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Computerized axial tomography in the early diagnosis of tuberous sclerosis.

Tuberous sclerosis is characterized by epilepsy, mental retardation, and adenoma sebaceum. Computerized axial tomography (CAT) is a noninvasive laboratory test that can assist in the diagnosis of this syndrome radiologically. A positive CAT scan is often present before the calcifications are noted on skull x-rays and the pathognomonic cutaneous findings appear. Four cases of tuberous sclerosis are presented with their diagnostic CAT scan findings.

Adolescent↗

Cluster growths in adenoma sebaceum associated with tuberous sclerosis.

Cluster growths resembling bunches of grapes on the face of a 20-year-old woman are reported. Clinical and histopathologic findings were compatible with a diagnosis of tuberous sclerosis, and we believe that this is the first case report of a massive growth of adenoma sebaceum in a patient with tuberous sclerosis.

Adult↗

A case of probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis.

We describe a woman with a probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis. Other findings included syndactyly, typical facies, dental abnormalities, dermatoglyphic hypoplasia, epidermal ridge sweat pore count slightly below normal, and keratosis pilaris. Clinical studies and genetic analysis excluded the diagnosis of tuberous sclerosis in our patient. We conclude that she has ectodermal dysplasia associated with mental retardation. This association has been described previously; it suggests the possible interrelationship of a community of ectodermal dysplasia syndromes with a distinctive structural hair abnormality (pili torti et canaliculi), variable midfacial malformations, limb defects, and other features such as mental retardation. The similarity of our patient to that described by Whiting et al. and Abramovits-Ackerman et al. suggests the autonomy of this syndrome.

Adult↗

[Neuro-imaging of tuberous sclerosis].

Tuberous sclerosis is a phakomatosis with central nervous system manifestations characterized by 4 lesions detectable on neuro-imaging: tubers, white matter abnormalities, subependymal nodules and subependymal astrocytomas. The first three are benign lesions composed of by identical cytological lesions varying only in size and location. At CT, enhancement of subependymal nodules is usually considered as evidence of transformation to subependymal giant cell astrocytoma. This latter poses the problem of its relative benignity: hydrocephalus source of morbidity or even mortality. From a series of 22 cases, the authors review the characteristics of these abnormalities.

Humans↗

Oro-facial lesions of tuberous sclerosis.

The occurrence of tuberous sclerosis among Indians has not been reported earlier. In the Ernakulam District, Kerala, in a kindred of 27, seven cases with oro-facial or facial lesions of tuberous sclerosis were observed. None of the individuals was mentally retarded, nor was there any history of systemic anomalies. The cases in this series possibly represent an incomplete form (Forme frustes) of the syndrome. The pedigree in the present material supports the autosomal dominant inheritance.

Adult↗

Renal and hepatic angiomyolipomas in a child without evidence of tuberous sclerosis.

A renal neoplasia, displaying the typical features of angiomyolipoma (an admixture of smooth muscle cells, mature adipocytes and tangles of thick-walled blood vessels) was found in a nine-year-old boy. In addition, cytoplasmic crystalloid structures and HMB 45 positivity were found in smooth muscle cells. Similar findings were also observed in a small nodule of the liver. According to literature data, angiomyolipoma is very rare in children and almost exclusively associated with tuberous sclerosis. Our case suggest that the diagnostic hypothesis of angiomyolipoma can not be disregarded when a renal mass is identified in a young patient even in a clinical setting other than tuberous sclerosis.

Angiomyolipoma↗

Diffuse bilateral glomerulocystic disease of the kidneys and multiple cardiac rhabdomyomas in a newborn. Relationship with tuberous sclerosis and review of the literature.

A case of glomerulocystic disease of the kidneys in a newborn is described. The kidneys were very large and diffusely cystic. Histologically, all portions of the nephron were involved and some of the cysts were lined by a prominent hyperplastic eosinophilic epithelium. This, together with the presence of numerous cardiac rhabdomyomas, a nodular haemangiomatous harmartoma and histiocytoid cell nests in the spleen were strongly suggestive of tuberous sclerosis. The relation between glomerulocystic kidney disease and tuberous sclerosis is discussed.

Diagnosis, Differential↗

Tuberous sclerosis: report of two cases studied by computer-assisted cranial tomography within one week after birth.

Two neonates with tuberous sclerosis are reported. The patients presented convulsive seizures 30 mins or 5 days after birth. Computer-assisted cranial tomography (CT) on admission showed typical paraventricular calcifications in Case 1 and a calcified mass in Case 2. In addition to the CT findings, the diagnosis was made on the basis of the depigmented skin, and the mother with tuberous sclerosis in Case 1 and the pathological findings after surgery in Case 2. The importance of CT as a diagnostic procedure for this disease within 1 wk after birth is emphasized.

Brain↗

Cerebellar involvement in tuberous sclerosis.

