Materiały źródłowe

• #1 Therapeutic Approaches to Tuberous Sclerosis Complex: From Available Therapies to Promising Drug Targets

  https://www.mdpi.com/2218-273X/14/9/1190

  Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by heterozygous loss-of-function pathogenic variants in the tumour suppressor genes TSC1 and TSC2 encoding the tuberin and hamartin proteins, respectively. […] Even though several therapeutic options are available for the treatment of TSC, there is further need for a better understanding of the pathophysiological basis of the neurologic and other manifestations seen in TSC, and for novel therapeutic approaches. This review provides an overview of the main current therapies for TSC and discusses recent studies highlighting the repurposing of approved drugs and the emerging role of novel targets for future drug design. […] A multidisciplinary approach with regular follow-up from childhood to adulthood is mandatory for the management of TSC. Several therapeutic options are available for the treatment of focal seizures and infantile spasms associated with TSC, including vigabatrin, hormonal therapy, epilepsy surgery, a ketogenic diet, and vagus nerve stimulation.

• #2 Tuberous sclerosis – Wikipedia

  https://en.wikipedia.org/wiki/Tuberous_sclerosis

  Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. […] The various symptoms and complications from TSC may appear throughout life, requiring continued surveillance and adjustment to treatments. […] TSC can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. […] Tuberous sclerosis complex affects multiple organ systems so a multidisciplinary team of medical professionals is required. […] The mTOR inhibitor everolimus was approved in the US for treatment of TSC-related tumors in the brain (subependymal giant cell astrocytoma) in 2010 and in the kidneys (renal angiomyolipoma) in 2012.

• #3 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  There is no cure for tuberous sclerosis complex (TSC). Treatment focuses on early identification and monitoring of potentially progressive lesions to prevent complications. Management strategies aim to minimize disease-associated issues and provide symptomatic relief. This includes regular screening and use of targeted therapies, such as mTOR inhibitors (eg, everolimus), to manage certain tumor growths and improve outcomes. Multidisciplinary care is often required to address manifestations across various organ systems, such as antiepileptic drugs (AEDs) for seizure control, behavioral interventions for cognitive or psychiatric symptoms, and surgical options for severe cases involving organ dysfunction or tumor removal. […] The mTOR inhibitor everolimus is approved for multiple indications in tuberous sclerosis complex (TSC) in the United States and Europe. It is approved for use in adults with renal angiomyolipoma associated with TSC who do not require immediate surgical intervention. It is also approved for both adults and children 1 year and older who have subependymal giant cell astrocytoma (SEGA) related to TSC and need therapeutic intervention but are not candidates for curative surgical resection. The drug is also indicated for the treatment of TSC-associated focal-onset seizures in adults and children 2 years and older.

• #4 Tuberous Sclerosis Treatment Program

  https://www.massgeneral.org/neurology/tsc/treatments-and-services

  Despite continuing advances in TSC research, there is not yet a cure for the disorder. For now, medical treatments can only address TSC’s symptoms, with the objective of identifying and managing potential problems. […] Experts are hopeful that current clinical trials and genetics research will lead to treatments for the disorder itself, and one day even a cure for TSC. […] Symptoms of TSC can vary widely from one individual to another. As a result, treatments must also vary and be specific to each individual’s set of symptoms. […] People who are mildly affected by TSC can lead healthy, productive lives with little or no treatment, aside from periodic examinations. Those who are much more severely affected, suffering from epileptic seizures, debilitating cognitive or behavioral problems, or advanced kidney or lung dysfunction, may require much more extensive and intensive medical treatment.

• #5 Monitoring & managing patients with TSC:current perspectives | JMDH

  https://www.dovepress.com/monitoring-and-managing-patients-with-tuberous-sclerosis-complex-curre-peer-reviewed-fulltext-article-JMDH

  Tuberous sclerosis complex (TSC) is a rare genetic disease of autosomal dominant transmission that, in most cases, results from the presence of pathogenic variants of the TSC1 or TSC2 genes, encoding hamartin and tuberin, respectively. […] The past few years have witnessed a dramatic leap not only in the diagnosis and management of TSC patients, with standard monitoring recommendations, but also in the therapeutic field, with the use of mTORC1 inhibitors. […] In the past few years, research and new technologies allowed the advancement in diagnosis and management of TSC patients, promoting not only a multidisciplinary approach, but also the clinical use of mTORC1 inhibitors, such as sirolimus and everolimus, for the treatment of several clinical manifestations associated to the condition. These drugs proved sustained regression of brain tumors, renal angiomyolipomas, liver angiomyolipomas, and pulmonary lymphangioleiomyomatosis (LAM).

• #6 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  There is no cure for tuberous sclerosis complex (TSC). Treatment focuses on early identification and monitoring of potentially progressive lesions to prevent complications. Management strategies aim to minimize disease-associated issues and provide symptomatic relief. This includes regular screening and use of targeted therapies, such as mTOR inhibitors (eg, everolimus), to manage certain tumor growths and improve outcomes. Multidisciplinary care is often required to address manifestations across various organ systems, such as antiepileptic drugs (AEDs) for seizure control, behavioral interventions for cognitive or psychiatric symptoms, and surgical options for severe cases involving organ dysfunction or tumor removal. […] The mTOR inhibitor everolimus is approved for multiple indications in tuberous sclerosis complex (TSC) in the United States and Europe. It is approved for use in adults with renal angiomyolipoma associated with TSC who do not require immediate surgical intervention. It is also approved for both adults and children 1 year and older who have subependymal giant cell astrocytoma (SEGA) related to TSC and need therapeutic intervention but are not candidates for curative surgical resection. The drug is also indicated for the treatment of TSC-associated focal-onset seizures in adults and children 2 years and older.

• #7 Therapeutic Approaches to Tuberous Sclerosis Complex: From Available Therapies to Promising Drug Targets

  https://www.mdpi.com/2218-273X/14/9/1190

  In recent years, mTOR inhibitors (mTORi), such as sirolimus and everolimus, have also been increasingly used for the treatment of the other various manifestations of TSC, including kidney AMLs, SEGAs, facial angiofibromas, and lymphangioleiomas. […] According to the International TSC Consensus Guidelines, the first-line treatment for TSC-associated epilepsy is vigabatrin, which is more effective if introduced early. […] Several studies have confirmed that mTORC inhibition could be a valid therapeutic strategy in TSC. […] Everolimus, a synthetic analogue of rapamycin, is an mTOR inhibitor (mTORi) approved by the EMA as Votubia (EMA/229443/2018) as an adjunctive treatment in patients from 2 years of age with partial-onset seizures related to TSC that have not responded to other treatments, and for the treatment of SEGAs and AMLs.

