Epilepsia partialis continua a clinical and electroencephalography study

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1 Seizure 2002; 11: doi: /seiz , available online at on Epilepsia partialis continua a clinical and electroencephalography study J. D. PANDIAN, S. V. THOMAS, B. SANTOSHKUMAR, K. RADHAKRISHNAN, P. S. SARMA, S. JOSEPH & C. KESAVADAS Departments of Neurology, Neuroradiology and Achutha Menon Centre for Health Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum , Kerala, India Correspondence to: Dr Jeyaraj Durai Pandian, MD DM, Division of Neurology, Christian Medical College, Ludhiana, Punjab, India. jeyarajpandian@hotmail.com Epilepsia partialis continua (EPC) is a rare type of localization-related motor epilepsy. Clinical spectrum, electroencephalography (EEG) characteristics and various prognostic factors in EPC were studied in 20 patients. Patients who fulfilled the criteria for EPC between the years 1985 and 1999 were included in this retrospective and prospective study. The mean age was 18 years (range 5 months 70 years). Eleven patients (55%) had Type 1 EPC and in the remaining nine (45%) patients there were features of Type 2 EPC. Among children Rasmussen s encephalitis and viral encephalitis were the commonest cause for EPC. Encephalitis and vascular aetiology were frequently observed in adults. Tuberculous meningitis and tuberculomas occurred evenly in both the groups. The cause was unknown in two cases. Focal EEG abnormalities commonly consisted of discrete spikes, sharp waves (or) slow wave activity and periodic lateralized epileptiform discharges. The mean duration of follow up was 9.6 months with a range between 1 month and 4 years. Cognitive decline, motor deficits and pharmacoresistance to drugs were significantly seen among children with Type 2 EPC. Patients with Type 1 EPC had mild impairment of functional status with good response to treatment. The long-term prognosis depends upon the underlying cause. c 2002 Published by Elsevier Science Ltd on behalf of BEA Trading Ltd. Key words: EPC; prognosis; aetiology; Rasmussen s encephalitis. INTRODUCTION Epilepsia partialis continua (EPC) is a partial somatomotor status characterized by clonic muscular twitching repeated at fairly regular, short intervals in one part of the body for a period of days or weeks 1. Thomas et al. 2 in their review of 32 cases defined EPC as regular or irregular clonic muscular twitches affecting a limited part of the body, occurring for a minimum of 1 hour and recurring at intervals of no more than 10 seconds. Cockerell et al. 3 restricted the definition of EPC to continuous muscle jerks of cortical origin in their series of 36 cases. EPC is rather uncommon with a prevalence rate of less than one per million 3. There are several causes for EPC such as encephalitis, abscess, granuloma, infarct, haemorrhage, subdural haematoma, neoplasm, multiple sclerosis, trauma, metabolic encephalopathy, Rasmussen s syndrome, multisystem disease, hyperglycaemia and Creutzfeldt Jakob disease 2, 3. The clinical course and prognosis of EPC varies widely. There are only a few case reports of EPC reported from this country in the literature 4 7. This study attempts to characterize EPC in its clinical spectrum, electroencephalography (EEG) findings and prognosis. METHODS This study was undertaken in the Comprehensive Epilepsy Program of Sree Chitra Tirunal Institute for Medical Sciences and Technology, which is a tertiary referral centre for neurologic and cardiac disorders, in Trivandrum, southern India. We adopted the criteria proposed by Thomas et al. 2 for the diagnosis of EPC i.e. regular or irregular clonic muscular twitches affecting a limited part of the body, occurring for a minimum of 1 hour, and recurring at intervals of no more than 10 seconds. Cases were ascertained from the medical records of the Institute for the /02/ $35.00/0 c 2002 Published by Elsevier Science Ltd on behalf of BEA Trading Ltd.

