Reflex Seizures are Frequent in Patients with Down Syndrome and Epilepsy

In a retrospective study of 30 Down syndrome (DS) patients with epilepsy, we found 6 cases (20%) with reflex seizures. One patient had benign myoclonic epilepsy of infancy with clinical photosensitivity. The other 5 cases had all startle-induced epileptic seizures and a form of symptomatic epilepsy. Three patients had a Lenox-Gastaut syndrome, one had generalized symptomatic epilepsy, and one had partial symptomatic epilepsy (PSE). Reflex epilepsy was also used as a classification category in the PSE case, as most or all seizures were stimulus-related in this patient. Seizures precipitated by stimuli were stereotyped in 4 patients, but 2 patients responded to stimuli with different types of seizures. The actual occurrence of reflex seizures in DS patients with epilepsy is probably underestimated. These cases seem to confirm previous reports showing deficiencies in cortical inhibition in the brain of DS patients.     

Down syndrome, Alzheimer's disease and seizures

Neuropathologically, Alzheimer-type abnormalities are demonstrated in patients with Down syndrome (DS), both demented and nondemented and more than a half of patients with DS above 50 years develop Alzheimer's disease (AD). The apolipoprotein E epsilon4 allele, oestrogen deficiency, high levels of Abeta1-42 peptide, elevated expression of BACE2, and valine polymorphism of prion protein gene are associated with earlier onset of dementia in DS individuals. Advanced AD alone may be an important risk factor for new-onset seizures in older adults and age above 60 years is a recognized risk factor for poor outcome from convulsive and nonconvulsive status epilepticus. DS patients aged over 45 years are significantly more likely to develop Alzheimer's disease than those less than 45 years and up to 84% demented individuals with DS develop seizures. Late-onset epilepsy in DS is associated with AD, while early-onset epilepsy is associated with an absence of dementia. In AD patients with a younger age of dementia onset are particularly susceptible to seizures. DS adults with epilepsy score significantly higher overall on the adaptive behaviour profile. Language function declined significantly more rapidly in AD patients with seizures and there is a good correlation between the severity of EEG abnormalities and cognitive impairment whereas in DS slowing of the dominant occipital rhythm is related to AD and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration.     

Delayed diagnosis of juvenile myoclonic epilepsy.

Fifteen cases of juvenile myoclonic epilepsy (JME) were identified from one hundred and eighty consecutive patients referred to a new epilepsy clinic at St Thomas' Hospital between April 1989 and December 1990, a prevalence of 8.3%. Of these, only one was referred with a putative diagnosis of JME. Diagnosis of the other patients on referral included "epilepsy", "grand mal", "temporal lobe epilepsy", "photoconvulsive epilepsy" and "alcohol-induced epilepsy". At least 11 of the 15 patients had been seen by a neurologist in the United Kingdom before referral. Definitive diagnosis was delayed by a mean of 14.5 years. In seven patients inappropriate anticonvulsants had been prescribed. Control of seizures was improved in most patients after diagnosis. Factors responsible for the delay in diagnosis include lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and high prevalence of focal abnormalities on the EEG. Precipitation of fits by alcohol and sleep deprivation may not be recognised by the physician as part of the syndrome of JME. Diagnosis may also be delayed in patients whose absence and generalised tonic-clonic seizures pre-date myoclonic jerks.     

Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized epilepsies

PURPOSE: Several studies have shown that carbamazepine (CBZ) may aggravate idiopathic generalized epilepsy (IGE). Oxcarbazepine (OXC) is a new drug chemically related to CBZ. We report six cases of juvenile IGE with a clear aggravation by OXC. METHODS: We retrospectively studied all patients with IGE first referred to our epilepsy department between January 2001 and June 2003 and treated with OXC. RESULTS: During this period, six patients were identified. All had an aggravation of their epilepsy in both clinical and EEG activities. OXC had been used because of an incorrect diagnosis of focal epilepsy or generalized tonic-clonic seizures (GTCSs) of undetermined origin (no syndromic classification of the epilepsy). Before OXC, only one patient had experienced a worsening of seizures with an inadequate drug (CBZ). Four had juvenile myoclonic epilepsy, one had juvenile absence epilepsy, and one had IGE that could not be classified into a precise syndrome. OXC (dosage range, 300-1,200 mg/day) was used in monotherapy in all of them except for one patient. Aggravation consisted of a clear aggravation of myoclonic jerks (five cases) or de novo myoclonic jerks (one case). Three patients had exacerbation of absence seizures. One patient had worsened dramatically and had absence status, and one had de novo absences after OXC treatment. The effects of OXC on GTCSs were less dramatic, with no worsening in frequency in three and a slight increase in three. CONCLUSIONS: OXC can be added to the list of antiepileptic drugs that can exacerbate myoclonic and absence seizures in IGE.     

