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AN UNRECOGNISED SYNDROME OF BENIGN FOCAL EPILEPTIC SEIZURES IN TEENAGERS?
1070 AN UNRECOGNISED SYNDROME OF BENIGN FOCAL EPILEPTIC SEIZURES IN TEENAGERS?
J.
P. LOISEAU
M. ORGOGOZO
Clinique Neurologique, Université de Bordeaux II, Hôpital Pellegrin, 33076 Bordeaux, France 145 out of 1570 patients whose first fit occurred between the ages of 10 and 20 years and began as a focal seizure had no further fits for at least 5 years. This benign (non-recurring) form of focal seizures appears to be a distinct clinical entity. Its features, based on an analysis of the case-notes of 83 of the 145 cases, include: appearance of fit between the ages of 12-18 years in 84% cases; a higher incidence among males; an absence of family history of fits and of other factors predisposing to fits; normal electroencephalogram (E.E.G.) or non-specific, non-focal E.E.G. changes; and progression to generalised fits in 80·3%. The diagnosis can be suspected at presentation but confirmed only after a recurrence-free period without treatment.
Summary
Introduction IRRESPECTIVE of age of onset, partial epileptic seizures are more likely to reflect focal brain lesions than are generalised seizures,’ although this difference is less clear than previously believed.2 The incidence of brain tumours which present as fits (seizures) is much lower among children and adolescents than among adults,3 yet the prognosis for children and adolescents with partiaÌ epilepsy is generally poor.4-6 But focal epilepsies can be benign-that is, when they are not associated with brain lesions and disappear regardless of treatment. A typical example is the
"benign epilepsy with temporal-rolandic spikes", which occurs in children and always disappears at puberty.7 Our attention has been caught, during the past 18 years, by a symptom-complex which does not seem to have been described before-the occurrence or a burst of such seizures, which does not recur. In no case were these isolated episodes associated with a brain lesion. Patients and Methods A retrospective survey of 1570 patients seen between the age of 10-20 years during the past 20 years by one of us (P.L.,) for their first fit showed that 145 cases satisfied the following criteria-(1) seizures which were focal or, if generalised, which began as focal seizures, but excluding benign epilepsy with rolandic focus;’ and (2) no further fits for at least 5 years. 20 of them had been followed-up for more than 5 years. The others were contacted by telephone or by post. By these means another 63 patients were traced (50 by telephone, 13 by post), and could be included in the study (February, 1978). These 83 cases had been followed-up for a mean of 9-9±1-8 years (range, 5-17 years). Their records were reviewed for clinical and electroencephalographic data.
bably of the
be
seen
before age 10,
suggested by the shape (see accompanying figure). as
age-distribution (2) Higher incidence among males.-In this series 72% were males compared with only 34% in a group of 355 patients aged 12-17 years with partial seizures of all kind (unpublished). (3) Lack of family or personal history predisposing to epilepsy.-Only 2 cases had a family history of epilepsy (1 generalised, and 1 benign partial of the type studied here). 2 had a history of severe neonatal anoxia, 1 of bacterial meningitis, and 1 of viral meningitis. (4) Normal neurological and mental states in almost curve
all cases.-No clinical deficits were found, neither at the time of the fit nor at the end of the follow-up period, except in the 2 patients with sequelae of neonatal anoxia. (5) Characteristic seizures.-The seizures are usually characterised by a succession of symptoms associated with stepwise involvement of primary or secondary cortical areas but not of temporal or associated areas. According to the international classification of epileptic seizures,8 58 of our patients had focal motor or sensorymotor seizures, 23 had focal sensory seizures, and only 2 had complex partial (psychomotor or temporal-lobe) seizures. Since 14 patients had 2-5 fits a day, a total of 115 seizures were reported. About half the seizures had one main feature which allowed them to be classified as versive (13 cases) or jacksonian (12) or non-jacksonian (14) motor and or sensory seizures. Arrest of speech (2 cases), autonomic (2), or vertiginous (1) seizures were reported much less frequently. 37 patients had seizures with more than one main feature—e.g., of motor and visual symptoms, motor symptoms and vertigo, motor and sensory symptoms. Loss of consciousness, resulting in a fall in most cases, was almost the rule (96 seizures, 80-3%), and was more often delayed (93 cases) than immediate. A true tonic-clonic generalised seizure was noted in only 49% of these 96 seizures. (6) Normal findings or non-specific non-focal abnormalities on E.E.G.-E.E.G.S were taken in all cases (within the first 4 days in 3 patients, during the 5-7th day in 18, or even later in 21 cases); 5 records were lost. Of the 78 E.E.G.s available, 50 were absolutely normal at rest, and 14 showed slight diffuse abnormalities or hyperventilation. Bilateral posterior or diffuse slow waves were seen in 15 cases, more often in the first 4 days. A mild dysrhythmia was present in the last 13, of
Results The main features of this proposed clinical entity are: (1) Occurrence before age 20.-70 cases out of the 83 (84%) had their fit between the ages of 12 and 18 years, the peak age of occurrence being 13-14 years. The syndrome seems to be exceptional after age 20, but can pro-
Age-distribution of 83 patients at appearance of seizure.
