Nocturnal paroxysmal dystonia related to a prerolandic dysplasia

Epilepsy Research 43 (2001) 1 – 9 www.elsevier.com/locate/epilepsyres

Nocturnal paroxysmal dystonia related to a prerolandic dysplasia Santiago Arroyo a,*, Joan Santamaria a, Javier F. Setoain b, Francisco Lomen˜a b, Nuria Bargallo c, Eduardo Tolosa a b

a Ser6icio de Neurologı´a, Hospital Clinic i Pro6incial de Barcelona, c/Villarroel 170, Barcelona 08036, Spain Ser6icio de Medicina Nuclear, Hospital Clinic i Pro6incial de Barcelona, c/Villarroel 170, Barcelona 08036, Spain c Ser6icio de Neuroradiologı´a, Hospital Clinic i Pro6incial de Barcelona, c/Villarroel 170, Barcelona 08036, Spain

Received 7 October 1999; received in revised form 4 June 2000; accepted 14 June 2000

Abstract Nocturnal paroxysmal dystonia (NPD) is a rare disorder characterized by attacks of short-lived dystonic, tonic and choreoatetoid movements occurring mainly during sleep. Although seizures are believed to arise from the frontal lobe, their localization is, however, uncertain due to the lack of ictal clinical-EEG correlations. Two patients are reported with episodes clinically compatible with NPD who also experienced occasional generalized tonic-clonic seizures in which there was a frontal (prerolandic) dysplasia detected by MRI. In one patient interictal/ictal SPECTs suggested that the seizure focus was over the area of dysplasia. Both patients support the notion that NPD is a type of epilepsy arising from the frontal lobe, possibly originating in the prerolandic region. © 2001 Published by Elsevier Science B.V. Keywords: Nocturnal paroxysmal dystonia; Dystonia; Choreoathetosis; Complex partial seizures; Frontal lobe seizures; Migration disorders; Dysplasia

1. Introduction Lugaresi and Cirignotta (Lugaresi and Cirignotta, 1981) described in 1981 a new type of epilepsy characterized by attacks of dystonic, choreoathetoid, and ballistic movements occurring primarily during NREM sleep. The attacks were brief, lasting less than one minute and usually occurred several times during sleep. They * Corresponding author. Tel.: +34-3-2275414; fax: +34-32275454.

termed this disorder hypnogenic (nocturnal) paroxysmal dystonia (NPD) and in a latter communication postulated NPD to be a form of epilepsy (Lugaresi et al., 1986). Since then, the epileptic origin of NPD has been controversial due to the frequent lack of clear-cut epileptiform EEG activity both interictally and during the seizures (Maccario and Lustman, 1990; Tinuper et al., 1990; Sellal et al., 1991; Veggiotti et al., 1993; Provini et al., 1999), as well as the similarity of ictal motor manifestations to those encountered in some movement disorders such as paroxysmal

0920-1211/00/$ - see front matter © 2001 Published by Elsevier Science B.V. PII: S 0 9 2 0 - 1 2 1 1 ( 0 0 ) 0 0 1 5 5 - 8

2

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

kinesogenic choreoathetosis (Kertesz, 1967; Camac et al., 1990) or paroxysmal dystonic choreoathetosis (Lance, 1977). In recent years, however, there has been increasing evidence favoring the epileptic nature of these attacks (Lugaresi and Cirignotta, 1981; Lugaresi et al., 1986, 1991; Tinuper et al., 1990; Sellal et al., 1991; Provini et al., 1999) reasons being: first, by the occasional association with generalized tonic-clonic seizures (Tinuper et al., 1990; Veggiotti et al., 1993). Second, by some typical episodes which are immediately followed by tonic-clonic activity (Tinuper et al., 1990). Third, epileptogenic interictal or ictal EEG activity occurs in some patients (Tinuper et al., 1990; Veggiotti et al., 1993). Fourth, patients respond to antiepileptic drugs, carbamazepine (Lugaresi and Cirignotta, 1981; Lugaresi et al., 1986; Tinuper et al., 1990; Sellal et al., 1991), as well as others (Rajasekharan, 1990). The localization of NPD in the frontal lobe has rarely been corroborated. Interictal and ictal EEGs often show diffuse patterns and rarely frontal lobe lesions are reported. In one report (Sellal et al., 1991), two of 23 patients with NPD had a lesion: one an anterior temporal cavernous angioma and another a hyperintense frontal lobe lesion, possibly ischemic. Interestingly, the resection of the cavernous angioma relieved the seizures (Sellal, 1993). A recent large series of patients with nocturnal frontal lobe epilepsy (half of whom had NPD) showed a lesion in 14% of them (Provini et al., 1999). Lesions were diverse (archnoid cysts, vascular malformations, ischemic, gliosis and dysplasias) and were localized in various areas of the brain (occipital, frontal, and temporal). The relationship between the localization of the lesion and the origin of the lesion or the type of ‘seizure’ (NPD, nocturnal wandering or paroxysmal arousal) was not stated. Finally, one patient has been studied with intracranial electrodes (Lombroso, 1995). Ictal discharges were observed in the supplementary motor area and ipsilateral caudate nucleus, suggesting an origin in these areas, despite the absence of supplementary motor area motor manifestations of the seizures. In this report two patients are presented with NPD attacks associated with interictal or ictal

