19 (2010) 326–329

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Seizure

journal homepage: www.elsevier.com/locate/yseiz

Partial presenting as focal atonic seizure: A case report

Jun Zhao a, Pegah Afra b, Bola Adamolekun a,* a Department of , University of Tennessee Health Science Center, 415 Link Building, 855 Monroe Avenue, Memphis, TN 38163, USA b Department of Neurology, University of Utah, USA

ARTICLE INFO ABSTRACT

Article history: A case of atonic localized to the frontal lobe by video-EEG monitoring is reported. The patient is a Received 27 November 2009 38-year-old female with intractable atonic seizures characterized by abrupt onset of facial grimacing and Received in revised form 1 April 2010 a slow head drop. The onset of atonic seizures was about 6 years before presentation. Video-EEG Accepted 23 April 2010 monitoring showed that her atonic seizures were emanating from the right frontal head region. A high voltage spike and slow wave discharge invariably coincided with the onset of atonic seizures in the Keywords: patient, similar to the interruption of tonic muscular activity time-locked to a spike on the EEG described Atonic seizure in epileptic negative myoclonus; a syndrome associated with epileptic activity in the premotor cortex. Frontal lobe Since routine MRI imaging in this patient was normal, diffusion tensor imaging (DTI) was applied to Partial seizure Diffusion tensor imaging analyze the white matter integrity of the normal-appearing white matter in the frontal lobes of the patient. We compared the fractional anisotropy, parallel diffusivity and perpendicular diffusivity of normal-appearing white matter in the right versus left frontal lobe. Our results showed no significant difference between the two sides. Possible reasons for the normal DTI findings are discussed. Published by Elsevier Ireland Ltd on behalf of British Epilepsy Association.

1. Introduction epilepsy with prolonged video-EEG monitoring and MRI.8 In their patient with , MRI of the was normal. In Atonic seizures are epileptic attacks characterized by a sudden another study of focal inhibitory seizures, magnetic resonance loss or diminution of muscle tone, which may be confined to a imaging (MRI) of the brain did not reveal structural lesions.9 segment (limb, jaw, head) or involve all postural muscles, leading When MRI of the brain does not reveal structural lesions in to a slumping to the ground (epileptic drop attacks).1,2 In atonic patients with atonic seizures whose focality is confirmed by EEG, seizures, the loss or diminution of muscle tone is without apparent other imaging modalities may be considered. Diffusion properties preceding myoclonic or tonic events.1 The seizure usually lasts less of brain tissues have shown high sensitivity to pathological than 15 s and patients remain conscious or only have very brief loss changes in white matter and can potentially identify epileptogenic of consciousness.3 lesions.10 Diffusion tensor imaging (DTI) is a magnetic resonance Atonic seizures are usually classified as generalized seizures.2,4 imaging technique which measures water molecule diffusion in They are well known to occur commonly in the Lennox-Gastaut three dimensions and also measures diffusion anisotropy.11 DTI syndrome of early childhood5,6 although the introduction of video- provides quantitative information for detecting micro-structural electroencephalographic (EEG) monitoring has clarified that pure abnormalities of white matter, it can detect lesions in regions that atonic seizures characterized only by loss or diminution tone are appear normal on traditional magnetic resonance imaging (so distinctly rare in that population.7 called normal-appearing white matter, NAWM).12 Atonic seizures have also been reported to occur in the context We report one patient with atonic seizures of frontal lobe origin of partial epilepsy in adults.7,8 In such cases, video-EEG monitoring diagnosed and localized by video/EEG monitoring. We applied DTI is mandatory to achieve a correct diagnosis, while magnetic to analyze the white matter integrity of the normal-appearing resonance imaging (MRI) is needed to evaluate for specific white matter in the frontal lobes of the patient. etiologies, such as cortical malformations.7 Satow et al. investi- gated atonic seizures in two patients with frontal and parietal lobe 2. Patients and methods

2.1. Case report

* Corresponding author. Tel.: +1 901 4484916; fax: +1 901 4487440. E-mail addresses: [email protected], [email protected], The patient is a 38-year-old, right handed white female referred [email protected] (B. Adamolekun). to us for evaluation and management of intractable seizures. Her

