Seizure 20 (2011) 340–342
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Short communication
Bilateral temporal lobe epilepsy confirmed with intracranial EEG in chorea-acanthocytosis Benedikt Bader a,1,*, Christian Vollmar a,c,1, Nibal Ackl a, Anne Ebert a, Christian la Fouge`re b, Soheyl Noachtar a, Adrian Danek a a b c
Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universita¨t, Marchioninistr. 15, 81377 Mu¨nchen, Germany Klinik und Poliklinik fu¨r Nuklearmedizin, Ludwig-Maximilians-Universita¨t, Marchioninistr. 15, 81377 Mu¨nchen, Germany Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, UK
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 June 2010 Received in revised form 10 December 2010 Accepted 14 December 2010
Chorea-acanthocytosis (ChAc) is an uncommon basal ganglia disorder, in which the movement disorder element may be obscured by the predominance of seizures. We report a pertinent case of a patient who had undergone extensive evaluation for epilepsy, including intracranial EEG before finally the diagnosis of ChAc was made and confirmed by Western blot. We suggest that in patients with epilepsy, particularly of temporal lobe origin and with onset in the third decade with inconclusive findings on clinical examination and neuroimaging such as dyskinesias, dystonia and basal ganglia involvement, ChAc should be considered. ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Chorea-acanthocytosis Temporal lobe epilepsy Epilepsy surgery Intracranial EEG recording VPS13A Chorea
1. Introduction
2. Case report
Chorea-acanthocytosis (ChAc) is an autosomal-recessive disorder caused by mutations in the VPS13A gene coding for the chorein protein1,2 and is recognized as a core neuroacanthocytosis syndrome.3,4 Due to its rarity the diagnosis of ChAc is often assigned late. Commonly, ChAc first affects patients at about 30 years of age, usually with seizures, orofacial tics or neuropsychiatric symptoms followed by chorea, tongue protrusion dystonia and head drops as typical hallmarks of the disease.5,6 Other frequent findings are hyporeflexia/areflexia and chronically elevated serum creatine kinase levels. Epileptic seizures of (mesial-) temporal origin can be a predominant feature in ChAc.7,8 Usually, seizures are controlled with antiepileptics but individual patients may prove to be resistant to drug treatment. We give a detailed report of a patient with epilepsy-dominant chorea-acanthocytosis and pharmacoresistance (briefly mentioned earlier as case 3 by Scheid et al.8) who appears to be the only case of ChAc so far in which invasive presurgical epilepsy evaluation has been performed.
Starting at the age of 31, this male electrician suffered from somatosensory auras (hand paraesthesia), psychic auras (sensation of fear) and abdominal auras (rising sensation, feeling sick) about once per month. Any of these auras could evolve into a generalized tonic–clonic seizure approximately once every three months. Herpes encephalitis had been suspected initially on the basis of right temporal contrast enhancement and bilateral parahippocampal edema on MRI that was performed after the occurrence of the first generalized seizures (actual images were not available for reevaluation). This diagnosis was not confirmed by cerebrospinal fluid analysis nor could suggestive postinflammatory changes be seen in subsequent MRI. At the age of 35, the patient noted progressive tics, choreatic movements, orofacial dyskinesias and sporadic tongue and lip biting. However, the patient’s seizures did not respond to adequate treatment with oxcarbazepine, lamotrigine, valproate and clonazepam. Thus, at the age of 36 the patient underwent a presurgical epilepsy evaluation. Despite somatosensory auras of a possible extra-temporal origin (hand-paraesthesia), video EEG monitoring with scalp electrodes revealed only bitemporal interictal epileptiform discharges and EEG seizure patterns arising from the temporal regions on the right (eight seizure patterns observed) and on the left (four seizure patterns). MRI demonstrated bilateral hippocampal sclerosis, which was pronounced on the right. Given
* Corresponding author. Tel.: +49 89 7095 7827; fax: +49 89 7095 6671. E-mail address:
[email protected] (B. Bader). 1 These authors contributed equally.
