- Email: [email protected]
Ictal video-polygraphic features of perioral myoclonia with absences
Epilepsy & Behavior 21 (2011) 314–317
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Case Report
Ictal video-polygraphic features of perioral myoclonia with absences Giuseppe d'Orsi a,⁎, Vincenzo Demaio b, Marina Trivisano a, Maria Grazia Pascarella a, Luigi M. Specchio a a b
Epilepsy Center—Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy Opera Don Uva, Bisceglie, Italy
a r t i c l e
i n f o
Article history: Received 2 January 2011 Revised 29 March 2011 Accepted 31 March 2011 Available online 14 May 2011 Keywords: Perioral myoclonia with absences Video-polygraphy Idiopathic generalized epilepsy Classification Electromyography
a b s t r a c t There have been few case reports of perioral myoclonia with absences (POMA) because of the lack of videopolygraphic recordings clarifying the electroencephalogram (EEG)–electromyogram (EMG) correlations. We describe one of the first video-polygraphic studies of POMA in a patient who underwent repeated and prolonged split-screen video-polygraphic recordings. The ictal EEG showed generalized and irregular discharges of spikes or multiple spikes and slow waves, while two concomitant EMG patterns appeared: (1) a rhythmic enhancement of the orbicularis oris and masseter muscles on both sides with minimal asymmetry corresponding to perioral movements, and (2) a progressive increment in muscular tone in the mylohyoideus muscle corresponding to oroalimentary automatisms. Myoclonic jerks were inconstantly time-locked to the spike component of the spike–wave complex. The evidence of a complex pattern of activation of the facial muscles suggests that the involvement of subcortical central pattern generators, related to masticatory activity, through the disinhibitory effect of the spike–wave discharge is a possible pathophysiological mechanism underlying POMA. © 2011 Elsevier Inc. All rights reserved.
1. Introduction
2. Case study
Perioral myoclonia with absences (POMA), which is not officially recognized by the International League Against Epilepsy, is probably an idiopathic generalized epilepsy [1,2]. It is often misdiagnosed as focal epilepsy. Several authors have described an electroclinical picture [3–6] characterized by (1) absences with rhythmic myoclonia in the perioral muscles, resulting in twitching of the corners of the mouth or sometimes leading to rhythmic jaw movements; (2) ictal EEGs showing generalized irregular discharges of spikes or multispikes and slow waves associated with fluctuations of spike amplitude; and (3) a clinical course that is not benign with a poor response to antiepileptic drugs. Video-polygraphic recordings documenting the correlation of myoclonia with the spike–wave activity have been reported only once [6], and more video-polygraphic studies are necessary to confirm this syndrome as a separate entity among idiopathic generalized epilepsies [2]. Here, we describe the clinical and video-polygraphic features of a patient with POMA who had been misdiagnosed with focal epilepsy and was correctly diagnosed after video-polygraphic recordings.
The patient, a 47-year-old man, had severe asphyxia at birth, delayed development, and mental retardation (Wechsler Intelligence Scale for Children—Revised [WISC-R] Total IQ = 54). Family history was significant for familial mesial temporal lobe epilepsy (in one sister and her son) with prominent déjà vu and medication responsiveness. Starting at the age of 2, the patient manifested generalized tonic–clonic seizures that occurred once a month. At the same time he experienced weekly brief seizures characterized by loss of contact, with perioral movements that were interpreted as oral automatisms, typical of focal temporal seizures. The interictal EEG showed diffuse discharges of spikes and slow waves, sometime prevalent in bitemporal regions. The patient was treated with 800 mg/day carbamazepine, which was ineffective, as was treatment with phenobarbital, valproic acid, and ethosuximide. When he was 47 years old, his parents were referred to our epilepsy center after they noted a progressive deterioration of consciousness with repetitive daily seizures, characterized by oral movements during lapses of consciousness. At that time, the patient was on 800 mg/day carbamazepine and 1000 mg/day valproate. Brain MRI revealed frontal atrophy. The patient underwent multiple sessions of videopolygraphic monitoring, during which POMA was documented. EEG electrodes were placed according to the 10–20 International system with bipolar montage; other parameters included ECG, thoracic breathing, and electromyographic activity from the right and left elevator muscles of the upper eyelid, the right and left orbicularis
⁎ Corresponding author at: Epilepsy Center—Clinic of Nervous System Diseases, Department of Neurological Sciences, University of Foggia, Riuniti Hospital, Via Luigi Pinto 1, 71100 Foggia, Italy. Fax: + 39 0881 736080. E-mail address: [email protected] (G. d'Orsi). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.03.040
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