1059-1311/$ – see front matter. Published by Elsevier Ireland Ltd on behalf of British Epilepsy Association. doi:10.1016/j.seizure.2010.04.014 J. Zhao et al. / Seizure 19 (2010) 326–329 327

first seizure was a generalized tonic-clonic seizure without , at hemisphere. Small oval ROIs of 9–12 pixels (31.64–42.18 mm2) the age of 23 years. The onset of her seizures was preceded by a car were placed on images acquired without diffusion gradients accident when she was 21-year-old, during which she hit her head (b =0s/mm2). ROIs were then superimposed on same sections on the steering wheel with loss of consciousness. Imaging studies from the maps of FA and the three eigenvalues respectively. at that time were normal. She has had a total of about eight The fractional anisotropy (FA), the largest diffusion direction generalized tonic-clonic seizures in the past 10 years. Her last DA (l1), and diffusivity perpendicular to the axon fiber DR generalized tonic-clonic seizure was about a year prior to (DR = (l2+l3)/2), for each ROI all three parameters in both presentation. She began to have drop attacks, characterized by hemispheres were obtained. Data were analyzed using Excel head drop and loss of tone in all limbs, onset at the age of 32 years. 2007(Microsoft, USA). A paired t-test was performed to compare If the patient was standing at the onset of seizure, she would fall data between the left and right side in the patient. The analysis backwards or forwards and had sustained scalp and facial was repeated in FA, DA, and DR of the NAWM. lacerations on several occasions. The drop attacks were associated with impairment of consciousness. The drop attacks had increased 4. Results in frequency over the years, and were occurring at a frequency of 2–3 times a day at the time of presentation to our clinic. She had 4.1. Video/EEG monitoring been tried on therapeutic doses of Dilantin, Zonegran, Keppra and Lamictal, with no efficacy. She did not tolerate low doses of During the admission patient had 15 seizures, which were Depakote. Her anti-epileptic medication at presentation to our confirmed by family members to be her habitual seizures. The clinic was Topamax 250 mg BID. patient was sitting or lying in bed during all her seizures. The A review of her past medical history showed that the patient seizure semiology was quite stereotypical, starting with an abrupt had a normal delivery and development, and did not have a history onset of unresponsiveness, followed by facial grimacing and loss of of febrile seizures. She completed 2 years of college education and neck muscle tone, which manifested as a slow head drop in either worked as a marketer for several years. Her physical examination direction depending on her head position at seizure onset. Her was normal and her neurological examination did not show any head drop occurred over 2–3 s. Unfortunately, limb EMGs were not focal deficits. A routine scalp EEG done prior to referral to our clinic monitored in this case, but limb hypotonia was confirmed during was noted to show bilateral spike and slow wave discharges which several events by clinical examination and ictal EEG did not show were thought to be compatible with primary . any contamination by EMG artifacts. An MRI of the head with contrast, also completed prior to referral The patient’s inter-ictal EEG showed intermittent bilateral to our clinic, was normal. spike and slow wave discharges as well as intermittent spikes emanating from the right frontal head region. 3. Methods All ictal EEGs were very stereotyped, starting with right frontal spike and slow wave activity, followed by a bilateral, high 3.1. Video/EEG monitoring amplitude spike and slow wave discharge which always coincided with the onset of head drop (Figs. 1 and 2). Thereafter, there was Informed consent was obtained and the purpose of the seizure diffuse background suppression for 4–6 s, followed by low voltage, monitoring study was explained to the patient. She was admitted rhythmic 15–20 Hz activity which appeared maximal in the right to the Comprehensive Seizure Monitoring Unit of the Methodist frontal head region. The ictal EEG record then built up into diffuse University Hospital in Memphis, TN for 5 days. Digital EEG semi-rhythmic spike and slow wave activity which appeared (NICOLET BMSI 6000) was recorded with scalp electrodes placed maximal in the frontal head regions. according to the 10–20 system, with a sampling rate of 200 Hz. The low-frequency filter was set to 0.1 Hz and high frequency filter was 4.2. DTI results set to 70 Hz. EEG data were analyzed offline, and the display montage was adjusted as needed. Fractional anisotropy (FA) data from NAWM on the frontal lobes in both left and right hemispheres are shown in Table 1. There was 3.2. MR imaging acquisition protocol no significant right–left asymmetry in FA value. Data of directional diffusivities DA and DR are also shown in Table 1. Both right versus MRI and DTI were acquired with a 1.5 T MR scanner (Siemens, left side DA or DR in frontal NAWM were compared. There were no Erlangen, Germany). DTI was performed with single-shot pulsed- significant differences between right and left side. gradient, echo-planar imaging protocol (TR = 8000 ms, TE = 109 ms, FOV = 240 Â 240 mm, matrix = 128 Â 128, in-plane 4.3. Clinical course resolution = 1.875 Â 1.875, section thickness = 3 mm). Diffusion gradients were applied in 12 non-collinear directions. At each slice The inter-ictal and ictal EEG findings during 5 days of video-EEG position, two b values (0 and 1000 s/mm2) were applied monitoring indicated that the patient had atonic focal seizures individually. emanating from the right frontal head region. She was continued on Topamax. Vimpat (Lacosamide) was added and titrated up to 3.3. DTI data analysis 200 mg BID with significant reduction in seizure frequency.

