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Seizures in Patients With Multiple Sclerosis Seen at Mayo Clinic, Rochester, Minn, 1990–1998
Mayo Clin Proc, October 2001, Vol 76
Seizures and Multiple Sclerosis
983
Original Article Original Article
Seizures in Patients With Multiple Sclerosis Seen at Mayo Clinic, Rochester, Minn, 1990-1998 Original ArticleOriginal ArticOriginal Ar- , MD; AND MOSES RODRIGUEZ, MD Original ArticleOriginal PAUL A. NYQUIST , MD, MPH; Article G REGORY D. CASCINO ticle Original Article • Objective: To evaluate seizure type, electroencephalo-
(27.4%). Electroencephalography was performed in 43 pa-
Original Article tients. Electroencephalographic findings included diffuse
graphic findings, and response to antiepileptic drug (AED) treatment in patients with multiple sclerosis (MS) and coexistent seizure activity. • Patients and Methods: We reviewed the medical records of all patients seen at the Mayo Clinic in Rochester, Minn, with the diagnosis of MS and seizures between 1990 and 1998. • Results: During the study period, 5715 patients with MS were identified. Of these 5715 patients, 51 (0.89%) experienced seizure activity. The most common ictal behavior was a generalized tonic-clonic seizure in 35 patients (68.6%). Simple or complex partial seizures occurred in 11 patients (21.6%), and 18 patients (35.3%) had only 1 seizure episode. Focal motor status epilepticus, ie, epilepsia partialis continua, occurred in 3 patients (5.9%) and was associated with cognitive impairment. In 37 patients (72.5%), the initial seizure presentation was after the diagnosis of MS. A seizure resulted in the diagnosis of MS or occurred before the diagnosis of MS but after other symptoms or signs of demyelinating disease in 14 patients
or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spike-and-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Of the 45 patients who received AED therapy, 35 (77.8%) had an excellent response, ie, they were seizure free. Five treated patients (11.1%) had an intractable seizure disorder. • Conclusion: Most of the patients with MS who experienced seizure activity had a benign and transient disorder that was responsive to AED treatment or required no therapy. Mayo Clin Proc. 2001;76:983-986 AED = antiepileptic drug; EDSS = Expanded Disability Status Scale; EEG = electroencephalography; EPC = epilepsia partialis continua; MRI = magnetic resonance imaging; MS = multiple sclerosis
M
PATIENTS AND METHODS We identified all patients with MS who were evaluated at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and January 1, 1998, through the Rochester Epidemiology Project. The diagnosis of MS, clinical progression of the disorder, and patients’ Expanded Disability Status Scale (EDSS) scores were determined according to previous criteria.16,17 The EDSS score was always based on the evaluation at the time of the most recent neurologic examination. The EDSS score ranged from 0 (normal) to 10 (death due to MS). Patient correspondence, medical records, and hospital notes were reviewed to determine the occurrence of seizure activity and to verify the ictal behavior, EEG findings, and outcome of AED treatment. In selected patients findings on magnetic resonance imaging (MRI) of the head were also evaluated.
ultiple sclerosis (MS) is a potentially chronic neurologic disease that can affect persons of any age and be associated with a progressive and disabling course.1,2 Patients with MS are at greater risk for the development of seizures than age-matched controls.3-16 In a study from Iceland, the risk of seizure occurrence in patients with MS was 3 times greater than that in the general population.3 Previous studies have emphasized the predominance of partial seizure activity and the presence of seizures as the initial symptom of MS.4-9 The clinical course of patients with seizures and the response to antiepileptic drug (AED) treatment are unclear.3-9 The objectives of the current study were to evaluate the types of seizures, electroencephalographic (EEG) findings, and effect of AED treatment in patients with a demyelinating disorder who experience seizure activity. From the Department of Neurology, Mayo Clinic, Rochester, Minn. Dr Nyquist is now with the National Institute of Neurological Disorders and Stroke, Bethesda, Md.