2 438 J. D. Pandian et al. period All patients underwent detailed neurological examination, neuroimaging (CT scan and/or MRI scan) and EEG using standard protocol (except for one patient). Video EEG was performed in three patients. Based on the clinical and EEG characteristics EPCs were divided into two types 8, 9. Intermittent, pseudorhythmic movement caused by contraction of one or several muscle groups characterizes Type 1 EPC, which is often due to local non-progressive lesion in the central sensorimotor cortex. The myoclonus may spread into neighboring muscles and even initiate a complex partial seizure, sometimes with secondary generalization. Type 2 EPC, occurs in the context of a progressive lesion of the central nervous system, typically in Rasmussen s encephalitis. Involvement of muscle groups is frequently bilateral and multiple seizure types may be seen. In Type 1 EPC there are focal interictal abnormalities in EEG, without correlations between spikes or sharp waves and the myoclonic jerks, whereas in Type 2 EPC the background activity is slowed and extensive paroxysmal activity is present on frequent subclinical ictal discharges. Patient follow up was carried out by clinical review or postal enquiry, the functional status, presence of disabilities, the characteristics of EPC and other seizure types were ascertained. Statistical analysis We used the SPSS package for statistical analysis. Statistical significance between the groups for different variables was assessed by chi-square test or Fisher s exact test, as appropriate. A P value of < 0.05 was considered significant. RESULTS During the period of study, , there were 20 patients, (nine males and 11 females) who satisfied the inclusion criteria for EPC. Their mean age was 18 years (range 15 months 70 years). There were 12 patients below 15 years and eight patients above 15 years. The mean age of onset of EPC was 19.6 years (range 1 70 years). In 12 patients (60%) EPC was the presenting symptom. The clinical characteristics of EPC are given in Table 1. The right side of the body was affected in 11 (55%) patients and the left side in nine (45%) patients. EPC involved face, shoulder and hand more frequently than legs and distal more than proximal body parts. In the majority of patients the frequency of jerks was less than 10 per minute. Stimulus sensitivity for the jerk was observed in eight (40%) patients. Sleep failed to suppress EPC in any of them. The duration of EPC ranged from 1 day to 6 years (mean duration 6.9 months). Patients also had other types of seizures, which included simple partial seizure (17), complex partial seizure (two) and generalized tonic clonic seizures (seven). Eight patients (40%) presented with status epilepticus. Table 1: Clinical characteristics of EPC (n = 20). Topography of EPC (n) Percentage Part of the body Face and arm Shoulder, arm and hand Hand only 4 20 Leg only 1 5 Frequency of seizures <10 jerks min jerks min Unknown 1 5 Jerk sensitivity Stimulus sensitive 8 40 Movement sensitive 6 30 Unknown 6 30 Duration of EPC <7 days days months months 4 20 >1 year 2 10 General physical and systemic examination revealed abnormalities in 9 (45%) patients such as short stature, clubbing, filarial lymphoedema, tuberculous lymphadenitis, thyromegaly, hepatomegaly and ventricular septal defect. Neurological signs were observed in 16 (80%) patients such as hemiparesis (11), cognitive deficits (four), gaze palsy (two), facial palsy (two) and optic atrophy (one). Six patients presented in altered sensorium including three in coma. EEG Interictal EEG was abnormal in 16 (80%) patients and normal in three patients (16%). Interictal EEG was not available for one patient (Table 2). EEG background abnormalities included generalized slowing (10) or focal slowing (six). Ictal EEG was recorded in 11 patients and it was abnormal in nine (82%) of them. Video EEG was done in three patients, in one patient 19 partial seizures of right hemispheric onset were recorded. Seven complex partial seizures of left hemispheric onset were observed in one patient, whereas video-eeg recording did not show ictal or interictal abnormalities in one patient. The findings of neuroimaging are shown in Table 3.

3 EPC a clinical and EEG study 439 Table 2: Interictal and ictal EEG changes in EPC. EEG abnormalities (n) Percentage Interictal EEG transients Focal spikes and sharp waves 8 42 Multifocal 2 11 PLEDs a 4 21 Interictal EEG background Generalized slowing Focal slowing 6 32 Ictal EEG Decremental pattern 1 9 Low voltage fast activity Hz theta activity 5 45 Spike and slow-wave discharges 7 64 Delta slowing 3 27 Post-ictal Lateralized slowing 5 45 Lateralized suppression 1 9 Generalized suppression 2 18 Generalized slowing 2 18 a PLEDs: periodic lateralized epileptiform discharges. Fig. 2: Coronal T2 weighted-fse sequence reveals prominence of right temporal horn and frontal horn of lateral ventricle (case of Rasmussen s encephalitis). Table 3: Neuroimaging findings. CT scan CT scan MRI (n)(%) (n)(%) Abnormal 10 (38) 13 (93) Hemispheric atrophy 1 (6) 3 (21) Cerebellar hypoplasia 1 (6) 1 (7) Midbrain and pontine atrophy 1 (7) Subdural haematoma 1 (6) Subarachnoid haemorrhage 1 (6) Infarct 1 (6) 6 (43) Tuberculoma 1 (6) 1 (7) Encephalitis 1 (7) Total In one patient with haemorrhagic infarct, digital subtraction angiography showed superior saggital sinus thrombosis (Fig. 1). The various aetiologies for EPC according to age are enumerated in Table 4. Fig. 3: Ictal EEG shows onset of seizure from right hemisphere (frontal) with secondary bilateral synchrony. Treatment Fig. 1: Digital substraction angiography in a 2 year old child (venous phase) shows total occlusion of superior saggital sinus and transverse sinus. Eighteen patients were on polytherapy with various combinations of antiepileptic drugs (AED) and only one patient was on monotherapy. Diazepam infusion was used to control EPC in five patients and pentothal sodium in four patients. Nimodipine infusion was given in one patient. Four patients needed ventilatory support. The majority of the patients (n = 15) did not receive any specific intravenous infusion of AED for control of EPC. Specific treatment of meningitis and encephalitis were also administered.

