IMAGING FINDINGS OF TUBEROUS SCLEROSIS.pptx

TUBEROUS SCLEROSIS

1. IMAGING OF TUBEROUS SCLEROSIS BY DR. CHETAN

2. Introduction Tuberous sclerosis (TS) is an autosomal dominant inherited neurocutaneous syndrome characterized by a variety of hamartomatous lesions in various organs. TS can affect both sexes and all ethnic groups. The estimated prevalence ranges from one in 6000 to one in 12 000 , and approximately two-thirds of the cases are sporadic . Classically , TS demonstrates a triad of clinical features (Vogt triad): mental retardation, epilepsy, and adenoma sebaceum . 

3. However , it should be recognized that half of TS patients have normal intelligence and that a quarter do not have epilepsy

4. Dermatologic Involvement TS can present with a variety of skin lesions, including hypopigmented macules , facial angiofibromas , shagreen patches, and ungula fibromas . Hypopigmented macules , which have been called “ash leaf spots” after the European mountain ash tree, occur in more than 90% of patients with TS . They are generally detected in infancy or early childhood and are typically round at one end and tapered at the other.  

5. Facial angiofibromas , also known as “adenoma sebaceum ,” are seen in approximately 75% of patients . The lesions typically appear in adolescence as small red papules in the malar area, with a so-called “butterfly distribution” . Shagreen patches are typically found as grayish-green or light brown areas in the lumbosacral region in 20%–30% of patients .

6.  Ungula fibromas are nodular lesions located beneath the nails of the toes or fingers. The lesions can be found in approximately 20% of patients, especially in adolescents and adults . Detection of these skin lesions can be a first step in diagnosing TS, since they are the only major diagnostic criteria that can be evaluated at clinical examination .

7.  Facial angiofibroma in a 19-year-old man. Photograph demonstrates multiple dome-shaped papules in the malar area, with a butterfly distribution .

8. Neurologic Involvement A variety of intracranial manifestations of TS are known.Four common CNS abnormalities are cortical tubers, subependymal nodules, subependymal giant cell astrocytomas (SGCAs), and white matter abnormalities. Except for SGCAs, these abnormalities can be seen in almost all patients with TS.The estimated prevalence of cortical tuber and/or subependymal nodule is 95%–100% and that of white matter abnormalities is 40%–90% .

9.   Other rare CNS manifestations include mild dilatation of lateral ventricles due to atrophy or dysgenesis , cerebellar atrophy, infarction caused by occlusive vascular disorders, cerebral aneurysm, dysgenesis of the corpus callosum , Chiari malformation, microcephaly , macroencephaly , arachnoid cyst, neurofibromatosis, and chordoma .

10. Cortical Tubers Cortical tubers are developmental abnormalities of the cerebral cortex in patients with TS, characterized by a loss of the normal six-layer structure of the cortex and the presence of dysmorphic neurons and large astrocytes . They are considered to be closely related to the neurologic manifestations of TS, including epilepsy, cognitive disability, and neurolobehavioral abnormalities

11.  Patients with numerous cortical tubers tend to have more cognitive impairment and more difficulty with seizure control . Autism is commonly seen in patients with frontal and parietotemporal tubers . Approximately 50% of cortical tubers are seen in the frontal lobe, although they can appear anywhere in the parenchyma from the cortex to white matter .

12. Magnetic resonance (MR) imaging is more applicable than computed tomography (CT) for detection of cortical tubers . Usually , cortical tubers have increased signal intensity on T2-weighted images and decreased signal intensity on T1-weighted images. After administration of contrast material, only 10% of cortical tubers show enhancement .

13. In neonates and infants with cortical tubers, some nodules can be missed on T2-weighted images and demonstrated only on T1-weighted images, since they appear to have similar relaxation times to that of unmyelinated brain

14. In older children and adults, the peripheral component of cortical tubers is frequently isointense to normal gray matter with all pulse sequences, while the inner component is iso - to hypointense to white matter on T1-weighted images and has high intensity on T2 weighted images . Calcification and central cystic degeneration can sometimes occur.