RESULTS Of 5715 consecutive patients with MS evaluated during the study period, 136 experienced seizure activity. Of these 136 patients, 51 were excluded because the diagnosis of
Address reprint requests and correspondence to Gregory D. Cascino, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]). Mayo Clin Proc. 2001;76:983-986
983
© 2001 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
984
Seizures and Multiple Sclerosis
Mayo Clin Proc, October 2001, Vol 76
Table 1. Reasons for Excluding 85 Patients Excluding factors
No. of patients
Inability to confirm diagnosis of MS Previous diagnosis of epilepsy Inability to confirm history of seizures Central nervous system infection* Subdural hematoma* Stroke* Hypoxic encephalopathy* Primary brain tumor* Metastatic brain tumor* Drug withdrawal* Metabolic condition*
51 11 7 3 3 3 2 2 1 1 1
*Seizures were related to the remote symptomatic neurologic disorder and not demyelinating disease. MS = multiple sclerosis.
MS could not be confirmed with use of established criteria.8 Additionally, 34 patients were excluded who had a history of a remote symptomatic neurologic disorder that was the presumed etiology for seizures (Table 1). The remaining 51 patients with MS and seizure activity were included in the current series. Seizure Type and EEG Findings The relationship between the occurrence of seizure activity and the diagnosis of MS is summarized in Table 2. In 37 patients the seizure activity occurred after the diagnosis of a demyelinating disorder (Table 2). A seizure was the first symptom in 3 of 14 patients who experienced an ictal episode resulting in the diagnosis of MS (Table 2). Eleven patients experienced a seizure or recurrent seizures before the diagnosis of MS but after the development of neurologic signs or symptoms of the central nervous system disease (Table 2). Findings on a neurologic examination and evaluation, ie, neuroimaging studies, supported the diagnosis of MS in all 14 patients. No other symptomTable 2. Timing of Seizure(s) in 51 Patients With Multiple Sclerosis Seizure and MS Seizure as initial neurologic event resulting in diagnosis of MS* Seizure after first symptoms of MS but before diagnosis of MS Seizure after first signs of MS but before diagnosis of MS Seizure after diagnosis of MS
No. (%) of patients 3 (5.9) 5 (9.8) 6 (11.8) 37 (72.5)
*Neurologic evaluation in all 3 patients indicated that a demyelinating disorder was the presumed etiology of seizure activity. MS = multiple sclerosis.
atic etiology for seizure activity was identified in these patients. The seizure classification was evaluated in the 51 patients (Table 3). Five patients had an indeterminate seizure type (9.8%), and 35 patients (68.6%) experienced generalized tonic-clonic seizures. The ictal behavior indicated focal features, suggesting a secondarily generalized seizure in 14 of these patients (27.4%). Complex partial seizures occurred in 7 patients (13.7%), and 4 patients (7.8%) had simple partial seizures. Of the 4 patients with simple partial seizures, 3 (5.8%) had epilepsia partialis continua (EPC) with focal motor status epilepticus. The description of the ictal semiology was inadequate to classify seizure type in 5 patients (9.8%). Of the 51 patients, 18 (35.3%) had only 1 seizure episode. In 43 patients, 119 sleep-awake EEG recordings were obtained. Patients were graded according to the EEG study that revealed the most significant abnormality, with selected individuals having more than 1 alteration. One of us (G.D.C.) retrospectively reviewed the electrophysiological studies in these patients. Findings on EEG were diffuse or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spikeand-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Periodic lateralizing epileptiform discharges were observed in 2 patients (4.7%), and recorded frontotemporal electrographic seizures were present in 2 patients (4.7%). One patient (2.3%) had EPC during an EEG study. The individual EEG patterns identified were not predictive of AED response or long-term outcome except for the recorded EPC in 1 patient who