4 440 J. D. Pandian et al. Table 4: Aetiology of EPC. Aetiology (n) Percentage 1. Tuberculous meningitis Tuberculoma Encephalitis Vascular Infarct 1 5 Haemorrhagic infarct 1 5 Subarachnoid haemorrhage 1 5 Subdural haematoma 1 5 Superior saggital sinus thrombosis Mitochondrial disorder Rasmussen s encephalitis Unknown 2 10 Comparison between Type 1 and Type 2 EPC Eleven patients (55%) had Type 1 EPC and the remaining nine (45%) had Type 2 EPC. Type 1 EPC was associated with age older than 15 years ( P< 0.02); less cognitive deficits ( P> 0.04) better response to AED ( P< 0.01) and higher chance of remission ( P< 0.001). Patients with persistent EPC had moderate or severe disability while those without persistent EPC had only little or no disability ( P< 0.02). Similarly those with persistent EPC had more risk of cognitive decline (P< 0.04). Prognosis Follow up was complete for 10 (50%) patients. The mean duration of follow up was 9.6 months and the range was 1 month 4 years. Five patients were independent for activities of daily living. One patient had mild disability, two had moderate disability and three patients had severe disability. Cognitive and motor deficits were demonstrable in four (44%) patients. In seven (70%) patients, there was no recurrence of EPC but three patients (30%) had persistent EPC. The course and prognosis of EPC varied according to the age, pattern and type of EPC. Patients with Type 2 EPC and in whom the EPC were persistent were <15 years. They had significant cognitive deficits, disabilities and poor response to treatment. The good prognostic factors were the age of onset (>15 years, P< 0.04), type 1 EPC (P> 0.001), and EPC occurring over a short period of time (P< 0.02). P< DISCUSSION In this study we ascertained 20 cases of EPC diagnosed clinically in the period between 1985 and In 12 (60%) patients EPC was the presenting symptom and EPC followed other seizure types in the remaining eight patients. In the series of Thomas et al (53%) patients presented with EPC with peak intensity at the onset. In the present study the face, shoulder, arm and hand were more affected with predilection for distal muscles. Findings referable to lower limbs were less well demonstrated. This topographic distribution of EPC was similarly observed in the study by Thomas et al. 2. The predilection for involvement of a certain body part appears to be proportionate to its cortical representation. EEG was abnormal in 16 (84%) patients in the interictal phase and 82% of cases in the ictal phase. Three patients had normal EEG even when there was EPC. EEG is very helpful in distinguishing EPC from various other types of paroxysmal movement disorders. However, a normal EEG does not refute the diagnosis of epilepsy or a cortical origin of the disorder 2, 3 as it can be normal in about onefifth of patients with EPC. EEG may fail to show epileptiform activity because the cortical activity may be too small to show up over prominent background activity or because the dipole of the discharge may be oriented at an unfavourable angle with respect to the recording electrodes on the scalp. Neuroimaging is very important in the work up of EPC. MRI appears to have distinct superiority over CT scan in the evaluation of EPC as the former was almost three times (93% vs. 38%) as sensitive as the latter. Nevertheless, the extent of cerebral damage as revealed by CT scan or MRI may not correlate with severity of EPC. Patients with Rasmussen s encephalitis with severe EPC may have only minimal atrophy or no change in imaging, whereas extensive cerebral infarction may not be associated with EPC. This may be because strokes produce gross neuronal damage, whereas in Rasmussen s there is preservation of larger populations of cortical neurons that are able to give rise to ictal discharges 3. In our series among children Rasmussen s encephalitis and viral encephalitis were the commonest causes for EPC. Among the adults, encephalitis and vascular mechanisms constituted commonest aetiologies. In two patients the aetiology was unknown. This pattern was comparable with other series of EPC, where atherosclerotic cerebral vascular disease and encephalitis were the commonest aetiologies 1, 3, 10, 11. Tuberculous meningitis and tuberculoma was the aetiology of EPC in four patients which is not reported in other series 2, 3. This is probably due to the high prevalence of neurotuberculosis in India 12. These