15. Cortical tubers in a 40-year-old woman.  Axial T2-weighted MR image depicts cortical tubers as hyperintense lesions (arrows).

16. Axial fluid-attenuation inversion-recovery MR image also demonstrates cortical tubers as hyperintense foci (arrows)

17. Subependymal Nodules Subependymal nodules represent hamartomatous change in subependymal tissue and usually occur as multiple nodules. The prevalence of patients with more than 10 subependymal nodules ranges from 12% to 57% . Leung et al revealed no correlation between subependymal nodules and clinical severity of disease

18. CT is a useful tool for detection of subependymal nodules, since they are associated with calcification far more commonly (88%) than are cortical tubers. Unenhanced CT typically depicts multiple small foci with dense calcification along the lateral ventricles bilaterally 

19. At MR imaging, subependymal nodules are hyperintense on T1-weighted images and iso - to hyperintense on T2-weighted images . Subependymal nodules tend to have lower signal intensity on T2-weighted image than do cortical tubers, probably because subependymal nodules have high water content .

20.   Subependymal calcified tubers in a 9-month-old boy. Unenhanced CT clearly demonstrates multiple subependymal tubers with bilateral calcification along the walls of the lateral ventricles.

21.   Subependymal tubers in a 26-year-old woman. Axial T1-weighted MR image clearly demonstrates bilateral subependymal tubers with intermediate signal intensity (arrows).

22. contrast-enhanced T1-weighted MR images show enhancing subependymal nodule ( black arrow ) projecting into lumen of left lateral ventricle. Subependymal nodules, which contain more calcification, tend to become less enhanced, as in case of nodule ( white arrow ) located near left atrium.

23.   Subependymal giant cell astrocytoma SGCAs are characterized by proliferative astrocytes and giant cells, with a prevalence 1.7%–26% in patients with TS . The typical location of SGCAs is in the foramen of Monro , leading to obstructive hydrocephalus . Typically, the initial symptom of SGCAs is increased intracranial pressure, frequently with acute onset .

24. Different from other cerebral astrocytomas , SGCAs have benign biologic and pathologic features ( ie , slow growth, minimal or no attendant brain edema, and minimal invasiveness). It is widely accepted that SGCAs are derived from subependymal nodules; this is supported by the existence of intermediate cells between hamartomatous nodules and SGCAs and by serial CT studies indicating growth of nodules into SGCAs . The peak age of occurrence is 8–18 years, 

25. Compared with subependymal nodules, SGCAs tend to be larger tumors (>1 cm) with more intense enhancement. When subependymal nodules are located near the foramen of Monro and they measure more than 5 mm in diameter, are not or are incompletely calcified, and are enhanced by gadolinium.

26. Subependymal giant cell astrocytoma in a 24-year-old man.  Unenhanced CT image demonstrates high-attenuation tumor around the foramen of Monro (arrow). Calcified subependymal tubers are also seen.

27. Unenhanced CT image at superior level to that reveals secondary hydrocephalus.

28. 9-year-old girl with tuberous sclerosis complex and partial complex seizures. Coronal contrast-enhanced T1-weighted image shows homogeneously enhancing multilobulated subependymal giant cell astrocytoma ( black arrow )  in region of left foramen of Monro . Patient has undergone left temporal lobe resection ( white arrow ).

29. White Matter Abnormalities White matter abnormalities in patients with TS include  (a)  superficial white matter abnormalities associated with cortical tubers,  (b)  radial white matter bands, and  (c)   cystlike white matter lesions. Superficial white matter abnormalities are related to almost all cortical tubers. The reported frequency of radial white matter abnormalities is 15%–27% and of cystlike lesions is 15%–44% . 