1059-1311/$ – see front matter ß 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.seizure.2010.12.007
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B. Bader et al. / Seizure 20 (2011) 340–342
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Fig. 1. Compared to a template of healthy controls, 18F-FDG PET of this patient with seizures in the context of chorea-acanthocytosis shows bilateral hypometabolism in the striatum (A). Interictal 18F-FDG PET shows hypometabolism in the left mesial anterior temporal lobe (B), while ictal 99mTc-ECD SPECT (C) shows focal hyperperfusion in the same area.
this asymmetry, which was consistent with the ictal EEG, there was the possibility that all seizures arose from the right mesial temporal lobe and subsequently spread to the left. In this case, resective epilepsy surgery with right anteromesial temporal resection would have been a treatment option. Therefore, at the age of 37 bilateral temporal subdural strip electrodes were introduced surgically and video EEG monitoring was performed. The recordings confirmed bilateral temporal interictal spikes but also documented independent bilateral temporal seizure onset (curiously with onset more frequent from the left). This disqualified the patient for resective surgery, in particular because of the discrepancy between more prominent seizure onset on the left and more prominent hippocampal sclerosis on the right. Apart from being unlikely to control seizures, this constellation carries a high risk of postsurgical cognitive impairment. On one occasion during the monitoring evaluation, the patient had nonconvulsive status epilepticus that manifested as a state of confusion lasting for six minutes and was associated with a left temporal seizure pattern. An interictal cerebral 18F-FDG PET scan showed left temporal hypometabolism, consistent with the predominant seizure onset
zone which was concordant with ictal 99mTc-ECD SPECT scan findings showing hyperperfusion in the same area (Fig. 1B and C). Interestingly, the striatum showed bilateral hypometabolism in 18FFDG PET (Fig. 1A) and hypoperfusion in 99mTc-ECD SPECT (not shown) which were not noted at the time of the examination. Neuropsychological evaluation at ages 35 and 39 showed constant findings in verbal learning and verbal memory that were far below average (1st percentile in the California verbal learning test) but demonstrated a slight increase in working memory and recall in neuropsychological screening instruments (mini mental state examination was 25 and 27; SIDAM-score9 42 and 47, respectively) most likely related to variations in the physical and mental state of the patient at the time of the examination. Visual learning, visual memory, executive functions and attention evaluation remained unremarkable. In conclusion, the diagnosis of bilateral temporal lobe epilepsy due to suspected temporal herpes encephalitis was made. 3. Comment By the age of 39, increasingly prominent facial tics and orofacial dyskinesia as well as areflexia and personality changes in the
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presence of basal ganglia hypometabolism led to a suspected diagnosis of underlying ChAc. This diagnosis was confirmed by Western blotting (absence of chorein).8 During two years of followup, the patient has remained seizure free on lamotrigine and levetiracetam. The patient developed epilepsy nine years before the diagnosis of ChAc was made and four years before motor symptoms of ChAc became obvious. Earlier, his subtle orofacial dyskinesias were misinterpreted as signs of the epilepsy syndrome since its semiology involved oral automatisms such as lip smacking, chewing or tongue movements. Blood tests repeatedly showed increased creatine kinase levels, which were also attributed to seizures, but in fact represent a typical finding in ChAc. After the diagnosis of ChAc had been confirmed, available MRI images taken at ages 36 and 37 were reevaluated and found to be compatible with mild caudate atrophy; prominent hippocampal alterations were also visible. This is consistent with other reports of neuroimaging in ChAc. In epilepsy-dominated ChAc cases hippocampal atrophy and sclerosis can also be seen early on,8 but it remains unclear whether these changes are related to recurrent seizures or to the underlying neurodegenerative disorder. However, they might be closely linked to memory dysfunction in ChAc. Hypometabolism of the basal ganglia has repeatedly been described in ChAc.10 The patient showed striatal impairment on 18F-FDG PET and 99mTc-ECD SPECT at an early stage of ChAc without a prominent movement disorder. This is similar to preclinical findings in Huntington’s disease11 and in McLeod neuroacanthocytosis.12 In our case PET and SPECT together with extrapyramidal clinical signs prompted the diagnosis of ChAc. These tracer techniques were more sensitive to detect the neurodegenerative basal ganglia process than a purely visual analysis of the MRI when such a disorder was not suspected. Due to the progressive neurodegenerative character of ChAc, resective epilepsy surgery is generally inappropriate in this condition and should only be considered in cases with seizures of a clearly unifocal origin.8 However, this can be difficult to prove if the results from the various diagnostic methods are inconsistent. In our patient, the degree of hippocampal sclerosis on MRI and the ictal scalp EEG were lateralized to the right, whereas interictal epileptic discharges were distributed between the left and the right. On the other hand, neuropsychological assessment with a pronounced impairment in verbal episodic memory indicated left hemispheric dysfunction. Invasive video EEG monitoring with intracranial electrodes is the only method to definitely identify seizure onset zones. In our patient the invasive approach confirmed bilateral temporal seizure onset and thus ruled out resective surgery. In ChAc patients, bilateral or multifocal seizures appear likely. This explains why an exact syndromic diagnosis of epilepsy is rarely made in ChAc. In some ChAc patients without EEG video monitoring even the differentiation between generalized or focal epilepsy remains unsolved. This distinction, however, is of great importance for the evaluation of the best possible treatment option and, therefore, one should always aim for a syndromic classification of epilepsy in ChAc. As was observed in our case, nonconvulsive status epilepticus (NCSE) marked only by a transient confusional state may occur in ChAc. Behavioral or cognitive changes with sudden onset and a fleeting nature may therefore indicate NCSE. An EEG can help to identify this treatable cause of mental state deterioration.
