Further Inpatient Care
See the list below:
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Patients with TSC may experience frequent exacerbations of their seizures that may require inpatient adjustment of AEDs.
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Patients with TSC may have retroperitoneal hemorrhage and/or hematuria from larger (>4-6 cm) 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 end-stage renal disease may require inpatient treatment for dialysis or management of hypertension or electrolyte disturbance.
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Patients with LAM may require acute inpatient treatment for pneumothorax, chylothorax, or dyspnea. Lung transplantation may be undertaken for end-stage pulmonary disease.
Complications
See the list below:
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Death: Death is usually either sudden unexplained death in epilepsy or related to an accident involving a seizure. Critical hydrocephalus from undiagnosed giant cell astrocytoma, cardiac arrhythmia, hemorrhagic complications of renal AMLs, and rupture of occult arterial aneurysms also contribute to increased mortality.
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Injuries (especially facial) from seizures resulting in falls
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Dose-related, idiosyncratic, or long-term adverse effects of AEDs
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Renal, cardiac, or metabolic complications from the ketogenic diet
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Inappropriate surgery or therapies: Clinicians unfamiliar with TSC frequently make recommendations that are unwarranted given the unique nature of the hamartomas associated with the disorder. For example, nephrectomies (even bilateral) may be undertaken to rule out the extremely low possibility of a renal cell carcinoma rather than performing serial MRI and follow-up. Patients may not receive embolization to prevent potentially fatal hemorrhage from arterial aneurysms associated with large AMLs. Invariably benign hamartomas of the liver, spleen, or other viscera are needlessly biopsied or resected on the fear that they may reflect malignancies. Children with TSC and infantile spasms are treated with agents other than vigabatrin owing to misplaced anxiety on the part of their neurologists.
Prognosis
The prognosis of patients with TSC is not as grim as has been typically thought. Higher numbers of tubers, earlier onset and intractability of seizures, and infantile spasms are associated with (but do not guarantee) worse cognitive and behavioral outcomes (see images below). Cardiac lesions almost always spontaneously regress, although supportive care may be necessary for a time. Pulmonary and renal lesions affect prognosis on the basis of their extent and severity.
Multiple tubers in a child with tuberous sclerosis, normal intelligence, and well-controlled seizures. High tuber count does not invariably mean poor neurological outcome.
All tubers are not equal. This child has a smaller number of tubers than the patient shown in the previous image, but the tubers are larger in size. She too has normal intelligence and is seizure free on medication.
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Enhancing subependymal nodules, including a probable giant cell astrocytoma in the region of the foramen of Monro. Subependymal nodules may increase in size over time from one scan to the next, and then stabilize. This lesion had not changed with serial imaging over 2 years. The patient remains asymptomatic and is monitored closely for any deterioration.
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Hydrocephalus from a subependymal giant cell astrocytoma in a patient with tuberous sclerosis. The patient presented with acute blindness and ataxia.
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Facial angiofibromas in a young man with tuberous sclerosis complex.
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Dysplastic periungual fibroma involving the great toe in a patient with tuberous sclerosis.
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Gingival fibromas (see arrows) in a patient with tuberous sclerosis. A stain outlines dental pits and craters. Gingival hyperplasia from other causes (eg, phenytoin use) is more diffuse and usually not nodular/focal in nature.
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Typical ash leaf macules; the reddish, nodular area at the upper lumbar area is a shagreen patch.
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Atrial rhabdomyoma as seen on cardiac CT scan in a patient with tuberous sclerosis.
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Nonobstructive ventricular rhabdomyomas in a patient with tuberous sclerosis.
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Ventricular rhabdomyomas may diffusely infiltrate the myocardium, as in this patient with tuberous sclerosis. The patient presented with cardiac failure and hydrops at birth. After a period of intensive supportive care and inotropic therapy, she now has essentially normal cardiac function and is on no medications.
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Multifocal pulmonary cysts characteristic of lymphangiomyomatosis. As many as 40% of women with tuberous sclerosis have pulmonary cysts on chest CT scan.
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Massive bilateral angiomyolipomas in a woman with tuberous sclerosis. She also has lymphangiomyomatosis.
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Pre-embolization angiography of the patient with angiomyolipomas shown the previous image. Dysplastic arterial vessels are demonstrated.
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Vessels to the angiomyolipoma shown in the previous image have been occluded with coils. This should produce regression of the lesion and prevention of hemorrhage. Functional intervening renal parenchyma is preserved.
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Enamel pitting in tuberous sclerosis. Pinpoint size pitting (A) and crater size pitting (B) are visible. Red dye is used to enhance recognition.
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Basilar artery aneurysm in a 2-year-old girl with tuberous sclerosis. The arrow shows the anterior aspect of the aneurysm where it abuts the clivus. The lesion was not present on MRI performed 11 months earlier.
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This presumed tuber was first noted in the left frontal region. It expanded in size, affecting adjacent structures across the midline and resulting in calcifications still evident in the right frontal region. The tuber then spontaneously involuted. About 20% of tubers may show changes in imaging characteristics over time, requiring close imaging follow-up. This patient remained asymptomatic from the mass effect, and his seizures resolved as the lesion involuted.
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This father and all 3 children have tuberous sclerosis complex. The children are now grown up and of normal intelligence, including the young lady at left who is cushingoid from therapy with adrenocorticotropic hormone for infantile spasms.
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The child whose CT scan is shown presented with medically intractable epilepsy thought to be due to partial hemimegalencephaly. She became seizure free after partial hemispherectomy. Pathology was consistent with a cortical tuber. She was subsequently found to have multiple ash leaf macules and diagnosed with tuberous sclerosis.
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Multiple tubers in a child with tuberous sclerosis, normal intelligence, and well-controlled seizures. High tuber count does not invariably mean poor neurological outcome.
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All tubers are not equal. This child has a smaller number of tubers than the patient shown in the previous image, but the tubers are larger in size. She too has normal intelligence and is seizure free on medication.
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Mammalian target of rapamycin (mTOR) activates the protein S6 kinase, which enhances cell growth and protein synthesis. It, in turn, is regulated by multiple factors, including insulin, amino acids, the drugs rapamycin and its congeners (eg, RAD001), and the TSC gene products via the GTPase-activating protein Rheb.
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Subependymal giant cell astrocytoma prior to stereotactic insertion of balloon catheter as seen on T2-weighted MRI.
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Modified angioplasty catheter used in creation of surgical tract for astrocytoma resection.
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Catheter placed in proximity to lesion, balloon inflated.
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Postoperative T2-weighted MRI in a patient with subependymal giant cell astrocytoma showing gross total resection of giant cell astrocytoma with minimal disruption of overlying cortex.
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Mean reduction in simple and complex partial seizures in patients with tuberous sclerosis complex (TSC) who were treated with vagus nerve stimulator at the author's institution at 6 and 12 months. Overall reduction in secondarily generalized seizures was 22% at 12 months (N = 17; 10 boys, 7 girls, aged 3-12 y).
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Regression of a giant cell astrocytoma after approximately 15 months oral rapamycin therapy in a 4-year-old patient with tuberous sclerosis.
