Nocturnal paroxysmal dystonia related to a prerolandic dysplasia

Epilepsy Research 43 (2001) 1–9

Nocturnal paroxysmal dystonia related to a prerolandicdysplasia

Santiago Arroyo a,*, Joan Santamaria a, Javier F. Setoain b,Francisco Lomena b, Nuria Bargallo c, Eduardo Tolosa a

a Ser6icio de Neurologıa, Hospital Clinic i Pro6incial de Barcelona, c/Villarroel 170, Barcelona 08036, Spainb Ser6icio de Medicina Nuclear, Hospital Clinic i Pro6incial de Barcelona, c/Villarroel 170, Barcelona 08036, Spain

c Ser6icio de Neuroradiologıa, 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 andchoreoatetoid 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 reportedwith episodes clinically compatible with NPD who also experienced occasional generalized tonic-clonic seizures in whichthere was a frontal (prerolandic) dysplasia detected by MRI. In one patient interictal/ictal SPECTs suggested that theseizure focus was over the area of dysplasia. Both patients support the notion that NPD is a type of epilepsy arisingfrom 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; Migrationdisorders; Dysplasia

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1. Introduction

Lugaresi and Cirignotta (Lugaresi and Cirig-notta, 1981) described in 1981 a new type ofepilepsy characterized by attacks of dystonic,choreoathetoid, and ballistic movements occur-ring primarily during NREM sleep. The attackswere brief, lasting less than one minute and usu-ally occurred several times during sleep. They

termed this disorder hypnogenic (nocturnal)paroxysmal dystonia (NPD) and in a latter com-munication postulated NPD to be a form ofepilepsy (Lugaresi et al., 1986). Since then, theepileptic origin of NPD has been controversialdue to the frequent lack of clear-cut epileptiformEEG activity both interictally and during theseizures (Maccario and Lustman, 1990; Tinuper etal., 1990; Sellal et al., 1991; Veggiotti et al., 1993;Provini et al., 1999), as well as the similarity ofictal motor manifestations to those encountered insome movement disorders such as paroxysmal

* Corresponding author. Tel.: +34-3-2275414; fax: +34-3-2275454.

0920-1211/00/$ - see front matter © 2001 Published by Elsevier Science B.V.

PII: S 0920 -1211 (00 )00155 -8

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–92

kinesogenic choreoathetosis (Kertesz, 1967; Ca-mac et al., 1990) or paroxysmal dystonic choreoa-thetosis (Lance, 1977). In recent years, however,there has been increasing evidence favoring theepileptic nature of these attacks (Lugaresi andCirignotta, 1981; Lugaresi et al., 1986, 1991; Tin-uper et al., 1990; Sellal et al., 1991; Provini et al.,1999) reasons being: first, by the occasional asso-ciation with generalized tonic-clonic seizures (Tin-uper et al., 1990; Veggiotti et al., 1993). Second,by some typical episodes which are immediatelyfollowed by tonic-clonic activity (Tinuper et al.,1990). Third, epileptogenic interictal or ictal EEGactivity occurs in some patients (Tinuper et al.,1990; Veggiotti et al., 1993). Fourth, patients re-spond to antiepileptic drugs, carbamazepine (Lu-garesi and Cirignotta, 1981; Lugaresi et al., 1986;Tinuper et al., 1990; Sellal et al., 1991), as well asothers (Rajasekharan, 1990).

The localization of NPD in the frontal lobe hasrarely been corroborated. Interictal and ictalEEGs often show diffuse patterns and rarely fron-tal lobe lesions are reported. In one report (Sellalet al., 1991), two of 23 patients with NPD had alesion: one an anterior temporal cavernous an-gioma and another a hyperintense frontal lobelesion, possibly ischemic. Interestingly, the resec-tion of the cavernous angioma relieved theseizures (Sellal, 1993). A recent large series ofpatients with nocturnal frontal lobe epilepsy (halfof whom had NPD) showed a lesion in 14% ofthem (Provini et al., 1999). Lesions were diverse(archnoid cysts, vascular malformations, ischemic,gliosis and dysplasias) and were localized in vari-ous areas of the brain (occipital, frontal, andtemporal). The relationship between the localiza-tion of the lesion and the origin of the lesion orthe type of ‘seizure’ (NPD, nocturnal wanderingor paroxysmal arousal) was not stated. Finally,one patient has been studied with intracranialelectrodes (Lombroso, 1995). Ictal dischargeswere observed in the supplementary motor areaand ipsilateral caudate nucleus, suggesting anorigin in these areas, despite the absence of sup-plementary motor area motor manifestations ofthe seizures.

In this report two patients are presented withNPD attacks associated with interictal or ictal

EEG epileptogenic activity and dysplasia in theprerolandic cortex supporting the suggestion thatthis rare type of seizure disorder may be of frontallobe origin.