Post-processing of diffusion tensor was performed using DTI Studio software (Johns Hopkins University, Baltimore, MD, http:// cmrm.med.jhmi.edu). All DTI raw data were visually inspected Table 1 Diffusion tensor measurement (mean Æ SD) in patient. before applying DTI tensor calculation. No obvious motion artifacts were visualized. Regions of interest (ROIs) were placed Diffusion tensor Right NAWM Left NAWM P-value bilaterally on normal-appearing white matter (NAWM) of the measurement frontal lobe. The most inferior slices started where the frontal FA 0.37 Æ 0.04 0.37 Æ 0.04 0.79 horns of the lateral ventricle were firstly visualized. Frontal lobe DA 1.66 Æ 0.09 1.63 Æ 0.05 0.38 DR 0.96 Æ 0.07 0.94 Æ 0.07 0.60 white matter was sampled on 5 contiguous sections in each 328 J. Zhao et al. / Seizure 19 (2010) 326–329

Fig. 1. Ictal EEG showing right frontal onset followed by bilateral high voltage spike discharge which invariably coincided with clinical onset of atonic seizure. There is subsequent diffuse electrodecrement and fast activity.

Fig. 2. Ictal EEG displayed with referential montage, showing evolution of ictal activity into diffuse spike and slow wave activity.

5. Discussion Although EMGs were not recorded in our patient, the ictal EEG (Figs. 1 and 2) clearly showed that there was no apparent The clinical semiology of our patient’s seizures was character- contamination of the ictal scalp EEG by EMG activity. In addition, ized by abrupt onset of impaired consciousness and facial limb hypotonia was confirmed by clinical examination during the grimacing, followed by atonic head drop. These clinical features seizures. These facts in concert with the atonic head drop, confirm are remarkably similar to the clinical presentation of the patient that the seizures were atonic, and helped distinguish the ictal with frontal lobe atonic seizure described by Satow et al.8 Our grimacing in our case from the facial grimacing that may patient’s head drops occurred slowly over 2–3 s, again similar to sometimes occur in frontal lobe seizures with tonic motor the slow atonic falls described by Satow et al. manifestations. J. Zhao et al. / Seizure 19 (2010) 326–329 329