Cerebellar involvement in tuberous sclerosis is apparently less than cerebral involvement. In this article, we report CT and MR imaging findings in four tuberous sclerosis patients with apparent cerebellar changes. In one patient with extensive folial calcifications, hypoplasia of the superior vermis, and agenesis of the inferior vermis were associated findings, and clinical correspondence was evident, consisting of a decreased ability to coordinate movements.

Adolescent↗

alpha-[11C]-Methyl-L-tryptophan PET identifies the epileptogenic tuber and correlates with interictal spike frequency.

Epilepsy surgery has been successfully performed in patients with tuberous sclerosis complex (TSC) and seizures arising from a restricted epileptogenic area. The outcome of cortical excision depends on accurate pre-surgical identification of the epileptogenic tuber. [11C] alpha-methyl-L-tryptophan (alpha-MTrp) was originally developed to measure serotonin synthesis in vivo with positron emission tomography (PET). However in pathologic conditions its uptake may also depend on the synthesis of quinolinic or kynurenic acid via the kynurenine pathway. Increased levels of serotonin and quinolinic acid have been observed in epileptogenic lesions, raising the possibility that alpha-MTrp PET may localize the epileptogenic area. The aim of this study was to correlate alpha-MTrp PET uptake with the localization of the epileptogenic area and with interictal spike frequency in patients with TSC. alpha-MTrp uptake was measured in 8 patients (2 males, mean age 29.6+/-14.9 years, range 3-50 years) with intractable partial epilepsy due to TSC. All patients underwent scalp EEG monitoring during the PET scan. In four (50%), increased uptake of alpha-MTrp occurred in the epileptogenic area alone. Two (25%) patients showed multifocal abnormalities and the remaining two (25%) did not show focal changes. PET localization was mostly seen in patients with frequent interictal abnormalities on the EEG. Furthermore, there was a significant correlation between alpha-MTrp uptake and the frequency of interictal spikes (r=0.6; P<0.05). alpha-MTrp PET is a promising diagnostic tool in the localization of the epileptogenic area in patients with TSC.

Adolescent↗

Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients.

Vigabatrin (VGB) has demonstrated high efficacy in infantile spasms (IS) due to tuberous sclerosis. Our first objective was to evaluate the cognitive long term effect outcome of children whose refractory spasms definitely disappeared when VGB was given as an add on drug. Our second objective was to determine the response of generalized epilepsy (infantile spasms) compared to partial epilepsy on cognitive impairment. A non selected series of 13 children underwent psychometric and behavioural evaluation before VGB initiation at a mean of 3 years on VGB treatment. Eight of them could perform detailed neuropsychological tests at follow-up. Seven had infantile spasms (Group I), they all were spasm free before 2 years of age and five remained with rare partial seizures (mean age, 5.5 years). Six others had partial epilepsy without spasms (Group II) and five remained with rare seizures (mean age, 7.5 years). Patients of Group I experienced dramatic changes. Developmental quotient (DQ) significantly rose in six out of seven by ten to more than 45 points (P = 0.03) and autistic behaviour disappeared in five out of the six who presented with. The four tested children had normal verbal level after 5 years and could integrate at school but they remained with marked visuospatial disabilities. By contrast, patients of Group II remained with an unchanged DQ of about 60 so that both groups had similar DQ levels on follow-up. The cessation of spasms with VGB is therefore associated with significant improvement of cognition and behaviour in children with tuberous sclerosis. Controlling secondary generalization induced by infantile spasms seems to be a key factor for mental development.

Anticonvulsants↗

Intraosseous fibrous lesions of the jaws: a manifestation of tuberous sclerosis.

Four patients previously diagnosed with tuberous sclerosis are reported with intraosseous fibrous lesions of the jaws. Review of the literature revealed comparable pathosis occurring in extragnathic bones and several previous reports of similar lesions within the jaws. Therefore, these intraosseous fibrous proliferations are thought to represent an intraoral manifestation of tuberous sclerosis and not coincidental findings. In all 4 cases, the tumors demonstrated significant collagenization with numerous interspersed plump fibroblasts. Although histopathologically similar, the features of the lesions are not specific and also can be found in desmoplastic fibromas and simple odontogenic fibromas. The definitive diagnosis requires appropriate clinicopathologic correlation.

Adolescent↗

Overexpression of tuberous sclerosis complex 2 exerts antitumor effect on oral cancer cell lines.

Tuberous sclerosis is caused by mutations in tuberous sclerosis complex (TSC) 2 on chromosome 16p13.3, encoding tuberin which is thought to be essential for p27(Kip1) to regulate the cell cycle. In this study, we conducted to examine whether overexpression of TSC2 can affect the growth of oral cancer cells which have different expression level of p27(Kip1) protein. We constructed an expression vector containing sense-oriented rat TSC2 cDNA with pcDNA3.1. We transfected oral cancer cells, B88t (high expression of p27(Kip1) protein) and HI (low expression of p27(Kip1) protein) with the sense expression vector to up-regulate the expression of TSC2 gene. Overexpression of TSC2 exerted the growth inhibitory effect of B88t and HI in vitro and in vivo. These findings suggest that overexpression of TSC2 may exert the antitumor effect on oral cancer cells whether they have high expression of p27(Kip1) protein or not.