experienced progressive cognitive decline and death related to MS. MRI Review Head MRI studies in 19 patients who underwent structural neuroimaging at Mayo Clinic were reviewed retrospectively; MRI studies obtained elsewhere were not available for analysis. All the MRI scans were performed after the initial seizure episode. The mean duration from the time of the first seizure to the MRI study was 34 months (range, 0-204 months). All patients had neuroimaging evidence of demyelinating disease with predominantly periventricular white matter alterations. No other structural intra-axial lesions were evident. One patient had a region of gadolinium-DTPA enhancement, and 10 patients had generalized cortical atrophy. The MRI findings were not correlated with the ictal behavior or EEG studies because the imaging procedures were available only in selected patients and were not always contemporary with the observed seizure activity.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
AED Treatment and Outcome Forty-five patients (88.2%) received medical treatment after the occurrence of seizure activity (Table 4); 30 patients (58.8%) received only 1 AED, and 15 (29.4%) received more than 1 AED, either as monotherapy or polypharmacy. Of the 45 patients who received AED therapy, 35 (77.8%) were seizure free during follow-up. Ten patients (22.2%) had recurrent seizures despite medical treatment. Five treated patients (11.1%) developed an intractable seizure disorder, ie, disabling seizures refractory to AED therapy. No significant relationship was noted between response to AED medication and progression of MS. The EDSS score (t test, P=.68) at the time of last follow-up did not correlate with the occurrence of seizure activity (t test, P=.80). Twenty-one patients (41.2%) had an EDSS score lower than 4, and 10 (19.6%) had an EDSS score of 8 or higher. Of the 3 patients with EPC, 2 had severe disabilities and cognitive impairment. These 2 patients had intractable seizures and died shortly after developing EPC due to their demyelinating disorder. DISCUSSION Seizures can be physically disabling, psychosocially disabling, or both in patients with MS and can further impair the patient’s quality of life. The potential adverse effects of AEDs can be serious and aggravate other symptoms or signs of a demyelinating disorder, eg, ataxia and dizziness. Evidence regarding the occurrence and importance of seizure activity in patients with MS is conflicting. Early studies were unable to identify an increased risk of seizures in patients with a demyelinating disorder.5-7 Appropriate population-based epidemiological studies have indicated the epileptogenic potential of the pathological lesions associated with MS.3 Multiple sclerosis is an established independent risk factor for the occurrence of seizures.3 Seizure activity can occur before the development of other symptoms and can be the initial sign of a demyelinating disorder. Seizures are relatively uncommon in such patients and may be related to other remote symptomatic neurologic disorders. Most patients in the current study had a benign and transient seizure disorder that responded to medical treatment or they experienced only 1 seizure. The most frequently occurring seizure type was a generalized tonicclonic seizure with or without focal features. Ictal behavior associated with a complex partial seizure occurred in 7 of the 51 patients. Eighteen patients experienced a single seizure episode without recurrence. Of the 45 patients who received an AED medication, 35 were rendered seizure free. Ten of the 45 patients treated with pharmacotherapy had recurrent seizures, 5 of whom had an intractable sei-
Seizures and Multiple Sclerosis
985
Table 3. Seizure Activity in Patients With Multiple Sclerosis Seizure type
No. (%) of patients
Generalized tonic-clonic* Complex partial Simple partial† Indeterminate
35 (68.6) 7 (13.7) 4 (7.8) 5 (9.8)
*Of the 35 patients, 14 had confirmed secondarily generalized tonic-clonic seizures. †Of the 4 patients with simple partial seizures, 3 experienced epilepsia partialis continua.
