Neurofibromatosis Type One and West Syndrome: A Relatively Benign Association

Motté, Jacques; Billard, C.; Fejerman, Natalio; Sfaello, Z; Arroyo, H; Dulac, Olivier

doi:10.1111/j.1528-1157.1993.tb00452.x

Cited by 21 publications

(8 citation statements)

References 15 publications

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“…To our knowledge, neurofibromatosis is the only condition in which symptomatic IS meet the EEG characteristics of idiopathic WS in most cases. Motte et al were able to show that this was the case in 13 of 15 cases in their series (22). However, in contrast to patients with Down syndrome and IS, patients with neurofibromatosis recovered normal cognitive functions after having WS.…”

Section: Discussionmentioning

confidence: 88%

Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Silva¹,

Cieuta²,

Guerrini

et al. 1996

Epilepsia

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The combination of West syndrome (WS) and Down syndrome appears not to be coincidental. Fourteen patients free of cardiac malformation or history of perinatal hypoxia were referred and investigated before they had received any treatment and were followed to the mean age of 4.5 years (range 19 months to 14 years). Spasms had onset at the mean age of 8 months (range 4-18 months) in cluster and were symmetrical. Hypsarrhythmia was symmetrical and, after intravenous diazepam (4 patients, 0.5 mg/kg) it disappeared, without any remaining focus. Recorded spasms during a cluster were "independent," with recurrence of hypsarrhythmia between successive spasms, and thus had the ictal and interictal EEG characteristics of idiopathic WS. Seven patients exhibited other types of seizures after WS, consisting of myoclonic jerks, atonic, tonic-clonic or absence seizures, which proved quite easy to control with valproate and/or ethosuximide.

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Section: Discussionmentioning

confidence: 88%

Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Silva¹,

Cieuta²,

Guerrini

et al. 1996

Epilepsia

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“…Furthermore, IS have been described in case reports of patients with neurofibromatosis type 1 (NF1). Although this association between IS and NF1 has been proposed to be more than purely coincidental (Motte et al, 1993;Ruggieri et al, 2009), a causative link has not been demonstrated and the incidence of IS in NF1 patients is certainly lower than in other genetic diseases of the mTOR pathway, like TSC. Neurofibromin 1, the gene implicated in NF1 is known to overactivate the mTOR pathway, by inactivating TSC2 (Johannessen et al, 2005).…”

Section: Effects Of Mtor Inhibitor In Human Cortexmentioning

confidence: 97%

“…Other disorders with overactivated mTORC1 include PMSE (mutations of STRADalpha ) (Puffenberger et al., 2007; Orlova et al., 2010) and PTENopathies (Cowden syndrome, Bannayan‐Riley‐Ruvalcaba syndrome and Proteus syndrome) where loss of function mutation of PTEN are seen (Cross, 2005; Bastos et al., 2008; Pilarski et al., 2011). Neurofibromatosis type 1, which is due to neurofibromin 1 ( NF1 ) mutations, may also lead to overactivation of the mTOR pathway (Motte et al., 1993; Ruggieri et al., 2009). The incidence of epilepsy, including IS, in neurofibromatosis type 1 is lower than in other neurocutaneous disorders.…”

Section: Genetic Dysregulation Of the Mtor Pathway Associated With Ementioning

confidence: 99%

“…Although it has been speculated that the association of epilepsy and neurofibromatosis 1 may be more than coincidental, there is no definite proof of a causative role of NF1 in human epilepsies [hence the (?) in the figure] (Motte et al, 1993;Ruggieri et al, 2009). Epilepsia ILAE size and differentiation in CD (Baybis et al, 2004;Miyata et al, 2004;Ljungberg et al, 2006).…”

Section: The Mtor Pathway In Cortical Dysplasiasmentioning

confidence: 99%

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Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

Galanopoulou¹,

Gorter²,

Cepeda³

2012

Epilepsia

143

105

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Summary The mTOR signaling pathway regulates cell growth, differentiation, proliferation and metabolism. Loss of function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy and neurodevelopmental disorders. These include tuberous sclerosis, which is due to mutations in TSC1 or TSC2 genes, mutations in phosphatase and tensin homolog (PTEN) as in Cowden syndrome, polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (PMSE) due to mutations in the STE20-related kinase adaptor alpha (STRADalpha), and neurofibromatosis type 1 attributed to neurofibromin 1 mutations. Inhibition of the mTOR pathway with rapamycin may prevent epilepsy and improve the underlying pathology in mouse models with disrupted mTOR signaling, due to PTEN or TSC mutations. However the timing and duration of its administration appear critical in defining the seizure and pathology-related outcomes. Rapamycin application in human cortical slices from patients with cortical dysplasias reduces the 4-aminopyridine induced oscillations. In the multiple-hit model of infantile spasms, pulse high dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms and has disease-modifying effects by partially improving cognitive deficits. In post-status epilepticus models of temporal lobe epilepsy, rapamycin may ameliorate the development of epilepsy-related pathology and reduce the expression of spontaneous seizures, but its effects depend on the timing and duration of administration, and possibly the model used. The observed recurrence of seizures and epilepsy-related pathology after rapamycin discontinuation suggests the need for continuous administration to maintain the benefit. However, the use of pulse administration protocols may be useful in certain age-specific epilepsy syndromes, like infantile spasms, whereas repetitive pulse rapamycin protocols may suffice to sustain a long-term benefit in genetic disorders of the mTOR pathway. In summary, mTOR dysregulation has been implicated in several genetic and acquired forms of epileptogenesis. The use of mTOR inhibitors can reverse some of these epileptogenic processes although their effects depend upon the timing and dose of administration as well as the model used.

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“…13,22,23 Etiology is the most important factor in predicting neurologic prognosis, including developmental outcome and long-term epilepsy. 87,88 Other factors that have been associated with a good prognosis include a normal neu-rologic examination and development at onset, absence of other seizure types at onset, older age of onset, short duration of spasms, and early effective treatment of spasms (reported with ACTH). 12,14,22,23 Although cases of symptomatic infantile spasms generally have a poor prognosis, neurofibromatosis and Down syndrome are notable exceptions, both with a relatively benign course associated with infantile spasms.…”

Section: Prognosis Of Infantile Spasmsmentioning

confidence: 99%

Infantile Spasms and Lennox-Gastaut Syndrome

Trevathan

2002

J Child Neurol

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Infantile spasms and Lennox-Gastaut syndrome are rare but are important to child neurologists because of the intractable nature of the seizures and the serious neurologic comorbidities. New antiepileptic drugs offer more alternatives for treating both infantile spasms and Lennox-Gastaut syndrome. Selected children with infantile spasms are candidates for epilepsy surgery. Vagus nerve stimulation, corpus callosotomy, and the ketogenic diet are all options for selected children with Lennox-Gastaut syndrome. The epidemiology, clinical manifestations of the seizures, electroencephalographic characteristics, prognosis, and treatment options are reviewed for infantile spasms and Lennox-Gastaut syndrome. Additional therapies are needed for both infantile spasms and Lennox-Gastaut syndrome as many children fail to achieve adequate seizure control in spite of newer treatments.

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Neurofibromatosis Type One and West Syndrome: A Relatively Benign Association

Cited by 21 publications

References 15 publications

Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Early Clinical and EEG Features of Infantile Spasms in Down Syndrome

Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

Infantile Spasms and Lennox-Gastaut Syndrome

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