Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex

We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. The patient underwent several partial tumor resections complicated by intraoperative cardiac arrest. The tumor has been regrowing and produced severe clinical symptoms. Everolimus treatment resulted in marked tumor regression, significant improvement in patient’s ambulation and cessation of seizures. Moreover, the therapy was well tolerated. These findings indicate that everolimus treatment should be considered as a therapeutic option alternative to surgery in patients with tuberous sclerosis complex.     

Right Ventricular Dysplasia with Massive Thromboemboli in Tuberous Sclerosis Complex

A 12-year-old boy visited the emergency room for severe dyspnea. He was diagnosed with tuberous sclerosis at 5 years of age, and right ventricular dysplasia was detected at 11 years of age. Thromboemboli in right ventricle and bilateral pulmonary arteries were confirmed with two-dimensional echocardiography and computed tomography. We report the case of a patient with tuberous sclerosis who presented with huge thrombi in a dysplastic right ventricle and massive bilateral pulmonary thromboemboli without evidence of a cardiac tumor.     

Coarctation of the aorta and renal artery stenosis in tuberous sclerosis

Among neurocutaneous disorders, coarctation of the abdominal aorta and renal artery stenosis have traditionally been associated with neurofibromatosis. We report a 5-year-old girl who, during the evaluation of asymptomatic hypertension, was discovered to have bilateral renal artery stenosis, coarctation of the abdominal aorta, renal cysts and typical skin lesions of tuberous clerosis. Renal vascular hypertension has not been reported previously in tuberous sclerosis. We conclude that the tuberous sclerosis complex should be expanded to include vascular malformations and that hypertension should not be assumed to be secondary to renal hamartomata or cysts in patients with tuberous sclerosis.     

A large infiltrating fibrous hamartoma of infancy in the abdominal wall with rare associated tuberous sclerosis

Tuberous sclerosis is a complex autosomal-dominant neurocutaneous syndrome characterized by hamartomatous malformations of fibrous and connective tissues in various organs. Although various histologic types of soft-tissue masses can occur with tuberous sclerosis, we present a unique case of fibrous hamartoma of infancy presenting as large infiltrating cutaneous and subcutaneous masses in the abdominal wall in a 4-year-old boy with tuberous sclerosis. Although the co-occurrence of tuberous sclerosis and fibrous hamartoma of infancy is very rare, it should be considered in the differential diagnosis of subcutaneous soft-tissue masses found in children with tuberous sclerosis.     

Tuberous sclerosis--a multi system disease

Tuberous sclerosis is a genetic disease with autosomal dominant inheritance, associated with hamartomata in several organs and various skin findings. A case of a ten year old boy is presented here to highlight the multisystem involvement in tuberous sclerosis. The child had seizures, facial papular naevi and periungual fibromas. MRI revealed cortical tubers, white matter lesions and subependymal nodules. Orbital ultrasound showed retinal hamartoma on the left side. Ultrasound of the abdomen revealed a soft tissue mass at the upper pole of left kidney with a small cyst in right kidney.     

Asymptomatic Fatty Changes in the Myocardium of a Patient With Tuberous Sclerosis

Rhabdomyomas are the most common primary cardiac tumors in childhood. They usually occur on ventricular and septal walls. In approximately half of the cases, rhabdomyoma is associated with tuberous sclerosis. Most rhabdomyomas regress during the first years of life. We present MRI findings of fatty replacement of the myocardium which was probably after spontaneous regression of solid mass (rhabdomyoma) in a 16-year-old boy with tuberous sclerosis.     

Polycystic kidneys as the presenting feature of tuberous sclerosis

Tuberous sclerosis is an inherited neurocutaneous disorder characterized by seizures, mental retardation, cutaneous lesions and visceral hamartomas. We describe a 17-year-old boy in whom polycystic kidneys of the adult type were fortuitously detected on routine check-up. The patient enjoyed good health and had no evidence of renal dysfunction. Closer scrutiny of his past history and his physical and laboratory findings disclosed that he had tuberous sclerosis. Our case adds to the scant reported experience with the association of tuberous sclerosis and adult-type polycystic kidneys, and suggests that a search of additional manifestations of tuberous sclerosis is warranted in children in whom adult-type polycystic renal disease is detected.     

