TSC Consensus Group Management Recommendations

Twelve subcommittees, each led by a clinician with advanced expertise in TSC and the relevant medical subspecialty, were organized to focus on specific disease focus topics that have important clinical management implications in TSC: (1) dermatology and dentistry; (2) nephrology; (3) pulmonology; (4) cardiology; (5) ophthalmology; (6) gastroenterology; (7) endocrinology; (8) genetics; (9) epilepsy; (10) TSC-associated neuropsychiatric disorders; (11) brain structure, tubers, and tumors; and (12) coordination of clinical care. Each subcommittee was charged with formulating key clinical questions to address within its focus area, reviewing relevant literature, evaluating the strength of data, and providing a recommendation based on evaluated literature or, if data were lacking, an expert opinion based on experience or case studies or other appropriate method. If no recommendation could be provided because there was no consensus or conflicting evidence was found of equal value or weight, the subcommittee was to provide recommendations for future research that would help resolve the conflict.
A centralized literature search was performed on March 12, 2012, for all consensus group subcommittees to use. This search used PUBMED and SCOPUS databases of all articles published between 1997 (year before last consensus conference) and 2012 (current), regardless of language. Search terms for PUBMED consisted of “tuberous sclerosis” and “humans” and “diagnosis OR therapy.” Search terms for SCOPUS consisted of “tuberous sclerosis” and “diagnosis OR treatment.” A total of 2692 articles were identified with this approach. Each consensus group subcommittee was then able to determine additional terms pertinent to its organ system or disease focus area to further refine articles to be reviewed and evaluated. Additional literature searches, if deemed necessary by individual subcommittees to address key clinical questions not captured by the central literature search, could be performed as needed (e.g., epilepsy surgery or organ transplantation guidelines relevant but not specific to TSC).
The evidence-based framework based on the approach of the National Comprehensive Cancer Network (NCCN) Clinical Guidelines¹⁷ was used to grade strength of evidence and resulting recommendations. The NCCN framework allows recommendations based on all classes of evidence by categorizing recommendations with regard to the type and strength of evidence used to support the recommendation and is well-suited for application across many organ systems and specialties for a rare disease such as TSC with multisystem involvement. NCCN Clinical Guidelines category 1 recommendations are based on high-level evidence and uniform consensus, whereas category 2 recommendations are based on lower-level evidence and either uniform consensus or consensus. Category 3 recommendations are those for which a consensus cannot be reached, regardless of evidence. Additional details regarding this framework, including definitions for high- and low-level evidence, are provided in Table 1.
For the purposes of this summary document, the 2012 International Tuberous Sclerosis Complex Consensus Group surveillance and management recommendations are organized into two sections: (1) recommendations applicable at the time of initial diagnosis and (2) recommendations applicable to follow-up health care. There is some overlap with this approach because some features discovered upon initial diagnosis may require immediate intervention, additional workup, or specialist referral. By necessity, discussion in this summary is limited to the most relevant and salient points. More detailed discussion of specific recommendations for the different TSC disease focus areas, supporting evidence thereof, and other special considerations will be published separately by each International Tuberous Sclerosis Consensus Complex Group subcommittee.