EEG epileptogenic activity and dysplasia in the prerolandic cortex supporting the suggestion that this rare type of seizure disorder may be of frontal lobe origin.

2. Case reports

2.1. Patient c 1 The patient is a 36 year right-handed man born at term after a normal pregnancy and delivery and who had normal developmental milestones. There was no history of severe cranial trauma, or meningoencephalitis. He began having abnormal episodes at the age of eight. These episodes were brief (less than 1 min) and were described as awakening with an abnormal cephalic sensation and a painful sensation in the right arm followed by abnormal posturing and movements of arms and legs. He experienced five to 20 episodes a day, most of them during sleep. These episodes were not triggered by drugs, alcohol, movement or emotions. He had them continuously during his life, except for two periods, between 14 and 16 years and between 25 and 28 years, during which he was seizure free. During the first period he did not recall the medication he was taking; the second coincided with a period during which he stopped taking antiepileptic drugs. He had also experienced three generalized tonic-clonic seizures. The patient had not been controlled with antiepileptic medication (carbamazepine, phenobarbital, clonazepam, primidone, clobazam, phenytoin, valproic acid, lamotrigine, vigabatrine) in different combinations. Medications had been used to the maximal tolerated dose without clearcut response. He had also been treated with levodopa/carbidopa and anticholinergics without success. The patient was admitted in the epilepsy monitoring unit for assessment and video-EEG recording. Neurological examination was normal. Treatment consisted of carbamazepine 1400 mg/ day. Video-EEG recording was performed with a 64 channel Nicolett BMSI 5000 (Madison, WI). One hundred and three typical seizures were recorded. Most of the seizures were brief, awoke

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

him from NREM sleep and initially consisted of an abnormal cephalic feeling along with a painful sensation on the right arm. This was followed by an arrhythmic slow flexing movement of the same arm. Next, there was a hypertonic symmetrical facial (painful?) expression with coreoathetoid movements of the right arm, dystonic posturing of the left leg in extension and arrhythmic flexion-extension movements of the left limbs with cephalic deviation towards the left. These episodes lasted 15 – 40 s. The patient was unable to talk and was unresponsive but recalled one or two of three words presented during the episodes. Ictal EEG showed arousal and low voltage diffuse beta activity. During prolonged (up to 40 s) seizures induced by antiepileptic drug withdrawal and af-

3

ter the initial diffuse beta activity, there was rhythmical theta activity over centroparietal regions bilaterally, but more prominent over the left. Interictal EEG activity was normal. An MRI (Magneton SP Siemens 1.5 Teslas, coronal cuts with 3 mm thickness, no gap) showed a focal cortico-subcortical hyperintense area in the left dorsolateral prerolandic region suggestive of a dysplasia (Fig. 1). An interictal 99mTc-HMPAO SPECT (Elseint Helix, double head gamma camera fitted with fanm beam collimators. Injection of 740 MBq) showed that the same area was hyperperfused and there also was left thalamic hyperperfusion (Fig. 2). Ictal 99mTc-HMPAO SPECT showed hypoperfusion at the same site of the lesion (Fig. 2). Neuropsychological testing

Fig. 1. Coronal FLASH-3D (30/6/2 [repetition time/echo time/excitations], 40° flip angle) (A), coronal TSE T2-weighted (4600/90/1) (B), and axial SE T2-weighted (2500/90/1) (C) MRI images from patient c1. A thick left prerolandic gyrus is identified in Flash-3D image showing high signal in T2Wi (arrows). Also note incidental prominent Virchow-Robin spaces.