• #8 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  There is no cure for tuberous sclerosis complex (TSC). Treatment focuses on early identification and monitoring of potentially progressive lesions to prevent complications. Management strategies aim to minimize disease-associated issues and provide symptomatic relief. This includes regular screening and use of targeted therapies, such as mTOR inhibitors (eg, everolimus), to manage certain tumor growths and improve outcomes. Multidisciplinary care is often required to address manifestations across various organ systems, such as antiepileptic drugs (AEDs) for seizure control, behavioral interventions for cognitive or psychiatric symptoms, and surgical options for severe cases involving organ dysfunction or tumor removal. […] The mTOR inhibitor everolimus is approved for multiple indications in tuberous sclerosis complex (TSC) in the United States and Europe. It is approved for use in adults with renal angiomyolipoma associated with TSC who do not require immediate surgical intervention. It is also approved for both adults and children 1 year and older who have subependymal giant cell astrocytoma (SEGA) related to TSC and need therapeutic intervention but are not candidates for curative surgical resection. The drug is also indicated for the treatment of TSC-associated focal-onset seizures in adults and children 2 years and older.

• #9 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Everolimus is an mTOR inhibitor approved for treatment of TSC-associated focal (partial-onset) seizures. In clinical trials, children with TSC treated adjunctively with everolimus had 29% to 40% reductions in seizure frequency. The starting dose is 5 mg/m2/day, which may be increased in increments of 5 mg to reach trough concentrations of 5 to 15 ng/mL. Regular laboratory monitoring is required including blood counts, renal function, liver function, lipid profile and glucose. […] Cannabidiol is also approved for the treatment of seizures in TSC. In clinical trials, participants with TSC treated with cannabidiol had a median 23% reduction in seizures from baseline relative to placebo. The recommended starting dose is 2.5 mg/kg orally twice daily, which may be increased weekly in increments of 2.5 mg/kg twice daily to a recommended maintenance dose of 12.5 mg/kg twice daily. Lower doses should be used in patients with hepatic insufficiency and those who are treated concomitantly with everolimus; interactions with other antiseizure medications can contribute to toxicity. Regular laboratory monitoring of liver function is required.

• #10 Clinical management of tuberous sclerosis complex over the lifetime of a patient

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5683262/

  Tuberous sclerosis complex (TSC) is a genetic disorder characterized by nonmalignant tumors (hamartomas) that can occur in various organ systems, including the brain, kidneys, lungs, skin, eyes, and heart. […] Once a diagnosis is made, TSC management strategies should be tailored to address the symptoms and risks most relevant to the age of the patient. Improved understanding of the genetic basis of TSC and of the central issue of mTOR overactivation has led to use of pharmacotherapies such as the mTOR inhibitors everolimus and sirolimus in the treatment of TSC disease. […] Everolimus has demonstrated efficacy in treating both SEGA and angiomyolipoma associated with TSC in Phase II and III studies. […] Everolimus may be effective in causing regression. […] It is important to recognize the differences between pediatric and adult patients with TSC with respect to diagnosis, monitoring, and appropriate management.

• #11 Monitoring & managing patients with TSC:current perspectives | JMDH

  https://www.dovepress.com/monitoring-and-managing-patients-with-tuberous-sclerosis-complex-curre-peer-reviewed-fulltext-article-JMDH

  Of the different mTOR inhibitors, only rapamycin (also known as sirolimus) and their active derivative everolimus have been clinically evaluated for the management of TSC patients. […] Rapamycin is a natural macrolide, and its mechanisms of action are common for their analogues, both working by binding to and forming a complex with FKBP12, which then inhibits mTORC1. […] Two major clinical trials, EXIST-1 (efficacy and safety of everolimus for subependymal giant cell astrocytomas SEGAs associated with TSC) and EXIST-2 (everolimus for angiomyolipoma associated with TSC or sporadic lymphangioleiomyomatosis), demonstrated beneficial effects of everolimus in both cases, allowed the approval of this drug for the treatment of those TSC-associated manifestations. […] There are various case reports and multiple prospective clinical trials showing sirolimus benefit in TSC patients, inducing regression of kidney angiomyolipomas, SEGAs and liver angiomyolipomas, but tumor volume tended to increase after therapy withdrawal.

• #12 Renal disease in tuberous sclerosis complex: pathogenesis and therapy | Nature Reviews Nephrology

  https://www.nature.com/articles/s41581-018-0059-6

  Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome caused by germline inactivating mutations in either allele of the tumour suppressor genes TSC1 or TSC2. […] Annual surveillance of renal disease is recommended for most patients with TSC. […] Nephron-sparing treatments for TSC-related renal disease (rapalogues, embolization and partial nephrectomy) should always be prioritized. […] mTORC1 hyperactivation increases oxidative stress, rendering TSC-related tumour cells vulnerable to agents that increase oxidative stress or inhibit antioxidant biosynthesis. […] Siroky, B. J. et al. Improvement in renal cystic disease of tuberous sclerosis complex after treatment with mammalian target of rapamycin inhibitor. […] Bissler, J. J. et al. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial.

• #13 New Research Hopes to Advance Tuberous Sclerosis Treatment

  https://www.brainandlife.org/articles/new-therapies-show-promise-in-treating-this-neurologic-condition-but

  Results like Griffin’s prompted the FDA to approve everolimus in 2010, after a study revealed that one-third of the 28 patients studied experienced a reduction of 50 percent or greater in the size of their largest tumor within six months of starting everolimus treatment (and none of the patients developed a new tumor while taking the drug). […] „The most dramatic reduction in tumor volume occurs within the first three months of everolimus therapy,” says Dr. Sahin. […] „Right now, treatment for TSC continues to be symptomatic, but the preliminary evidence we’re seeing with the rapamycin-like drugs is very encouraging,” says Dr. Thiele. […] „TSC is not uncommon, and there needs to be a heightened awareness of the disease among all types of clinicians,” says Dr. Thiele. „New treatments are emerging, but even with the treatments we have now, if we know a person has TSC, there’s a lot we can do to keep him or her healthy.”

• #14 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Other ASMs commonly used in TSC include clobazam, lamotrigine, lacosamide, levetiracetam, oxcarbazepine, perampanel, topiramate, valproic acid, brivaracetam, and carbamazepine. Most seizure types, other than infantile spasms, in TSC are not responsive to pharmacotherapy and polypharmacy is common. Vagus nerve stimulation and the use of a ketogenic diet may be considered for pharmacoresistant seizures. Epilepsy surgery, discussed further below, may be indicated. […] The mTOR inhibitors sirolimus and everolimus, developed initially as immunosuppressants, have clinical value for aspects of TSC. A topical gel formulation of sirolimus (0.2%) has been approved by the Food and Drug Administration (FDA) as of April 2022 for treatment of facial angiofibromas in TSC in those age 6 years or more. Everolimus was shown in clinical trials to reduce the volume of SEGAs and is approved for the treatment of SEGAs not amenable to surgical resection. Renal angiomyolipomas can be treated with mTOR inhibitors, as can lung tumors. As noted, everolimus is also used as an antiseizure medication for treatment of seizures.

