Neurological and neuropsychiatric aspects of tuberous sclerosis complex
Abstract
Tuberous sclerosis (also known as tuberous sclerosis complex [TSC]) is a multisystem genetic disorder that affects almost every organ in the body. Mutations in the TSC1 or TSC2 genes lead to disruption of the TSC1-TSC2 intracellular protein complex, causing overactivation of the mammalian target of rapamycin (mTOR) protein complex. The surveillance and management guidelines and clinical criteria for tuberous sclerosis were revised in 2012, and mTOR inhibitors are now recommended as treatment options for subependymal giant cell astrocytomas and renal angiomyolipomas-two common features of the disease. However, most morbidity and mortality caused by tuberous sclerosis is associated with neurological and neuropsychiatric manifestations. Treatment of epilepsy associated with tuberous sclerosis remains a major challenge, with more than 60% of patients having ongoing seizures. Tuberous-sclerosis-associated neuropsychiatric disorders (TAND) are multilevel and occur in most individuals with the disorder, but are rarely assessed and treated. Clinical trials of mTOR inhibitors to treat seizures and TAND are underway. Management of the neurological and neuropsychiatric manifestations of the disorder should be coordinated with treatment of other organ systems. In view of the age-related expression of manifestations from infancy to adulthood, continuity of clinical care and ongoing monitoring is paramount, and particular attention is needed to plan transition of patient care from childhoo…
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Beginning in mid-to-late adulthood, a subset of individuals with TSC demonstrate cognitive decline that clinically overlaps with Alzheimer's disease dementia.
“Notably, beginning in mid-to-late adulthood, a subset of individuals with TSC demonstrate cognitive decline that clinically overlaps with Alzheimer's disease (AD) dementia (8-10).”
Individuals with tuberous sclerosis complex can develop a progressive neuropsychiatric syndrome known as tuberous sclerosis-associated neuropsychiatric disorders (TAND).
“Individuals with tuberous sclerosis complex can develop a progressive neuropsychiatric syndrome known as tuberous sclerosis–associated neuropsychiatric disorders.”
From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [4]
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- Authors
- Curatolo, P., Moavero, R., & de Vries, P. J.
- Affiliations
- Policlinico Tor Vergata (IT)
- University of Rome Tor Vergata (IT)
- Corresponding author
- Curatolo, Paolo
- Venue
- The Lancet Neurology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 14
- Issue
- 7
- Pages
- 733-745
- ISSN
- 1474-4422 (ISSN-L)
- OpenAlex
- W2100428079
- Cited by
- 600
- References
- 8
- Citations by year
- 2026: 46 · 2025: 44 · 2024: 43 · 2023: 43 · 2022: 62 · 2021: 91 · 2020: 66 · 2019: 48 · 2018: 56 · 2017: 41 · 2016: 47 · 2015: 13
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Neurology (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
- Keywords
- tuberous sclerosis complex, TSC1 gene, TSC2 gene, mTOR signaling, neuropsychiatric symptoms, epilepsy, subependymal giant cell astrocytoma, renal angiomyolipoma, mTOR inhibitors, seizure treatment, transition to adult care, clinical management guidelines
- MeSH terms
- Mental Disorders, Clinical Trials as Topic, Humans, Nervous System Diseases, Tuberous Sclerosis
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