1071 whom only 5 had paroxysmal sharp waves on hyperventilation. No typical spike-and-wave complex was seen in any case, nor was any focal E.E.G. abnormality. (7) No history of recurrence during the period of follow-up.-The role of anticonvulsive drugs in preventing recurrence cannot be established in our patients. Only 3 of them had no treatment, 16 were treated for less than a year, and 26 for a longer time. In the other cases the duration of treatment, although presumably short, is not known.
POSSIBLE MATERNAL EFFECT ON SEVERITY OF NEUROFIBROMATOSIS MARVIN MILLER
JUDITH G. HALL
Departments of Medicine and Pediatrics, University of Washington School of Medicine, and Division of Medical Genetics, Children’s Orthopedic Hospital and Medical Center, Seattle, Washington 98105, U.S.A.
62
patients with neurofibromatosis (from 54 families) whose signs or symptoms began in childhood were assessed as to the severity
Summary
Discussion The frequency of isolated fits among patients with focal seizures whose first seizure occurred between the ages of 10 and 20 years is high. Most of the cases (70 out of 83) had their attack between the ages of 12-18 years; these 70 cases made up 24% of all focal epilepsies followed-up for more than 5 years. Despite the retrospective approach used here to identify patients with benign focal epilepsy, this condition can be suspected on clinical and electroencephalographic grounds. The seizures, which begin as focal seizures and often become generalised, are usually isolated, but they may appear in clusters, in which case the seizures have the same clinical pattern but with variations corresponding to a more or less widespread epileptic discharge. Psychomotor seizures are not included as benign focal seizures since they are likely to recur. In a personal series, only 3 out of 157 cases of psychomotor seizures did not recur, compared with 66 out of 157 cases with focal seizures. Since the type of seizures seen in benign focal epilepsy may also signify the onset of chronic epilepsy, a diagnosis cannot be made when a patient is first seen. If benign focal seizures are suspected in a teenager, the diagnosis can only be made after the completion of a recurrence-free period without drug treatment. A 2-year delay has been advised.3 The witholding of drug treatment is justified by the sometimes serious biological and psychological effects produced by most anticonvulsants. Since a brain tumour is only rarely the cause of seizures in adolescence3 diagnostic procedures other than computerised tomography should be avoided, especially for the investigation of a single attack. The absence of focal neurological and E.E.G. signs also suggests that a brain tumour is unlikely to be present so that a clinical and E.E.G. follow-up period of reasonable duration is probably the best way to manage these patients. The recognition of this entity allows unnecessary investigation and anticonvulsant drug therapy to be avoided.
of disease and whether the individual was a new mutation or born to an affected father or mother. The morbidity of disease was much more severe in cases born to affected mothers than in those born to affected fathers or those who were new mutations. This finding suggests that there may be a maternal effect in neurofibromatosis similar to that which has been observed in myotonic dystrophy. This effect may be humorally mediated. Introduction NEUROFIBROMATOSIS is one of the commonest autosomal dominant conditions in man, yet its pathogenesis and clinical variability remain poorly understood. The data from this study suggest why the disease may be more severe in a subgroup of patients.
Methods The medical records of patients aged under 18 years seen at the Children’s Orthopedic Hospital and Medical Center and at the University of Washington Hospital in Seattle for signs or symptoms suggestive of neurofibromatosis were reviewed. Patients were considered to have neurofibromatosis if they had more than five café-au-lait spots greater than 1.5 cm in diameter.