oculi, the right and left masseter, the right and left orbicularis oris, the chin and mylohyoideus muscles, the right and left deltoid muscles, and the right and left tibialis anterior muscles. Simultaneous ictal video-polygraphy produced four major findings. 1. The EEG showed generalized discharges of spikes or multiple spikes and slow waves (3–4 Hz) with frequent irregularities in the number and amplitude of spikes in the spike–wave complex (Fig. 1). Hyperventilation, closed eyes, fluctuations in vigilance, and recordings made during the afternoon and evening all enhanced these discharges. In particular, during fluctuations in vigilance, prolonged discharges (30–40 seconds) of spikes or multiple spikes and slow waves appeared, usually asymmetrically, giving the impression of a localized predominant focus in the right temporal region. Muscular artifacts, caused by perioral movements, often masked temporal regions (especially right temporal region). The interictal EEG showed brief (1–2 seconds) generalized discharges of spikes or multiple spikes and slow waves, and focal abnormalities (theta waves and spike–wave complexes) localized in the right temporal region. There was no photosensitivity. 2. From an electromyographic point of view (Fig. 2), the first change (first phase) was a rhythmic enhancement of the EMG activity observed in some cranial muscles (chin and, especially, orbicularis oris and masseter on both sides with minimal asymmetry) that lasted b1 second and clinically corresponded to perioral movements and, rarely, protrusion of the lips. Subsequently, a progressive increment was detected in muscular tone of the mylohyoideus muscle (second phase), clinically corresponding to oroalimentary automatisms (mastication and swallowing). EMG activity in the limb muscles
315
did not show consistent modifications. From the clinical and electromyographic points of view, during fluctuations in vigilance, the two phases were evident; contrarily, during wakefulness, the first phase was clinically minimal or unnoticed, and was exclusively evident in polygraphic channels. Rarely, oroalimentary automatisms preceded perioral movements. Myoclonic jerks, sometimes asymmetrical or prevalent on one side, were inconstantly related to the spike of the spike–wave complex (Fig. 3). 3. The ECG was normal in this study. 4. During hyperventilation, thoracic breathing revealed respiratory modifications in the form of apnea or hypoventilation that clinically corresponded to impairment of contact. Clinical and polygraphic features improved (in terms of reduction of EEG abnormalities and seizure frequency, from daily to monthly and yearly) after addition of lamotrigine (100 mg/day) to the valproate (1000 mg/day) and withdrawal of carbamazepine. 3. Discussion Myoclonic manifestations that are limited to facial areas and associated with generalized spike–wave discharges have been reported in childhood absence epilepsy (CAE), in eyelid myoclonia with absences (EMA), and in POMA [1,3–8]. Involvement of the facial areas has occasionally been described in patients with epilepsy with myoclonic absences, although myoclonic manifestations were prominent at the proximal muscular segments of the limbs [9]. It has been documented that in patients with CAE, the occurrence of rhythmic myoclonic jerks of the facial or neck muscles correlating to the spike component of
Fig. 1. Ictal polygraphy. During fluctuations in vigilance, there were generalized discharge of spikes and slow waves, with irregularities in the number and amplitude of spikes in the spike–wave complex. Muscular artifacts clinically corresponding to perioral movements masked the right temporal regions. The ECG and thoracic breathing were normal.
316
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
Fig. 2. Ictal EMG. Rhythmic enhancement of EMG activity was observed bilaterally in the orbicularis oris and masseter with minimal asymmetry, corresponding clinically to perioral movements (A), followed by a progressive increment in muscular tone in the mylohyoideus muscle, corresponding clinically to mastication and swallowing (B).
spike–wave complexes did not influence the benign course of the disease [7]. In EMA, eyelid myoclonia of varying severity (i.e., jerking of the eyelids often associated with jerky upward deviation of the eyeballs and retropulsion of the head) often occurs with irregular polyspike– wave complexes with the characteristic eye closure-related discharges, but without a time relationship between muscular activity and the EEG paroxysm [1,8]. Eyelid myoclonia is highly resistant to treatment and
often occurs without apparent absences. Because myoclonia may be minimal in both syndromes, frequently it may be overlooked or mistakenly diagnosed as facial tics [1] so ictal video/EEG and videopolygraphic recordings are mandatory. In POMA, perioral myoclonia is associated with generalized discharges of spikes or multiple spikes and slow waves with frequent irregularities in the number of spikes in the spike–wave complex, in spike amplitude, and in occurrence of
Fig. 3. Ictal EEG–EMG correlations. Myoclonic jerks, prevalent in the right orbicularis oris, were inconstantly time-locked to the spike component of the spike–wave complex. In particular, the onset of the first EMG myoclonic twitch (at the left in the figure) is related to the apex of the slow wave.