• #15 Tuberous Sclerosis Complex: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1112322-treatment

  The mTOR inhibitor sirolimus is FDA-approved for the treatment of lymphangioleiomyomatosis, a condition that can be associated with TSC. […] It may also be used off-label to manage certain TSC-related features. Topical sirolimus has FDA approval for treating facial angiofibroma in patients with TSC aged 6 years and older. […] Surgery […] Surgical treatment of patients with TSC can include the following: […] Focal cortical resection/thermal ablation […] Corpus callosotomy […] Vagus nerve stimulation […] In addition, SEGAs require resection if they produce hydrocephalus or significant mass effect. If a gross total resection can be achieved, recurrence is unlikely. […] See Treatment and Medication for more detail.

• #16 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Although there is no cure for tuberous sclerosis, treatment can help manage specific symptoms. For example: […] Anti-seizure medicines may be prescribed to control seizures. Other medicines may help manage heart rhythm problems, behavior problems or other symptoms. A medicine called everolimus (Afinitor, Zortress) may be used to treat certain types of brain and kidney growths that can’t be removed with surgery. Using these medicines early in care may help reduce the risk of seizures. The topical ointment form of a medicine called sirolimus (Hyftor) may help treat acnelike skin growths. […] If a growth affects the function of a specific organ such as the kidney, brain or heart the growth may be removed with surgery. Sometimes surgery helps control seizures caused by brain growths that don’t respond to medicine. Surgical procedures such as dermabrasion or laser treatment may improve the appearance of skin growths.

• #17 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  The main complication of tuberous sclerosis complex (TSC) requiring long-term medical therapy is epilepsy. Antiepileptic drugs (AEDs) are the mainstay of therapy for patients with TSC. Unfortunately, no one medical treatment gives satisfactory relief for all or even most patients. Patients with TSC may experience frequent exacerbations of their seizures that may require inpatient adjustment of AEDs. A combination of medical treatment modalities frequently is required. […] Although facial angiofibromas are benign tumors, they can be bothersome for TSC patients and there is no effective treatment. Laser therapy has been used with good responses, but it causes painful complications and is associated with a very high recurrence rate. Studies have shown that topical rapamycin is effective for treating facial angiofibromas in TSC patients without significant adverse effects.

• #18 Tuberous sclerosis

  https://dermnetnz.org/topics/tuberous-sclerosis

  Tuberous sclerosis is a multisystem disorder, so treatment from a team of specialist doctors is usually necessary. […] Skin lesions, particularly facial angiofibromas, may be psychologically distressing for some patients. Laser treatment or electrosurgery can be used to remove angiofibromas. […] The topical mTOR inhibitor sirolimus 0.2% gel (also called rapamycin) has proved helpful in reducing angiofibromas in a clinical trial involving 36 adults and children. One study has also reported improvement in hypopigmented macules. A larger prospective, multicentre, randomised, double-blind, vehicle-controlled trial enrolled 179 patients with tuberous sclerosis-related facial angiofibromas and found improvement in more than 80% of patients treated with topical 1% rapamycin with most occurring in the first month. It was well tolerated.

• #19 Monitoring & managing patients with TSC:current perspectives | JMDH

  https://www.dovepress.com/monitoring-and-managing-patients-with-tuberous-sclerosis-complex-curre-peer-reviewed-fulltext-article-JMDH

  The oral treatment with mTOR inhibitors is associated to increased risk of infections, stomatitis, acne, amenorrhea, hypercholesterolemia, and other metabolic disturbances. […] It has been demonstrated that discontinuation of treatment leads to rebound growth of tumors in the majority of patients, and considerations about this subject are important, since for clinical benefit to be sustained, chronic treatment with mTORC1 inhibitors is necessary, raising concern about the long-term adverse effects described above. […] Everolimus is approved for the treatment of TSC-associated angiomyolipomas and mTOR inhibitors are recommended as the first-line treatment for asymptomatic, growing renal angiomyolipomas 3 cm. […] Selective embolization, kidney-sparing resection or ablative therapy are acceptable second-line therapies for asymptomatic lesions.

• #20 Monitoring & managing patients with TSC:current perspectives | JMDH

  https://www.dovepress.com/monitoring-and-managing-patients-with-tuberous-sclerosis-complex-curre-peer-reviewed-fulltext-article-JMDH

  The oral treatment with mTOR inhibitors is associated to increased risk of infections, stomatitis, acne, amenorrhea, hypercholesterolemia, and other metabolic disturbances. […] It has been demonstrated that discontinuation of treatment leads to rebound growth of tumors in the majority of patients, and considerations about this subject are important, since for clinical benefit to be sustained, chronic treatment with mTORC1 inhibitors is necessary, raising concern about the long-term adverse effects described above. […] Everolimus is approved for the treatment of TSC-associated angiomyolipomas and mTOR inhibitors are recommended as the first-line treatment for asymptomatic, growing renal angiomyolipomas 3 cm. […] Selective embolization, kidney-sparing resection or ablative therapy are acceptable second-line therapies for asymptomatic lesions.

• #21 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  The main complication of tuberous sclerosis complex (TSC) requiring long-term medical therapy is epilepsy. Antiepileptic drugs (AEDs) are the mainstay of therapy for patients with TSC. Unfortunately, no one medical treatment gives satisfactory relief for all or even most patients. Patients with TSC may experience frequent exacerbations of their seizures that may require inpatient adjustment of AEDs. A combination of medical treatment modalities frequently is required. […] Although facial angiofibromas are benign tumors, they can be bothersome for TSC patients and there is no effective treatment. Laser therapy has been used with good responses, but it causes painful complications and is associated with a very high recurrence rate. Studies have shown that topical rapamycin is effective for treating facial angiofibromas in TSC patients without significant adverse effects.

• #22 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  TSC Treatment […] Recent evidence suggests that early pharmacologic intervention, possibly before seizure onset, may reduce the severity of both epilepsy and neuropsychiatric manifestations of TSC. The timing of intervention may relate to the development of epileptiform abnormalities on screening EEG in infants with TSC even prior to clinical seizures. For patients with TSC who have not developed seizures, their families should be counseled on seizure recognition, especially as infantile spasms can be subtle events clinically. Antiseizure medications (ASMs), epilepsy surgery, dietary modification, and treatment with mTOR inhibitors are options to consider for TSC. Importantly, therapies for neuropsychiatric comorbidities and interventions to improve quality of life are also available. […] Vigabatrin is a first-line treatment for infantile spasms in TSC and should be started as soon as this seizure type is confirmed. Most infantile spasms are significantly reduced or even stopped with vigabatrin. There is a risk of visual impairments when vigabatrin is taken over prolonged periods; however, this is uncommon with treatment for the duration of time when infantile spasms occur. If sufficient response does not occur with vigabatrin, prednisone/prednisolone or adrenocorticotropic hormone (ACTH) may be beneficial.