The severity of the disease was graded as follows: Grade O.-Café-au-lait spots or uncomplicated
neuro-
fibroma(s). Grade 1.—Mild
complications of neurofibromatosis (e.g., mild
scoliosis, precocious puberty, behaviour problem). Grade 2.-Moderate complications of neurofibromatosis (e.g.,
hemihypertrophy, mild mental deficiency, controlled seizures). Grade 3.-Severe complications of neurofibromatosis (e.g., enucleation of the eye, intracranial masses, pseudarthrosis, severe mental deficiency, uncontrolled seizures, severe scolio-
sis). as to whether they were: (1) a new affected father, or (3) born to an affected mother. The 62 patients came from 54 families. The disease was considered to be due to new mutation only if both parents had definitely been examined and deemed not to have neurofibromatosis.
Patients
were
also classified
mutation, (2) born
Requests for reprints should be addressed to P.L., Universite de Bordeaux II, Clinique Neurologique, H6pital Pellegrin, Place Amelie Raba Leon, 33076 Bordeaux Cedex, France.
to an
Results REFERENCES
1. Penfield, W., Jasper,
and the Functional Anatomy of the Human Brain; p. 896. Boston, 1954. 2. Gastaut, H., Gastaut, J. L. Epilepsia, 1976, 17, 325. 3. Juul-Jensen, P. Acta neurol. scand., 1964, 40, (suppl. 5) 1. 4. Rodin, E. A. The Prognosis of Patients with Epilepsy; p. 455. Springfield, Illinois, 1968. 5. Holowach, J., Thurston, D. L., O’Leary, J. New Engl. J.Med. 1972, 286, 169. 6. Hess, R. Archs psychiat. Nervenkr. 1958, 197, 568. 7. Loiseau, P., Beaussart, M. Epilepsia, 1973, 14, 281. 8. Gastaut, H. ibid. 1970, 11, 102. M.
Epilepsy
,
The accompanying table classifies the patients by family history and compares the observed number to the expected number in each category. Expected numbers are based on data from Crowe, Schull, and Neel,l who found that: (1) 50% of all individuals with neurofibromatosis were new mutations, and 50% had an affected parent, and (2) the relative fertility of affected females was 0-73 while that of affected males was 0-41, so that 32% were born in affected mothers, and 18% to affected
J.
P. LOISEAU
M. ORGOGOZO
Clinique Neurologique, Université de Bordeaux II, Hôpital Pellegrin, 33076 Bordeaux, France 145 out of 1570 patients whose first fit occurred between the ages of 10 and 20 years and began as a focal seizure had no further fits for at least 5 years. This benign (non-recurring) form of focal seizures appears to be a distinct clinical entity. Its features, based on an analysis of the case-notes of 83 of the 145 cases, include: appearance of fit between the ages of 12-18 years in 84% cases; a higher incidence among males; an absence of family history of fits and of other factors predisposing to fits; normal electroencephalogram (E.E.G.) or non-specific, non-focal E.E.G. changes; and progression to generalised fits in 80·3%. The diagnosis can be suspected at presentation but confirmed only after a recurrence-free period without treatment.
Summary
Introduction IRRESPECTIVE of age of onset, partial epileptic seizures are more likely to reflect focal brain lesions than are generalised seizures,’ although this difference is less clear than previously believed.2 The incidence of brain tumours which present as fits (seizures) is much lower among children and adolescents than among adults,3 yet the prognosis for children and adolescents with partiaÌ epilepsy is generally poor.4-6 But focal epilepsies can be benign-that is, when they are not associated with brain lesions and disappear regardless of treatment. A typical example is the
"benign epilepsy with temporal-rolandic spikes", which occurs in children and always disappears at puberty.7 Our attention has been caught, during the past 18 years, by a symptom-complex which does not seem to have been described before-the occurrence or a burst of such seizures, which does not recur. In no case were these isolated episodes associated with a brain lesion. Patients and Methods A retrospective survey of 1570 patients seen between the age of 10-20 years during the past 20 years by one of us (P.L.,) for their first fit showed that 145 cases satisfied the following criteria-(1) seizures which were focal or, if generalised, which began as focal seizures, but excluding benign epilepsy with rolandic focus;’ and (2) no further fits for at least 5 years. 20 of them had been followed-up for more than 5 years. The others were contacted by telephone or by post. By these means another 63 patients were traced (50 by telephone, 13 by post), and could be included in the study (February, 1978). These 83 cases had been followed-up for a mean of 9-9±1-8 years (range, 5-17 years). Their records were reviewed for clinical and electroencephalographic data.