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
fragmentation [1–6]. The clinical course is not benign, because absences and generalized tonic–clonic seizures may be resistant to antiepileptic drug treatment and may be lifelong. Moreover, POMA is usually observed in patients with normal neurological status [1–3], whereas our patient presented with delayed development and mental retardation. In our opinion, the association with an abnormal neurological condition was merely coincidental, in light of the positive family history for the idiopathic trait. Perioral myoclonia with absences is usually documented by video/ EEG [3–6], revealing perioral myoclonia (such as rhythmic contractions of perioral muscles causing protrusion of the lips, twitching of the corners of the mouth, or jaw jerking) that sometimes, particularly in treated patients [1], may be subtle and easily overlooked on EEG analysis. Nevertheless, video/EEG cannot be used to make a firm diagnosis in all patients with POMA, and it is difficult to assess the relationship between myoclonus and paroxysmal activity without complete polygraphic recordings from multiple EMG channels. In fact, on the basis of only the clinical and electroencephalographic features, our patient had been diagnosed with a cryptogenic focal epilepsy for many years. A full polygraphic investigation was necessary to obtain the correct diagnosis, showing the two principal phases with motor manifestations limited to the facial muscles within the spectrum of an idiopathic generalized epilepsy and not a cryptogenic focal epilepsy. In fact, the presence of myoclonic manifestations limited to facial areas, sometimes asymmetrical or prevalent in one side, confirmed the previous pathophysiological speculations, which explained the association with generalized epileptic activity. In both juvenile myoclonic epilepsy [10,11] and POMA it is possible that, in a condition of diffuse hyperexcitability, prevalent and asymmetrical cortical dysfunctions can result in asymmetrical myoclonic manifestations. Moreover, the impression of an EEG-localized focus is in accordance with several findings in patients with generalized epilepsy, as well as extensive investigations of spontaneous absence seizures in rats [12]. These findings show a cortical focus as the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and suggest rapid intracortical spread of seizure activity. On inspection of the ictal EEG–EMG correlations (Fig. 3), the association between the spike– wave complexes and the myoclonic potential (and, in particular, the spike component of the spike–wave complexes) is inconstant and a 1:1 relationship is lacking (as it occurs in myoclonic absences). This finding, and the evidence of a more complex pattern of activation of the facial muscles (including oroalimentary automatisms) shown in Figs. 1 and 2, suggests a pathophysiological mechanism for the involvement of subcortical central pattern generators related to masticatory activity through the disinhibitory effect of the spike– wave discharge [13]. In fact, a certain number of automatisms, referred to as epileptic, are the indirect effects of cortical discharges on distant central pattern generators that cause these stereotyped and cyclically repeated behaviors (i.e., masticatory automatisms). Finally, in our patient the clinical and polygraphic features improved after withdrawal of carbamazepine. In fact, a paradoxical
317
increase in seizure frequency may occur as a distinct adverse primary action of antiepileptic drugs in specific seizure types or in syndromic forms. Carbamazepine, in particular, has been reported to precipitate a variety of seizures (also myoclonic seizures) in patients with generalized epilepsies characterized by bursts of diffuse and bilaterally synchronous spike-and-wave EEG activity [14]. Physicians treating epilepsy must be aware that antiepileptic drugs can exacerbate seizures and/or EEG, and cause developmental regression. Prompt recognition of clinical and EEG deterioration and intervention may help avoid or reverse these paradoxical reactions. Ethical approval We have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest statement The authors have no conflicts of interest to declare. References [1] Panayiotopoulos C. Syndromes of idiopathic generalized epilepsies not recognized by the International League Against Epilepsy. Epilepsia 2005;46:57–66. [2] Rubboli G, Gardella E, Capovilla G. Idiopathic generalized epilepsy (IGE) syndromes in development: IGE with absences of early childhood, IGE with phantom absences, and perioral myoclonia with absences. Epilepsia 2009;50(Suppl 5):24–8. [3] Panayiotopoulos CP, Ferrie CD, Giannakodimos S, Robinson RO. Perioral myoclonia with absences: a new syndrome. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey; 1994. p. 143–53. [4] Clemens B. Perioral myoclonia with absences? A case report with EEG and voltage mapping analysis. Brain Dev 1997;19:353–8. [5] Bilgic B, Baykan B, Gurses C, Gokyigit A. Perioral myoclonia with absence seizures: a rare epileptic syndrome. Epileptic Disord 2001;3:23–7. [6] Baykan B, Noachtar S. Perioral myoclonia with absences: an overlooked and misdiagnosed generalized seizure type. Epilepsy Behav 2005;6:460–2. [7] Capovilla G, Rubboli G, Beccaria F, et al. A clinical spectrum of the myoclonic manifestations associated with typical absences in childhood absence epilepsy: a video-polygraphic study. Epileptic Disord 2001;3:57–62. [8] Striano S, Capovilla G, Sofia V, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;50(Suppl 5):15–9. [9] Tassinari CA, Michelucci R, Gardella E, Rubboli G. Epilepsy with myoclonic absences. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. 2nd ed. Philadelphia: Wolters Kluwer–Lippincott Williams & Wilkins; 2008. p. 2413–6. [10] Lancman ME, Asconape JJ, Penry JK. Clinical and EEG asymmetries in juvenile myoclonic epilepsy. Epilepsia 1994;35:302–6. [11] Usui N, Kotagal P, Matsumoto R, Kellinghaus C, Luders HO. Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy. Epilepsia 2005;46:1668–76. [12] Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, da Silva FH Lopes. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 2002;22:1480–95. [13] Tassinari CA, Rubboli G, Gardella E, et al. Central pattern generators for a common semiology in fronto-limbic seizures and in parasomnias. a neuroethologic approach. Neurol Sci 2005;26(Suppl 3):225–32. [14] Perucca E, Gram L, Avanzini G, Dulac o. Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998;39(1):5–17.
Contents lists available at ScienceDirect
Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Case Report
Ictal video-polygraphic features of perioral myoclonia with absences Giuseppe d'Orsi a,⁎, Vincenzo Demaio b, Marina Trivisano a, Maria Grazia Pascarella a, Luigi M. Specchio a a b
Epilepsy Center—Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy Opera Don Uva, Bisceglie, Italy
a r t i c l e
i n f o
Article history: Received 2 January 2011 Revised 29 March 2011 Accepted 31 March 2011 Available online 14 May 2011 Keywords: Perioral myoclonia with absences Video-polygraphy Idiopathic generalized epilepsy Classification Electromyography
a b s t r a c t There have been few case reports of perioral myoclonia with absences (POMA) because of the lack of videopolygraphic recordings clarifying the electroencephalogram (EEG)–electromyogram (EMG) correlations. We describe one of the first video-polygraphic studies of POMA in a patient who underwent repeated and prolonged split-screen video-polygraphic recordings. The ictal EEG showed generalized and irregular discharges of spikes or multiple spikes and slow waves, while two concomitant EMG patterns appeared: (1) a rhythmic enhancement of the orbicularis oris and masseter muscles on both sides with minimal asymmetry corresponding to perioral movements, and (2) a progressive increment in muscular tone in the mylohyoideus muscle corresponding to oroalimentary automatisms. Myoclonic jerks were inconstantly time-locked to the spike component of the spike–wave complex. The evidence of a complex pattern of activation of the facial muscles suggests that the involvement of subcortical central pattern generators, related to masticatory activity, through the disinhibitory effect of the spike–wave discharge is a possible pathophysiological mechanism underlying POMA. © 2011 Elsevier Inc. All rights reserved.
