Epilepsy associated with Leukoaraiosis mainly affects temporal lobe: a casual or causal relationship?
Introduction
Epilepsy and stroke are common neurologic disorders and their association has been extensively documented (Hauser et al., 1991, Tellez-Zenteno et al., 2005). Seizures occurring after a cerebrovascular event should be considered “early” if they occur at the onset or within 7 days (Beghi et al., 2010); otherwise, they should be considered late. “Early” or “provoked” seizures are not necessarily followed by epilepsy; conversely, “late” or “remote symptomatic” seizures are the expression of an enduring brain predisposition to develop seizures (Kessler et al., 2002). This is in keeping with the results of a population-based study (Hesdorffer et al., 2009) that documented a significantly higher risk of recurrence for individuals with a first unprovoked post-stroke seizure, compared to those with a first acute symptomatic seizure. According to the new operational definition of epilepsy (Fisher et al., 2014), the occurrence of the first unprovoked seizure is sufficient to diagnose post-stroke epilepsy.
Several studies have elucidated epidemiologic and prognostic characteristics of post-stroke seizures and vascular epilepsy (Awada et al., 1999, Bladin et al., 2000, Lamy et al., 2013, Graham et al., 2013, Huang et al., 2014), but little attention has been dedicated to epilepsy associated with leukoaraiosis (Schreiner et al., 1995, Maxwell et al., 2013) in the absence of a manifest stroke. Data about the involvement of blood vessels in epileptogenesis come from experimental studies on animal models and surgically removed human brain tissue (Mott et al., 2009, Biagini et al., 2008, Gualtieri et al., 2012, Gualtieri et al., 2013). In particular, focal hippocampal and extra-hippocampal lesions, likely of ischaemic origin, were visible after pilocarpine-induced status epilepticus in adult rats, and these lesions contributed to the development of epileptogenesis (Biagini et al., 2008, Gualtieri et al., 2012). Clinical and electroencephalographic features of epilepsy occurring in the context of cerebrovascular disease of any kind have been poorly investigated. This is probably due to the lack of collaboration between stroke physicians and epileptologists: this led to focus on studies on the clinical characteristics of strokes rather than on electro-clinical features of seizures in post-stroke epilepsies. In the present study we identified features of both cerebrovascular disease (e.g. aetiology of strokes, involved brain territories, severity of leukoaraiosis) and epileptogenic focus (electro-clinical data) in order to compare anatomo-electro-clinical findings between patients with epilepsy associated with leukoaraiosis only (EAL) and patients with epilepsy associated with a well defined vascular lesion, i.e. post-stroke epilepsy (PSE).
Section snippets
Methods
Two hundred and eighty-three subjects consecutively observed from January 1, 2000 to March 31, 2014 in three Epilepsy Centres (located in Reggio Calabria, Catanzaro, and Catania, Italy) were retrospectively evaluated. Patients were recruited from both Emergency Department and an epilepsy centre in Reggio Calabria, and from epilepsy centres only in Catanzaro and Catania. According to the Italian regulations, this observational, retrospective study did not require approval by ethics committee.
Results
Of the 283 screened subjects, 117 were included, 166 were excluded and causes of exclusion are detailed in Figure 1. Fifty-eight out of 117 included patients presented with PSE, while 59 had EAL. Explicative cases of EAL (Figure 2) and PSE (Figure 3) are reported. Figure 2 illustrates the case of a 70-year-old woman who presented with seizures consisting in a “burning sensation” ascending from abdomen to head, followed by unresponsiveness. Periventricular and deep white matter FLAIR
Discussion
This is the first study aimed to correlate clinical, neurophysiological and imaging data in subjects with epilepsy and cerebrovascular disease and to compare features of epilepsy in stroke patients and in subjects with leukoaraiosis only. This study has three main findings. First, about half subjects with epilepsy showed leukoaraiosis only. Second, EEG abnormalities were associated with a higher probability of having PSE. Finally, when comparing PSE and EAL groups, lobar localization was
Conclusion
Our data suggest that in a proportion of subjects a causal relationship between vascular lesion and epilepsy is straightforward and the term PSE seems appropriate. Conversely, in a large amount of subjects with leukoaraiosis only, a casual association between vascular lesions and epilepsy cannot be excluded. Further studies are needed to clarify this topic.