• #23 Therapeutic Approaches to Tuberous Sclerosis Complex: From Available Therapies to Promising Drug Targets

  https://www.mdpi.com/2218-273X/14/9/1190

  In recent years, mTOR inhibitors (mTORi), such as sirolimus and everolimus, have also been increasingly used for the treatment of the other various manifestations of TSC, including kidney AMLs, SEGAs, facial angiofibromas, and lymphangioleiomas. […] According to the International TSC Consensus Guidelines, the first-line treatment for TSC-associated epilepsy is vigabatrin, which is more effective if introduced early. […] Several studies have confirmed that mTORC inhibition could be a valid therapeutic strategy in TSC. […] Everolimus, a synthetic analogue of rapamycin, is an mTOR inhibitor (mTORi) approved by the EMA as Votubia (EMA/229443/2018) as an adjunctive treatment in patients from 2 years of age with partial-onset seizures related to TSC that have not responded to other treatments, and for the treatment of SEGAs and AMLs.

• #24 Treatments | Tuberous Sclerosis Center | Washington University in St. Louis

  https://tuberoussclerosiscenter.wustl.edu/about-tsc/treatments/

  Tuberous sclerosis complex (TSC) manifests differently in each patient. At the Washington University Tuberous Sclerosis Clinic, we manage and treat each patient with TSC on an individual basis. […] Seizures can be treated with a number of available seizure medications (antiepileptic drugs or AEDs), although many patients with TSC have poorly-controlled seizures despite multiple trials of medications. […] Vigabatrin is a seizure medication that has extremely good efficacy for infantile spasms in patients with TSC. However, vigabatrin can cause significant side effects with visual field constriction or loss of peripheral vision. […] For patients with poorly-controlled seizures on medication, there are potential non-medical options that can be considered. Recently it has become clear that epilepsy in at least a subset of patients with TSC may benefit significantly from brain surgery to remove active tubers, especially if one or a limited number of tubers can be identified that are causing the seizures.

• #25 Treatment-resistant epilepsy and tuberous sclerosis complex | NDT

  https://www.dovepress.com/treatment-resistant-epilepsy-and-tuberous-sclerosis-complex-treatment–peer-reviewed-fulltext-article-NDT

  If the patients epilepsy is refractory to vigabatrin monotherapy, second-line treatment for TSC-associated infantile spasms includes corticosteroids/hormonal treatment with ACTH and/or prednisolone, as well as topiramate or clobazam. […] Given that TSC is the result of aberrant mTOR signaling, mTOR inhibitors such as everolimus and sirolimus, analogs of rapamycin, offer targeted, disease-specific treatment in TSC. […] The EXIST-1 and EXIST-3 trials have shown that everolimus is effective in decreasing the size and progression of SEGAs, as well as maintaining a sustained decrease in seizure frequency in children older than 2 years. […] Epidiolex is a synthetic cannabinoid with a 50:1 ratio of cannabidiol to tetrahydrocannabinol. […] The ketogenic diet is an effective nonpharmacological, low-carbohydrate, high-fat diet for drug-resistant epilepsy of various etiologies that mimics the physiological state of fasting or starvation to use ketones as the body’s main energy source.

• #26 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Other ASMs commonly used in TSC include clobazam, lamotrigine, lacosamide, levetiracetam, oxcarbazepine, perampanel, topiramate, valproic acid, brivaracetam, and carbamazepine. Most seizure types, other than infantile spasms, in TSC are not responsive to pharmacotherapy and polypharmacy is common. Vagus nerve stimulation and the use of a ketogenic diet may be considered for pharmacoresistant seizures. Epilepsy surgery, discussed further below, may be indicated. […] The mTOR inhibitors sirolimus and everolimus, developed initially as immunosuppressants, have clinical value for aspects of TSC. A topical gel formulation of sirolimus (0.2%) has been approved by the Food and Drug Administration (FDA) as of April 2022 for treatment of facial angiofibromas in TSC in those age 6 years or more. Everolimus was shown in clinical trials to reduce the volume of SEGAs and is approved for the treatment of SEGAs not amenable to surgical resection. Renal angiomyolipomas can be treated with mTOR inhibitors, as can lung tumors. As noted, everolimus is also used as an antiseizure medication for treatment of seizures.

• #27 Tuberous Sclerosis Complex | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/tuberous-sclerosis-complex

  TSC is a lifelong condition. Currently theres no cure, but there are treatments to help manage TSC symptoms. Since TSC is unique to each person, an individualized treatment plan will provide the best possible symptom management. […] Antiseizure medications may help control seizures. Vigabatrin can help treat infantile spasms. The U.S. Food and Drug Administration (FDA) approved cannabidiol to treat seizures in people with TSC, except for babies younger than one year. Everolimus (an mTOR inhibitor) has also been approved to treat intractable seizures (those not well-controlled by medicine) as well as certain brain and kidney tumors associated with TSC. […] A topical rapamycin (an mTOR inhibitor) gel has been approved to treat facial angiofibromas, and oral rapamycin has been approved to treat LAM.

• #28 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Everolimus is an mTOR inhibitor approved for treatment of TSC-associated focal (partial-onset) seizures. In clinical trials, children with TSC treated adjunctively with everolimus had 29% to 40% reductions in seizure frequency. The starting dose is 5 mg/m2/day, which may be increased in increments of 5 mg to reach trough concentrations of 5 to 15 ng/mL. Regular laboratory monitoring is required including blood counts, renal function, liver function, lipid profile and glucose. […] Cannabidiol is also approved for the treatment of seizures in TSC. In clinical trials, participants with TSC treated with cannabidiol had a median 23% reduction in seizures from baseline relative to placebo. The recommended starting dose is 2.5 mg/kg orally twice daily, which may be increased weekly in increments of 2.5 mg/kg twice daily to a recommended maintenance dose of 12.5 mg/kg twice daily. Lower doses should be used in patients with hepatic insufficiency and those who are treated concomitantly with everolimus; interactions with other antiseizure medications can contribute to toxicity. Regular laboratory monitoring of liver function is required.