30. Superficial white matter abnormalities reflect reduced myelin or increased gliotic reaction and are seen as high-intensity areas on T2-weighted images and decreased-intensity areas on T1-weighted images

31. Radial white matter bands reflect altered development along the migratory pathways of neurons and glial cells. They usually involve cerebral white matter bilaterally (predominantly frontal lobes) and uncommonly cerebellar white matter

32. At MR imaging, thin straight or curvilinear bands of hyperintensity on T2-weighted images and iso - to hypointensity to normal white matter on T1-weighted images run from ventricular or juxtaventricular white matter to the deep surface of cortical tubers or normal-appearing cortex

33. Radial white matter bands in an 8-month-old boy. Axial fluid-attenuation inversion-recovery MR image demonstrates linear radial white matter bands extending from the cortex to the lateral ventricles (arrows). Cortical tubers are also seen (arrowheads).

34. 8-year-old boy with tuberous sclerosis complex. Axial FLAIR MR image shows cortical and subcortical tuber ( black arrow ) and radial migration line ( white arrow ).

35. White matter cystlike lesions are located in deep white matter, typically near the lateral ventricles . These lesions are considered rare, yet they are purported to occur in up to 44% of TS patients . Although the pathogenesis of cystlike lesions remains unclear, they are considered to reflect cystic degeneration of white matter or dilated perivascular spaces 

36. At MR imaging, small well-demarcated lesions of similar intensity to that of cerebrospinal fluid with all sequences are seen in white matter .

37. Cystic white matter lesion in a 13-year-old girl.  (a)  Axial T2-weighted and  (b)  T1-weighted MR images show a well-demarcated lesion (arrow) in the left frontal white matter, isointense to cerebrospinal fluid.

38. Cardiac Involvement Cardiac rhabdomyoma is a benign striated muscle tumor characterized by the presence of “spider cells,” which are so named because of their radial cytoplasmic extensions. Cardiac rhabdomyomas usually (approximately 75%) occur before the age of 1 year and can even occur in a fetus

39. It is one of the common manifestations of TS, with a frequency of 50%–65 %; conversely, 40%–80% of patients with cardiac rhabdomyoma have TS . Therefore, if a cardiac rhabdomyoma is found at echocardiography, TS is highly suspected, even if there are no typical clinical symptoms or family history of TS.

40. Pulmonary and Thoracic Involvement Pulmonary involvement of TS includes lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). Pulmonary manifestations are estimated to occur in approximately 1%–2.3% of TS patients, but recent reports indicate that pulmonary LAM can be found radiologically in 26%–39% of female patients with TS .

41. MMPH is a rare disorder that has been described in few literature reports. Other rare thoracic involvements include LAM involvement of the mediastinum or thoracic duct and aortic or pulmonary artery aneurysm

42. lymphangioleiomyomatosis   Pulmonary LAM is a rare entity of unknown etiology that almost exclusively affects women and is characterized by diffuse interstitial proliferation of bundles of smooth muscle cells and cystic change in the pulmonary parenchyma. The diagnosis in affected patients is usually made in early adulthood, and the symptoms are commonly dyspnea on exertion or recurrent pneumothorax .

43. The clinical course of pulmonary LAM is usually slow and progressive, ultimately leading to respiratory failure. The 10-year survival rate was 79% in a study of 69 patients with pulmonary LAM . Pneumothorax and chylous pleural effusion or ascites are two major complications of LAM.

44.  The typical CT finding is round, thin-walled cysts of variable size and contour . Generally , the distribution of the cysts is symmetric and uniform throughout the lungs . Communication between the cysts and the airway is indicated by the fact that the size of the cysts decreases on expiratory CT images . In some cases of pulmonary LAM, reticular opacities can be seen, which may reflect interstitial edema due to obstruction of the lymphatic vessels

45.  Pulmonary LAM in a 29-year-old woman. Thin-section CT scan demonstrates multiple lung cysts with well-defined thin walls. These cysts are distributed randomly throughout the lung.

46.  Pulmonary LAM in a 37-year-old woman. Thin-section CT image shows bilateral numerous cysts associated with reticular opacities.

47. Pneumothorax associated with pulmonary LAM in a 37-year-old woman. CT image of the chest demonstrates multiple lung cysts, suggesting pulmonary LAM. Pneumothorax can be seen in the right thoracic cavity (arrows).