2. Case reports

2.1. Patient c1

The patient is a 36 year right-handed man bornat term after a normal pregnancy and deliveryand who had normal developmental milestones.There was no history of severe cranial trauma, ormeningoencephalitis. He began having abnormalepisodes at the age of eight. These episodes werebrief (less than 1 min) and were described asawakening with an abnormal cephalic sensationand a painful sensation in the right arm followedby abnormal posturing and movements of armsand legs. He experienced five to 20 episodes a day,most of them during sleep. These episodes werenot triggered by drugs, alcohol, movement oremotions. He had them continuously during hislife, except for two periods, between 14 and 16years and between 25 and 28 years, during whichhe was seizure free. During the first period he didnot recall the medication he was taking; the sec-ond coincided with a period during which hestopped taking antiepileptic drugs. He had alsoexperienced three generalized tonic-clonic seiz-ures. The patient had not been controlled withantiepileptic medication (carbamazepine, pheno-barbital, clonazepam, primidone, clobazam,phenytoin, valproic acid, lamotrigine, vigabatrine)in different combinations. Medications had beenused to the maximal tolerated dose without clear-cut response. He had also been treated withlevodopa/carbidopa and anticholinergics withoutsuccess.

The patient was admitted in the epilepsy moni-toring unit for assessment and video-EEG record-ing. Neurological examination was normal.Treatment consisted of carbamazepine 1400 mg/day. Video-EEG recording was performed with a64 channel Nicolett BMSI 5000 (Madison, WI).One hundred and three typical seizures wererecorded. Most of the seizures were brief, awoke

S. Arroyo et al. / Epilepsy Research 43 (2001) 1–9 3

him from NREM sleep and initially consisted ofan abnormal cephalic feeling along with a painfulsensation on the right arm. This was followed byan arrhythmic slow flexing movement of the samearm. Next, there was a hypertonic symmetricalfacial (painful?) expression with coreoathetoidmovements of the right arm, dystonic posturing ofthe left leg in extension and arrhythmic flexion-ex-tension movements of the left limbs with cephalicdeviation towards the left. These episodes lasted15–40 s. The patient was unable to talk and wasunresponsive but recalled one or two of threewords presented during the episodes. Ictal EEGshowed arousal and low voltage diffuse beta ac-tivity. During prolonged (up to 40 s) seizuresinduced by antiepileptic drug withdrawal and af-

ter the initial diffuse beta activity, there wasrhythmical theta activity over centroparietal re-gions bilaterally, but more prominent over theleft. Interictal EEG activity was normal. An MRI(Magneton SP Siemens 1.5 Teslas, coronal cutswith 3 mm thickness, no gap) showed a focalcortico-subcortical hyperintense area in the leftdorsolateral prerolandic region suggestive of adysplasia (Fig. 1). An interictal 99mTc-HMPAOSPECT (Elseint Helix, double head gamma cam-era fitted with fanm beam collimators. Injectionof 740 MBq) showed that the same area washyperperfused and there also was left thalamichyperperfusion (Fig. 2). Ictal 99mTc-HMPAOSPECT showed hypoperfusion at the same site ofthe 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-3Dimage showing high signal in T2Wi (arrows). Also note incidental prominent Virchow-Robin spaces.


Fig. 1. (Continued)

showed a normal IQ and memory with no frontallobe deficits. The patient was discharged on car-bamazepine and clobazam and has not hadseizures for 2 years.

2.2. Patient c2

The patient is a 36 year old left-handed manwith seizures since age 14. He was born at termafter a normal pregnancy and delivery and hadnormal developmental milestones. There was nohistory of severe cranial trauma, or meningoen-cephalitis. Seizures were described as an abnormalsensation in the right arm (which he describes as aheavy arm or loss of strength) followed by abnor-mal movements of the extremities. Most seizureslasted 10–30 s. Although initially his seizuresoccurred both awake and during sleep, for the

past few years most of them occurred only duringsleep with a frequency of one to four a night.Seizures were not triggered by drugs, alcohol,movement, or emotions. He had only experiencedone generalized tonic-clonic seizure after anti-epileptic medication withdrawal. The seizureshave been uncontrolled with multiple antiepilepticmedications (carbamazepine, lamotrigine, pheny-toin, valproic acid, and vigabatrine) in differentcombinations. He was admitted in the video-EEGmonitoring unit for evaluation. Neurological ex-amination was normal. He had 29 typical seizures,most of them occurring out of NREM sleep. Theseizures were initiated with an abnormal sensationin the right arm. This was followed by hypertonicposturing with extension of the right arm andarrhythmic dystonic-choreoatetotic movements inarms and legs, but more prominent on the right


arm. Finally, there was bilateral blinking more onthe right, right facial contraction, and right sidedcephalic clonic movements. Interictal EEGshowed bursts of left fronto-parietal delta activityand occasional medium voltage spikes over theleft frontal regions. Ictal EEG showed low-voltagediffuse beta activity and muscular artifact. AnMRI showed a left cortical hyperintense pre-rolandic lesion compatible with dysplasia (Fig. 3).Since his discharge (18 months) he has continuedto be uncontrolled by antiepileptic medication.