• #29 Neuropsychiatric Manifestations of Tuberous Sclerosis and Management Options: A Narrative Review

  https://www.psychiatrist.com/pcc/neuropsychiatric-manifestations-tuberous-sclerosis-management-options-narrative-review/

  The use of psychotropic agents should be considered against the probable effect of decreasing the seizure threshold in patients with TSC. The exacerbation of seizures and reduced therapeutic efficacy may occur at the therapeutic dose of some psychotropic drugs due to pharmacodynamic interactions between psychotropic and antiepileptic medications. Antipsychotics, mainly new-generation agents such as olanzapine, quetiapine, aripiprazole, and risperidone, have low seizure rates at therapeutic doses. These atypical antipsychotics are reported to be efficacious in reducing aggression, hyperactivity, and self-harm in patients with TSC and have better side effect profiles than typical antipsychotics. […] Antiepileptic drugs are used to prevent seizures in TSC patients, but these drugs also have notable effects on numerous psychiatric and behavioral manifestations. In one study, valproic acid and lamotrigine were commonly prescribed, followed by benzodiazepines and oxcarbazepine with unspecified favorable outcomes. For ADHD, methylphenidate and dexmethylphenidate were most often used, whereas guanfacine and clonidine were reported to worsen symptoms.

• #30 Neuropsychiatric Manifestations of Tuberous Sclerosis and Management Options: A Narrative Review

  https://www.psychiatrist.com/pcc/neuropsychiatric-manifestations-tuberous-sclerosis-management-options-narrative-review/

  The use of psychotropic agents should be considered against the probable effect of decreasing the seizure threshold in patients with TSC. The exacerbation of seizures and reduced therapeutic efficacy may occur at the therapeutic dose of some psychotropic drugs due to pharmacodynamic interactions between psychotropic and antiepileptic medications. Antipsychotics, mainly new-generation agents such as olanzapine, quetiapine, aripiprazole, and risperidone, have low seizure rates at therapeutic doses. These atypical antipsychotics are reported to be efficacious in reducing aggression, hyperactivity, and self-harm in patients with TSC and have better side effect profiles than typical antipsychotics. […] Antiepileptic drugs are used to prevent seizures in TSC patients, but these drugs also have notable effects on numerous psychiatric and behavioral manifestations. In one study, valproic acid and lamotrigine were commonly prescribed, followed by benzodiazepines and oxcarbazepine with unspecified favorable outcomes. For ADHD, methylphenidate and dexmethylphenidate were most often used, whereas guanfacine and clonidine were reported to worsen symptoms.

• #31 Tuberous Sclerosis Complex: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1112322-treatment

  The mTOR inhibitor sirolimus is FDA-approved for the treatment of lymphangioleiomyomatosis, a condition that can be associated with TSC. […] It may also be used off-label to manage certain TSC-related features. Topical sirolimus has FDA approval for treating facial angiofibroma in patients with TSC aged 6 years and older. […] Surgery […] Surgical treatment of patients with TSC can include the following: […] Focal cortical resection/thermal ablation […] Corpus callosotomy […] Vagus nerve stimulation […] In addition, SEGAs require resection if they produce hydrocephalus or significant mass effect. If a gross total resection can be achieved, recurrence is unlikely. […] See Treatment and Medication for more detail.

• #32 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  Patients with TSC may have retroperitoneal hemorrhage and/or hematuria from larger ( 46 cm) angiomyolipomas (AMLs). These sometimes can be catastrophic and require emergent supportive care. Once the patient’s condition is stabilized, embolization rather than resection is the preferred method of treatment for AMLs that have bled. […] Patients with lymphangioleiomyomatosis (LAM) may require acute inpatient treatment for pneumothorax, chylothorax, or dyspnea. Sirolimus is FDA-approved for treating LAM and everolimus may be used off-label. […] Surgical care for seizures in a patient with tuberous sclerosis complex (TSC) can involve focal cortical resection/thermal ablation, corpus callosotomy, or vagus nerve stimulation. […] Subependymal giant cell astrocytoma (SEGAs) require resection if they produce hydrocephalus or significant mass effect. If a gross total resection can be achieved, recurrence is unlikely.

• #33 Tuberous Sclerosis Treatment Program

  https://www.massgeneral.org/neurology/tsc/treatments-and-services

  Neurologists and neurosurgeons may control seizures, including infantile spasms and other types of epilepsy, with antiepileptic medications, vagus nerve stimulation, or surgical removal of cortical tubers, thought to be the cause of seizures. […] Dermatologists may use laser surgery or other surgical techniques to remove skin lesions such as facial angiofibromas, periungual fibromas, and, in some cases, shagreen patches and forehead plaques. […] Neurosurgeons may surgically remove one of these brain lesions in the event that it threatens to block the flow of cerebrospinal fluid and cause a buildup of pressure inside the cranium. In some cases, SEGAs grow back and must be removed again. […] Because TSC is a lifelong condition with a wide variety of symptoms, individuals should be monitored regularly by a physician with experience in treating people with the disorder.

• #34 Tuberous Sclerosis Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/tuberous-sclerosis

  Surgical resection of a brain tumor can relieve hydrocephalus and sometimes epilepsy, too. If complete resection is achieved, the brain tumor rarely recurs. […] If hydrocephalus does not resolve after tumor resection, shunt placement is performed to relieve pressure and alleviate symptoms. Shunt placement involves surgically inserting a shunt that reroutes the fluid, allowing it to safely drain into either the abdomen or a receptacle outside of the brain. […] For individuals who cannot undergo traditional surgery, more options are available. Laser ablation is a minimally invasive procedure that may be used to reach a structure that would otherwise be impossible to reach safely. Or, chemotherapy may be used instead to treat a brain tumor. […] To treat epilepsy, our neurosurgeons take the most conservative approach first, which in this case means that they begin nonsurgically, with anticonvulsant medication; if this does not provide adequate symptom relief, epilepsy surgery may be considered.

• #35 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Because the many cortical tubers of TSC represent potential for multiple epileptogenic foci, surgical resection previously had been thought to be less of an option. More recently, it has been recognized that even in patients with TSC there may be seizure freedom or palliation from resection of a particular structural lesion that is concordant with seizure description or EEG findings. Surgical resection may be beneficial, reducing or eliminating seizures for months to years. Although other foci may remain and prevent lifelong seizure freedom, even a temporary reduction in seizure frequency and severity can improve quality of life and neuropsychiatric outcomes. Even if seizure freedom is not long-lasting and other seizure types develop, this period of reduced or no seizures may prevent seizures from developing in other areas of the brain or may protect brain development for a time. Individuals who benefit from these surgeries may still be candidates for other interventions, including further resections, as needed later in life.

