Tuberous sclerosis complex prognosis [Neurosurgery Wiki]

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====== Tuberous sclerosis complex prognosis ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1bI4sPzH9iMsTqhwOQ_XKCXKVI8ggagOIvzVDrl3N0k4xDJY6J/?limit=15&utm_campaign=pubmed-2&fc=20241231164353}}

[[Tuberous sclerosis complex]] prognosis for individuals varies widely depending on the [[severity]] of the [[symptom]]s, the [[organ]]s involved, and the presence of [[complication]]s. 

===== Key factors =====

1. **Seizures**: Seizures are a common symptom of TSC and can vary in severity. In many cases, seizures can be controlled with medication, but in severe cases, they may be difficult to manage. The early onset of seizures, especially in infants, can sometimes be a predictor of developmental delays or intellectual disability.

2. **Intellectual and developmental outcomes**: Intellectual disability can occur in some individuals with TSC, with a wide range of severity. Around 30-50% of individuals with TSC may experience some level of intellectual disability, but many individuals also have normal intellectual development. Developmental delay, autism spectrum disorder, and behavioral challenges are also common.

3. **Renal issues**: Renal problems, such as kidney cysts and renal angiomyolipomas, are common in TSC. These conditions can lead to kidney function problems, including potential kidney failure in severe cases. Regular monitoring of kidney function is important.
Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a rare renal tumor primarily associated with female patients and those with tuberous sclerosis complex (TSC)
((Mahmoud M, Trabulsi M. Eosinophilic solid and cystic renal cell carcinoma: A case study with pathological correlates. Int J Surg Case Rep. 2024 Dec 14;126:110738. doi: 10.1016/j.ijscr.2024.110738. Epub ahead of print. PMID: 39700587.))

4. **Cardiac involvement**: Cardiac rhabdomyomas are often seen in TSC and can affect heart function. Most of these tumors tend to resolve over time, but in some cases, they may lead to heart-related issues.

5. **Lung involvement**: Lymphangioleiomyomatosis (LAM) is a lung disease associated with TSC, affecting predominantly women. LAM can lead to progressive respiratory problems, and in severe cases, it may require lung transplantation.

6. **Skin manifestations**: Skin lesions like facial angiofibromas, hypomelanotic macules, and shagreen patches are common in TSC. These are typically not life-threatening but may require cosmetic management or treatment for related symptoms.

7. **Neurodevelopmental surveillance**: Regular neurological assessments are essential to monitor the presence of [[tuber]]s (abnormal growths in the brain) and to manage related developmental issues or seizures.

Overall, individuals with TSC can have a normal life expectancy if symptoms are well-managed and complications are addressed early. However, the severity of the condition can range from mild to severe, and the presence of complications in multiple organs may influence long-term health outcomes. Multidisciplinary care involving neurologists, nephrologists, cardiologists, pulmonologists, and genetic counselors is crucial for managing TSC.
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Intellectual disability was present in 57% of individuals with [[tuberous sclerosis complex]] (TSC). Those with TSC without [[intellectual disability]] had significantly lower mean IQ compared to unaffected siblings. Earlier onset and greater severity of seizures in the first 2 years were observed in individuals with a slower gain in intellectual ability. Risk pathways through seizures in the first 2 years predict long-term cognitive outcomes in individuals with TSC
((Tye C, Mcewen FS, Liang H, Underwood L, Woodhouse E, Barker ED, Sheerin F, Yates JRW, Bolton PF; Tuberous Sclerosis 2000 Study Group. Long-term cognitive outcomes in tuberous sclerosis complex. Dev Med Child Neurol. 2020 Mar;62(3):322-329. doi: 10.1111/dmcn.14356. Epub 2019 Sep 19. PMID: 31538337; PMCID: PMC7027810.)).
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Multicenter, retrospective analysis of 70 subjects with TSC following surgery for relief of epilepsy revealed significant associations between younger age at seizure onset, present/prior history of infantile spasms, interictal focality (bilateral versus unilateral), and absence of residual postoperative predominant tuber, and poorer postoperative outcome (p < 0.01). Ictal multifocality, mental retardation, and discordant EEG and MRI data showed a negative trend toward outcome, but were not significant
((Madhavan D, Schaffer S, Yankovsky A, Arzimanoglou A, Renaldo F, Zaroff CM, LaJoie J, Weiner HL, Andermann E, Franz DN, Leonard J, Connolly M, Cascino GD, Devinsky O. Surgical outcome in tuberous sclerosis complex: a multicenter survey. Epilepsia. 2007 Aug;48(8):1625-8. doi: 10.1111/j.1528-1167.2007.01112.x. Epub 2007 May 1. PMID: 17484758.)).

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In a nationwide multi-center study on resective epilepsy surgery, resulted in improved seizure outcomes and quality of life and intelligence quotient improvements in patients with tuberous sclerosis complex. Seizure freedom was often achieved in patients with an outstanding tuber on MRI, total removal of epileptogenic tubers, and tuberectomy plus. Quality of life and intelligence quotient improvements were frequently observed in patients with postoperative seizure freedom and preoperative low intelligence quotient
((Liu S, Yu T, Guan Y, Zhang K, Ding P, Chen L, Shan Y, Guo Q, Liu Q, Yao Y,
Yang M, Zhang S, Lin Y, Zhao R, Mao Z, Zhang J, Zhang C, Zhang R, Yang Z, Qian R,
Li Y, Zhang G, Yuan L, Yang W, Tian H, Zhang H, Li W, Zhang X, Yin J, Guo Y, Zou 
L, Qin J, Fang F, Wang X, Ge M, Liang S. Resective epilepsy surgery in tuberous
sclerosis complex: a nationwide multicentre retrospective study from China.
Brain. 2020 Jan 18. pii: awz411. doi: 10.1093/brain/awz411. [Epub ahead of print]
PubMed PMID: 31953931.
)).

===== Experimental observational studies =====

[[Network hypersynchrony]] is emerging as an important system-level mechanism underlying [[seizure]]s, as well as cognitive and behavioral [[impairment]]s, in children with structural brain abnormalities. Chari et al. from the [[Great Ormond Street Hospital]] investigated patterns of single-neuron action potential behavior in 206 neurons recorded from tubers, transmantle tails of tubers, and normal-looking cortex in 3 children with [[tuberous sclerosis]]. The patterns of neuronal firing on a neuron-by-neuron (autocorrelation) basis did not reveal any differences as a function of anatomy. However, at the level of functional networks (cross-correlation), there is a much larger propensity towards hypersynchrony of tuber-tuber neurons than in neurons from any other anatomical site. This suggests that tubers are the primary drivers of adverse [[tuberous sclerosis complex]] [[prognosis]] in [[child]]ren
((Chari A, Hernan AE, Mahoney JM, Thornton R, Tahir MZ, Tisdall MM, Scott RC. Single unit-derived connectivity networks in tuberous sclerosis complex reveal propensity for network hypersynchrony driven by tuber-tuber interactions. Sci Rep. 2024 Dec 30;14(1):31654. doi: 10.1038/s41598-024-80634-5. PMID: 39738230.)).
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Chari et al.'s study significantly advances the understanding of the role of network hypersynchrony in TSC, particularly in the context of seizures and cognitive impairments in children. The findings underscore the importance of considering functional network disturbances, rather than focusing solely on individual neurons when investigating neurological disorders. However, the study's limitations, including the small sample size and lack of direct clinical correlation, suggest that further research is necessary to fully understand the implications of these findings for clinical practice and therapeutic development.