zure disorder. The EEG findings varied and were not of prognostic importance. In this study, the presence of seizure activity did not correlate with the progression of MS or with the EDSS. This finding may have been related to the relatively low EDSS scores or the infrequency of seizure activity. Patients with EPC associated with demyelinating disease may represent an unfavorable prognostic group as evidenced by the accompanying progressive neurocognitive decline in 3 patients and the fatal outcome in 2 patients. The potential limitations associated with this study must be recognized. Difficulties associated with a retrospective population-based study are obtaining high case ascertainment and accurate clinical information. The high quality of the medical records used for the Rochester Epidemiology Project serves to minimize but does not eliminate these concerns.1 Fourteen patients were included despite the diagnosis of MS after seizure activity. Of these 14 patients, 11 had other neurologic symptoms and/or signs of a demyelinating disorder before seizure activity. A seizure was the first “symptom” of MS in 3 of these 14 patients. In all 14 patients the neurologist indicated the presence of a demyelinating disease. No other potential etiologic factors for seizure activity were identified in these 14 patients. Finally, head MRI studies were performed at our institution in a minority of patients. Therefore, a correlation between the neuroimaging findings and the presence of seizure activity could not be performed. Table 4. Outcome in 45 Patients Treated With Antiepileptic Drug Medication Outcome
No. (%) of patients
Seizure free Recurrent seizures Intractable epilepsy*
35 (77.8) 10 (22.2) 5 (11.1)
*Medically refractory seizures that are physically or psychologically disabling. The 5 patients with intractable epilepsy are included in the group with recurrent seizures.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
986
Seizures and Multiple Sclerosis
REFERENCES 1.
2.
3.
4. 5. 6.
7.
8.
Wynn DR, Rodriguez M, O’Fallon WM, Kurland LT. A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology. 1990;40:780-786. Moreau T, Manceau E, Lucas B, Lemesle M, Urbinelli R, Giroud M. Incidence of multiple sclerosis in Dijon, France: a populationbased ascertainment. Neurol Res. 2000;22:156-159. Olafsson E, Benedikz J, Hauser WA. Risk of epilepsy in patients with multiple sclerosis: a population-based study in Iceland. Epilepsia. 1999;40:745-747. Kinnunen E, Wikstrom J. Prevalence and prognosis of epilepsy in patients with multiple sclerosis. Epilepsia. 1986;27:729-733. Ghezzi A, Montanini R, Basso PF, Zaffaroni M, Massimo E, Cazzullo CL. Epilepsy in multiple sclerosis. Eur Neurol. 1990;30:218-223. Lindegard B. Diseases associated with multiple sclerosis and epilepsy: a population cohort study of 159,200 middle-aged, urban, native Swedes observed over 10 years (1970-79). Acta Neurol Scand. 1985;71:267-277. Thompson AJ, Kermode AG, Moseley IF, Mac Manus DG, McDonald WI. Seizures due to multiple sclerosis: seven patients with MRI correlations. J Neurol Neurosurg Psychiatry. 1993;56: 1317-1320. Moreau T, Sochurkova D, Lemesle M, et al. Epilepsy in patients with multiple sclerosis: radiological-clinical correlations. Epilepsia. 1998;39:893-896.
Mayo Clin Proc, October 2001, Vol 76
9. 10.
11.
12.
13. 14.
15.
16.
17.
Engel J Jr. Seizures and Epilepsy. Philadelphia, Pa: FA Davis Co; 1989:443-474. Bolay H, Ay H, Saygi S, Ciger A, Saribas O. Late onset absence seizures in multiple sclerosis: a case report. Clin Electroencephalogr. 1995;26:124-130. Bertol V, Gros MB, Ara JR, Uson M, Perez MI, Oliveros A. Multiple sclerosis as a cause of partial complex epilepsy [in Spanish]. Rev Neurol. 1997;25:78-79. Spatt J, Goldenberg G, Mamoli B. Simple dysphasic seizures as the sole manifestation of relapse in multiple sclerosis. Epilepsia. 1994;35:1342-1345. Hess DC, Sethi KD. Epilepsia partialis continua in multiple sclerosis. Int J Neurosci. 1990;50:109-111. Maingueneau F, Honnorat J, Isnard J, et al. Partial non-convulsive status epilepsy in multiple sclerosis [in French]. Neurophysiol Clin. 1999;29:463-472. Matthews WB, Compston A, Allen IV, Martyn CN. McAlpine’s Multiple Sclerosis. 2nd ed. Edinburgh, Scotland: Churchill Livingstone; 1991:61-63. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13:227-231. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. 1983;33: 1444-1452.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Seizures and Multiple Sclerosis
