Epilepsy In Down Syndrome Research Articles

Investigation of Etiology, Treatment Outcomes and Risk Factors of Epilepsy in Down Syndrome

Objective: Although epilepsy does not appear in the classic definitions of Down syndrome (DS), the prevalence of epilepsy is higher in these cases than in the general population. The purpose of this retrospective study was to evaluate the demographic, neuroradiological, and electrophysiological characteristics, and responses to treatment of patients with DS undergoing epileptic seizure. Methods: Karyotype analysis, time of onset of seizures, types of seizure, electroencephalography (EEG) characteristic, antiepileptic drug used, and comorbidity were considered during evaluation. EEG and magnetic resonance imaging at the time of first admission were assessed during patient evaluation. Results: Patients with DS (n=43) were enrolled in this study. Twenty-three of them were subjects with epilepsy. Seventeen (73.9%) of the 23 patients were boys and six (26.1%) were girls. The mean age of the patients was 21.7 months (standard deviation ± 4.8), and mean age at onset of seizures was 12.6 months. Comorbidity other than epilepsy was present in 13 (56.5%) patients. The most common seizure type, in 14 cases (60.9%), was focal seizures, four of which involved epilepsy developing following stroke secondary to cardiac surgery. Hypothyroidism was observed in all six patients with epileptic spasm. Only four of 20 patients without epilepsy have non-neurologic comorbidities. Conclusion: This study may support the knowledge regarding the relationship between hypothyroidism and epilepsy in DS. Non-neurologic comorbidities are a significant risk factor for epilepsy in DS.

Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity.

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer’s disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS.

S166. Evoked potentials under anesthesia in children with Down Syndrome

Children with Down Syndrome frequently have surgical procedures including those that might require intraoperative neuromonitoring, most frequently in our centre using somatosensory and motor evoked potentials, (SSEPs and MEPs). The SSEP is recorded at both peripheral, spinal and cortical sites. The amplitude of the response is dependent on the size of the sensory volley. Under anesthesia, during surgical procedures, each patient serves as their own control, and comparisons to control subjects are not valid. We age matched 7 ‘healthy’ children with and without Down Syndrome undergoing spinal surgery. We compared the amplitude of the cortical and peripheral responses for ‘equivalent’ stimulation currents. We also measured the voltage required to generate similar amplitude MEPs in the muscles using transcranial electrical stimulation. Stimulation parameters (frequency, train length etc) were constant between Down Syndrome and other children. The amplitude of the peripheral responses of the SSEP did not vary between groups, but the amplitude of the cortical potentials was 12 times higher in Down Syndrome than control subjects. The voltage required to produce a MEP in the tibialis anterior muscle of 100 μV in a Down Syndrome child was 1/3–1/4 of that required in a control child. We did not observe any differences in latencies between the groups. Individuals with Down Syndrome show higher amplitude cortical somatosensory evoked potentials and a lower threshold for eliciting potentials that originate in the cortex. These two observations may be related to the well established, higher incidence of epilepsy in Down Syndrome. These findings indicate a higher degree of cortical excitability in Down Syndrome. Possible reasons for this may be changes in the mechanism of inhibition in the cortex or a true increase in the excitability of the cortex. Other studies have indicated that Down Syndrome has a higher degree of cortical connectivity, across many brain regions. The evoked potential changes may also be a reflection of this connectivity, but we do not understand the mechanism at present.

Myoclonic epilepsy in Down syndrome and Alzheimer disease

IntroductionPatients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalised polyspike-wave discharges. MethodWe present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalised tonic–clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed. ResultsIn all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalised polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam. ConclusionsThe association of generalised epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterise the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.

Down症候群に合併した遅発性ミオクロニーてんかんの一例

Down症候群に合併した遅発性ミオクロニーてんかんの一例

62. Video-polygraphic features of myoclonic epilepsy in down syndrome with Alzheimer’s disease

Little is known about the video-polygraphic features of senile myoclonic epilepsy, a myoclonic epilepsy associated with Alzhemeir’s disease in adult Down patients. Ten patients (M/F: 4/6), 51–70 years old (median 54.6 years), were submitted to clinical and neurophysiological (polygraphic recording with jerk-locked back-averaging) investigation. Three clinical-polygraphic phases emerged. The first phase was characterized by a late onset (>50 yrs) of a slowly progressive cognitive decline associated with generalized epileptiform abnormalities during sleep. After about one year, there was a gradual onset of second phase with a worsening of cognitive disorders associated with myoclonic seizures, usually occurred on awakening, and/or occasional and apparently generalized tonic-clonic seizures. Polygraphic features showed generalized fast spike-waves with bilateral myoclonic jerks, especially at awakenings. Finally, a third phase followed with dementia, ataxia, myoclonus and photosensitivity with rhythmic myoclonic jerks at a frequency of 12–24 Hz. Burst-locked electroencephalographic averaging generated a controlateral positive–negative central transient preceding the myoclonus EMG discharge by 20–24 ms, compatible with a cortical origin. Our patients showed a distinctive clinical - polygraphic picture (myoclonus, epileptic seizures, signs of neurological deterioration, particularly dementia and ataxia) suggestive of a progressive myoclonic epilepsy.

