to different somatosensory stimuli (Manford et al. 1996).

Our case also highlights the need for careful clinical interpretation of preoperative investigations and a consideration of the limitations of each test. Regional abnormalities on FDG/flumazanil PET imaging strongly correlate with the epileptogenic region in children with focal seizures (Muzik et al. 2000). Initial PET imaging performed on our patient implicated the left temporal and inferior frontal areas in seizure-origin. However, the study was performed during the immediate post-ictal period when PET findings are often inconsistent (Chugani et al. 1993). Relative hypermetabolism may also be recorded in the hemisphere of ictal onset, falsely suggesting ‘hypometabolism’ in the contralateral hemisphere (Henry and Chugani 2008).

This case demonstrates some of the challenges in the assessment of MRI-negative, frontal lobe epilepsy, particularly in the presence of discordant preoperative investigations. Our patient had an additional level of complexity due to early symptoms ipsilateral to the seizure focus. The resective strategy was guided primarily by ictal onset zone and maximal interictal subdural EEG abnormalities, and included the region of hyperperfusion on ictal SPECT. Although the right SSMA was significantly involved, the independent, potential epileptogenicity over the left dictated a more conservative corticectomy of the convexity alone; the long term success of this approach in our patient is awaited.

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