983
Original Article Original Article
Seizures in Patients With Multiple Sclerosis Seen at Mayo Clinic, Rochester, Minn, 1990-1998 Original ArticleOriginal ArticOriginal Ar- , MD; AND MOSES RODRIGUEZ, MD Original ArticleOriginal PAUL A. NYQUIST , MD, MPH; Article G REGORY D. CASCINO ticle Original Article • Objective: To evaluate seizure type, electroencephalo-
(27.4%). Electroencephalography was performed in 43 pa-
Original Article tients. Electroencephalographic findings included diffuse
graphic findings, and response to antiepileptic drug (AED) treatment in patients with multiple sclerosis (MS) and coexistent seizure activity. • Patients and Methods: We reviewed the medical records of all patients seen at the Mayo Clinic in Rochester, Minn, with the diagnosis of MS and seizures between 1990 and 1998. • Results: During the study period, 5715 patients with MS were identified. Of these 5715 patients, 51 (0.89%) experienced seizure activity. The most common ictal behavior was a generalized tonic-clonic seizure in 35 patients (68.6%). Simple or complex partial seizures occurred in 11 patients (21.6%), and 18 patients (35.3%) had only 1 seizure episode. Focal motor status epilepticus, ie, epilepsia partialis continua, occurred in 3 patients (5.9%) and was associated with cognitive impairment. In 37 patients (72.5%), the initial seizure presentation was after the diagnosis of MS. A seizure resulted in the diagnosis of MS or occurred before the diagnosis of MS but after other symptoms or signs of demyelinating disease in 14 patients
or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spike-and-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Of the 45 patients who received AED therapy, 35 (77.8%) had an excellent response, ie, they were seizure free. Five treated patients (11.1%) had an intractable seizure disorder. • Conclusion: Most of the patients with MS who experienced seizure activity had a benign and transient disorder that was responsive to AED treatment or required no therapy. Mayo Clin Proc. 2001;76:983-986 AED = antiepileptic drug; EDSS = Expanded Disability Status Scale; EEG = electroencephalography; EPC = epilepsia partialis continua; MRI = magnetic resonance imaging; MS = multiple sclerosis
M
PATIENTS AND METHODS We identified all patients with MS who were evaluated at the Mayo Clinic in Rochester, Minn, between January 1, 1990, and January 1, 1998, through the Rochester Epidemiology Project. The diagnosis of MS, clinical progression of the disorder, and patients’ Expanded Disability Status Scale (EDSS) scores were determined according to previous criteria.16,17 The EDSS score was always based on the evaluation at the time of the most recent neurologic examination. The EDSS score ranged from 0 (normal) to 10 (death due to MS). Patient correspondence, medical records, and hospital notes were reviewed to determine the occurrence of seizure activity and to verify the ictal behavior, EEG findings, and outcome of AED treatment. In selected patients findings on magnetic resonance imaging (MRI) of the head were also evaluated.
ultiple sclerosis (MS) is a potentially chronic neurologic disease that can affect persons of any age and be associated with a progressive and disabling course.1,2 Patients with MS are at greater risk for the development of seizures than age-matched controls.3-16 In a study from Iceland, the risk of seizure occurrence in patients with MS was 3 times greater than that in the general population.3 Previous studies have emphasized the predominance of partial seizure activity and the presence of seizures as the initial symptom of MS.4-9 The clinical course of patients with seizures and the response to antiepileptic drug (AED) treatment are unclear.3-9 The objectives of the current study were to evaluate the types of seizures, electroencephalographic (EEG) findings, and effect of AED treatment in patients with a demyelinating disorder who experience seizure activity. From the Department of Neurology, Mayo Clinic, Rochester, Minn. Dr Nyquist is now with the National Institute of Neurological Disorders and Stroke, Bethesda, Md.