• #36 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  SEGAs that are symptomatic should be resected acutely, and cerebrospinal fluid (CSF) shunt diversion may be needed. For growing but otherwise asymptomatic SEGA, resective surgery or treatment with mTOR inhibitors is warranted. Nephrectomy for renal angiomyolipoma should be avoided in favor of embolization and corticosteroid treatment for angiomyolipomas hemorrhaging acutely. Kidney-sparing resection may also be considered. If lung tumors occur, lung transplant may be considered. Consider excision or laser surgery for symptomatic, rapidly changing, or disfiguring skin lesions. […] From the time of diagnosis and across the lifespan, the TAND checklist can be used to evaluate those with TSC for neuropsychiatric effects and comorbidities. Mood disorders, autism, anxiety, and behavioral issues are common, and all can be therapeutically addressed with interventions from psychologists, psychiatrists, occupational/vocational therapists, and speech-language pathologists. In many comprehensive epilepsy centers or TSC centers, a developmental psychologist and neuropsychologist are available. At the center where the author practices, consultation with these professionals at least once annually is considered standard of care.

• #37 Monitoring & managing patients with TSC:current perspectives | JMDH

  https://www.dovepress.com/monitoring-and-managing-patients-with-tuberous-sclerosis-complex-curre-peer-reviewed-fulltext-article-JMDH

  Nephrectomy should be avoided whenever possible, because of the high incidence of complications and increased risk of future renal failure. […] Everolimus is indicated for the treatment of patients with SEGA regardless of age, who require therapeutic intervention, but are not eligible for surgery. […] Both sirolimus and everolimus proved to reduce seizure frequency in TSC-related refractory epilepsy.

• #38 Tuberous Sclerosis | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30666

  The 2012 TSC consensus recommended that patients undergo lifetime surveillance to monitor for common manifestations. […] A comprehensive dermatologic evaluation may aid in the early recognition of angiofibromas that may eventually cause cosmetic disfigurations requiring laser therapy or surgical removal. […] Skin and dermatologic manifestations are also often responsive to mTOR inhibitors. […] Anticonvulsants are often required for TSC-associated epilepsy, especially vigabatrin for infantile spasms. […] As recommended by the 2012 consensus for tuberous sclerosis, treatment of acutely symptomatic subependymal giant cell astrocytomas (SEGA) (primarily complications of obstructive hydrocephalus) is surgical resection. […] For renal angiomyolipomas larger than 3.5 cm, arterial embolization is recommended to avoid total nephrectomy and decrease the incidence of renal complications.

• #39 Tuberous sclerosis

  https://dermnetnz.org/topics/tuberous-sclerosis

  Tuberous sclerosis is a multisystem disorder, so treatment from a team of specialist doctors is usually necessary. […] Skin lesions, particularly facial angiofibromas, may be psychologically distressing for some patients. Laser treatment or electrosurgery can be used to remove angiofibromas. […] The topical mTOR inhibitor sirolimus 0.2% gel (also called rapamycin) has proved helpful in reducing angiofibromas in a clinical trial involving 36 adults and children. One study has also reported improvement in hypopigmented macules. A larger prospective, multicentre, randomised, double-blind, vehicle-controlled trial enrolled 179 patients with tuberous sclerosis-related facial angiofibromas and found improvement in more than 80% of patients treated with topical 1% rapamycin with most occurring in the first month. It was well tolerated.

• #40 Tuberous Sclerosis Complex (TSC) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/tuberous-sclerosis-complex-tsc

  Unfortunately, there is no cure for tuberous sclerosis complex yet. But there are many effective treatment options for most symptoms. […] Antiepileptic medications can help treat and control infantile spasms and other types of seizures associated with TSC. […] Laser surgery and topical creams can reduce the appearance of some of the skin lesions associated with TSC. This is especially true for facial lesions. Treating the lesions early, while they are still small, can make them easier to manage. […] Surgical procedures are sometimes necessary to remove tumors and help preserve the function of affected organs. […] Many behavioral therapies and educational approaches can be effective for children with developmental disorders, such as autism spectrum disorders. […] Many of the complications of TSC can be managed more effectively if they are treated early. Early diagnosis, behavioral therapy, and alternative educational approaches can be very helpful to children with developmental disorders. Therefore, it is important to monitor your child closely for any symptoms related to TSC.

• #41 Tuberous Sclerosis Complex Treatment & Management: Approach Considerations, mTOR Kinase Inhibitors, Medical Care

  https://emedicine.medscape.com/article/1177711-treatment

  Epilepsy and other neurological problems are the most common causes of morbidity in tuberous sclerosis complex (TSC). Pediatric and/or adult neurologic consultation is recommended. […] The ketogenic diet is composed of a 2:1, 3:1, 4:1, or higher ratio of fats (ketogenic foods) to proteins and carbohydrates (antiketogenic foods). In general, the benefits of the diet for people with epilepsy include fewer seizures, less drowsiness, better behavior, and need for fewer concomitant antiepileptic drugs (AEDs). Several case series and retrospective reviews have noted benefit of the ketogenic diet and similar diets for seizures in tuberous sclerosis complex (TSC).

• #42 New Research Hopes to Advance Tuberous Sclerosis Treatment

  https://www.brainandlife.org/articles/new-therapies-show-promise-in-treating-this-neurologic-condition-but

  Several studies show that infantile spasms are better controlled with vigabatrin than ACTH. […] „Kids who go on the ketogenic diet, regardless of the type of seizures they’re having, often become seizure-freeand those are kids that have been on at least four medications before trying the diet,” claims Dr. Thiele. „It’s the most successful treatment we have for seizures caused by TSC.” […] Another option is vagal nerve stimulation (VNS), which sends regular, mild pulses of electrical energy to the brain. […] Until recently, undergoing surgery to remove TSC tubers was considered only after all other methods, including the ketogenic diet and VNS, had failed. […] Now, many patients undergo surgery early in the disease processeven months after birth. […] „One of the big pushes over the last 10 years is the recognition that TSC patients who do not meet the classic selection criteria for epilepsy surgery may still benefit from surgery,” says Dr. Weiner.

• #43

  https://www.nhs.uk/conditions/tuberous-sclerosis/treatment/

  Tuberous sclerosis is a lifelong condition that requires long-term care and support from a range of different healthcare professionals. […] Their care plan is likely to include details about any treatment or support they need, as well as the routine tests that will be necessary to monitor their condition. […] Medicines to control the seizures (anti-epileptic drugs) will usually be tried first, although they’re not always effective for people with tuberous sclerosis. […] If medication does not control the seizures, one of the following procedures may be recommended: surgery to remove any tumours in your brain that may be causing the seizures, vagus nerve stimulation (VNS) where a small electrical device is implanted under the skin to send pulses of electricity to the brain, a special diet the ketogenic diet or a modified version of it.