4

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

Fig. 1. (Continued)

showed a normal IQ and memory with no frontal lobe deficits. The patient was discharged on carbamazepine and clobazam and has not had seizures for 2 years.

2.2. Patient c 2 The patient is a 36 year old left-handed man with seizures since age 14. He was born at term after a normal pregnancy and delivery and had normal developmental milestones. There was no history of severe cranial trauma, or meningoencephalitis. Seizures were described as an abnormal sensation in the right arm (which he describes as a heavy arm or loss of strength) followed by abnormal movements of the extremities. Most seizures lasted 10–30 s. Although initially his seizures occurred both awake and during sleep, for the

past few years most of them occurred only during sleep with a frequency of one to four a night. Seizures were not triggered by drugs, alcohol, movement, or emotions. He had only experienced one generalized tonic-clonic seizure after antiepileptic medication withdrawal. The seizures have been uncontrolled with multiple antiepileptic medications (carbamazepine, lamotrigine, phenytoin, valproic acid, and vigabatrine) in different combinations. He was admitted in the video-EEG monitoring unit for evaluation. Neurological examination was normal. He had 29 typical seizures, most of them occurring out of NREM sleep. The seizures were initiated with an abnormal sensation in the right arm. This was followed by hypertonic posturing with extension of the right arm and arrhythmic dystonic-choreoatetotic movements in arms and legs, but more prominent on the right

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

arm. Finally, there was bilateral blinking more on the right, right facial contraction, and right sided cephalic clonic movements. Interictal EEG showed bursts of left fronto-parietal delta activity and occasional medium voltage spikes over the left frontal regions. Ictal EEG showed low-voltage diffuse beta activity and muscular artifact. An MRI showed a left cortical hyperintense prerolandic lesion compatible with dysplasia (Fig. 3). Since his discharge (18 months) he has continued to be uncontrolled by antiepileptic medication.

3. Discussion The patients described in this report can be characterized as having nocturnal paroxysmal dystonia (Lugaresi and Cirignotta, 1981; Lugaresi

5

et al., 1986, 1991). Seizures were short-lasting attacks of stereotyped dystonic and choreoatetotic movements of the arms and legs, most of them occurring during NREM sleep and with no ictal EEG activity or a diffuse ictal pattern. Some features of both patients were somehow atypical although well reported in the previous literature: both patients had a sensory aura as has been reported in some patients (Lugaresi et al., 1986); some occasional seizures occurred while awake (observed in 34% of the patients with this disorder (Provini et al., 1999)); movements started asymmetrically in one extremity (a feature seen in 8% of cases (Provini et al., 1999)); one of the patients had epileptiform interictal EEG (seen in up to 45% of patients with this disorder (Provini et al., 1999)); they did not respond to carbamazepine (as seen in 32% of patients (Provini et al., 1999)); and

Fig. 2. Interictal axial and coronal slices of a 99mTc-HMPAO-SPECT from patient c1. In the ictal SPECT, 99mTc-HMPAO was injected 31 s after seizure onset and 5 s before the end of the electrographic seizure. There is interictal focal hyperperfusion of the left premotor area (arrows) and focal hypoperfusion at the same site during the ictal scan (arrows).

6

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

Fig. 3. Coronal FLASH-3D (30/6/2, 40° flip angle) (A), coronal TSE T2-weighted (4500/90/1) (B), and axial SE T2-weighted (2500/15/1) (C) MRI images from patient c 2. A thick left prerolandic gyrus isointense to gray matter in Flash-3D and hyperintense in T2Wi images is observed (arrows).