Disclosure of conflicts of interest
Dr.Beghi serves on the editorial advisory boards of Amyotrophic Lateral Sclerosis, Clinical Neurology & Neurosurgery, and Neuroepidemiology; he has received funding for travel and speaker honoraria from UCB-Pharma, Sanofi-Aventis, GSK, EISAI; funding from GSK for educational presentations, and from AIFA, Sanofi-Aventis, Janssen-Cilag, EISAI, Lombardy Region, Istituto Superiore di Sanità and American ALS Association for the coordinating activity ofRCT and observational study protocol.
All the
Acknowledgements
Sara Gasparini, Edoardo Ferlazzo, Ettore Beghi, Vito Sofia, Laura Mumoli, Angelo Labate, Vittoria Cianci, Daniela Fatuzzo, Marina Angela Bellavia, Antonio Gambardella and Umberto Aguglia are part of the epilepsy study group of the Italian Neurological Society that encouraged this study.
References (36)
- et al.
Family history and frontal lobe seizures predict long-term remission in newly diagnosed cryptogenic focal epilepsy
Epilepsy Res.
(2013) - et al.
Increased perivascular laminin predicts damage to astrocytes in CA3 and piriform cortex following chemoconvulsive treatment
Neuroscience
(2012) - et al.
Over-expression of laminin correlates to recovery of vasogenic edema following status epilepticus
Neuroscience
(2014) - et al.
Prevalence and subtypes of radiological cerebrovascular disease in late-onset isolated seizures and epilepsy
Clin. Neurol. Neurosurg.
(2013) - et al.
Kainic acid and 3-Nitropropionic acid induced expression of laminin in vascular elements of the rat brain
Brain Res.
(2010) - et al.
Epileptic seizures in subcortical vascular encephalopathy
J. Neurol. Sci.
(1995) - et al.
Cerebral microinfarcts: the invisible lesions
Lancet Neurol.
(2012) - et al.
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration
Lancet Neurol.
(2013) - et al.
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial TOAST. Trial of Org 10172 in acute stroke treatment
Stroke
(1993) - et al.
Age at onset predicts good seizure outcome in sporadic non-lesional and mesial temporal sclerosis based temporal lobe epilepsy
J. Neurol. Neurosurg. Psychiatry
(2011)
Diagnostic and Statistical Manual of Mental Disorders
Committee on Nomenclature and Statistics
Late epileptic seizures after cerebral infarction
Acta Neurol. Scand.
Recommendation for a definition of acute symptomatic seizure
Epilepsia
Epileptic seizures following subcortical infarcts
Cerebrovasc. Dis.
Proepilpetic influence of a focal vascular lesion affecting enthorinal cortex-CA3 connections after status epilepticus
J. Neuropathol. Exp. Neurol.
Seizures after stroke: a prospective multicenter study
Arch Neurol.
Proposal for revised clinical and electroencephalographic classification of epileptic seizures
Epilepsia
Proposal for Revised Classification of Epilepsies and Epileptic Syndromes
Epilepsia
Cited by (40)
Strategic infarct location for post-stroke seizure
2022, NeuroImage: ClinicalLate-onset epilepsy predicts stroke: Systematic review and meta-analysis
2021, Epilepsy and BehaviorModeling poststroke epilepsy and preclinical development of drugs for poststroke epilepsy
2020, Epilepsy and BehaviorSeizures in the context of occult cerebrovascular disease
2020, Epilepsy and BehaviorCerebrovascular disease burden in late-onset non-lesional focal epilepsy
2019, SeizureCitation Excerpt :It is a mainly age-related feature and is particularly associated with hypertension and diabetes [11]. The relationship between LOE and occult cerebrovascular disease has not been well established as there is limited supporting clinical evidence [4,8–10]. In the absence of a manifest stroke, some authors have put forth the theory that epilepsy may be associated with leukoaraiosis; however, there is no consensus on the epileptogenic role of this abnormality [9,10,12,13].