Hemimegalencephaly and tuberous sclerosis complex: A rare yet challenging association

Sidira, Christina; Vargiami, Euthymia; Dragoumi, Pinelopi; Zafeiriou, Dimitrios

doi:10.1016/j.ejpn.2020.12.007

Cited by 10 publications

(10 citation statements)

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“…The presence of brain enlargement is consistent with the increased brain weight that has also been observed by others [ 51 ]. Numerous studies show that mutations in different genes acting as regulators of mTOR signalling and, consequently, the activation of the mTOR pathway lead to megalencephaly or hemimegalencephaly [ 52 , 53 , 54 , 55 , 56 ]. Our results are also in line with previous studies that used a mouse model of TSC, Tsc2 flox/ko ;hGFAP-Cre.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, other studies showed that Tsc1 GFAP KO mice developed dramatic, diffuse megalencephaly and higher brain weights compared to control mice [ 59 ]. It should also be emphasised that hemimegalencephaly has been demonstrated in some patients with TSC along with abnormal myelination patterns and gyral abnormalities in the enlarged hemisphere [ 53 , 60 , 61 , 62 ]. Although megalencephaly and hemimegalencephaly are not typical symptoms of TSC, the case reports confirm the involvement of the activation of the mTOR pathway in processes leading to brain overgrowth, similar to our studies with Tsc2 +/− mice.…”

Section: Discussionmentioning

confidence: 99%

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Synaptic Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders

Czapski

Babiec

Jęśko

et al. 2021

IJMS

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Tuberous sclerosis complex (TSC) is a rare, multi-system genetic disease with serious neurological and mental symptoms, including autism. Mutations in the TSC1/TSC2 genes lead to the overactivation of mTOR signalling, which is also linked to nonsyndromic autism. Our aim was to analyse synaptic pathology in a transgenic model of TSC: two-month-old male B6;129S4-Tsc2tm1Djk/J mice with Tsc2 haploinsufficiency. Significant brain-region-dependent alterations in the expression of several synaptic proteins were identified. The most prominent changes were observed in the immunoreactivity of presynaptic VAMP1/2 (ca. 50% increase) and phospho-synapsin-1 (Ser62/67) (ca. 80% increase). Transmission electron microscopy demonstrated serious ultrastructural abnormalities in synapses such as a blurred structure of synaptic density and a significantly increased number of synaptic vesicles. The impairment of synaptic mitochondrial ultrastructure was represented by excessive elongation, swelling, and blurred crista contours. Polyribosomes in the cytoplasm and swollen Golgi apparatus suggest possible impairment of protein metabolism. Moreover, the delamination of myelin and the presence of vacuolar structures in the cell nucleus were observed. We also report that Tsc2+/− mice displayed increased brain weights and sizes. The behavioural analysis demonstrated the impairment of memory function, as established in the novel object recognition test. To summarise, our data indicate serious synaptic impairment in the brains of male Tsc2+/− mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synaptic Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders

Czapski

Babiec

Jęśko

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Hemimegalencephaly is a rare genetic condition and cortical malformation associated with seizures and is marked by the enlargement of one cerebral hemisphere. 2 HME is broadly divided into three types: isolated, syndromic, and total. Isolated HME has no association with hemicorporal hypertrophy, while syndromic HME has an association with ipsilateral hemicorporal hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

“…Hemimegalencephaly is a rare genetic condition and cortical malformation associated with seizures and is marked by the enlargement of one cerebral hemisphere 2 . HME is broadly divided into three types: isolated, syndromic, and total.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of the disease is thought to be characterized by abnormal activation of the mTOR signaling pathway 2 because mTOR inhibitors such as everolimus play a key role in the treatment of hemimegalencephaly. Occasionally, the seizures associated with HME are difficult to control with AEDs and hemispherectomy is an effective treatment option for drug‐resistant seizures 4 .…”

Section: Discussionmentioning

confidence: 99%

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