some seizures had epileptic patterns (seen in up to 66% of patients (Provini et al., 1999)). The association of the episodes with generalized tonic-clonic seizures and the presence of ictal or interictal EEG abnormalities suggested the epileptic nature of the attacks. Ictal EEG in both patients was mostly non localizing and showed a low voltage diffuse beta pattern, features frequently seen in frontal lobe seizures (Arroyo et al., 1994; Salanova et al., 1995). It was believed that these seizures were of frontal lobe origin in view of the presence of interictal frontal spikes in one patient and ictal EEG activity and 99mTc-HMPAO SPECT interictal/ictal perfusion changes in the other. Moreover, there

was a dysplastic lesion on the prerolandic cortex in both of them. In addition, ictal asymmetry in the clinical manifestations of the seizures with greater motor involvement of the arm contralateral to the lesion, also suggested their relation to the prerolandic lesion (Manford et al., 1996). Thus, the seizures in these patients probably originated near or at the dysplastic prerolandic lesion. The ictal semiology of the seizures is difficult to interpret due to complex pattern of movements. There were, however, some clues pointing to a frontal lobe locus like speech arrest, no loss of consciousness, and predominance of motor activity on the right extremities. The pattern of movements resembled seizures originating from the

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

lateral frontal cortex (inferior frontal gyrus) (Bancaud and Tailarach, 1992; Williamson, 1992) and did not resemble supplementary motor area seizures due to the absence of the typical posture (abduction and lifting of the contralateral upper limb) or to seizures from the rolandic strip. 99m TC-HMPAO SPECT in patients with temporal or extratemporal lobe seizures usually shows a focal region of hypoperfusion interictally and hyperperfusion when injected during the seizure. However, in patient c2 the contrary was seen (interictal lesion-related localized hyperperfusion and ictal hypoperfusion). Although unusual, these findings are known to occur in patients with migration disorders and allow seizure focus localization (Henkes et al., 1991; Matsuda et al., 1995).

7

The presence of a dysplasia associated with NPD seizures has recently been reported in three cases of a large series of patients (Provini et al., 1999). The relationship of the dysplasia to the seizures has not, however, been confirmed by imaging-video-EEG correlation or ictal intracraneal electrode recording. Cortical dysplasias (in frontal, parietal and temporal regions) have also occasionally been associated to non-paroxysmal dystonic hemiplegia or choreoathetosis (Leuzzi et al., 1993). Interestingly, many of the patients presented in the literature with NPD had normal CT scans and did not have high resolution MRI imaging (Lugaresi et al., 1986; Tinuper et al., 1990; Sellal et al., 1991; Meierkord et al., 1992; Veggiotti et al., 1993). It was suspected that

Fig. 3. (Continued)

8

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

Fig. 3. (Continued)

migration disorders might be encountered in other patients with NPD seizures if high resolution MRI is performed. It could be hypothesized that the dystonic and choreoatetotic movements expressed in the NPD seizures reflect the participation of the basal ganglia in the expression of these seizures. It is well known that there are strong connections between prerolandic (premotor) frontal lobe regions and basal ganglia and thalamus (Brinkman and Porter, 1983). Seizure activity could spread from prerolandic cortex to basal ganglia possibly producing a temporary arrest of cortical control of neostriatum (Lance, 1977). The occurrence of these seizures mainly during sleep, also suggests that the NREM sleep oscillatory thalamic activity

is important for gating the abnormal cortical/ basal ganglia circuits. Moreover, there has been a report of seizures recorded with intracranial electrodes in a patient with NPD (Lombroso, 1995) in which ictal discharges were observed in the caudate nucleus as well as in the cortex. It was concluded that nocturnal paroxysmal dystonia is a seizure disorder that could be related to prerolandic lesions, specifically prerolandic dysplasia. Acknowledgements We are grateful to Dr Ronald P. Lesser for his comments and suggestions and to Mark Edison for editing the manuscript.