P40 – 1882 What is the predominant feature of epilepsy in Down syndrome?

P40 – 1882 What is the predominant feature of epilepsy in Down syndrome?

Electroclinical Features and Long-Term Outcome of Cryptogenic Epilepsy in Children with Down Syndrome

To describe the electroclinical features and the long-term outcomes of epilepsy in a large cohort of males and females with Down syndrome who developed epilepsy in childhood. Subjects with Down syndrome and cryptogenic epilepsy with onset in childhood were identified retrospectively from the databases of 16 Italian epilepsy centers over a 40-year period. For each subject, age at onset of seizures, seizure semiology and frequency, electroencephalography characteristics, treatment with antiepileptic drugs, and long-term clinical and electroencephalography outcomes were analyzed. A total of 104 subjects (64 males [61.5%], 40 females [38.5%]) were identified. Seizure onset occurred within 1 year of birth in 54 subjects (51.9%), between 1 and 12 years in 42 subjects (40.4%), and after 12 years in 8 subjects (7.7%). Males had a younger age of seizure onset than females. Of the 104 subjects, 51 (49.0%) had infantile spasms (IS), 35 (33.7%) had partial seizures (PS), and 18 (17.3%) had generalized seizures (GS). Febrile seizures were recorded in 5 (4.8%) subjects. Intractable seizures were observed in 23 (22.1%) subjects, including 5 (9.8%) with IS, 8 (44.4%) with PS, and 10 (31.3%) with GS. Cryptogenic epilepsy in Down syndrome may develop during the first year of life in the form of IS or, successively, as PS or GS. Electroclinical features of IS resemble those of idiopathic West syndrome, with a favorable response to treatment with adrenocorticotropic hormone seen. Patients experiencing PS and GS may be resistant to therapy with antiepileptic drugs.

Late onset myoclonic epilepsy in Down syndrome and dementia

Specific forms of epilepsy may be found at various ages in Down Syndrome (DS) and a sharp increase in the incidence of epilepsy with age has been documented. A specific type of myoclonic epilepsy associated with cognitive decline has been reported as “senile myoclonic epilepsy” or “late onset myoclonic epilepsy in DS” (LOMEDS). We report a new case of LOMEDS, documented by clinical and neurophysiological evaluation and psychometric assessment (DSDS and DMR). MF, male, affected by DS, was referred in 2004 at 40 years of age; he had no personal or familial history of epilepsy. Since one year, the patient presented cognitive deterioration, characterized by regression of language abilities, loss of memory, and loss of sphincters control. A brain TC showed mild brainstem and sub-cortical atrophy. In 2006, myoclonic jerks involving upper limbs occurred mainly after awakening. EEG showed a low voltage 8 Hz background activity with diffuse slow activity, intermingled with spikes or polyspikes, persisting during NREM sleep. MF was initially treated with clonazepam and after with topiramate, resulting in partial seizures control. MRI (2008) demonstrated diffuse brain atrophy, associated with marked ventricular enlargement. At the psychometric evaluation, onset of dementia was evident late in 2004, with transition to the middle stage in 2006. Last assessment (2009) showed the clinical signs of a late stage of deterioration, with loss of verbal abilities and autonomous ambulation. Using levetiracetam till 2,000 mg/die, myoclonic jerks decreased but are still present every day after awakening. On the EEG slow and poorly organized background activity with bilateral polyspike-wave discharges was recorded. Therefore, we documented a parallel progression of dementia and myoclonic epilepsy in a DS subject.