• #44 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  Other ASMs commonly used in TSC include clobazam, lamotrigine, lacosamide, levetiracetam, oxcarbazepine, perampanel, topiramate, valproic acid, brivaracetam, and carbamazepine. Most seizure types, other than infantile spasms, in TSC are not responsive to pharmacotherapy and polypharmacy is common. Vagus nerve stimulation and the use of a ketogenic diet may be considered for pharmacoresistant seizures. Epilepsy surgery, discussed further below, may be indicated. […] The mTOR inhibitors sirolimus and everolimus, developed initially as immunosuppressants, have clinical value for aspects of TSC. A topical gel formulation of sirolimus (0.2%) has been approved by the Food and Drug Administration (FDA) as of April 2022 for treatment of facial angiofibromas in TSC in those age 6 years or more. Everolimus was shown in clinical trials to reduce the volume of SEGAs and is approved for the treatment of SEGAs not amenable to surgical resection. Renal angiomyolipomas can be treated with mTOR inhibitors, as can lung tumors. As noted, everolimus is also used as an antiseizure medication for treatment of seizures.

• #45 Treatment-resistant epilepsy and tuberous sclerosis complex | NDT

  https://www.dovepress.com/treatment-resistant-epilepsy-and-tuberous-sclerosis-complex-treatment–peer-reviewed-fulltext-article-NDT

  The multilesional nature of cortical tubers in TSC poses significant challenges in the assessment of a patient’s surgical options. […] Given the refractory nature of TSC-associated epilepsy, for patients that are not surgical candidates for resective surgery, they may benefit from neuomodulation with vagus nerve stimulation (VNS), deep brain stimulation (DBS), or brain-responsive neurostimulation (RNS). […] TSC-associated epilepsy can be challenging to treat; however, with advances in the understanding of the epileptogenesis in TSC, mTOR signaling including the role of the GATOR complex, and the advent of mTOR inhibitors, we have entered a new era in precision therapy for TSC.

• #46 Pediatric tuberous sclerosis complex (TSC) – Children’s Health Neurology

  https://www.childrens.com/specialties-services/conditions/tuberous-sclerosis

  With appropriate, ongoing treatment, many people with TSC have a typical life expectancy. Your childs care team will refer them to appropriate therapies to help them achieve their best possible health. […] Medicine can relieve various symptoms of tuberous sclerosis. Certain drugs can treat mood and behavior problems. Your childs medical team may also recommend medication to treat: […] Drug treatment can shrink these tumors in people with TSC. […] Antiseizure medication can control seizures. However, more than 50% of patients with TSC who have epilepsy do not respond to standard antiseizure medications. If this is the case for your child, our team of experts works together to find an effective treatment plan, including evaluating if neurosurgery may help curb seizures. […] If seizures happen so often that they affect your childs quality of life, surgery may be necessary. Surgeons may remove the section of the brain where seizures begin. […] At Childrens Health, we offer less-invasive brain surgery that doesnt require a large incision and helps children recover faster. […] Your childs doctor may recommend: Vagal nerve stimulation (VNS), Responsive neurostimulation (RNS), Deep brain stimulation (DBS).

• #47 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Early intervention services, such as occupational, physical or speech therapy, may be helpful. These therapies can help children with tuberous sclerosis who have special needs in these areas. The therapies can improve children’s ability to manage daily tasks and activities. […] Early intervention and special needs services can help children with developmental delays and behavior issues adapt to the classroom. This can help them meet their full potential. When needed, social, vocational and rehabilitation services may continue throughout life. […] Talking with a mental health provider may help people accept and adjust to living with tuberous sclerosis. A mental health provider also can help with behavior, social or emotional issues and suggest resources. […] Tuberous sclerosis is a lifelong condition that requires careful monitoring and follow-up because many symptoms may take years to develop. A schedule of regular appointments with your health care provider throughout life may include tests such as those done during diagnosis. Finding and managing problems early can help prevent complications.

• #48 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Early intervention services, such as occupational, physical or speech therapy, may be helpful. These therapies can help children with tuberous sclerosis who have special needs in these areas. The therapies can improve children’s ability to manage daily tasks and activities. […] Early intervention and special needs services can help children with developmental delays and behavior issues adapt to the classroom. This can help them meet their full potential. When needed, social, vocational and rehabilitation services may continue throughout life. […] Talking with a mental health provider may help people accept and adjust to living with tuberous sclerosis. A mental health provider also can help with behavior, social or emotional issues and suggest resources. […] Tuberous sclerosis is a lifelong condition that requires careful monitoring and follow-up because many symptoms may take years to develop. A schedule of regular appointments with your health care provider throughout life may include tests such as those done during diagnosis. Finding and managing problems early can help prevent complications.

• #49 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Early intervention services, such as occupational, physical or speech therapy, may be helpful. These therapies can help children with tuberous sclerosis who have special needs in these areas. The therapies can improve children’s ability to manage daily tasks and activities. […] Early intervention and special needs services can help children with developmental delays and behavior issues adapt to the classroom. This can help them meet their full potential. When needed, social, vocational and rehabilitation services may continue throughout life. […] Talking with a mental health provider may help people accept and adjust to living with tuberous sclerosis. A mental health provider also can help with behavior, social or emotional issues and suggest resources. […] Tuberous sclerosis is a lifelong condition that requires careful monitoring and follow-up because many symptoms may take years to develop. A schedule of regular appointments with your health care provider throughout life may include tests such as those done during diagnosis. Finding and managing problems early can help prevent complications.

• #50 Tuberous Sclerosis Complex (TSC) | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/tuberous-sclerosis-complex-tsc

  Unfortunately, there is no cure for tuberous sclerosis complex yet. But there are many effective treatment options for most symptoms. […] Antiepileptic medications can help treat and control infantile spasms and other types of seizures associated with TSC. […] Laser surgery and topical creams can reduce the appearance of some of the skin lesions associated with TSC. This is especially true for facial lesions. Treating the lesions early, while they are still small, can make them easier to manage. […] Surgical procedures are sometimes necessary to remove tumors and help preserve the function of affected organs. […] Many behavioral therapies and educational approaches can be effective for children with developmental disorders, such as autism spectrum disorders. […] Many of the complications of TSC can be managed more effectively if they are treated early. Early diagnosis, behavioral therapy, and alternative educational approaches can be very helpful to children with developmental disorders. Therefore, it is important to monitor your child closely for any symptoms related to TSC.