bably of the
be
seen
before age 10,
suggested by the shape (see accompanying figure). as
age-distribution (2) Higher incidence among males.-In this series 72% were males compared with only 34% in a group of 355 patients aged 12-17 years with partial seizures of all kind (unpublished). (3) Lack of family or personal history predisposing to epilepsy.-Only 2 cases had a family history of epilepsy (1 generalised, and 1 benign partial of the type studied here). 2 had a history of severe neonatal anoxia, 1 of bacterial meningitis, and 1 of viral meningitis. (4) Normal neurological and mental states in almost curve
all cases.-No clinical deficits were found, neither at the time of the fit nor at the end of the follow-up period, except in the 2 patients with sequelae of neonatal anoxia. (5) Characteristic seizures.-The seizures are usually characterised by a succession of symptoms associated with stepwise involvement of primary or secondary cortical areas but not of temporal or associated areas. According to the international classification of epileptic seizures,8 58 of our patients had focal motor or sensorymotor seizures, 23 had focal sensory seizures, and only 2 had complex partial (psychomotor or temporal-lobe) seizures. Since 14 patients had 2-5 fits a day, a total of 115 seizures were reported. About half the seizures had one main feature which allowed them to be classified as versive (13 cases) or jacksonian (12) or non-jacksonian (14) motor and or sensory seizures. Arrest of speech (2 cases), autonomic (2), or vertiginous (1) seizures were reported much less frequently. 37 patients had seizures with more than one main feature—e.g., of motor and visual symptoms, motor symptoms and vertigo, motor and sensory symptoms. Loss of consciousness, resulting in a fall in most cases, was almost the rule (96 seizures, 80-3%), and was more often delayed (93 cases) than immediate. A true tonic-clonic generalised seizure was noted in only 49% of these 96 seizures. (6) Normal findings or non-specific non-focal abnormalities on E.E.G.-E.E.G.S were taken in all cases (within the first 4 days in 3 patients, during the 5-7th day in 18, or even later in 21 cases); 5 records were lost. Of the 78 E.E.G.s available, 50 were absolutely normal at rest, and 14 showed slight diffuse abnormalities or hyperventilation. Bilateral posterior or diffuse slow waves were seen in 15 cases, more often in the first 4 days. A mild dysrhythmia was present in the last 13, of
Results The main features of this proposed clinical entity are: (1) Occurrence before age 20.-70 cases out of the 83 (84%) had their fit between the ages of 12 and 18 years, the peak age of occurrence being 13-14 years. The syndrome seems to be exceptional after age 20, but can pro-
Age-distribution of 83 patients at appearance of seizure.
1071 whom only 5 had paroxysmal sharp waves on hyperventilation. No typical spike-and-wave complex was seen in any case, nor was any focal E.E.G. abnormality. (7) No history of recurrence during the period of follow-up.-The role of anticonvulsive drugs in preventing recurrence cannot be established in our patients. Only 3 of them had no treatment, 16 were treated for less than a year, and 26 for a longer time. In the other cases the duration of treatment, although presumably short, is not known.
POSSIBLE MATERNAL EFFECT ON SEVERITY OF NEUROFIBROMATOSIS MARVIN MILLER
JUDITH G. HALL
Departments of Medicine and Pediatrics, University of Washington School of Medicine, and Division of Medical Genetics, Children’s Orthopedic Hospital and Medical Center, Seattle, Washington 98105, U.S.A.