48. Chylothorax and chylous ascites due to LAM in a 21-year old woman. Coronal MRI image demonstrates bilateral loculated pleural effusion and ascites . Retroperitoneal LAM is also seen (arrows). Aspiration of the pleural effusion proved it to be a chylous effusion.

49.  multifocal micronodular pneumocyte hyperplasia (MMPH).  MMPH is a rare pulmonary disorder that can be associated with TS. It is characterized by multicentric , well-demarcated nodular proliferation of type II pneumocytes along alveolar septa. Since the hamartomatous nature of micronodular epithelial proliferations has been emphasized, the terms  multiple adenomatoid tumors ,  acinar atypical adenomatoid proliferation of epithelium ,    have been proposed as being more descriptive names.

50.  MMPH can occur in patients with or without LAM, predominantly in female patients. Clinically , patients with MMPH may present with dyspnea , cough, and mild to moderate hypoxemia. Unlike with pulmonary LAM, treatment is usually unnecessary because MMPH does not appear to be fatal and progressive.

51. At thin-section CT, multiple tiny nodules (1–8 mm in diameter) are diffusely scattered throughout the lung in a random distribution . Although differentiation of MMPH from miliary metastatic or granulomatous disease is difficult. MMPH should be considered in the differential diagnosis when multiple tiny pulmonary nodules are present in patients with TS

52. MMPH in a 19-year-old man. CT scan demonstrates multiple tiny nodules (arrows), with random distribution in the lungs.

53. Renal and Retroperitoneal Involvement Renal involvement of TS includes renal angiomyolipoma (AML), renal cysts, and renal cell carcinoma . Renal AML is one of the common manifestations, with a frequency of 55%–75% in patients with TS . The second most common renal manifestation of TS is renal cysts.

54. Renal AML AMLs are the most common benign tumors of the kidney, characterized by variable amounts of abnormal vessels, immature smooth-muscle and fat cells. Although renal AMLs are sometimes asymptomatic and are incidentally discovered, they may cause variable symptoms in as many as 87% of patients, including abdominal pain, nausea, vomiting, palpable mass, hematuria , anemia, and hypertension. 

55.   Compared with sporadic lesions, AMLs seen in patients with TS tend to manifest at a younger age and to be multiple, larger, and bilateral and to grow. The most alarming complication of renal AMLs is rupture due to their abnormal vasculature, frequently associated with aneurysms . Patients with a ruptured renal AML often present with pain or shock at acute onset.

56. Typical CT findings of renal AMLs are noncalcified cortical tumors containing fat of less than −20 HU . Although unenhanced CT with thin sections is useful for detecting small amounts of fat, intratumoral fat cannot be detected in approximately 4.5% of all renal AMLs . These tumors frequently become clinically problematic because differentiating them from renal cell carcinomas is difficult.

57. AMLs with minimal fat should be considered when the tumor demonstrates  ( a)   hyperattenuation at unenhanced CT,  ( b)  homogeneous enhancement ,   (c)   hypointensity on T2-weighted MR images, and  ( d)  homogeneous isoechogenicity at ultrasonography .  

58. When intrarenal , perinephric , or retroperitoneal hemorrhage is seen, a ruptured AML should be suspected . If the bleeding masks the fat component of the tumor, it may be difficult to differentiate it from a ruptured renal cell carcinoma. In such cases, biphasic contrast-enhanced CT may be useful for differentiating these two entities 

59.   Renal AMLs in a 38-year-old woman. Axial unenhanced CT image demonstrates multiple fat-containing tumors in the kidneys.

60.  Renal AMLs with minimal fat in a 19-year-old man.  (a) Unenhanced CT image demonstrates multiple high-attenuation tumors in the kidneys.  (b)  Contrast-enhanced CT image shows homogeneous enhancement of the tumor

61.  Ruptured renal AML in a 35-year-old woman.  (a) Unenhanced CT image shows a fat-containing tumor in the left kidney. Hyperattenuating material suggestive of hemorrhage is also seen in and around the tumor.

62. Contrast-enhanced CT image demonstrates an aneurysm in the tumor (arrow).

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