3. Discussion

The patients described in this report can becharacterized as having nocturnal paroxysmaldystonia (Lugaresi and Cirignotta, 1981; Lugaresi

et al., 1986, 1991). Seizures were short-lastingattacks of stereotyped dystonic and choreoatetoticmovements of the arms and legs, most of themoccurring during NREM sleep and with no ictalEEG activity or a diffuse ictal pattern. Somefeatures of both patients were somehow atypicalalthough well reported in the previous literature:both patients had a sensory aura as has beenreported 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 asym-metrically in one extremity (a feature seen in 8%of cases (Provini et al., 1999)); one of the patientshad epileptiform interictal EEG (seen in up to45% of patients with this disorder (Provini et al.,1999)); they did not respond to carbamazepine (asseen 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 wasinjected 31 s after seizure onset and 5 s before the end of the electrographic seizure. There is interictal focal hyperperfusion of theleft premotor area (arrows) and focal hypoperfusion at the same site during the ictal scan (arrows).


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 c2. A thick left prerolandic gyrus isointense to gray matter in Flash-3D and hyperintensein T2Wi images is observed (arrows).

some seizures had epileptic patterns (seen in up to66% of patients (Provini et al., 1999)). The associ-ation of the episodes with generalized tonic-clonicseizures and the presence of ictal or interictalEEG abnormalities suggested the epileptic natureof the attacks. Ictal EEG in both patients wasmostly non localizing and showed a low voltagediffuse beta pattern, features frequently seen infrontal lobe seizures (Arroyo et al., 1994;Salanova et al., 1995).

It was believed that these seizures were of fron-tal lobe origin in view of the presence of interictalfrontal spikes in one patient and ictal EEG activ-ity and 99mTc-HMPAO SPECT interictal/ictalperfusion changes in the other. Moreover, there

was a dysplastic lesion on the prerolandic cortexin both of them. In addition, ictal asymmetry inthe clinical manifestations of the seizures withgreater motor involvement of the arm contralat-eral to the lesion, also suggested their relation tothe prerolandic lesion (Manford et al., 1996).Thus, the seizures in these patients probably orig-inated near or at the dysplastic prerolandic lesion.

The ictal semiology of the seizures is difficult tointerpret due to complex pattern of movements.There were, however, some clues pointing to afrontal lobe locus like speech arrest, no loss ofconsciousness, and predominance of motor activ-ity on the right extremities. The pattern of move-ments resembled seizures originating from the


lateral frontal cortex (inferior frontal gyrus) (Ban-caud and Tailarach, 1992; Williamson, 1992) anddid not resemble supplementary motor areaseizures due to the absence of the typical posture(abduction and lifting of the contralateral upperlimb) or to seizures from the rolandic strip.

99mTC-HMPAO SPECT in patients with tem-poral or extratemporal lobe seizures usuallyshows a focal region of hypoperfusion interictallyand hyperperfusion when injected during theseizure. However, in patient c2 the contrary wasseen (interictal lesion-related localized hyperperfu-sion and ictal hypoperfusion). Although unusual,these findings are known to occur in patients withmigration disorders and allow seizure focus local-ization (Henkes et al., 1991; Matsuda et al., 1995).

The presence of a dysplasia associated withNPD seizures has recently been reported in threecases of a large series of patients (Provini et al.,1999). The relationship of the dysplasia to theseizures has not, however, been confirmed byimaging-video-EEG correlation or ictal in-tracraneal electrode recording. Cortical dysplasias(in frontal, parietal and temporal regions) havealso occasionally been associated to non-paroxys-mal dystonic hemiplegia or choreoathetosis(Leuzzi et al., 1993). Interestingly, many of thepatients presented in the literature with NPD hadnormal CT scans and did not have high resolutionMRI imaging (Lugaresi et al., 1986; Tinuper etal., 1990; Sellal et al., 1991; Meierkord et al.,1992; Veggiotti et al., 1993). It was suspected that

Fig. 3. (Continued)


Fig. 3. (Continued)

migration disorders might be encountered in otherpatients with NPD seizures if high resolutionMRI is performed.