Fall related to epileptic seizures in the elderly

It is well known that both falls and epileptic seizures are very frequent and harmful in the elderly. Moreover, although seizures may cause falls, their relationship is poorly documented in this population. We report four women (mean age: 84.5 years) who presented falls with: late‐onset focal seizures of possible parietal (Case 1) or frontal localisation (Case 2), early onset with late aggravation of juvenile myoclonic epilepsy (Case 3), and generalised situation‐related myoclonic seizures (Case 4). Falls were presumably associated with tonic posturing of left (Case 1) or right (Case 2) hemibody, to bilateral and massive myoclonic jerks (Cases 3 and 4) with a loss of consciousness (Case 3). The diagnosis of seizures was difficult and routine EEG was unremarkable in Cases 1 and 2, requiring video‐EEG monitoring to capture the clinical events. Adequate treatment offered recovery from seizures and falls in all patients. Other mechanisms of seizure‐induced falls in older patients and their management are discussed. In conclusion, falls may be caused by different seizure types and appear to be underestimated due to difficulties in seizure diagnosis in the elderly. Recognizing falls related to seizures is important in geriatric practice, as it facilitates adequate management.     

Senile myoclonic epilepsy in Down syndrome: a video and EEG presentation of two cases.

Myoclonic epilepsy is being increasingly recognized as a late-onset complication in middle-aged or elderly patients with Down syndrome, in association with cognitive decline. We show video and EEG recordings of two patients, both aged 56 years, diagnosed with this condition. At onset, myoclonic epilepsy in elderly DS patients may resemble, in its clinical expression, the classical juvenile myoclonic epilepsy with the characteristic occurrence of jerks on awakening. It is clearly associated with an Alzheimer-type dementia, and may also occur in non-DS patients with Alzheimer's disease: hence the possible denomination of "senile myoclonic epilepsy". [Published with video sequences].     

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy

ObjectiveTo report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment.MethodsA retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively.ResultsFour patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10–12), and the mean age of starting lacosamide was 17.5 years (range 16–21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300–600).ConclusionAdjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.     

Clinical factors of drug resistance in juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is a comparatively benign form of idiopathic generalised epilepsy. Little is known about the prevalence of difficult to treat or drug resistant patients. Among 155 consecutive patients with newly diagnosed juvenile myoclonic epilepsy evaluated between 1981 and 1998 and followed up for at least 1 year (61 men, 94 women; aged 15-70 years, mean 33 (SD 10.3); onset of juvenile myoclonic epilepsy at the age of 14.5 (SD 3.7), range 6-26; follow up 1-52 years, mean 13.5 (SD 9.9)), there were 15 pseudoresistant patients (9.7%: lack of compliance (eight), insufficient treatment (three), abnormal lifestyle (four)) and 24 patients (15.5%) who had persisting seizures despite adequate therapy and lifestyle. Clinical features associated with drug resistance were (1) the presence of psychiatric problems (58.3% v 19%; chi(2) p<0.001) and (2) independently, the combination of seizure types (Fischer's exact 2 by 4, p=0.0026). Three types were present in 62.5% of resistant patients versus 23.3% in non-resistant patients (chi(2), p=0.0001). None of the resistant patients had myoclonic jerks as the only seizure type or a combination of absences and myoclonic jerks. Family history of epilepsy, age at onset of seizures, sex, presence of photoparoxysmal response, results of conventional neuroimagings (CT and MRI), and delayed diagnosis were not significantly associated with drug resistance. There is thus a significant subgroup of patients with juvenile myoclonic epilepsy who pose difficult therapeutic problems, and the prevalence of resistant cases may be increased in the experience of a referral epilepsy centre.     

Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is an age-related form of idiopathic generalized epilepsy (mean age of onset: 12-14 years). The diagnosis is based on a cluster of clinical features: types of seizures, namely myoclonic jerks associated with generalized tonic-clonic or clonic-tonic-clonic seizures in 90% of the cases, absence seizures in one third of the cases; triggering factors and circadian rhythm of seizures on awakening or after sleep deprivation; a characteristic EEG pattern, i.e. bilateral symmetrical polyspike-waves. The clinical pattern is so suggestive that in clinical practice EEG is not necessary. Seventy percent of the patients are seizure-free with one-drug therapy. Treatment must be life-long, as relapse occurs in most cases after drug withdrawal, whatever the duration of control.     

Dravet syndrome: Early electroclinical findings and long‐term outcome in adolescents and adults

To describe the outcome of Dravet syndrome (DS) in adolescents and adults we conducted a longitudinal retrospective study of two independent cohorts of 34 adolescents (group 1) and 50 adults (group 2). In both cohorts, we collected information about genetic mutation, and semiology of seizures at onset and during disease course. At the last evaluation, we considered the following features: epilepsy (distinguishing myoclonic/complete and nonmyoclonic/incomplete phenotype), neurologic signs, intellectual disability (ID), and behavioral disorders. Moreover, in both cohorts, we performed a correlation analysis between early characteristics of the disease and the outcome of DS with regard to seizure persistence, ID, behavioral disorder, and neurologic impairment at last evaluation. Group 1 includes 22 adolescents with complete form of DS and 12 with incomplete form; group 2 includes 35 adults with complete form and 15 with incomplete form. The seizures persisted in 73.6% of adolescents and in 80% of adults, but epilepsy severity progressively decreased through age. Seizure persistence correlated with the complete phenotype and with the occurrence of reflex seizures. At last evaluation, ID was moderate or severe in 70.5% of adolescents and in 80% of adults. The most severe cognitive and motor impairment was observed in patients with persisting seizures. The severity of cognition, language, and neurologic impairment at last evaluation correlated statistically with the complete phenotype. The study confirms that the global outcome of DS is poor in most cases, albeit epilepsy severity decreases throughout adulthood. The improvement of epilepsy throughout ages is not associated with improvement in intellectual abilities and motor skills; this confirms that the unfavorable outcome is not a pure consequence of epilepsy.     

Clinical and neuropsychological considerations in a case of unrecognized myoclonic epileptic jerks dramatically controlled by levetiracetam

The International League Against Epilepsy (ILAE) classification recognizes 2 forms of myoclonic epilepsy with a good prognosis: benign myoclonic epilepsy of infancy (BMEI) and juvenile myoclonic epilepsy (JME); recent studies confirm the efficacy of levetiracetam (LEV) in treating idiopathic generalized epilepsies (IGE) in patients with myoclonic seizures. We report a girl referred to our Child Neuropsychiatry Unit at age 9 years because of massive myoclonic jerks, previously diagnosed as tics. Neuropsychological examination evidenced mild cognitive impairment. The clinical and electroencephalogram (EEG) data led to diagnosis of BMEI with late presentation. A dramatic suppression of interictal and ictal epileptiform activity was achieved after only one intake of LEV. Another neuropsychological examination after 6 months of treatment showed performance improvement probably related to EEG modifications. LEV may be suitable for the first-line treatment of myoclonic idiopathic seizures.     

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy

The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.     

