Adult motor phenotype differentiates Dravet syndrome from Lennox‐Gastaut syndrome and links <i><scp>SCN</scp>1A</i> to early onset parkinsonian features

Aljaafari, Danah; Fasano, Alfonso; Nascimento, Fábio A.; Lang, Anthony E.; Andrade, Danielle M.

doi:10.1111/epi.13692

Cited by 36 publications

(46 citation statements)

References 13 publications

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“…Long-term AED use and the seizures themselves are often blamed for the negative issues that patients experience. This study, which found 75% of patients experience gait disturbances, supports the recent finding that gait issues are a unique characteristic of DS, even when compared with Lennox-Gastaut syndrome, whose patients share a long history of multiple AED use and frequent seizures [16]. Certain conditions that appear age-related in this survey such as osteopenia and broken bones may indeed be the result of long-term medication use and are common in the general population with epilepsy [17].…”

Section: Dravet Syndrome Vs Epilepsy In Generalsupporting

confidence: 86%

Dravet syndrome: Characteristics, comorbidities, and caregiver concerns

Villas

Meskis

Goodliffe

2017

Epilepsy & Behavior

145

169

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The Dravet Syndrome Foundation (DSF) conducted the largest in-depth survey of parents and caregivers of patients with Dravet syndrome (DS) to date, in order to (1) identify top concerns among caregivers, (2) establish an approximate frequency of characteristics and comorbidities of DS beyond seizures, and (3) provide direction for clinicians and researchers looking to study the effects of DS on the patient and family unit. Two hundred fifty-six responses were received representing a patient age range of 9months to 32years with a median age group of 7-10years (IQR=8). In an open response, caregivers ranked speech/communication, impacts on siblings, and cognitive impairment as their top concerns after seizure control, and nearly two-thirds of caregivers reported having suffered from depression. Some characteristics of DS such as gait issues increased with patient age, while others, including photosensitivity, hypotonia, and ataxia, were present from a young age. Comorbidities such as sleep disturbances and cardiac abnormalities were more frequently reported than in previous studies and some (including bradycardia) were correlated with SCN1A mutation status. This survey supports the concept of Dravet syndrome as a disease of the central nervous system with far-reaching effects and highlights the importance of the patient voice in determining appropriate research objectives. While seizure frequency is a relatively well-understood objective, seizures represent only a portion of parent and caregiver concerns. Studying the characteristics of DS described herein may identify additional outcomes significant for research.

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Section: Dravet Syndrome Vs Epilepsy In Generalsupporting

confidence: 86%

Dravet syndrome: Characteristics, comorbidities, and caregiver concerns

Villas

Meskis

Goodliffe

2017

Epilepsy & Behavior

145

169

View full text Add to dashboard Cite

show abstract

“…For example, ataxia and crouching gait seen in Dravet syndrome may be related to SCN1A mutations, 17 whereas spastic paralysis, seen in a small number of patients with Dravet syndrome, may be the sequelae of acute encephalopathy caused by status epilepticus. [18][19][20] Our analysis of patients in the lowest and highest seizure strata also did not reveal a significant difference between the two groups for autism, ADHD, and other behavioural problems. These discrepancies indicate that seizure frequency is not the only factor to explain comorbidities, as already shown in other smaller studies.…”

Section: Discussionmentioning

confidence: 47%

Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey

Lagae

Brambilla²,

Mingorance³

et al. 2017

Develop Med Child Neuro

148

219

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Aim To test the hypothesis that higher seizure burden in Dravet syndrome is associated with increased comorbidities and lower quality of life (QoL) in a large cohort of patients with Dravet syndrome and their caregivers in Europe. Method An extensive survey of caregivers of patients with Dravet syndrome on experiences of diagnosis, seizure burden, management, social and financial impact, and health services use was administered online in 10 languages. Results The survey received 584 unique responses from caregivers of paediatric (83%) and adult (17%) patients with Dravet syndrome (aged <1–48y). Despite broadly following current treatment guidance, less than 10% of patients were seizure free in the previous 3 months. Nearly all (99.6%) patients aged 5 years or older experienced at least one or more motor, speech, learning, or behavioural impairment. High seizure frequency was related to more reports of emergency treatment, comorbidities, and a lower QoL (as measured by the standardized instrument EQ‐5D‐5L). If not diagnosed at the first instance, the majority (83%) of adults, but less than 20% of 6‐ to 11‐year‐olds were diagnosed after 4 or more years. Interpretation Patients with Dravet syndrome with the highest current seizure frequency suffer from more comorbidities and have a lower QoL. Therefore, more effective antiepileptic treatments are needed. What this paper adds The survey captured about 15% of all patients with Dravet syndrome in Europe. Less than 10% of patients had current seizure freedom. Patients with a high current seizure burden have more comorbidities and lower quality of life.

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“…We speculate that this earlier developmental window may reduce the vulnerability of primary and sensory systems to potential impacts of LGS on thalamocortical maturation. Consistent with this hypothesis, some patients with LGS show a relative preservation of motor functions compared to patients with other epileptic encephalopathies . Additionally, abnormal metabolism on FDG‐PET typically spares primary cortex in LGS, and ictal SPECT and interictal EEG‐fMRI studies show reduced involvement of primary cortical areas during epileptic activity.…”

Section: Discussionmentioning

confidence: 66%

“…Consistent with this hypothesis, some patients with LGS show a relative preservation of motor functions compared to patients with other epileptic encephalopathies. 40 Additionally, abnormal metabolism on FDG-PET typically spares primary cortex in LGS, 2 and ictal SPECT 6 and interictal EEG-fMRI 3-5 studies show reduced involvement of primary cortical areas during epileptic activity.…”

Section: Discussionmentioning

confidence: 99%

Thalamocortical functional connectivity in Lennox–Gastaut syndrome is abnormally enhanced in executive‐control and default‐mode networks

et al. 2017

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Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that the mediodorsal and ventrolateral thalamus may be candidate targets for modulating abnormal network behavior underlying LGS, potentially via emerging thalamic neurostimulation therapies.

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Adult motor phenotype differentiates Dravet syndrome from Lennox‐Gastaut syndrome and links SCN1A to early onset parkinsonian features

Cited by 36 publications

References 13 publications

Dravet syndrome: Characteristics, comorbidities, and caregiver concerns

Dravet syndrome: Characteristics, comorbidities, and caregiver concerns

Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey

Thalamocortical functional connectivity in Lennox–Gastaut syndrome is abnormally enhanced in executive‐control and default‐mode networks

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