62
patients with neurofibromatosis (from 54 families) whose signs or symptoms began in childhood were assessed as to the severity
Summary
Discussion The frequency of isolated fits among patients with focal seizures whose first seizure occurred between the ages of 10 and 20 years is high. Most of the cases (70 out of 83) had their attack between the ages of 12-18 years; these 70 cases made up 24% of all focal epilepsies followed-up for more than 5 years. Despite the retrospective approach used here to identify patients with benign focal epilepsy, this condition can be suspected on clinical and electroencephalographic grounds. The seizures, which begin as focal seizures and often become generalised, are usually isolated, but they may appear in clusters, in which case the seizures have the same clinical pattern but with variations corresponding to a more or less widespread epileptic discharge. Psychomotor seizures are not included as benign focal seizures since they are likely to recur. In a personal series, only 3 out of 157 cases of psychomotor seizures did not recur, compared with 66 out of 157 cases with focal seizures. Since the type of seizures seen in benign focal epilepsy may also signify the onset of chronic epilepsy, a diagnosis cannot be made when a patient is first seen. If benign focal seizures are suspected in a teenager, the diagnosis can only be made after the completion of a recurrence-free period without drug treatment. A 2-year delay has been advised.3 The witholding of drug treatment is justified by the sometimes serious biological and psychological effects produced by most anticonvulsants. Since a brain tumour is only rarely the cause of seizures in adolescence3 diagnostic procedures other than computerised tomography should be avoided, especially for the investigation of a single attack. The absence of focal neurological and E.E.G. signs also suggests that a brain tumour is unlikely to be present so that a clinical and E.E.G. follow-up period of reasonable duration is probably the best way to manage these patients. The recognition of this entity allows unnecessary investigation and anticonvulsant drug therapy to be avoided.
of disease and whether the individual was a new mutation or born to an affected father or mother. The morbidity of disease was much more severe in cases born to affected mothers than in those born to affected fathers or those who were new mutations. This finding suggests that there may be a maternal effect in neurofibromatosis similar to that which has been observed in myotonic dystrophy. This effect may be humorally mediated. Introduction NEUROFIBROMATOSIS is one of the commonest autosomal dominant conditions in man, yet its pathogenesis and clinical variability remain poorly understood. The data from this study suggest why the disease may be more severe in a subgroup of patients.
Methods The medical records of patients aged under 18 years seen at the Children’s Orthopedic Hospital and Medical Center and at the University of Washington Hospital in Seattle for signs or symptoms suggestive of neurofibromatosis were reviewed. Patients were considered to have neurofibromatosis if they had more than five café-au-lait spots greater than 1.5 cm in diameter.
The severity of the disease was graded as follows: Grade O.-Café-au-lait spots or uncomplicated
neuro-
fibroma(s). Grade 1.—Mild
complications of neurofibromatosis (e.g., mild
scoliosis, precocious puberty, behaviour problem). Grade 2.-Moderate complications of neurofibromatosis (e.g.,
hemihypertrophy, mild mental deficiency, controlled seizures). Grade 3.-Severe complications of neurofibromatosis (e.g., enucleation of the eye, intracranial masses, pseudarthrosis, severe mental deficiency, uncontrolled seizures, severe scolio-
sis). as to whether they were: (1) a new affected father, or (3) born to an affected mother. The 62 patients came from 54 families. The disease was considered to be due to new mutation only if both parents had definitely been examined and deemed not to have neurofibromatosis.
Patients
were
also classified
mutation, (2) born
Requests for reprints should be addressed to P.L., Universite de Bordeaux II, Clinique Neurologique, H6pital Pellegrin, Place Amelie Raba Leon, 33076 Bordeaux Cedex, France.
to an
Results REFERENCES
1. Penfield, W., Jasper,
and the Functional Anatomy of the Human Brain; p. 896. Boston, 1954. 2. Gastaut, H., Gastaut, J. L. Epilepsia, 1976, 17, 325. 3. Juul-Jensen, P. Acta neurol. scand., 1964, 40, (suppl. 5) 1. 4. Rodin, E. A. The Prognosis of Patients with Epilepsy; p. 455. Springfield, Illinois, 1968. 5. Holowach, J., Thurston, D. L., O’Leary, J. New Engl. J.Med. 1972, 286, 169. 6. Hess, R. Archs psychiat. Nervenkr. 1958, 197, 568. 7. Loiseau, P., Beaussart, M. Epilepsia, 1973, 14, 281. 8. Gastaut, H. ibid. 1970, 11, 102. M.
Epilepsy
,
The accompanying table classifies the patients by family history and compares the observed number to the expected number in each category. Expected numbers are based on data from Crowe, Schull, and Neel,l who found that: (1) 50% of all individuals with neurofibromatosis were new mutations, and 50% had an affected parent, and (2) the relative fertility of affected females was 0-73 while that of affected males was 0-41, so that 32% were born in affected mothers, and 18% to affected