The ictal EEG pattern in our patient is also broadly similar to the compared to healthy controls and found no significant difference case reported by Satow et al., with diffuse attenuation followed by between FA of the side of seizure onset, when compared to the low voltage fast activity and repetitive spiking in both cases.8 A contralateral side in TLE patients.21 Obviously, our small sample distinct feature in our patient’s ictal EEG however, was the size also limits the power of the investigation. It is possible that presence of high voltage spike and slow wave discharges which future studies with more subjects may reveal subtle changes in invariably appeared to coincide with the onset of her atonic white matter diffusivity in frontal lobe atonic seizures. seizures, based on our careful review of the patient’s video-EEG records; in the absence of polygraphic study of postural and limb References muscles. This is reminiscent of the ‘‘spike-related epileptic silent 1. Blume WT, Luders HO, Mizrhai E, Tassinari CA, van Emde Boas W, Engel J. 13 periods’’ described by Tassinari, which are periods of muscle Glossary of descriptive terminology for ictal semiology: report of the ILAE task inhibition strictly related to a diffuse or focal spike. It also appears force on classification and terminology. Epilepsia 2001;42:1212–8. to be compatible with the syndrome of ‘‘epileptic negative 2. Commission on Classification and Terminology of the International League against Epilepsy. Proposal for revised clinical and electroencephalographic 14 myoclonus’’ ; which is an interruption of tonic muscular activity, classification of epileptic seizures. Epilepsia 1981;22:489–501. time-locked to a spike on the EEG. Epileptic negative myoclonus 3. Pazzaglia P, D’Alessandro R, Ambrosetto G, Lugaresi E. Drop attacks: an ominous has been shown to be associated with epileptic activity in the change in the evolution of partial epilepsy. Neurology 1985;35:1725–30. 15 4. Engel J. A proposed diagnostic scheme for people with epileptic seizures and premotor cortex, including the supplementary motor area. It has with epilepsy: report of the ILAE task force on classification and terminology. also been reported to occur from cortical malformation in the post- Epilepsia 2001;42:1–9. central gyrus.16 5. Oguni H, Fukuyama Y, Imaizumi Y, Uehara T. Video-EEG analysis of drop seizures in myoclonic astatic epilepsy of early childhood (Doose syndrome). However, it is relevant to note that epileptic negative Epilepsia 1992;33:805–13. myoclonus is an epileptic motor phenomenon of much shorter 6. Niedermeyer E. The : diagnosis and management. Baltimore: Urban & duration than in our case, with usual durations less than 500 ms17 Schwarzenberg; 1990. 7. Tassinari CA, Michelucci R, Shigematsu H, Seino M. Atonic and myoclonic-atonic and clinically appearing as a brief lapse of muscular tone, or as an seizures. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. abrupt epileptic drop attack in more severe cases. In one case of Philadelphia: Lippincott Williams & Wilkins; 2008. p. 601–9. epileptic negative myoclonus, the duration of the negative 8. Satow T, Ikeda A, Yamamoto J, Takayama M, Matsuhashi M, Ohara S, et al. 17 Partial epilepsy manifesting atonic seizures. Report of two cases. Epilepsia myoclonus was 30–340 ms. 2002;43:1425–31. Atonic seizures involving the frontal lobe can be explained by 9. Bussie`re M, Pelz D, Reid RH, Young GB. Prolonged deficits after focal inhibitory inhibitory mechanisms in the negative motor area. There are two seizures. Neurocrital Care 2005;2:29–37. areas in the frontal lobe where electric stimulation could cause the 10. Rugg-Gunn FJ, Eriksson SH, Symms MR, Barker GJ, Ducan JS. Diffusion tensor imaging of cryptogenic and acquired partial epilepsies. Brain 2001;124:627–36. inhibition of voluntary movements. To distinguish these two 11. Basser PJ. Inferring microstructural features and the physiological state of negative motor areas, investigators18 proposed the term primary tissues from diffusion-weighted images. NMR Biomed 2005;8:333–44. negative motor area (PNMA, in reference to the area of the inferior 12. Werring DJ, Clark CA, Barker GJ, Thompson AJ, Miller DH. Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis. frontal gyrus immediately in the front of the primary face motor Neurology 1999;52:1626–32. region) and supplementary negative motor area (SNMA, in regard 13. Tassinari CA, Regis H, Gastaut H. A particular form of muscular inhibition in to the mesial portion of the superior frontal gyrus immediately in epilepsy: the related epileptic silent period (R.E.S.P.). Proc Austr Assoc Neurol 19 1968;5:595–602. front of the supplementary sensorimotor area). Ikeda et al. 14. Tassinari CA, Rubboli G, Parmeggiani L, et al. Epileptic negative myoclonus. In: reported two patients with negative motor seizure presenting as Fahn S, Hallet M, Luders HO, Marsden CD, editors. Negative motor phenomena. praxis, with ictal subdural EEG suggesting epileptogenic focus in Philadelphia: Lippincott-Raven Publishers; 1995. p. 181–197. 15. Rubboli G, Parmeggiani L, Tassinari CA. Frontal inhibitory spike component the mesial frontal area (SNMA). Cortical stimulation in that area associated with epileptic negative myoclonus. Electroencephalogr Clin Neuro- elicited similar negative seizure phenomenon in one of the physiol 1995;95:201–5. patients. Another study reported three patients who had 16. Noachtar S, Holthausen H, Luders HO. Epileptic negative myoclonus. Subdural EEG recordings indicate a post-central generator. Neurology 1997;49(6):1534–7. contralateral ictal paresis, with subdural recordings localizing 17. Rubboli G, Mai R, Meletti S, Francione S, Cardinale F, Tassi L, et al. Negative 20 the ictal focus to the mesial frontal regions involving the SNMA. myoclonus induced by cortical electrical stimulation in epileptic patients. Brain Since the seizure onset in our patient was localized by video- 2006;129(1):65–81. EEG monitoring to the right frontal head region, we compared the 18. Lu¨ ders HO, Dinner DS, Morris HH, Wyllie E, Comair YG. Cortical electrical stimulation in humans. The negative motor areas. Advances in Neurology fractional anisotropy (FA), parallel diffusivity (DA) and perpendic- 1995;67:115–29. ular diffusivity (DR) of normal-appearing white matter (NAWM) in 19. Ikeda A, Hirasawa K, Kinoshita M, Hitomi T, Matsumoto R, Mitsueda T, et al. right versus left frontal lobe. Our results showed that there was no Negative motor seizure arising from the negative motor area: is it ictal apraxia? Epilepsia 2009;50(9):2072–84. significant difference between the two sides in our patient. 20. Noachtar S, Lu¨ ders HO. Focal akinetic seizures as documented by electroen- Although the results of FA in the temporal lobe may only be cephalography and video recordings. Neurology 1999;53:427–9. extrapolated to the frontal lobe with caution, our results are 21. Nilsson D, Go C, Rutka JT, Rydenhag B, Mabbott Dj. Snead OC, et al. Bilateral diffusion tensor abnormalities of temporal lobe and cingulate gyrus white similar to those of Nilsson et al. (2008), who found no significant matter in children with . Epilepsy Res 2008;81(2-3): difference of FA in the temporal lobe white matter in TLE patients 128–35.