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Tuberous Sclerosis

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Textbook of Pediatric Neurosurgery

Abstract

Tuberous sclerosis complex (TSC) is a genetically determined neurocutaneous syndrome with a broad spectrum of clinical manifestations, ranging from minimal symptoms to severe disabling disorders, which may require strict follow-up and complex care. It is characterized by the presence of hamartomas involving multiple organs, including brain, as result of inactivating mutations in either one of the two tumor suppressor genes TSC1/TSC2. Their inactivated protein complex results in an overactivation of the mammalian target of rapamycin (mTOR) signaling cascade leading to excessive cell growth, metabolism, proliferation, and cell survival. More and more, base research is providing new insights on its pathophysiology, redirecting the therapeuthic strategies on new tailored pharmacological treatments (rapamycin inhibitors mTOR), whose results, however, are still matter of debate and under further investigation. Thus, TSC represents a still open challenge for neurosurgeons, who must deal with two of the most characteristic brain lesions, representing a major source of morbidity and mortality in these patients: cortical tubers with the associated drug-resistant epilepsy and subependymal giant cells tumors (SEGAs).

Seizures are the most common neurological symptom of TSC, involving more than 80% of the patients. They often occur within the first year of life, interfering with neuropsychiatric, social, and cognitive development; therefore, requiring prompt identification and treatment. Despite multiple antiepileptic drug combinations and the recent trials on the effect of rapamycin in controlling seizures, in about two third of cases, the patients present high-frequency drug-resistant epilepsy, requiring surgical treatment. Lesionectomy or tuberectomy currently make about 60% of patients seizure-free (especially, if guided by intraoperative electrocortical monitoring), when there is a concordance of epileptogenic zone and tubers. On the contrary, disappointing results are obtained in the cases with multiple interictal foci and infantile spasms, and for most of these cases callosotomy and vagal nerve stimulation maintain a palliative role.

SEGAs are slow growing tumors, localized at the caudothalamic groove, whose diagnostic feature is the progressive growth on consecutive imaging. They can be associated with obstructive hydrocephalus, focal neurological deficit, and even sudden death. The indication for treatment includes new onset of symptoms or radiological evidence of tumor growth: surgical indication is considered on the base of the localization, size of the tumor, presence of hydrocephalus, and surgeon’s expertise. For patients who present contraindications to the surgical approach, mTOR inhibitors therapy can be administered, obtaining generally a rapid reduction in tumor volume at beginning and a prevalently stabilization of the residual mass at long term; however, potential relapse is reported at withdrawing of the therapy and collateral effect are not nil.

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Authors and Affiliations

  1. Department of Neurosurgery, Policlinico Tor Vergata Medical School, Rome, Italy

    Federica Novegno

  2. Pediatric Neurosurgery, International Neuroscience Institute, Hannover, Germany

    Concezio Di Rocco

Authors
  1. Federica Novegno
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  2. Concezio Di Rocco
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Corresponding author

Correspondence to Federica Novegno .

Editor information

Editors and Affiliations

  1. International Neuroscience Institute, Hannover, Germany

    Concezio Di Rocco

  2. Oakland Medical Center, Oakland, California, USA

    Dachling Pang

  3. University of Toronto Hospital for Sick Children, Toronto, Ontario, Canada

    James T. Rutka

Section Editor information

  1. Director of Pediatric Neurosurgery, International Neuroscience Institute, Hannover, Germany

    Concezio Di Rocco

  2. Pediatric Neurosurgery, Institute of Neurosurgery, Catholic University Medical School, Largo “A. Gemelli”,8, 00168, Rome, Italy

    Gianpiero Tamburrini

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Novegno, F., Di Rocco, C. (2017). Tuberous Sclerosis. In: Di Rocco, C., Pang, D., Rutka, J. (eds) Textbook of Pediatric Neurosurgery. Springer, Cham. https://doi.org/10.1007/978-3-319-31512-6_45-1

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