Diagnosis and treatment of cardiac rhabdomyomas

A diagnosis of primary cardiac tumors was achieved by two-dimensional echocardiography in 3 patients. Two of them were female neonates, born of the 29th and 40th gestational week who had shown intrauterine arrhythmias. Subsequently, we were able to diagnose tuberous sclerosis in both. The third child, a 121/2 year old boy, with already diagnosed tuberous sclerosis, presented an electrocardiographical preexcitation syndrome. Because of the multiplicity of the tumors and the association with tuberous sclerosis we presumed that the tumors were rhabdomyomas. As it is known that rhabdomyomas show no, or only a minimal postnatal growth, we decided neither to perform a heart catheterization nor to treat them surgically unless the children show hemodynamical deterioration, although the tumors were huge in both neonates. The subsequent 14 months showed a clear regression in the size of the tumors. One of the neonates was successfully treated with amiodarone because of ventricular tachycardia. The second neonate didn't require any treatment. We conclude that: Surgical management is only necessary in patients presenting with cardiac insufficiency and/or arrhythmias that are resistant to conventional medical treatment. Primary cardiac tumors should be looked for in patients presenting with arrhythmias, even when occurring already during intrauterine life. Diagnostic measures in order to diagnose tuberous sclerosis in patients with cardiac tumors are necessary and vice versa.     

Diagnostic value of clinical features and supplementary investigations in tuberous sclerosis in children.

The author evaluates the usefulness of clinical features and some supplementary investigations in diagnosis of tuberous sclerosis in children. 52 children ranging in age from 1 month to 14 years took part in the study. Usually depigmented naevi were the first sign of tuberous sclerosis and were seen in 98% of affected children. Epileptic seizures occurred in 96% of patients, mostly during the first year of life. Axial computed tomography of brain seems to be very helpful in diagnosis of tuberous sclerosis in every age. Multiple periventricular calcifications were found in 98% of children. Two-dimensional echocardiography was especially useful in infants and children below 2 years of age. Retinal hamartomas were found in 25% of children with tuberous sclerosis. In some cases these changes were revealed during the first year of age. Abnormal EEGs were found in 90% of recordings. The EEGs tended to improve with increasing age. In 25% of children one of parents was affected by tuberous sclerosis. The careful skin examination of both parents can be especially helpful in children with doubtful diagnosis of tuberous sclerosis.     

Roentgenographic changes of the skeleton in a case of tuberous sclerosis (morbus Bourneville-Pringle) (author's transl)

Increasing sclerosis in the thoracolumbar spine has been followed up in a boy suffering from tuberous sclerosis. The earlist abnormality appearing as an irregular density in the radix of the posterior arch of the first lumbar vertebra has been detected at the age of one year. Until the ninth year of life the disease process has involved the vertebral column from T-8 to L-2. During the course roentgenograms revealed several diffuse areas of opacification with ill-defined outlines which tended to merge. As a rule all vertebrae were affected asymmetrically. Neither deformities of the vertebrae nor functional impairment of the axial skeleton have been found. Based on X ray appearance classification of characteristic and accessory bone abnormalities in tuberous sclerosis was discussed.     

Selective Arterial Embolization of Giant Renal Tuberous Sclerosis

Different minimally invasive methods have been proposed to treat renal manifestation of tuberous sclerosis complex (TSC), in order to preserve kidney parenchyma and avoid nephrectomy. The case of a boy with bleeding giant angiomyolipoma treated by selective arterial embolization is discussed. The extensive renal lesions resulted significantly decreased, with resolution of arterial hypertension and abdominal symptoms. Differential renal function increased from 26.6% to 32.6%. Renal involvement in TSC requires careful parenchymal-sparing procedures. Selective embolization of the main renal lesions should be considered as first line therapy.     

Cardiac rhabdomyomas and their association with tuberous sclerosis

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.     

Cardiac rhabdomyomas and their association with tuberous sclerosis.

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.     