It could be hypothesized that the dystonic andchoreoatetotic movements expressed in the NPDseizures reflect the participation of the basal gan-glia in the expression of these seizures. It is wellknown that there are strong connections betweenprerolandic (premotor) frontal lobe regions andbasal ganglia and thalamus (Brinkman andPorter, 1983). Seizure activity could spread fromprerolandic cortex to basal ganglia possibly pro-ducing a temporary arrest of cortical control ofneostriatum (Lance, 1977). The occurrence ofthese seizures mainly during sleep, also suggeststhat the NREM sleep oscillatory thalamic activity

is important for gating the abnormal cortical/basal ganglia circuits. Moreover, there has been areport of seizures recorded with intracranial elec-trodes in a patient with NPD (Lombroso, 1995) inwhich ictal discharges were observed in the cau-date nucleus as well as in the cortex.

It was concluded that nocturnal paroxysmaldystonia is a seizure disorder that could be relatedto prerolandic lesions, specifically prerolandicdysplasia.

Acknowledgements

We are grateful to Dr Ronald P. Lesser for hiscomments and suggestions and to Mark Edisonfor editing the manuscript.


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 electroencephalographicevidence for sites of origin of seizures with diffuse elec-trodecremental pattern. Epilepsia 35, 974–987.

Bancaud, J., Tailarach, J., 1992. Clinical semiology of frontallobe 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 areaand premotor area of monkey cerebral cortex: functionalorganization and activities of single neurons during perfor-mance of a learned movement. In: Desmedt, J.E. (Ed.),Motor Control Mechanisms in Health and Disease. RavenPress, New York, pp. 393–420.

Camac, A., Greene, P., Khandji, A., 1990. Paroxysmal kinesi-genic dystonic choreoathetosis associated with a thalamicinfarct. Mov. Disord. 5, 235–238.

Henkes, H., Hosten, N., Cordes, M., Neumann, K., Hansen,M.L., 1991. Increased rCBF in gray matter heterotopiasdetected by SPECT using 99mTc hexamethyl-propyle-namine oxime. Neuroradiology 33, 310–312.

Kertesz, A., 1967. Paroxysmal kinesigenic choreoathetosis. Anentity within the paroxysmal choreoathetosis syndrome.Description of 10 cases, including 1 autopsied. Neurology17, 680–690.

Lance, J.W., 1977. Familial paroxysmal dystonic choreoa-thetosis and its differentiation from related syndromes.Ann. Neurol. 2, 285–293.

Leuzzi, V., Ricciotti, V., Pelliccia, A., 1993. Hemiplegic dysto-nia associated with regional cortical dysplasia. Mov. Dis-ord. 8, 242–244.

Lombroso, C.T., 1995. Paroxysmal choreoathetosis: an epilep-tic or non-epileptic disorder? Ital. J. Neurol. Sci. 16, 271–277.

Lugaresi, E., Cirignotta, F., 1981. Hypnogenic paroxysmaldystonia: epileptic seizure or a new syndrome? Sleep 4,129–138.

Lugaresi, E., Cirignotta, F., Montagna, P., 1986. Nocturnalparoxysmal dystonia. J. Neurol. Neurosurg. Psychiatry 49,375–380.

Lugaresi, E., Cirignotta, F., Montagna, P., 1991. Nocturnalparoxysmal dystonia. Epilepsy Res. Suppl. 2, 137–140.

Maccario, M., Lustman, L.I., 1990. Paroxysmal nocturnaldystonia presenting as excessive daytime somnolence.Arch. Neurol. 47, 291–294.

Manford, M., Fish, D.R., Shorvon, S.D., 1996. An analysis ofclinical seizure patterns and their localizing value in frontaland temporal lobe epilepsies. Brain 119, 17–40.

Matsuda, H., Onuma, T., Yagishita, A., 1995. Brain SPECTimaging 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 paroxys-mal 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. Aclinical and polygraphic overview of 100 consecutive cases.Brain 122, 1017–1031.

Rajasekharan, N., 1990. Paroxysmal hypnogenic dystonia re-sponsive to phenytoin. Mov. Disord. 5, 180.

Salanova, V., Morris, H.H., Van Ness, P., Kotagal, P., Lud-ers, H.O., 1995. Frontal lobe seizures: electroclinical syn-dromes. 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 etmovements anormaux paroxystiques au corps du sommeil:dystonie paroxystique hypnogenique ou epilepsie partialle?Rev. Neurol. (Paris) 147, 121–128.

Tinuper, P., Cerullo, A., Cirignotta, F., Cortelli, P., Lugaresi,E., Montagna, P., 1990. Nocturnal paroxysmal dystoniawith short-lasting attacks: three cases with evidence for anepileptic 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 paroxysmaldystonia. Childs Nerv. Syst. 9, 458–461.

Williamson, P.D., 1992. Frontal lobe seizures. Problems indiagnosis and classification. In: Chauvel, P., Delgado-Es-cueta, A.V., Halgren, E., Bancaud, J. (Eds.), Advances inNeurology: Frontal Lobe Seizures and Epilepsies, vol. 57.Raven Press, New York, pp. 289–309.

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Nocturnal paroxysmal dystonia related to a prerolandic dysplasia