5 EPC a clinical and EEG study 441 patients had infarcts secondary to arteritis including two patients with tuberculoma. In the present series there were no patients with primary cerebral neoplasm and metabolic causes for EPC, this could be due to the ascertainment bias and also due to lack of documentation and identification of EPC. Response to medical therapy had been largely discouraging in EPC as observed earlier 2, 3. There were eight patients who responded to treatment with various AEDs. Five patients did not respond to any drugs. Response to an individual drug is difficult to assess since the majority was on polytherapy. Resective neurosurgery may be most effective treatment in well selected and carefully explored cases 13. Prognosis of EPC depended on the type of underlying disease as observed elsewhere 1, 3, 10. Patients with Type 1 EPC had a good prognosis in relation to cognitive deficits, physical disabilities and response to treatment. Type 1 EPC was seen in patients above 15 years and in the majority of them EPC was a consequence of stroke, encephalitis and tuberculous meningitis. CONCLUSIONS EPC is a special type of localization-related motor epilepsy that is characterized by clonic twitching of one group of muscles, repeated every few seconds and persisting for hours, days or longer. Differentiation between a progressive encephalopathy and a nonprogressive pathologic condition is the most important step in clinical evaluation of these cases. Early detection of treatable causes such as tuberculous meningitis, tuberculoma and encephalitis are very important in the management of EPC. The prognosis depends upon the age of onset, underlying disease and the type of EPC. REFERENCES 1. Juul-Jensen, P. and Denny-Brown, D. Epilepsia partialis continua: a clinical electroencephalographic and neuropathological study of nine cases. Archives of Neurology 1966; 15: Thomas, J. E., Reagan, T. J. and Klass, D. W. Epilepsia partialis continua. A review of 32 cases. Archives of Neurology 1977; 34: Cockerell, O. C., Rothwell, J., Thompson, P. D., Marsden, C. D. and Shorvon, S. D. Clinical and physiological features of epilepsia partialis continua. Cases ascertained in the UK. Brain 1996; 119: Bansal, S. K., Sawhney, I. M. S. and Chopra, J. S. Epilepsia partialis continua in Sjogren s syndrome. Epilepsia 1987; 28: Sabharwal, R. K., Gupta, M., Sharma, D. and Puri, V. Juvenile diabetes manifesting as epilepsia partialis continua. Journal of Association of Physicians of India 1989; 37: Dhanaraj, M. and Akilandam, R. Epilepsia partialis continua following diabetic non-ketotic hyperglycemia. Journal of Association of Physicians of India 1996; 44: Padma, M. V., Jain, S. and Maheswari, M. C. Oral clonazepam sensitive focal status epilepticus (FSE). Indian Journal of Pediatrics 1997; 64: Bancaud, J. Kojewnikow s syndrome (epilepsia partialis continua) in children. In: Epileptic Syndrome in Infancy, Childhood and Adolescence (Eds J. Roger, M. Bureau, C. Dravet, F. E. Dreifuss, A. Perret and P. Wolf). London, John Libbey, 1992: pp Bancaud, J. Kojewnikow s syndrome (epilepsia partialis continua) in children. In: Epileptic Syndromes in Infancy, Childhood and Adolescence (Eds J. Roger, C. Dravet, M. Bureau, F. E. Dreifuss and P. Wolf). London, John Libbey, 1985: pp Schomer, D. L. Focal status epilepticus and epilepsia partialis continua in adults and children. Epilepsia 1993; 34 (Suppl. 1): S29 S Gurer, G., Saygi, S. and Ciger, A. Epilepsia partialis continua: clinical and electrophysiological features of adult patients. Clinical Electroencephalography 2001; 32: Tandon, P. N., Bhatia, R. and Bhargawa, S. Tuberculous meningitis. In: Handbook of Clinical Neurology. Vol. 8 (Ed. A. A. Harris). Amsterdam, Elsevier Science, 1988: pp Biraben, A. and Chauvel, P. Epilepsia partialis continua. In: Epilepsy: a Comprehensive Text Book. Vol. 3 (Eds J. Engel Jr and T. A. Pedley). Philadelphia, PA, Lippincott-Raven Press, 1997: pp