Clinical features of epilepsy with pervasive developmental disorder

Purpose

To clarify the clinical features of patients with epilepsy and pervasive developmental disorder (PDD). Methods: We examined 12 outpatients with epilepsy as well as PDD at Seiai Rehabilitation Hospital. Results: The patients comprised 7 males and 5 females. The initial neurological symptoms appeared between 5 months and 4 years of age. The interval between the initial neurological symptoms/developmental delay and seizure onset ranged from several months to twenty years. The seizures started at 10–19 years of age in 8 out of the 12 cases. The types of seizures were astatic-drop in 2 cases, tonic-to-astatic in one, atypical absence (decreased consciousness) and generalized tonic clonic seizures (GTCS) in 3 cases, GTCS in 4 cases, or myoclonic and psychomotor in 2 cases. The mental development distributed from normal to extremely severe retardation. Paroxysmal abnormalities on eegs were focal at the frontal area in 7 cases (58%) and other findings in 5 cases. Presumptive risk factors were prenatal in 6 cases (family history for PDD in 1 case, for epilepsy in 1, twin pregnancy in 2 cases, and other in 2 cases), perinatal in 2 patients, postnatal in 1, and unknown in 3 cases. Conclusions: The seizures occurred most frequently after the onset of neurological symptoms or developmental delay. The frontal lobe dysfunction was associated with seizure onset in 58% of the cases based on the EEG findings. The risk factors were prenatal in 50% of the cases.     

Late-onset, praxis-induced myoclonic epilepsy

Praxis-induction of seizures is an interesting subset of reflex epilepsy in which seizures are induced by higher mental activities associated with the use of part of the body. Reflex traits have often been described in patients with juvenile myoclonic epilepsy. We report a patient presenting with praxis-induced myoclonic epilepsy at a late age. Ictal myoclonus was triggered by building a bird house and captured by video-polygraphic EEG recording. At 39 years old, the patient's age at onset of epilepsy was consistent with the syndrome of adult myoclonic epilepsy. Our case supports the notion of adult myoclonic epilepsy with possible occurrence of praxis-activation of seizures, as has been noted with the other idiopathic generalised epilepsies. [Published with videosequences].     

Trisomie?21, Demenz vom Alzheimer-Typ und Epilepsie

The prevalence of epilepsy in Down syndrome (DS) has increased markedly over the last few decades and, according to more recent studies, is estimated to be 8?C27%. When persons with DS develop Alzheimer disease (AD), more than two-thirds of the cases experience seizures for the first time. This is much more frequent than expected from non-Down syndrome patients with AD. Very similar semiology and courses of epilepsy in this situation have been described in case reports and small patient samples with myoclonic and generalized tonic-clonic seizures occurring, at least temporarily, after awakening.     

Myoclonic-astatic epilepsy of early childhood--clinical and EEG analysis of myoclonic-astatic seizures, and discussions on the nosology of the syndrome.

Purpose: The aim of this study is to elucidate the clinical and neurophysiological characteristics of the myoclonic, myoclonic-astatic, or astatic seizures in patients with myoclonic-astatic epilepsy (MAE) of early childhood, and to discuss on the nosology of this unique epileptic syndrome.Subjects: The subjects included 30 patients, who fulfilled the following modified International League Against Epilepsy (ILAE) criteria for MAE, and whose main seizures were captured by video-electroencephalographs (EEG) or polygraphs. The modified ILAE criteria includes: (1) normal development before onset of epilepsy and absence of organic cerebral abnormalities; (2) onset of myoclonic, myoclonic-astatic or astatic seizures between 7 months and 6 years of age; (3) presence of generalized spike- or polyspike-wave EEG discharges at 2-3 Hz, without focal spike discharges; and (4) exclusion of severe and benign myoclonic epilepsy (SME, BME) in infants and cryptogenic Lennox-Gastaut syndrome based on the ILAE definitions.Results: The seizures were investigated precisely by video-EEG (n=5), polygraph (n=2), and video-polygraph (n=23), which identified myoclonic seizures in 16 cases (myoclonic group), atonic seizures, with or without preceding minor myoclonus, in 11 cases (atonic group), and myoclonic-atonic seizures in three cases. All patients had a history of drop attacks, apart from ten patients with myoclonic seizures. Myoclonic seizures, involving mainly the axial muscles were classified into those with mild intensity not sufficient to cause the patients to fall (n=10) and those that are stronger and sufficient to cause astatic falling due to flexion of the waist or extension of the trunk (n=6). Patients in the atonic group fell straight downward, landed on their buttocks, and recovered immediately. Analysis of the ictal EEGs showed that all attacks corresponded to the generalized spike or polyspikes-and-wave complexes. In the atonic form, the spike-and-wave morphology was characterized by a positive-negative-deep-positive wave followed by a large negative slow wave. In two patients, the intensity of the atonia appeared to correspond to the depth of the positive component of the spike-and-wave complexes. We did not detect any significant differences in the clinical and EEG features and prognosis, between the atonic and myoclonic groups.Conclusions: Although the determination of exact seizure type is a prerequisite for diagnosing an epileptic syndrome, the strict differentiation of seizure type into either a myoclonic or atonic form, does not appear to have a significant impact on the outcome or in delineating this unique epileptic syndrome. At present, we consider it better to follow the current International Classification of Epileptic Syndromes and Epilepsies until a more appropriate system than the clinico-electrical approach for classifying patients with MAE is available.     

