Network hyperexcitability in a patient with partial reading epilepsy: Converging evidence from magnetoencephalography, diffusion tractography, and functional magnetic resonance imaging

https://doi.org/10.1016/j.clinph.2014.07.033Get rights and content

Highlights

  • By means of multimodal investigations, we delineated the spatial–temporal characteristics of reading-induced epileptic spikes in a patient with partial reading epilepsy.

  • Katakana reading initially induced epileptic activation of the left posterior basal temporal area, and eventually of the whole left fronto-temporal network.

  • Given hyperexcitability in the whole left fronto-temporal network normally recruited for reading, prolonged reading may result in epileptiform discharges and clinical seizures.

Abstract

Objective

The pathophysiological mechanisms of partial reading epilepsy are still unclear. We delineated the spatial–temporal characteristics of reading-induced epileptic spikes and hemodynamic activation in a patient with partial reading epilepsy.

Methods

Magnetoencephalography (MEG) was recorded during silent letter-by-letter reading, and the source of reading-induced spikes was estimated using equivalent current dipole (ECD) analysis. Diffusion tractography was employed to determine if the white matter pathway connected spike initiation and termination sites. Functional magnetic resonance imaging (fMRI) was employed to determine the spatial pattern of hemodynamic activation elicited by reading.

Results

In 91 spike events, ECDs were clustered in the left posterior basal temporal area (pBTA) during Katakana reading. In 8 of these 91 events, when the patient continued to read >30 min, another ECD cluster appeared in the left ventral precentral gyrus/frontal operculum with a time-difference of ∼24 ms. Probabilistic diffusion tractography revealed that the long segment of the arcuate fasciculus connected these two regions. fMRI conjunction analysis indicated that both Katakana and Kanji reading activated the left pBTA, but Katakana activated the left lateral frontal areas more extensively than Kanji.

Conclusions

Prolonged reading of Katakana induced hyper-activation of the cortical network involved in normal language function, concurrently serving as the seizure onset and symptomatogenic zones.

Significance

Reflex epilepsy is believed to result from intrinsic hyper-excitability in the cortical regions recruited during behavioral states that trigger seizures. Our case shows that reading epilepsy can arise from a hyperexcitable network of cortical regions. Physiological activation of this network can have cumulative effects, resulting in greater reciprocal network propagation and electroclinical seizures. These effects, in turn, may give insights into the brain networks recruited by reading.

Introduction

Reading epilepsy (RE) is a type of reflex epilepsy triggered by reading and usually does not involve spontaneous seizures. RE is the only reflex epilepsy classified as an idiopathic localization-related epilepsy syndrome (Commission on Classification and Terminology of the International League Against Epilepsy, 1989), but the heterogeneity of previously published observations makes this classification debatable. The current proposed diagnostic scheme defines it as a reflex epilepsy syndrome without specifying a generalized or focal subtype (Engel, International League Against Epilepsy (ILAE), 2001).

Based on previous reports of patients with seizures provoked by reading, two types of RE were identified (Koutroumanidis et al., 1998): myoclonic RE and partial RE. The former is characterized by myoclonic jerks of jaw without alexia at seizure onset and bilateral spikes on electroencephalography (EEG). The latter is rare and characterized by ictal alexia associated with a left posterior temporal ictal discharge.

The mechanism proposed to explain triggering of myoclonic RE in reading is the existence of the interaction between a hyperexcitable cortical focus and a cortico-reticular loop (Radhakrishnan et al., 1995). Functional imaging studies have also revealed the hyperexcitability within cortical and subcortical structures (e.g., bilateral globus pallidus, left striatum, and thalamus) (Archer et al., 2003, Salek-Haddadi et al., 2009, Vaudano et al., 2012). Conversely, the mechanism of partial RE in reading is thought to be local cortical hyperexcitability over the left posterior temporal area. This rare symptom has been described previously in a few patients with RE, but the mechanism remains elusive (Wolf, 1994, Radhakrishnan et al., 1995, Koutroumanidis et al., 1998, Maillard et al., 2010).

The Japanese writing system has two distinct orthographies, Kanji (morphograms) and Kana (syllabograms). Kanji characters are visual figures strongly associated with semantics; thus, their pronunciations depend on the context in which they appear. Kana is composed of phonological entities that are somewhat comparable with the alphabets in European languages. Kana orthography employs two visually distinct syllabaries called Hiragana and Katakana; the former is usually used in combination with a Kanji and the latter is used to write loanwords from European languages. Hiragana and Katakana share the same lexical representations and syllabary despite different shapes.

Here, we described a patient with partial RE provoked by reading Katakana characters, but not by Kanji or Hiragana characters. A combination of different noninvasive brain studies was used in the present study: magnetoencephalography (MEG), which detects the dynamic propagation of epileptic spikes, diffusion tensor imaging (DTI) fiber tractography, which is a direct method for depicting the structural connectivity of brain network, and functional magnetic resonance imaging (fMRI), which helps visualize the spatial patterns of neural activity (within cortical and subcortical areas) involved in reading.

The main purpose of this report was, in this rare case, to delineate mechanisms of seizure precipitation and propagation from the viewpoints of system network hyperexcitability. We also investigated the relationship between source localization of epileptic spikes and normal functions of the reading process.

Section snippets

Case presentation

A 28-year-old right-handed male had a history of infrequent generalized tonic–clonic seizures (GTCSs) in the last 13 years. The first GTCS occurred at the age of 15 years when the patient was at rest. Since then, seven seizures were provoked by Katakana reading. The patient described himself as follows. While reading Japanese sentences comprising Katakana letters, such as while looking for a particular movie title or music for several minutes in the movie rental shop, he became unable to read

Spikes triggered by Katakana reading

The covert letter-by-letter reading of Katakana evoked many MEG spikes that fulfilled the ECD criteria (103 times/3890 s) (the number of spikes/task duration in total of two sessions), whereas that of Hiragana and Kanji and the task of finding specific strings among the random-aligned marks provoked fewer ones (Hiragana: three times/641 s, Kanji: five times/585 s, finding specific strings: one time/358 s). In Katakana reading, 91 ECDs out of 103 spike complexes were calculated as a single ECD and

Discussion

The patient was diagnosed as partial RE because of (1) alexia and stiffness in his cheeks and (2) regional EEG and MEG spikes seen both interictally and during the aura. Absence of the oral myoclonus and generalized or bilateral spikes supports the diagnosis of partial RE. Although ictal EEG patterns were not recorded except for that of aura, clustered ECDs likely indicate that the seizure onset zone or the primary epileptic focus was located in the left pBTA. Based on his clinical findings,

Conclusions

Our results indicate that (1) selective subsystems including articulation and morphological processing served as the seizure onset and symptomatogenic zones and (2) network hyperexcitability within the left hemisphere contributed to the development of clinical seizures in a patient with partial RE. In conclusion, this multimodal case study implicated that, under certain predisposition of network hyperexcitability, prolonged reading could enhance physiological network activity and then epileptic

Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research (B) 26282218, 26293209, (C) 26330175 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT), and the Research Grants from the Japan Epilepsy Research Foundation. Conflict of Interest: The authors declare no competing financial interests.

References (27)

  • J.S. Archer et al.

    Spike-triggered fMRI in reading epilepsy: involvement of left frontal cortex working memory area

    Neurology

    (2003)
  • Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised...
  • J. Engel

    International League Against Epilepsy (ILAE). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE task force on classification and terminology

    Epilepsia

    (2001)
  • Cited by (0)

    View full text