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9

References Arroyo, S., Lesser, R.P., Fisher, R.S., Vining, E.P., Krauss, G.L., Bandeen Roche, K., Hart, J., Gordon, B., Uematsu, S., Webber, R., 1994. Clinical and electroencephalographic evidence for sites of origin of seizures with diffuse electrodecremental pattern. Epilepsia 35, 974–987. Bancaud, J., Tailarach, J., 1992. Clinical semiology of frontal lobe seizures. In: Chauvel, P., Delgado-Escueta, A.V. (Eds.), Advances in Neurology. Raven Press, New York, pp. 3 – 58. Brinkman, C., Porter, R., 1983. Supplementary motor area and premotor area of monkey cerebral cortex: functional organization and activities of single neurons during performance of a learned movement. In: Desmedt, J.E. (Ed.), Motor Control Mechanisms in Health and Disease. Raven Press, New York, pp. 393–420. Camac, A., Greene, P., Khandji, A., 1990. Paroxysmal kinesigenic dystonic choreoathetosis associated with a thalamic infarct. Mov. Disord. 5, 235–238. Henkes, H., Hosten, N., Cordes, M., Neumann, K., Hansen, M.L., 1991. Increased rCBF in gray matter heterotopias detected by SPECT using 99mTc hexamethyl-propylenamine oxime. Neuroradiology 33, 310–312. Kertesz, A., 1967. Paroxysmal kinesigenic choreoathetosis. An entity within the paroxysmal choreoathetosis syndrome. Description of 10 cases, including 1 autopsied. Neurology 17, 680 – 690. Lance, J.W., 1977. Familial paroxysmal dystonic choreoathetosis and its differentiation from related syndromes. Ann. Neurol. 2, 285 –293. Leuzzi, V., Ricciotti, V., Pelliccia, A., 1993. Hemiplegic dystonia associated with regional cortical dysplasia. Mov. Disord. 8, 242 – 244. Lombroso, C.T., 1995. Paroxysmal choreoathetosis: an epileptic or non-epileptic disorder? Ital. J. Neurol. Sci. 16, 271– 277. Lugaresi, E., Cirignotta, F., 1981. Hypnogenic paroxysmal dystonia: epileptic seizure or a new syndrome? Sleep 4, 129 – 138. Lugaresi, E., Cirignotta, F., Montagna, P., 1986. Nocturnal paroxysmal dystonia. J. Neurol. Neurosurg. Psychiatry 49, 375 – 380.

.

9

Lugaresi, E., Cirignotta, F., Montagna, P., 1991. Nocturnal paroxysmal dystonia. Epilepsy Res. Suppl. 2, 137 – 140. Maccario, M., Lustman, L.I., 1990. Paroxysmal nocturnal dystonia presenting as excessive daytime somnolence. Arch. Neurol. 47, 291 – 294. Manford, M., Fish, D.R., Shorvon, S.D., 1996. An analysis of clinical seizure patterns and their localizing value in frontal and temporal lobe epilepsies. Brain 119, 17 – 40. Matsuda, H., Onuma, T., Yagishita, A., 1995. Brain SPECT imaging for laminar heterotopia. J. Nucl. Med. 36, 238 – 240. Meierkord, H., Fish, D.R., Smith, S.J.M., Scott, C.A., Shorvon, S.D., Marsden, C.D., 1992. Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy? Mov. Disord. 7, 38 – 42. Provini, F., Plazzi, G., Tinuper, P., Vandi, S., Lugaresi, E., Montagna, P., 1999. Nocturnal frontal lobe epilepsy. A clinical and polygraphic overview of 100 consecutive cases. Brain 122, 1017 – 1031. Rajasekharan, N., 1990. Paroxysmal hypnogenic dystonia responsive to phenytoin. Mov. Disord. 5, 180. Salanova, V., Morris, H.H., Van Ness, P., Kotagal, P., Lu¨ders, H.O., 1995. Frontal lobe seizures: electroclinical syndromes. Epilepsia 36, 16 – 24. Sellal, F., 1993. Nocturnal paroxysmal dystonia. Mov. Disord. 8, 252 – 253. Sellal, F., Hirsch, E., Maquet, P., Salmon, E., Franck, G., Collard, M., Kurtz, D., Marescaux, C., 1991. Postures et movements anormaux paroxystiques au corps du sommeil: dystonie paroxystique hypnoge´nique ou e´pilepsie partialle? Rev. Neurol. (Paris) 147, 121 – 128. Tinuper, P., Cerullo, A., Cirignotta, F., Cortelli, P., Lugaresi, E., Montagna, P., 1990. Nocturnal paroxysmal dystonia with short-lasting attacks: three cases with evidence for an epileptic frontal lobe origin of seizures. Epilepsia 31, 549 – 556. Veggiotti, P., Zambrino, C.A., Balottin, U., Viri, M., Lanzi, G., 1993. Concurrent nocturnal and diurnal paroxysmal dystonia. Childs Nerv. Syst. 9, 458 – 461. Williamson, P.D., 1992. Frontal lobe seizures. Problems in diagnosis and classification. In: Chauvel, P., Delgado-Escueta, A.V., Halgren, E., Bancaud, J. (Eds.), Advances in Neurology: Frontal Lobe Seizures and Epilepsies, vol. 57. Raven Press, New York, pp. 289 – 309.