Intractable epilepsy and mild brain injury:

incidence, pathology and surgical outcome

‡ BAH M AN JABB ARI, ‡ OLGA

P ROK HORE N KO, y KAVE H KH AJAVI

and } HE RN AN DO M E N A

y Department of Neurology and Neurosurgery Service, Walter Reed Army MedicalCenter, Washington, DC, USA‡ Uniformed Services University, Bethesda, MD, USA} Department of Neuropathology, Armed Forces Institute of Pathology, Washington,DC, USA

(Received 18 December 2000; accepted 1 August 2001 )

Objective: To study the role of mild brain injury in intractable epilepsy.Methods: The medical charts of 86 patients who underwent surgery for intractable epilepsy werereviewed in regard to the history of mild brain injury, pathology and surgical outcome.Results: Nine of 86 patients had a previous history of mild brain injury (10.4%) compared to 2.5% of 80age and sex matched controls. Six of nine patients had non-neoplastic and three had neoplastic lesions.Post-surgical outcome was excellent in eight of nine patients (Engel class IA).Conclusions: The incidence of mild brain injury was 4-times higher in patients with intractable epilepsycompared to asymptomatic controls. The pathology was variable but in four of nine patients it wascompatible with the described pathology in traumatic brain injury. Both groups, with or without braininjury, had good surgical outcome (88% versus 70%).

Introduction

Head injury is a major cause of morbidity in industrialized societies. In the US,400 000± 500 000 individuals are hospitalized every year for traumatic brain injury

(TBI) [1, 2]. Consequences of head injury often result in neurological symptoms,increased disability and dependency on family members. The direct cost of TBI tothe US economy has been estimated at more than $4 billion annually [3].

Seizures and epilepsy are well known complications of TBI. Yablon’s [4] recentreview depicts important features of post-traumatic epilepsy (PTE). Trauma mayaccount for 20% of symptomatic and 5% of all epilepsies [5]. Approximately one halfto two-thirds of post-traumatic seizures manifest during the first 12 months and75± 80% within the first 2 years after trauma [6]. Early seizures occur in 5% of adultsand 10% of children. PTE occurs in 40± 53% of penetrating and 5± 20% of closedhead injuries [7± 9].

Although PTE has been extensively studied, the role of trauma in intractableepilepsy has not been well investigated. Temporal lobe epilepsy (TLE) is the mostcommon form of intractable epilepsy in adults. Approximately 30% of the patients

Brain Injury ISSN 0269± 9052 print/ISSN 1362± 301X online # 2002 Taylor & Francis Ltdhttp://www.tandf.co.uk/journals

DOI: 10.1080/02699050110102086

Correspondence to: Bahman Jabbari, MD, Department of Neurology, 4301 Jones Bridge Rd.,Bethesda, MD 20814, USA. e-mail: bjabbari@usuhs.mil

BRAIN INJURY, 2002, VOL. 16, NO. 6, 463 ± 467

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with TLE fail medical treatment. This retrospective case-control study attemptsto define the role of mild brain injury in the refractory epilepsy of temporallobe origin.

Methods

The records of all patients who had an anterior temporal lobectomy at Walter ReedArmy Medical Center (1985± 1999) were reviewed for management of intractableepilepsy. The charts were screened for history of mild head injury. Being a militaryinstitution, a history of trauma was routinely asked and documented (when present)in detail. For this study, mild brain injury was defined as a post-traumatic statemeeting these criteria: Loss of consciousness <6 hours, post-traumatic amnesia<24 hours, Glasgow Coma Scale 13± 15.

The exclusion criteria consisted of LOC beyond 6 hours, PTA beyond 24 hours,GCS <13 and evidence of multi-lobar post-traumatic encephalomalecia in MRI.All patients had comprehensive pre-surgical evaluation, which consisted of 3± 7 daysof video-electroencephalogram (EEG) monitoring, MRI, neuropsychologicalevaluation and Wada test. EEG localization was obtained by surface or subduralrecordings. The surgical outcome was assessed 6 weeks, 6 months, 12 months aftersurgery, and, thereafter, every year (at least 2 years). Outcome assessment includedevaluation of seizures frequency and intensity, quality of life, neuropsychologicalevaluation, and follow-up MRI.

Eighty age and sex-matched asymptomatic subjects were interviewed and askedspecifically about a history of mild brain injury. The subjects were dependentsof active duty personnel to match the studied population. The data from theseindividuals was used as control data for this study.

Results

The total number of patients with intractable TLE epilepsy (with or without headinjury) was 86, from which 66 were female. The female predominance reflected thefact that most of the patients were dependents of active duty soldiers. Nine of86 (10.4%) patients, five males and four females, had a history of mild head injury.Two of the 80 control subjects (2.5%) experienced this form of head trauma. In thepatient group, LOC ranged from 5 minutes to 6 hours and PTA ranged from 3± 24hours. Demographic information of patients, type of trauma, age at surgery and ageat the time of first seizure is presented in table 1. The age at the time of head traumavaried from 5± 24 years (mean 11.5) and the onset of seizures after head injury froma few hours to 27 years (mean 8.75). In two patients (table 1: patients 3 and 4) thelong remitted (years) seizures of infancy recurred within weeks after head trauma.