RESULTS Of 5715 consecutive patients with MS evaluated during the study period, 136 experienced seizure activity. Of these 136 patients, 51 were excluded because the diagnosis of
Address reprint requests and correspondence to Gregory D. Cascino, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]). Mayo Clin Proc. 2001;76:983-986
983
© 2001 Mayo Foundation for Medical Education and Research
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
984
Seizures and Multiple Sclerosis
Mayo Clin Proc, October 2001, Vol 76
Table 1. Reasons for Excluding 85 Patients Excluding factors
No. of patients
Inability to confirm diagnosis of MS Previous diagnosis of epilepsy Inability to confirm history of seizures Central nervous system infection* Subdural hematoma* Stroke* Hypoxic encephalopathy* Primary brain tumor* Metastatic brain tumor* Drug withdrawal* Metabolic condition*
51 11 7 3 3 3 2 2 1 1 1
*Seizures were related to the remote symptomatic neurologic disorder and not demyelinating disease. MS = multiple sclerosis.
MS could not be confirmed with use of established criteria.8 Additionally, 34 patients were excluded who had a history of a remote symptomatic neurologic disorder that was the presumed etiology for seizures (Table 1). The remaining 51 patients with MS and seizure activity were included in the current series. Seizure Type and EEG Findings The relationship between the occurrence of seizure activity and the diagnosis of MS is summarized in Table 2. In 37 patients the seizure activity occurred after the diagnosis of a demyelinating disorder (Table 2). A seizure was the first symptom in 3 of 14 patients who experienced an ictal episode resulting in the diagnosis of MS (Table 2). Eleven patients experienced a seizure or recurrent seizures before the diagnosis of MS but after the development of neurologic signs or symptoms of the central nervous system disease (Table 2). Findings on a neurologic examination and evaluation, ie, neuroimaging studies, supported the diagnosis of MS in all 14 patients. No other symptomTable 2. Timing of Seizure(s) in 51 Patients With Multiple Sclerosis Seizure and MS Seizure as initial neurologic event resulting in diagnosis of MS* Seizure after first symptoms of MS but before diagnosis of MS Seizure after first signs of MS but before diagnosis of MS Seizure after diagnosis of MS
No. (%) of patients 3 (5.9) 5 (9.8) 6 (11.8) 37 (72.5)
*Neurologic evaluation in all 3 patients indicated that a demyelinating disorder was the presumed etiology of seizure activity. MS = multiple sclerosis.
atic etiology for seizure activity was identified in these patients. The seizure classification was evaluated in the 51 patients (Table 3). Five patients had an indeterminate seizure type (9.8%), and 35 patients (68.6%) experienced generalized tonic-clonic seizures. The ictal behavior indicated focal features, suggesting a secondarily generalized seizure in 14 of these patients (27.4%). Complex partial seizures occurred in 7 patients (13.7%), and 4 patients (7.8%) had simple partial seizures. Of the 4 patients with simple partial seizures, 3 (5.8%) had epilepsia partialis continua (EPC) with focal motor status epilepticus. The description of the ictal semiology was inadequate to classify seizure type in 5 patients (9.8%). Of the 51 patients, 18 (35.3%) had only 1 seizure episode. In 43 patients, 119 sleep-awake EEG recordings were obtained. Patients were graded according to the EEG study that revealed the most significant abnormality, with selected individuals having more than 1 alteration. One of us (G.D.C.) retrospectively reviewed the electrophysiological studies in these patients. Findings on EEG were diffuse or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spikeand-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Periodic lateralizing epileptiform discharges were observed in 2 patients (4.7%), and recorded frontotemporal electrographic seizures were present in 2 patients (4.7%). One patient (2.3%) had EPC during an EEG study. The individual EEG patterns identified were not predictive of AED response or long-term outcome except for the recorded EPC in 1 