Animals↗

Care of adolescents with severe learning disability from tuberous sclerosis.

A postal study was completed by 138 members of the Tuberous Sclerosis Association for individuals with severe learning disabilities from tuberous sclerosis complex (TSC) (78 males, median 20 years of age; 60 females median 19 years 6 months of age) to investigate the abilities and care needs of these adolescents and young adults. Results were compared with a Salford community survey of young people with severe learning disability (SLD) from a variety of causes (42 males, median 17 years; 29 females, median 17 years 8 months of age). Those with SLD associated with TSC had a higher level of verbal disability and were more dependent for managing toileting and bathing. The young people with TSC were less able to interact socially, showing autistic behaviour. Sexually, they were less aware and less active. Only 20 were thought by their parents to have received sex education.

Activities of Daily Living↗

Unilateral reverse ocular bobbing caused by tuberous sclerosis.

A female aged 12 months with developmental delay and left-sided reverse ocular bobbing (rapid deviation of the eye upward and a slow return to the horizontal position) was observed. At birth, an upper left gingival mass, pathologically diagnosed as a benign granular cell tumour, was removed. On computed tomography (CT), left middle cerebral pedincular and midpontine lesions were seen. Magnetic resonance imaging revealed additional white matter hamartomas, corticosubcortical tubers, and subependymal nodules. The patient was re-examined at 36 months. Her general developmental quotient was equivalent to 23 months of age. Third cranial nerve functions and auditory brainstem response were normal. Her abnormal eye movements were still present. Reverse bobbing is usually observed in patients who are unconscious and who have significant pontine pathology and disruption of the reticular formation. This case is the first tuberous sclerosis-related ocular bobbing case to our knowledge and is interesting as the causative lesion was relatively mild, and ocular horizontal movements were preserved.

Brain Stem↗

Tuberous sclerosis with primary meningioma of the maxillary antrum.

Primary extracranial meningiomas are uncommon; they have been documented in the ear, skin, orbit, parapharyngeal space, parotid gland, mediastinum, and rarely the paranasal sinuses. Tuberous sclerosis is an autosomal dominant neurocutaneous syndrome characterized by multiple connective tissue tumours. We report the first case of a tuberous sclerosis patient with a maxillary antral meningioma.

Adolescent↗

Visual loss secondary to a giant aneurysm in a patient with tuberous sclerosis.

We report a fifty three year old man who presented with progressive visual loss. Investigation disclosed a giant aneurysm with optic nerve compression, which was successfully treated surgically. The patient had typical skin lesions of tuberous sclerosis, but did not suffer from a seizure disorder or mental retardation. In the past he had had an enucleation for glaucoma secondary to a retinal phakoma. Cerebral aneurysms are discussed in relation to the tuberous sclerosis disease process. After review of the literature, we propose that the aneurysms are secondary to dysplastic change in the vessel walls, this is in keeping with the abnormal tissue proliferations in this disease.

Carotid Artery Diseases↗

Both dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), and its peptic hydrolysates exhibited angiotensin converting enzyme inhibitory activities.

Dioscorin, the tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1), was purified to homogeneity by DE-52 ion-exchange chromatography. This purified dioscorin was shown by spectrophotometric methods to inhibit angiotensin converting enzyme (ACE) in a dose-dependent manner (12.5-750 microg, respectively, 20.83-62.5% inhibitions) using N-[3-(2-furyl)acryloyl]-Phe-Gly-Gly (FAPGG) as substrates. The 50% inhibition (IC(50)) of ACE activity was 6.404 microM dioscorin (250 microg corresponding to 7.81 nmol) compared to that of 0.00781 microM (0.0095 nmol) for captopril. The commercial bovine serum albumin and casein (bovine milk) showed less ACE inhibitory activity. The use of qualitative TLC also showed dioscorin as ACE inhibitors. Dioscorin showed mixed noncompetitive inhibitions against ACE; when 31.25 microg of dioscorin (0.8 microM) was added, the apparent inhibition constant (K(i)) was 2.738 microM. Pepsin was used for dioscorin hydrolysis at 37 degrees C for different times. It was found that the ACE inhibitory activity was increased from 51.32% to about 75% during 32 h hydrolysis. The smaller peptides were increased with increasing pepsin hydrolytic times. Dioscorin and its hydrolysates might be a potential for hypertension control when people consume yam tuber.

Angiotensin-Converting Enzyme Inhibitors↗