• #51 Tuberous sclerosis – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/tuberous-sclerosis/diagnosis-treatment/drc-20365971

  Early intervention services, such as occupational, physical or speech therapy, may be helpful. These therapies can help children with tuberous sclerosis who have special needs in these areas. The therapies can improve children’s ability to manage daily tasks and activities. […] Early intervention and special needs services can help children with developmental delays and behavior issues adapt to the classroom. This can help them meet their full potential. When needed, social, vocational and rehabilitation services may continue throughout life. […] Talking with a mental health provider may help people accept and adjust to living with tuberous sclerosis. A mental health provider also can help with behavior, social or emotional issues and suggest resources. […] Tuberous sclerosis is a lifelong condition that requires careful monitoring and follow-up because many symptoms may take years to develop. A schedule of regular appointments with your health care provider throughout life may include tests such as those done during diagnosis. Finding and managing problems early can help prevent complications.

• #52 Tuberous sclerosis | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/tuberous-sclerosis

  Guidelines for TSC care include regular tests to look for early signs of TSC in different parts of the body. These include regular MRI scans, blood tests and other tests. […] Finding signs of TSC early offers the person with TSC options for early treatment. Appropriate treatment can protect the health of the person with TSC.

• #53 Find out more about treatment for tuberous sclerosis

  https://lonestarneurology.net/blog/tuberous-sclerosis-treatment-options/

  To effectively control tuberous sclerosis, a comprehensive therapy approach is necessary. The goal is to: […] Tuberous sclerosis treatment involves a team of healthcare professionals. It includes neurologists, dermatologists, and genetic counselors. Medications can control convulsions and behavioral issues. Surgery can remove tumors or control specific problems. Also, therapies like physical, occupational, and speech therapy can help. They address developmental delays and improve functioning. […] There is no cure for the ailment. But healing aims to control signs and improve quality of life. This may involve: […] Understanding ailment is crucial for early detection and appropriate healing. […] According to our experience, medication options for tuberous sclerosis disease: […] Antiepileptic drugs (AEDs) are a common class of medications for tuberous sclerosis disease. These medications work by stabilizing abnormal electrical activity in the brain. And they reduce the frequency and severity of convulsions.

• #54 Tuberous Sclerosis Complex

  https://practicalneurology.com/diseases-diagnoses/child-neurology/tuberous-sclerosis-complex/31942/

  The multisystem involvement of TSC, neuropsychiatric effects, and comorbidities require team-based multidisciplinary care focused on treating symptoms and improving quality of life is recommended. Because epilepsy surgery is often indicated, these patients should be referred to tertiary epilepsy care centers early in the course of their condition, where such team-based care is often most accessible. Cardiologists, nephrologists, pulmonologists, ophthalmologists, dermatologists, and other specialists should join this team as needed as clinical manifestations develop. Although it may be difficult for families to travel to these centers, even an annual visit with collaboration and teleconsultation with the referring physician is beneficial.

• #55 2023 Tuberous Sclerosis Complex Highlight – Beyond Rapamycin: A Search for Curative Therapies in TSC, Tuberous Sclerosis Complex Research Program, Congressionally Directed Medical Research Programs

  https://cdmrp.health.mil/tscrp/research_highlights/23Jane_Yu_highlight

  The ultimate goal of this work is to use this new understanding to discover a treatment that will completely kill the cells in the tumors and thereby achieve a cure. […] Overall, the availability of a safe and curative drug would greatly expand the number of TSC patients who would benefit from an understanding of the biology of cells treated with rapamycin. […] New pathways could lead to new therapeutics that are truly curative.

• #56 2019 Tuberous Sclerosis Complex Highlight – Gene Therapy, a New Approach to Treating TSC, Tuberous Sclerosis Complex Research Program, Congressionally Directed Medical Research Programs

  https://cdmrp.health.mil/tscrp/research_highlights/19breakefield_highlight

  Having effective, clinically available treatments is of utmost importance to TSC patients. To that end, Dr. Breakefield and her lab are currently optimizing a vector for whole body systemic delivery, as well as investigating the biological impact of gene replacement. […] AAV vectors have proven safe and beneficial in gene therapy for a number of human diseases, and U.S. Food and Drug Administration-approved products are appearing this year, so Dr. Breakefields work gives promise to the possibility that application of this approach could lead to its effective use in treating TSC.

• #57 Azthena logo with the word Azthena

  https://www.news-medical.net/news/20210108/Gene-therapy-can-effectively-treat-mice-with-tuberous-sclerosis-complex-shows-study.aspx

  Patients with tuberous sclerosis complex, a genetic disorder characterized by the growth of noncancerous tumors in multiple organs of the body, have limited treatment options. […] Current treatments for tuberous sclerosis complex include surgery and/or lifelong treatment with drugs that cause immune suppression and potentially compromise early brain development. Therefore, there is a clear need to identify other therapeutic approaches for this disease. […] The U.S. Food and Drug Administration has approved a limited number of gene therapy products for use in humans, and the results from this study suggest that clinical trials are warranted to test the strategy’s potential in patients with tuberous sclerosis complex.

• #58 Clinical management of tuberous sclerosis complex over the lifetime of a patient

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5683262/

  Identification and management of LAM are required almost exclusively for women in adulthood, usually from the third to fourth decade onward. mTOR inhibitors are recommended for the treatment of TSC-associated LAM in patients with moderate-to-severe lung disease or rapid progression; for patients with respiratory failure, lung transplantation is considered. […] Early diagnosis and proactive treatment strategies initiated before the development of symptoms are becoming increasingly important.

• #59 Finding new treatment targets for tuberous sclerosis complex | Epilepsy Research Institute

  https://epilepsy-institute.org.uk/eri/research/features/finding-new-treatment-targets-for-tuberous-sclerosis-complex/

  Tuberous sclerosis complex (TSC) is a genetic condition causing non-cancerous (benign) tumours to develop in different parts of the body, including the brain. […] In a research project jointly funded by the Epilepsy Research Institute and Tuberous Sclerosis Association, Dr Amanda Almacellas Barbanoj is investigating new treatment targets for the condition. […] Here, Amanda explains how more specific therapies with fewer side effects could enable treatment for TSC to start at an earlier age. […] My hypothesis is that the mutations in TSC1/2 cause a ripple effect in the function of other genes important for brain development. Therefore, the aim of my project is to explore the other ways in which a mutation in TSC1/2 affects how neurons form and connect with each other. […] More importantly, this in-depth study of TSC1/2 role in the building of the brain will uncover potential targets of new therapies that could significantly improve the quality of life of the one million people living with TSC worldwide and their carers.

• #60 Innovative Treatment for Tuberous Sclerosis: A Look at Clinical Research – Science 37 Studies

  https://studies.science37.com/innovative-treatment-for-tuberous-sclerosis-a-look-at-clinical-research/

  As our understanding of TSC deepens, so does the potential for innovative treatments. Ongoing research into mTOR inhibitors and other targeted therapies offers hope for individuals living with TSC. […] These innovative therapies are still being tested, but they could change how we manage TSC and improve the quality of life for many patients.

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