Table 2 shows the seizure type, MRI findings, site of surgery, temporal pathol-ogy and surgical outcome. MRI was abnormal in six of nine patients. Pathologicalexamination in six patients showed non-neoplastic lesions and in three disclosedneoplasms (table 2). Non-neoplastic lesions included mesial temporal sclerosis(MTS), gliosis, mild inflammation, leptomeningeal fibrosis, ischemic neuronalinjury and an angioma. The non-tumour group had an earlier age of trauma(mean 5.4 years) compared to the tumour group (mean 17.2, table 1). Amongthe 77 patients without head trauma, 30 had gliosis/MTS (37%) and 12 (15%)had tumours. An excellent outcome, Engel’ s class A [10] was noted in 88% of

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the patients with trauma and 70% without trauma. One patient with Engel Class IIBoutcome had a grade II glioma.

Discussion

Approximately 12% of complex partial seizures in the general population could beattributed to head trauma [11]. In one study, the authors reported a history of headtrauma (severity not mentioned) in 16% of 162 patients with intractable temporalepilepsy [12]. A history of traumatic mild brain injury has been found in 10.4% ofpatients. This figure is four times higher than that of the asymptomatic controls.

Intractable epilepsy 465

Table 1. Age at surgery, time of trauma, seizure onset, type of trauma and past medical history

Age at the Age at the Age at the

time of time of time of

surgery head trauma seizure onset Type of head Past medical

Gender (years) (years) (years) trauma history

1 Male 18 6 13 Bicycle accident

2 Female 47 0.74, 14 41 Falling accident, hit the wall

3 Male 25 5 (1) at birth Head injury in amusement Wrapped cord

(2) at 5 years* park around the

neck at birth

4 Male 16 15 (1) at 9 Hit by baseball bat Bacterial

(2) at 15** meningitis at

8 months

5 Female 26 10 16 Fell from swing Neonatal

meningitis

6 Male 36 24 33 Parachuting injury

7 Female 31 5 23 Kicked by a horse

8 Female 29 17 24 Sport trauma

9 Male 24 13 16 Fell from a tree

* Sz at birth to 6 months, Sz free until HI (age 5).** Sz onset at 9 years. Sz free after age 11, Sz started again after trauma (age 15).

Table 2. Age, site of surgery, pathology, and surgical outcome in patients with history of mild brain injury

Age at the

time of

head injury Site of Surgical

(years) MRI surgery Pathology outcome

1 6 Hippocampal asymmetry, LTL Mild inflammation, gliosis, neuronal IA

increased signal changes

2 14 N LTL Hippocampal sclerosis IA

3 5 Encephalomalacia with glial LTL Mild inflammation, gliosis, neuronal IA

scarring changes

4 15 LTL mass LTL Astrocytoma, grade II IIB

5 10 N RTL Anoxic ischemic lesion IA

6 24 LTL mass LTL Ganglioglioma IA

7 5 Right hemiatrophy, increased RTL Mild inflammation, gliosis, fibrosis IA

signal

8 17 RTL mass RTL Angioma IA

9 13 N LTL Oligodendroglioma IA

LTL = left temporal lobe, RTL = right temporal lobe.

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The pathological findings of mild-to-moderate brain injury in the late stageinclude non-specific gliosis, neuronal cell loss, subtle inflammatory and ischemicchanges and hemosiderin deposits [13]. In this study, four of nine patients disclosedsimilar findings in the resected temporal tissue, with one of four depicting typicalfeatures of MTS. Earle et al. [14], in the original description of incisural sclerosis(mesial temporal sclerosisÐ MTS), proposed a role for head injury. MTS is the mostcommon pathology in intractable temporal lobe epilepsy and was reported in onestudy to be as high as 65% [15]. In another study, five of 14 patients with headtrauma and intractable seizures localized to the mesial temporal lobe showed theMTS pathology [13]. The authors defined MTS as more than 50% neuronal loss inthe CA1 sub-field and evidence of reorganization in the dentate molecular layer.Other authors have noticed that patients with seizures occurring around the timeof initial injury (trauma included), more often showed MTS in pathological ex-amination [12]. Marks et al. [11] reported that patients with MTS had an earlierage of head trauma compared to those who had only gliosis. Patients with MTS orgliosis had an earlier age of head trauma compared to the group with tumours (table2). The true incidence of MTS in population is possibly higher than that depictedhere, since these patients had piece-by-piece rather than en block resection.

Four of the patients had tumours. Some investigators have suggested a relation-ship between head trauma and cerebral neoplasm. In one study of 1178 gliomasand 330 meningiomas, an elevated risk for males was found between trauma anddevelopment of meningiomas [16]. Others noted that some patients with glio-blastoma multiforme might be at risk, if severe head injury occurred after age 15years [17]. Inskip et al. [18] investigated the incidence of brain tumours in 228 055Danish residents with a history of head trauma (including concussion) and followedthem for 8 years. An overall increased risk was found for hemangioblastomas andhemangiomas, but, when the first year was excluded, the incidence was not higherthan that of the normal population. Perez-Diaz et al. [19] reported two patientswith head trauma in whom an oligodendroglioma developed at the site of aprevious scar. In contrast with the aforementioned reports, Annegers et al. [20]did not find an increased incidence of brain tumours in a study of 2953 patientswith head injury.

Marks et al. [11] found that post-surgical outcome was considerably better inpatients with post-traumatic medial-temporal pathology compared to those withneocortical pathology. These patients’ surgical outcomes were good (eight of ninewere Class IA), but their small number would not allow outcome assessment basedon the location of temporal pathology.

In conclusion, this retrospective study shows a higher incidence of mild braininjury in patients with intractable temporal epilepsy compared to the control sub-jects. These patients had variable pathologic lesions and good post-surgical out-come. It is hoped that this data, despite its limitation, can serve future prospectiveinvestigations.

Acknowledgement

The data presented in this paper are private views of the authors and should not beconstrued as the views of the Department of Defense, US Army or the UniformedServices University of the Health sciences.

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