Tuberous Sclerosis

Neurodegenerative syndrome characterized by lesions of the skin, tumor growth, and seizures. Some patients present with mental retardation and autism. Rhabdomyoma of the heart and astrocytoma in the brain are frequent tumoral presentation.

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Bourneville Syndrome; Bourneville-Pringle Syndrome.

1:25,000 to 1:30,000 live births. Nearly 1 million people worldwide are known to have tuberous sclerosis, including approximately 50,000 in the United States.

Autosomal dominant with variable penetrance. De novo mutations have been confirmed on gene located on chromosome 9q33-34 and chromosome 16p13. If two or more siblings have tuberous sclerosis, one parent always has at least one skin manifestation of tuberous sclerosis. Sporadic transmission rate varies from 58 to 77%. If both parents are normal, a child with tuberous sclerosis must be a new mutation. It is believed that only 33% of all tuberous scleroses are inherited.

Multiorganic disease affecting mainly the brain and skin, but also the heart, lung, kidney, bone, and eye.

Heterogeneous disease with a wide clinical spectrum. The presence and importance of seizures is variable, as is the importance of mental retardation. In general, the youngest children at the moment of clinical presentation have the worse mental retardation. The diagnosis is based on clinical suspicion and demonstration of typical lesions on the skin or retina. A head MRI or CT scan often confirms the diagnosis. Epilepsy, mental retardation, “salaam” seizures, and angiofibromas of numerous organs with intracranial hamartomatous lesions involving subependymal nodules and cerebral cortical tubers are characteristic of this phacomatosis.

Clinical signs appear shortly after birth and worsen with age. Mental retardation and uncontrolled seizures occur in half of the cases. The principal finding is of tuber lesions on the skin or in the brain. Skin lesions include adenoma sebaceum (80% of cases), which are rarely present at birth (onset at 4 to 6 years of age), and angiofibromas appearing as pink or red papules in patches or a butterfly-shaped distribution around the nose, cheek, and chin. Ash-leaf spots (90% of patients) are hypopigmented ovalor leaf-shaped spots found on the trunk and limbs in a linear orientation. The Shagreen patches (35% of patients) are isolated, “leathery,” raised, and thickened plaques, with an orange-peel consistency that are grayish-green or light brown in color and most often located over the lumbosacral or gluteal region. Usually develop in late infancy or early childhood but may also be present at birth. Café-au-lait spots (7 to 16% of patients) and fibromas are also associated with tuberous sclerosis. Tubers may lead to seizures (90% of patients), which usually present as infantile spasms; 25 to 50% of infants with infantile spasms develop tuberous sclerosis. Older children will develop tonic, clonic, myoclonic, and akinetic Lennox-Gastaut syndrome. Hydrocephalus by obstructing cerebrospinal fluid circulation at the level of the foramen of Monroe. Mental retardation is present in 70% of patients. Tubers are growing tissular lesions that can transform into malignant lesions or calcify. The classical clinical triad is based on epilepsy, mental deficit, and adenomatous lesions. Pathognomonic lesions often appear between 4 and 6 years of age, presenting as thin, red nodules over the face, further enlarging and becoming coalescent. During adolescence, ungual fibroma appear. Other involved organs can include the heart conduction system with ectopic beats and conduction blocks. Heart rhabdomyoma is present in 50% of children with tuberous sclerosis during the neonatal period and may regress. Kidney injury is demonstrated by polycystic kidneys with hamartomas. Fibrous pulmonary changes may lead to pneumothoraces. Mortality is 50% at the age of 20 to 25 years. Abdominal aortic aneurysms have been reported in infants.

Epilepsy is often controlled with medication. However, this medication interferes with anesthetic management. Because of potential heart involvement, a preoperative echocardiography and an ECG may be useful. Evaluate renal function (echography, urea, creatinine, electrolytes, CT scan), neurological function (clinical, CT scan, MRI, EEG), airway for the presence of oral and/or laryngeal tumors (clinical, radiography, fiberoptic endoscopy, CT scan), and respiratory function (chest radiograph, CT scan, endoscopy, pulmonary function test, and arterial blood gas analysis).

Mainly dominated by the fear of epilepsy. For prolong or long or at-risk surgical operations, or if postoperative sedation is planned, a continuous EEG monitoring may be useful to detect subclinical epileptic phenomenon. Direct laryngoscopy and tracheal intubation can be difficult because of oral or laryngeal tumors that may be unknown and asymptomatic at the moment of induction of anesthesia. Adequate procedures and materiel should be available (oral or nasal canula, fiberoptic, laryngeal mask airway, retrograde intubation leader). Anesthetic management should preserve spontaneous ventilation until tracheal intubation is realized and lung ventilation confirmed. In case of cardiac tumors, perioperative monitoring is necessary. Intraoperative monitoring should include arterial baseline. Perioperative fluid regimen may consider either cardiomyopathy and renal function. Pulse oximetry can be difficult because of ungual fibroma. Regional anesthesia can be realized but the benefit of medullar blockades should be precisely evaluated in cases of cardiomyopathy or neurological tumors.

Avoid enflurane, ketamine, or other proepileptic drugs. Consider epileptic properties of some anesthetic drugs (e.g., methohexital, enflurane) and interaction with anticonvulsive medications. Avoid nephrotoxic drugs. Catecholamine should be used with caution in cases of cardiomyopathy. In a case of Wolff-Parkinson-White Syndrome, verapamil and digoxin should be avoided. The effects of anesthetic drugs should be considered (isoflurane and sevoflurane have been used successfully).

Mulberry Tumor: A form of tuberous sclerosis presenting with a characteristic nodular astrocytoma of the retina.

Lennox-Gastaut Syndrome: A severe form of epilepsy developing in children between 1 and 8 years of age. Developmental delay and impaired intellectual functioning. This disorder may be the result of brain trauma, infections, or genetic brain diseases (e.g., tuberous sclerosis). The seizures are tonic with severe stiffening of the body involving respiratory patterns and gas exchange, or atonic, leading to brief loss of muscle tone and consciousness, which leads to sudden falls and head trauma. Occasionally, myoclonic seizures may be encountered.

Westerhof Beemer Cormane Syndrome (Macules, Hereditary Congenital Hypopigmented and Hyperpigmented): Neurocutaneous syndrome. Autosomal dominant with mental retardation, retarded growth, and congenital hypomelanotic and hypermelanotic cutaneous macules.