4. Conclusion Chorea-acanthocytosis may primarily manifest with seizures. Thus, the diagnosis of ChAc should be considered in epilepsy patients with seizure onset between 25 and 40 years of age and signs of an associated movement disorder such as chorea, orofacial tics, and tongue protrusion dystonia with oral mutilation. The clinical diagnosis of ChAc may be further supported by reduced or absent reflexes as well as non-seizure related lip and tongue biting and chronically elevated creatine kinase levels. Some of these signs are typical features of ChAc but they can easily be misinterpreted in the context of epilepsy. Thus, additional, neuroimaging findings, such as striatal atrophy, hypometabolism or hypoperfusion, which are inconsistent with isolated epilepsy, can support a clinical diagnosis of ChAc. In the early stages of ChAc, atrophy of basal ganglia structures is only mild and morphometric analyses of MRI can be useful.13 Acknowledgements BB was financially supported by the Advocacy for Neuroacanthocytosis Patients as was the performance of the chorein Western blot, which was also made possible by the collaboration of Gertrud Kwiatkowski and Prof. Dr. Hans A. Kretzschmar at the Zentrum fu¨r Neuropathologie und Prionforschung, University of Munich (see www.euro-hd.net/html/na/network/docs for information on sample shipment). The work on this manuscript by BB and CV was supported by the Bayerische Forschungsstiftung (Grant PIZ-160-08). The authors thank Mrs. Katie Ogston for language revision of the manuscript. References 1. Rampoldi L, Dobson-Stone C, Rubio JP, Danek A, Chalmers RM, Wood NW, et al. A conserved sorting-associated protein is mutant in chorea-acanthocytosis. Nat Genet 2001;28:119–20. 2. Ueno S, Maruki Y, Nakamura M, Tomemori Y, Kamae K, Tanabe H, et al. The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nat Genet 2001;28:121–2. 3. Danek A. Neuroacanthocytosis Syndromes. Dodrecht: Springer; 2004. 4. Walker RH, Saiki S, Danek A. Neuroacanthocytosis Syndromes II. Heidelberg: Springer; 2008. 5. Bader B, Walker RH, Vogel M, Prosiegel M, McIntosh J, Danek A. Tongue protrusion and feeding dystonia: a hallmark of chorea-acanthocytosis. Mov Disord 2010;25:127–9. 6. Schneider SA, Lang AE, Moro E, Bader B, Danek A, Bhatia KP. Characteristic head drops and axial extension in advanced chorea-acanthocytosis. Mov Disord 2010. 10.1002/mds.23052. 7. Al Asmi A, Jansen AC, Badhwar A, Dubeau F, Tampieri D, Shustik C, et al. Familial temporal lobe epilepsy as a presenting feature of choreoacanthocytosis. Epilepsia 2005;46:1256–63. 8. Scheid R, Bader B, Ott DV, Merkenschlager A, Danek A. Development of mesial temporal lobe epilepsy in chorea-acanthocytosis. Neurology 2009;73:1419–22. 9. Zaudig M, Mittelhammer J, Hiller W, Pauls A, Thora C, Morinigo A, et al. SIDAM— a structured interview for the diagnosis of dementia of the Alzheimer type, multi-infarct dementia and dementias of other aetiology according to ICD-10 and DSM-III-R. Psychol Med 1991;21:225–36. 10. Leenders KL, Jung HH. Functional imaging in neuroacanthocytosis. In: Walker RH, Saiki S, Danek A, editors. Neuroacanthocytosis Syndromes II. Heidelberg: Springer; 2008. p. 163–73. 11. Kuwert T, Lange HW, Boecker H, Titz H, Herzog H, Aulich A, et al. Striatal glucose consumption in chorea-free subjects at risk of Huntington’s disease. J Neurol 1993;241:31–6. 12. Oechsner M, Buchert R, Beyer W, Danek A. Reduction of striatal glucose metabolism in McLeod choreoacanthocytosis. J Neurol Neurosurg Psychiatry 2001;70:517–20. 13. Huppertz HJ, Kroll-Seger J, Danek A, Weber B, Dorn T, Kassubek J. Automatic striatal volumetry allows for identification of patients with chorea-acanthocytosis at single subject level. J Neurol Transm 2008;115:1393–400.