1. Introduction
2. Case study
Perioral myoclonia with absences (POMA), which is not officially recognized by the International League Against Epilepsy, is probably an idiopathic generalized epilepsy [1,2]. It is often misdiagnosed as focal epilepsy. Several authors have described an electroclinical picture [3–6] characterized by (1) absences with rhythmic myoclonia in the perioral muscles, resulting in twitching of the corners of the mouth or sometimes leading to rhythmic jaw movements; (2) ictal EEGs showing generalized irregular discharges of spikes or multispikes and slow waves associated with fluctuations of spike amplitude; and (3) a clinical course that is not benign with a poor response to antiepileptic drugs. Video-polygraphic recordings documenting the correlation of myoclonia with the spike–wave activity have been reported only once [6], and more video-polygraphic studies are necessary to confirm this syndrome as a separate entity among idiopathic generalized epilepsies [2]. Here, we describe the clinical and video-polygraphic features of a patient with POMA who had been misdiagnosed with focal epilepsy and was correctly diagnosed after video-polygraphic recordings.
The patient, a 47-year-old man, had severe asphyxia at birth, delayed development, and mental retardation (Wechsler Intelligence Scale for Children—Revised [WISC-R] Total IQ = 54). Family history was significant for familial mesial temporal lobe epilepsy (in one sister and her son) with prominent déjà vu and medication responsiveness. Starting at the age of 2, the patient manifested generalized tonic–clonic seizures that occurred once a month. At the same time he experienced weekly brief seizures characterized by loss of contact, with perioral movements that were interpreted as oral automatisms, typical of focal temporal seizures. The interictal EEG showed diffuse discharges of spikes and slow waves, sometime prevalent in bitemporal regions. The patient was treated with 800 mg/day carbamazepine, which was ineffective, as was treatment with phenobarbital, valproic acid, and ethosuximide. When he was 47 years old, his parents were referred to our epilepsy center after they noted a progressive deterioration of consciousness with repetitive daily seizures, characterized by oral movements during lapses of consciousness. At that time, the patient was on 800 mg/day carbamazepine and 1000 mg/day valproate. Brain MRI revealed frontal atrophy. The patient underwent multiple sessions of videopolygraphic monitoring, during which POMA was documented. EEG electrodes were placed according to the 10–20 International system with bipolar montage; other parameters included ECG, thoracic breathing, and electromyographic activity from the right and left elevator muscles of the upper eyelid, the right and left orbicularis
⁎ Corresponding author at: Epilepsy Center—Clinic of Nervous System Diseases, Department of Neurological Sciences, University of Foggia, Riuniti Hospital, Via Luigi Pinto 1, 71100 Foggia, Italy. Fax: + 39 0881 736080. E-mail address: [email protected] (G. d'Orsi). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.03.040
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
oculi, the right and left masseter, the right and left orbicularis oris, the chin and mylohyoideus muscles, the right and left deltoid muscles, and the right and left tibialis anterior muscles. Simultaneous ictal video-polygraphy produced four major findings. 1. The EEG showed generalized discharges of spikes or multiple spikes and slow waves (3–4 Hz) with frequent irregularities in the number and amplitude of spikes in the spike–wave complex (Fig. 1). Hyperventilation, closed eyes, fluctuations in vigilance, and recordings made during the afternoon and evening all enhanced these discharges. In particular, during fluctuations in vigilance, prolonged discharges (30–40 seconds) of spikes or multiple spikes and slow waves appeared, usually asymmetrically, giving the impression of a localized predominant focus in the right temporal region. Muscular artifacts, caused by perioral movements, often masked temporal regions (especially right temporal region). The interictal EEG showed brief (1–2 seconds) generalized discharges of spikes or multiple spikes and slow waves, and focal abnormalities (theta waves and spike–wave complexes) localized in the right temporal region. There was no photosensitivity. 2. From an electromyographic point of view (Fig. 2), the first change (first phase) was a rhythmic enhancement of the EMG activity observed in some cranial muscles (chin and, especially, orbicularis oris and masseter on both sides with minimal asymmetry) that lasted b1 second and clinically corresponded to perioral movements and, rarely, protrusion of the lips. Subsequently, a progressive increment was detected in muscular tone of the mylohyoideus muscle (second phase), clinically corresponding to oroalimentary automatisms (mastication and swallowing). EMG activity in the limb muscles
315
did not show consistent modifications. From the clinical and electromyographic points of view, during fluctuations in vigilance, the two phases were evident; contrarily, during wakefulness, the first phase was clinically minimal or unnoticed, and was exclusively evident in polygraphic channels. Rarely, oroalimentary automatisms preceded perioral movements. Myoclonic jerks, sometimes asymmetrical or prevalent on one side, were inconstantly related to the spike of the spike–wave complex (Fig. 3). 3. The ECG was normal in this study. 4. During hyperventilation, thoracic breathing revealed respiratory modifications in the form of apnea or hypoventilation that clinically corresponded to impairment of contact. Clinical and polygraphic features improved (in terms of reduction of EEG abnormalities and seizure frequency, from daily to monthly and yearly) after addition of lamotrigine (100 mg/day) to the valproate (1000 mg/day) and withdrawal of carbamazepine. 3. Discussion Myoclonic manifestations that are limited to facial areas and associated with generalized spike–wave discharges have been reported in childhood absence epilepsy (CAE), in eyelid myoclonia with absences (EMA), and in POMA [1,3–8]. Involvement of the facial areas has occasionally been described in patients with epilepsy with myoclonic absences, although myoclonic manifestations were prominent at the proximal muscular segments of the limbs [9]. It has been documented that in patients with CAE, the occurrence of rhythmic myoclonic jerks of the facial or neck muscles correlating to the spike component of
Fig. 1. Ictal polygraphy. During fluctuations in vigilance, there were generalized discharge of spikes and slow waves, with irregularities in the number and amplitude of spikes in the spike–wave complex. Muscular artifacts clinically corresponding to perioral movements masked the right temporal regions. The ECG and thoracic breathing were normal.