Epilepsy and electroencephalographic features: comparative study of Down syndrome and non-syndromic mental retardation

INTRODUCTION: Down syndrome (DS) is the most common chromosomal abnormality causing mental retardation and its association with epilepsy is highly variable in childhood. Although the first descriptions of the syndrome did not report seizures, their association with epilepsy is relatively common. METHODS: were evaluated 68 individuals with DS and 83 with non-syndromic mental retardation (N-SMR). All patients underwent digital EEG, lasting at least 30 minutes and electrodes positioned according to the International 10-20 System of Electrode Placement. Data were analyzed using descriptive statistics and proportions were compared with Student's t-test and test of Differences between Proportions with p<0.05 considered statistically significant. RESULTS: DS: 27.9% had epilepsy (first seizure with 2.2±3.7 years). Fifteen (22.1%) patients had epileptiform discharges, 5 (7.4%) hypsarrhythmia, 5 (7.4%) focal pattern, 3 (4.4%) generalized pattern and 2 (2.9%) multifocal pattern. N-SMR: 33.7% patients had epilepsy (first seizure with 1.2±4.5 years). Twenty-three (27.7%) patients had epileptiform discharges, 10 (12.0%) focal pattern, 5 (6.0%) generalized pattern and 8 (9.6%) multifocal pattern. CONCLUSION: The difference between the occurrence of epilepsy in DS and N-SMR was not statistically significant, as well as between normal EEG, EEGs with focal pattern, generalized pattern and multifocal pattern. In SD group 7.4% have shown hypsarrhythmia.The comparison with N-SMR was not possible because none of these has shown this EEG abnormality.

Epilepsy in children with Down syndrome

This review discusses the various aspects of epilepsy in Down syndrome (DS) from the perspective of paediatric neurology. DS is the most common genetic cause of mental retardation (MR) with a reported prevalence of epilepsy of 1-13%. Infantile spasms (IS) or West syndrome (WS) is the most frequent epilepsy syndrome in children with DS. IS occur in 0.6-13% of children with DS, representing 4.5-47% of seizures in these children. Curiously, these patients have electroencephalographic (EEG) characteristics of idiopathic rather than symptomatic WS. Despite a lack of consensus on therapeutic approach, no significant difference has been reported among the different regimens with regards to achieving clinical remission or EEG normalisation. It appears that DS patients have better seizure control compared to other patients with symptomatic IS, and early initiation of appropriate treatment may contribute to the prevention of late seizure development and better developmental outcome. Lennox-Gastaut syndrome (LGS) also exhibits some distinctive features in children with DS including later onset and high incidence of reflex seizures. Other seizure types including partial and generalised tonic clonic seizures have also been described in children with DS. There is a high rate of EEG abnormalities in children with DS, even among children without epilepsy, however, no patterns specific to DS have been identified and EEG does not correlate with outcome. Various cellular and molecular mechanisms contribute to epileptogenesis in DS and offer an interesting field of study.

Senile Myoclonic Epilepsy in Down Syndrome with Dementia

Senile Myoclonic Epilepsy in Down Syndrome with Dementia

Improvement of myoclonic epilepsy in Down syndrome treated with levetiracetam

Late Onset Myoclonic Epilepsy in Down Syndrome (LOMEDS) is a recognized entity usually preceded by cognitive deterioration. We report two patients with LOMEDS and cognitive decline, aged 52 and 44 years. Continuous video-EEG recording showed generalised spike and slow wave complexes as an ictal correlate of the myoclonic jerks in both patients. Low dose levetiracetam resulted in rapid, sustained seizure freedom in both patients with no reported adverse events. As for other myoclonic epilepsies, levetiracetam appears to be effective for the treatment of LOMEDS, and may be considered as a first line agent for this disorder.

Epilepsy in Down syndrome—prevalence in three age groups

A prevalence study of epilepsy in patients with Down syndrome (n = 85) in three age-groups (14-16 years, 23-29 years, 50-60 years) was conducted in the county of Aarhus, Denmark. Seventy-two patients (85%) participated. An interview and a neurological examination were performed. An EEG was recorded in 50 patients. Twelve patients (17%) had epilepsy. ILAE-1981-classification: two with partial seizures, seven with primary generalized and three with unclassifiable generalized seizures. Two patients with epilepsy had a normal EEG and 13 patients without epilepsy had an abnormal EEG.

Epilepsy in down syndrome—prevalence in three age groups§

Epilepsy in down syndrome—prevalence in three age groups§

Epilepsy in childhood down syndrome

This report concerns 844 children with Down syndrome under 15 years of age. Of the 844 cases with Down syndrome, 1.4% have epilepsy at the present time. The types of seizures are as follows; infantile spasms in 4 cases (30.8%), generalized tonic-clonic convulsions in 6 (46.1%), Lennox-Gastaut syndrome in 1 (7.7%) and psychomotor seizure in 2 (15.4%). The onset of seizure was high in the first two years (73.7%). The occurrence of epilepsy in Down syndrome in childhood did not differ from that in the general population, but infantile spasms were prevalent in Down syndrome.