patient who experienced progressive cognitive decline and death related to MS. MRI Review Head MRI studies in 19 patients who underwent structural neuroimaging at Mayo Clinic were reviewed retrospectively; MRI studies obtained elsewhere were not available for analysis. All the MRI scans were performed after the initial seizure episode. The mean duration from the time of the first seizure to the MRI study was 34 months (range, 0-204 months). All patients had neuroimaging evidence of demyelinating disease with predominantly periventricular white matter alterations. No other structural intra-axial lesions were evident. One patient had a region of gadolinium-DTPA enhancement, and 10 patients had generalized cortical atrophy. The MRI findings were not correlated with the ictal behavior or EEG studies because the imaging procedures were available only in selected patients and were not always contemporary with the observed seizure activity.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
Mayo Clin Proc, October 2001, Vol 76
AED Treatment and Outcome Forty-five patients (88.2%) received medical treatment after the occurrence of seizure activity (Table 4); 30 patients (58.8%) received only 1 AED, and 15 (29.4%) received more than 1 AED, either as monotherapy or polypharmacy. Of the 45 patients who received AED therapy, 35 (77.8%) were seizure free during follow-up. Ten patients (22.2%) had recurrent seizures despite medical treatment. Five treated patients (11.1%) developed an intractable seizure disorder, ie, disabling seizures refractory to AED therapy. No significant relationship was noted between response to AED medication and progression of MS. The EDSS score (t test, P=.68) at the time of last follow-up did not correlate with the occurrence of seizure activity (t test, P=.80). Twenty-one patients (41.2%) had an EDSS score lower than 4, and 10 (19.6%) had an EDSS score of 8 or higher. Of the 3 patients with EPC, 2 had severe disabilities and cognitive impairment. These 2 patients had intractable seizures and died shortly after developing EPC due to their demyelinating disorder. DISCUSSION Seizures can be physically disabling, psychosocially disabling, or both in patients with MS and can further impair the patient’s quality of life. The potential adverse effects of AEDs can be serious and aggravate other symptoms or signs of a demyelinating disorder, eg, ataxia and dizziness. Evidence regarding the occurrence and importance of seizure activity in patients with MS is conflicting. Early studies were unable to identify an increased risk of seizures in patients with a demyelinating disorder.5-7 Appropriate population-based epidemiological studies have indicated the epileptogenic potential of the pathological lesions associated with MS.3 Multiple sclerosis is an established independent risk factor for the occurrence of seizures.3 Seizure activity can occur before the development of other symptoms and can be the initial sign of a demyelinating disorder. Seizures are relatively uncommon in such patients and may be related to other remote symptomatic neurologic disorders. Most patients in the current study had a benign and transient seizure disorder that responded to medical treatment or they experienced only 1 seizure. The most frequently occurring seizure type was a generalized tonicclonic seizure with or without focal features. Ictal behavior associated with a complex partial seizure occurred in 7 of the 51 patients. Eighteen patients experienced a single seizure episode without recurrence. Of the 45 patients who received an AED medication, 35 were rendered seizure free. Ten of the 45 patients treated with pharmacotherapy had recurrent seizures, 5 of whom had an intractable sei-
Seizures and Multiple Sclerosis
985
Table 3. Seizure Activity in Patients With Multiple Sclerosis Seizure type
No. (%) of patients
Generalized tonic-clonic* Complex partial Simple partial† Indeterminate
35 (68.6) 7 (13.7) 4 (7.8) 5 (9.8)
*Of the 35 patients, 14 had confirmed secondarily generalized tonic-clonic seizures. †Of the 4 patients with simple partial seizures, 3 experienced epilepsia partialis continua.