Cystic renal involvement in tuberous sclerosis

We describe two cases of unusual presentation of tuberous sclerosis with cystic renal involvement. A 19-month-old white male who was initially misdiagnosed as having polycystic kidney disease of "adult-type" developed petit mal seizures and small "ash-leaf" depigmented areas, raising a suspicion of tuberous sclerosis. Computerized tomography (CT) of the brain revealed periventricular calcifications, confirming the diagnosis of tuberous sclerosis. A 15 3/4-year-old black female with tuberous sclerosis showed acceleration of renal failure. Computerized tomography scan of the abdomen showed cystic lesions of the kidneys. In young children with cystic renal involvement but a negative family history of tuberous sclerosis or polycystic kidney disease, a CT scan of the brain should assist in the diagnosis. A CT scan or ultrasound examination of the abdomen will differentiate cystic renal lesions from angiomyolipoma of the kidneys.     

Neuroblastoma, tuberous sclerosis, and subependymal giant cell astrocytoma

A patient with Stage III paratesticular neuroblastoma diagnosed in infancy was treated with radiotherapy and chemotherapy. Typical depigmented "ash leaf" skin lesions of tuberous sclerosis appeared during early childhood. At 7 years of age he underwent craniotomy for a subependymal giant cell astrocytoma. The occurrence of neuroblastoma, tuberous sclerosis, and astrocytoma is unique, and supports the suggested relationship between neural crest tumors and hamartoma syndromes.     

Sinus node dysfunction in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant disease with potential for involvement of the skin, brain, lungs, kidneys, and heart. A case of prolonged sinus node pause and episodes of unresponsiveness in a 21-week-old infant with tuberous sclerosis is described. The infant subsequently underwent placement of an epicardial pacemaker. This case illustrates the importance of electrocardiographic studies in infants with tuberous sclerosis and seizure-like episodes.     

Malignant pigmented clear cell epithelioid cell tumor (PEComa) in an adolescent boy with widespread metastases: a rare entity in this age group

Malignant pigmented clear cell epithelioid cell tumor of the kidney is a rare variant of perivascular epithelioid cells tumors (PEComa) or epithelioid angiomyolipoma (AML). PEComa is characteristically composed purely of epitheloid cells. The fat cells and the blood vessels that are typical of classic AML are absent. Most epithelioid AML cases are benign; however, malignant epithelioid AML of the kidney has been occasionally reported in adults in association with tuberous sclerosis. We report the radiological-pathological features of a malignant pigmented clear cell epithelioid renal tumor in a 15-year-old boy presenting with extensive metastases but without clinical evidence of tuberous sclerosis.     

Tuberous sclerosis complex: a review of neurological aspects.

Tuberous sclerosis complex is characterized by hamartomatous lesions involving skin, brain, kidneys, eyes and heart. Pathologically, tuberous sclerosis is a disorder of cell migration, proliferation and differentiation. Cell lineage and cell migration disorders in the developing cortex of tuberous sclerosis complex patients might produce very different neurological phenotypes including epilepsy, cognitive impairment and autism. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral tuberous sclerosis. Epilepsy is the most common neurological feature, occurring in 96% of patients. Seizures often begin in the first months of life and are frequently severe and intractable. The treatment of seizures has recently benefited from the advent of the new anti-epileptic drugs. Selected drug-resistant patients with tuberous sclerosis complex could be considered for surgical treatment. Clear localization of the most active epileptogenic focus and the zone of the cortical abnormality may lead to tuberectomy and improved seizure control in selective drug-resistant patients. The finding of multiple areas of cerebral involvement should not automatically preclude epilepsy surgery in a child with intractable seizures and a well defined seizure origin.     

Thoracoabdominal imaging of tuberous sclerosis

Imaging of tuberous sclerosis complex has rapidly evolved over the last decade in association with increased understanding of the disease process and new treatment modalities. Tuberous sclerosis complex is best known for the neurological symptoms and the associated neuroimaging findings, and children with tuberous sclerosis complex require active surveillance of associated abnormalities in the chest, abdomen and pelvis. Common findings that require regular imaging surveillance are angiomyolipomas in the kidneys and lymphangioleiomyomatosis in the chest. However multiple rarer associations have been attributed to tuberous sclerosis complex and should be considered by radiologists reviewing any imaging in these children. In this review the authors discuss the spectrum of imaging findings in people with tuberous sclerosis complex, focusing on MR imaging findings in the chest, abdomen and pelvis.