Epidemiologic Study of Epilepsy in Young Singaporean Men

PURPOSE: This survey of 20,542 Singaporean men born in 1974 studied the clinical features of young men diagnosed with epilepsy on preenlistment screening. METHODS: All male citizens in Singapore are medically screened at age 18 years before enlistment for compulsory military service. Patients suspected to have epilepsy are then referred to government hospitals for further management. We interviewed the patients and their parents and reviewed their hospital records. RESULTS: Eighty-nine patients with epilepsy were identified, indicating a lifetime prevalence of 4.9/1,000 males by age 18 years. The lifetime prevalence of epilepsy among Chinese, Malays, and Indians were 5.2, 2.8, and 6.4/1,000, respectively; these differences were not statistically significant. The mean age of seizure onset was 11.1 years. Generalized seizures (65.2%) were commoner than partial seizures (34.8%); common seizure types included generalized tonic-clonic seizures (52.8%), complex partial seizures with secondary generalization (24.7%), and myoclonic seizures (5.6%). Common epileptic syndromes included temporal lobe epilepsy (16.9%), juvenile myoclonic epilepsy (5.6%), and frontal lobe epilepsy (2.2%). Eighty-four (94.4%) patients sought medical treatment, and seven (7.9%) patients sought additional traditional treatment. Although 70 (78.7%) patients responded to medication, 14 (15.7%) patients remained refractory to treatment. CONCLUSIONS: The lifetime prevalence of epilepsy in young Singaporean men was 4.9/1,000. The majority (65.2%) had generalized seizures. Temporal lobe epilepsy was the commonest (16.9%) defined epilepsy syndrome. More patients with epilepsy (94.4%) sought medical treatment, although 15.7% remained refractory to medication.     

Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy?

BACKGROUND: Juvenile myoclonic epilepsy is a frequent form of idiopathic generalized epilepsy that is usually and easily controlled by valproate monotherapy. However, juvenile myoclonic epilepsy is often misdiagnosed, and some drugs, especially carbamazepine and phenytoin, may have an aggravating effect. OBJECTIVES: To determine the risk of aggravation of juvenile myoclonic epilepsy in patients treated with carbamazepine and phenytoin. METHODS: Among 170 consecutive patients with juvenile myoclonic epilepsy (104 female, 66 male) referred between 1981 and 1998, the authors retrospectively found 40 patients (23%) who had received carbamazepine or phenytoin (duration of epilepsy at referral, 1 to 34 years; mean +/- SD, 13.8 +/- 8.5 years; follow-up, 3 to 50 years; mean +/- SD, 16.4 +/- 11 years). RESULTS: Twenty-three patients (57.5%) experienced aggravation of seizures, whereas 6 (15%) apparently benefited from these drugs. There was no effect in the remaining 11 cases (27.5%). Carbamazepine was prescribed to 28 patients: 19 (68%) had aggravated symptoms, including myoclonic status in two; 4 (14%) were improved, one in association with valproate and one in association with valproate and phenobarbital. Phenytoin was prescribed in 16 cases: 6 (38%) had aggravation and 2 (12%) were improved, including one in association with phenobarbital. Vigabatrin was given in only one case, in association with carbamazepine, and provoked a mixed absence and myoclonic status. CONCLUSIONS: Among commonly prescribed anticonvulsants, carbamazepine appears to have the strongest aggravating potential in patients with juvenile myoclonic epilepsy, whereas the aggravating effect of phenytoin is less prominent. Aggravation was mostly in the form of increased myoclonic jerks.