zure disorder. The EEG findings varied and were not of prognostic importance. In this study, the presence of seizure activity did not correlate with the progression of MS or with the EDSS. This finding may have been related to the relatively low EDSS scores or the infrequency of seizure activity. Patients with EPC associated with demyelinating disease may represent an unfavorable prognostic group as evidenced by the accompanying progressive neurocognitive decline in 3 patients and the fatal outcome in 2 patients. The potential limitations associated with this study must be recognized. Difficulties associated with a retrospective population-based study are obtaining high case ascertainment and accurate clinical information. The high quality of the medical records used for the Rochester Epidemiology Project serves to minimize but does not eliminate these concerns.1 Fourteen patients were included despite the diagnosis of MS after seizure activity. Of these 14 patients, 11 had other neurologic symptoms and/or signs of a demyelinating disorder before seizure activity. A seizure was the first “symptom” of MS in 3 of these 14 patients. In all 14 patients the neurologist indicated the presence of a demyelinating disease. No other potential etiologic factors for seizure activity were identified in these 14 patients. Finally, head MRI studies were performed at our institution in a minority of patients. Therefore, a correlation between the neuroimaging findings and the presence of seizure activity could not be performed. Table 4. Outcome in 45 Patients Treated With Antiepileptic Drug Medication Outcome
No. (%) of patients
Seizure free Recurrent seizures Intractable epilepsy*
35 (77.8) 10 (22.2) 5 (11.1)
*Medically refractory seizures that are physically or psychologically disabling. The 5 patients with intractable epilepsy are included in the group with recurrent seizures.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
986
Seizures and Multiple Sclerosis
REFERENCES 1.
2.
3.
4. 5. 6.
7.
8.
Wynn DR, Rodriguez M, O’Fallon WM, Kurland LT. A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota. Neurology. 1990;40:780-786. Moreau T, Manceau E, Lucas B, Lemesle M, Urbinelli R, Giroud M. Incidence of multiple sclerosis in Dijon, France: a populationbased ascertainment. Neurol Res. 2000;22:156-159. Olafsson E, Benedikz J, Hauser WA. Risk of epilepsy in patients with multiple sclerosis: a population-based study in Iceland. Epilepsia. 1999;40:745-747. Kinnunen E, Wikstrom J. Prevalence and prognosis of epilepsy in patients with multiple sclerosis. Epilepsia. 1986;27:729-733. Ghezzi A, Montanini R, Basso PF, Zaffaroni M, Massimo E, Cazzullo CL. Epilepsy in multiple sclerosis. Eur Neurol. 1990;30:218-223. Lindegard B. Diseases associated with multiple sclerosis and epilepsy: a population cohort study of 159,200 middle-aged, urban, native Swedes observed over 10 years (1970-79). Acta Neurol Scand. 1985;71:267-277. Thompson AJ, Kermode AG, Moseley IF, Mac Manus DG, McDonald WI. Seizures due to multiple sclerosis: seven patients with MRI correlations. J Neurol Neurosurg Psychiatry. 1993;56: 1317-1320. Moreau T, Sochurkova D, Lemesle M, et al. Epilepsy in patients with multiple sclerosis: radiological-clinical correlations. Epilepsia. 1998;39:893-896.
Mayo Clin Proc, October 2001, Vol 76
9. 10.
11.
12.
13. 14.
15.
16.
17.
Engel J Jr. Seizures and Epilepsy. Philadelphia, Pa: FA Davis Co; 1989:443-474. Bolay H, Ay H, Saygi S, Ciger A, Saribas O. Late onset absence seizures in multiple sclerosis: a case report. Clin Electroencephalogr. 1995;26:124-130. Bertol V, Gros MB, Ara JR, Uson M, Perez MI, Oliveros A. Multiple sclerosis as a cause of partial complex epilepsy [in Spanish]. Rev Neurol. 1997;25:78-79. Spatt J, Goldenberg G, Mamoli B. Simple dysphasic seizures as the sole manifestation of relapse in multiple sclerosis. Epilepsia. 1994;35:1342-1345. Hess DC, Sethi KD. Epilepsia partialis continua in multiple sclerosis. Int J Neurosci. 1990;50:109-111. Maingueneau F, Honnorat J, Isnard J, et al. Partial non-convulsive status epilepsy in multiple sclerosis [in French]. Neurophysiol Clin. 1999;29:463-472. Matthews WB, Compston A, Allen IV, Martyn CN. McAlpine’s Multiple Sclerosis. 2nd ed. Edinburgh, Scotland: Churchill Livingstone; 1991:61-63. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13:227-231. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. 1983;33: 1444-1452.
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.