316
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
Fig. 2. Ictal EMG. Rhythmic enhancement of EMG activity was observed bilaterally in the orbicularis oris and masseter with minimal asymmetry, corresponding clinically to perioral movements (A), followed by a progressive increment in muscular tone in the mylohyoideus muscle, corresponding clinically to mastication and swallowing (B).
spike–wave complexes did not influence the benign course of the disease [7]. In EMA, eyelid myoclonia of varying severity (i.e., jerking of the eyelids often associated with jerky upward deviation of the eyeballs and retropulsion of the head) often occurs with irregular polyspike– wave complexes with the characteristic eye closure-related discharges, but without a time relationship between muscular activity and the EEG paroxysm [1,8]. Eyelid myoclonia is highly resistant to treatment and
often occurs without apparent absences. Because myoclonia may be minimal in both syndromes, frequently it may be overlooked or mistakenly diagnosed as facial tics [1] so ictal video/EEG and videopolygraphic recordings are mandatory. In POMA, perioral myoclonia is associated with generalized discharges of spikes or multiple spikes and slow waves with frequent irregularities in the number of spikes in the spike–wave complex, in spike amplitude, and in occurrence of
Fig. 3. Ictal EEG–EMG correlations. Myoclonic jerks, prevalent in the right orbicularis oris, were inconstantly time-locked to the spike component of the spike–wave complex. In particular, the onset of the first EMG myoclonic twitch (at the left in the figure) is related to the apex of the slow wave.
G. d'Orsi et al. / Epilepsy & Behavior 21 (2011) 314–317
fragmentation [1–6]. The clinical course is not benign, because absences and generalized tonic–clonic seizures may be resistant to antiepileptic drug treatment and may be lifelong. Moreover, POMA is usually observed in patients with normal neurological status [1–3], whereas our patient presented with delayed development and mental retardation. In our opinion, the association with an abnormal neurological condition was merely coincidental, in light of the positive family history for the idiopathic trait. Perioral myoclonia with absences is usually documented by video/ EEG [3–6], revealing perioral myoclonia (such as rhythmic contractions of perioral muscles causing protrusion of the lips, twitching of the corners of the mouth, or jaw jerking) that sometimes, particularly in treated patients [1], may be subtle and easily overlooked on EEG analysis. Nevertheless, video/EEG cannot be used to make a firm diagnosis in all patients with POMA, and it is difficult to assess the relationship between myoclonus and paroxysmal activity without complete polygraphic recordings from multiple EMG channels. In fact, on the basis of only the clinical and electroencephalographic features, our patient had been diagnosed with a cryptogenic focal epilepsy for many years. A full polygraphic investigation was necessary to obtain the correct diagnosis, showing the two principal phases with motor manifestations limited to the facial muscles within the spectrum of an idiopathic generalized epilepsy and not a cryptogenic focal epilepsy. In fact, the presence of myoclonic manifestations limited to facial areas, sometimes asymmetrical or prevalent in one side, confirmed the previous pathophysiological speculations, which explained the association with generalized epileptic activity. In both juvenile myoclonic epilepsy [10,11] and POMA it is possible that, in a condition of diffuse hyperexcitability, prevalent and asymmetrical cortical dysfunctions can result in asymmetrical myoclonic manifestations. Moreover, the impression of an EEG-localized focus is in accordance with several findings in patients with generalized epilepsy, as well as extensive investigations of spontaneous absence seizures in rats [12]. These findings show a cortical focus as the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and suggest rapid intracortical spread of seizure activity. On inspection of the ictal EEG–EMG correlations (Fig. 3), the association between the spike– wave complexes and the myoclonic potential (and, in particular, the spike component of the spike–wave complexes) is inconstant and a 1:1 relationship is lacking (as it occurs in myoclonic absences). This finding, and the evidence of a more complex pattern of activation of the facial muscles (including oroalimentary automatisms) shown in Figs. 1 and 2, suggests a pathophysiological mechanism for the involvement of subcortical central pattern generators related to masticatory activity through the disinhibitory effect of the spike– wave discharge [13]. In fact, a certain number of automatisms, referred to as epileptic, are the indirect effects of cortical discharges on distant central pattern generators that cause these stereotyped and cyclically repeated behaviors (i.e., masticatory automatisms). Finally, in our patient the clinical and polygraphic features improved after withdrawal of carbamazepine. In fact, a paradoxical
317
increase in seizure frequency may occur as a distinct adverse primary action of antiepileptic drugs in specific seizure types or in syndromic forms. Carbamazepine, in particular, has been reported to precipitate a variety of seizures (also myoclonic seizures) in patients with generalized epilepsies characterized by bursts of diffuse and bilaterally synchronous spike-and-wave EEG activity [14]. Physicians treating epilepsy must be aware that antiepileptic drugs can exacerbate seizures and/or EEG, and cause developmental regression. Prompt recognition of clinical and EEG deterioration and intervention may help avoid or reverse these paradoxical reactions. Ethical approval We have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Conflict of interest statement The authors have no conflicts of interest to declare. References [1] Panayiotopoulos C. Syndromes of idiopathic generalized epilepsies not recognized by the International League Against Epilepsy. Epilepsia 2005;46:57–66. [2] Rubboli G, Gardella E, Capovilla G. Idiopathic generalized epilepsy (IGE) syndromes in development: IGE with absences of early childhood, IGE with phantom absences, and perioral myoclonia with absences. Epilepsia 2009;50(Suppl 5):24–8. [3] Panayiotopoulos CP, Ferrie CD, Giannakodimos S, Robinson RO. Perioral myoclonia with absences: a new syndrome. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey; 1994. p. 143–53. [4] Clemens B. Perioral myoclonia with absences? A case report with EEG and voltage mapping analysis. Brain Dev 1997;19:353–8. [5] Bilgic B, Baykan B, Gurses C, Gokyigit A. Perioral myoclonia with absence seizures: a rare epileptic syndrome. Epileptic Disord 2001;3:23–7. [6] Baykan B, Noachtar S. Perioral myoclonia with absences: an overlooked and misdiagnosed generalized seizure type. Epilepsy Behav 2005;6:460–2. [7] Capovilla G, Rubboli G, Beccaria F, et al. A clinical spectrum of the myoclonic manifestations associated with typical absences in childhood absence epilepsy: a video-polygraphic study. Epileptic Disord 2001;3:57–62. [8] Striano S, Capovilla G, Sofia V, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;50(Suppl 5):15–9. [9] Tassinari CA, Michelucci R, Gardella E, Rubboli G. Epilepsy with myoclonic absences. In: Engel J, Pedley TA, editors. Epilepsy: a comprehensive textbook. 2nd ed. Philadelphia: Wolters Kluwer–Lippincott Williams & Wilkins; 2008. p. 2413–6. [10] Lancman ME, Asconape JJ, Penry JK. Clinical and EEG asymmetries in juvenile myoclonic epilepsy. Epilepsia 1994;35:302–6. [11] Usui N, Kotagal P, Matsumoto R, Kellinghaus C, Luders HO. Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy. Epilepsia 2005;46:1668–76. [12] Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, da Silva FH Lopes. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 2002;22:1480–95. [13] Tassinari CA, Rubboli G, Gardella E, et al. Central pattern generators for a common semiology in fronto-limbic seizures and in parasomnias. a neuroethologic approach. Neurol Sci 2005;26(Suppl 3):225–32. [14] Perucca E, Gram L, Avanzini G, Dulac o. Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998;39(1):5–17.