Neuroimaging correlation with neurological severity in tuberous sclerosis complex.

OBJECTIVE: To delineate the relationship between neurological severity and neuroimage of lesion load including specific topography of supratentorial cortical tubers and white matter lesions in tuberous sclerosis complex (TSC). METHODS: Twenty-five TSC patients more than 2 years of age who underwent conventional and fluid-attenuated inversion recovery sequence (FLAIR) magnetic resonance imaging (MRI) were retrospectively studied. Neurological severity score was designated for three items: seizure, developmental delay and/or mental retardation, and autism. A neuroimaging scoring system was designed to evaluate the load of the cerebrum lesions with respect to location and size of cortical tubers and white matter lesions based on FLAIR MRI. RESULTS: A linear trend was observed between MRI lesion score and neurological severity score (r=0.511; p=0.009). The lesion score in the left temporal lobe has positive correlation to neurological severity score (r=0.609; p=0.001). CONCLUSIONS: The brain lesion load was positively correlated with neurological prognosis in TSC patients. Patients with larger lesion load in the left temporal lobe may be correlated with increased neurological severity in right-handed patients with TSC.     

结节性硬化症合并心脏横纹肌瘤15例临床分析

目的　研究结节性硬化症(TSC)相关的心脏横纹肌瘤(CRM)的临床特点。方法　收集15例合并CRM的TSC患儿的临床资料, 分析其临床特征及基因突变结果。结果　11例(73%)患儿为多发CRM, 肿瘤绝大部分位于左右心室, 在心脏彩超上显示多数呈类圆形强回声团, 边界清晰。3例患儿出现心律失常, 2例发生心力衰竭。2例患儿行基因检测, 均检测到TSC基因致病性突变, 分别为TSC1基因和TSC2基因突变。随访3例患儿(随访时间6个月~3年2个月), 其CRM均自发缩小或消退。结论 TSC患儿合并CRM多为多发, 部分患儿可出现心力衰竭及心律失常。心脏彩超是发现CRM的重要方法。CRM可能有自然消退的倾向。TSC基因检测可在分子遗传学上确诊TSC。     

Renal cell carcinoma in patients with tuberous sclerosis

An adolescent with anemia and weight loss was found to have bilateral renal cell carcinoma (hypernephroma). Further investigation revealed an underlying tuberous sclerosis that had escaped previous clinical detection. Several reports of this association were subsequently found when the world's literature was reviewed. Physicians treating patients with tuberous sclerosis should be aware of the possible development of these renal malignancies in their patients.     

Autism in tuberous sclerosis

Despite considerable progress in the last few years, the neurobiologic basis of autism in tuberous sclerosis complex is still largely unknown and its clinical management represents a major challenge for child neurologists. Recent evidence suggests that early-onset refractory epilepsy and functional deficits associated with the anatomical lesions in the temporal lobes may be associated with autism. No one factor alone (cognitive impairment, tuber localization, occurrence of infantile spasms, focal EEG abnormalities), can be causally linked with the abnormal behaviour. Autism may also reflect a direct effect of the abnormal genetic program. Incidence of autism associated with Tuberous Sclerosis may be significantly higher than the rates of cardiac and renal abnormalities, for which screening is routinely conducted in this population. Hopefully, early diagnosis of autism will allow for earlier treatment and the potential for better outcome for children with Tuberous Sclerosis.     

Evaluation of cardiac arrhythmias by electrocardiographic markers in pediatric patients who have tuberous sclerosis without cardiac rhabdomyoma

BackgroundTuberous sclerosis (TS) is an autosomal dominant and hereditary disorder. Cardiac rhabdomyoma and arrhythmias are the most deleterious risk factors linked to TS. Although arrhythmias in pediatric patients with TS who have cardiac rhabdomyoma have been frequently reported, arrhythmia in patients who have TS without rhabdomyoma is rarely reported in the literature. The study aimed to assess the susceptibility of pediatric patients who have TS without cardiac rhabdomyoma to cardiac arrhythmia using electrocardiographic (ECG) markers.MethodsThis prospective study included 10 patients who had TS without cardiac rhabdomyoma. The control group was made up of 30 healthy children of the same age and sex as the patient group. P wave, P wave dispersion, QT dispersion, QTc dispersion, TP-e interval, and TP-e interval dispersion were calculated on 12-lead surface ECGs for each patient in both groups and compared.ResultsP wave, P wave dispersion, QT dispersion, and QTc dispersion were found to be significantly higher in the patient group (P < 0.001). Furthermore, patients had a greater Tp-e interval and Tp-e interval dispersion than healthy children (P < 0.001).ConclusionPediatric patients with TS without cardiac rhabdomyoma might be prone to atrial and ventricular arrhythmias according to their prolonged ECG markers. Our findings suggest that patients with TS without cardiac rhabdomyoma need close monitoring for atrial and ventricular arrhythmias.     

Rapamycin (sirolimus) in tuberous sclerosis associated pediatric central nervous system tumors

Tuberous sclerosis complex (TSC) is associated with hamartomatous growths including subependymal giant cell astrocytomas (SEGAs). Since chemo‐radiation therapies offer scant benefit, oncologists had traditionally been little involved in managing SEGAs. Recent evidence demonstrating rapamycin efficacy in adults and children with TSC‐associated tumors foresee a practice change. We summarize our institutional experience and literature review that highlight potential benefits and hazards of rapamycin therapy, for TSC patients with SEGA, and other syndromal brain tumors. Pediatr Blood Cancer 2010;54:476–479. © 2009 Wiley‐Liss, Inc.     

Retinal involvement in tuberous sclerosis

In two infants hospitalized at the ages of three and one-half months and 11 months because of epileptic seizures, the diagnosis of tuberous sclerosis was reached upon the basis of retinal astrocytomas found in the fundus examination. It is recommended that indirect ophthalmoscopy be performed in all infants and young children referred with signs possibly related to this disease.     

Childhood autism in tuberous sclerosis

The article reports two cases of childhood autism in tuberous sclerosis (TS). Certain atypical features are highlighted. The probands did not show the common seizure types associated with either TS or autism. No ventricular dilatation, cerebral atrophy or temporal lobe involvement was evident. The high prevalence of childhood autism in TS probands with moderate to severe mental retardation has been emphasized.     

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex

Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.     

Selective epilepsy surgery in tuberous sclerosis

Abstract A patient with tuberous sclerosis diagnosed at the age of 5 years developed an intractable seizure disorder characterized by complex partial seizures numbering 10-20/day. Interictal electroencephalograms (EEG) showed a right frontal epileptogenic focus. A computerized tomography scan demonstrated calcification in the right frontal region at two sites, periventricular calcification and multiple low density lesions. Neuropsychological assessment showed a verbal intelligence quotient (IQ) of 69 and a performance IQ of 88. Telemetry and video monitoring recorded 10 seizures during which the EEG showed flattening of ongoing sharp wave activity in the right frontal region. Electrocorticography further identified and localized epileptogenic tissue in the right frontal cortex and surgical removal of involved tissue and the adjacent two tubers was carried out. Twelve months after surgery the patient has had only two brief seizures.     

Selective epilepsy surgery in tuberous sclerosis

A patient with tuberous sclerosis diagnosed at the age of 5 years developed an intractable seizure disorder characterized by complex partial seizures numbering 10-20/day. Interictal electroencephalograms (EEG) showed a right frontal epileptogenic focus. A computerized tomography scan demonstrated calcification in the right frontal region at two sites, periventricular calcification and multiple low density lesions. Neuropsychological assessment showed a verbal intelligence quotient (IQ) of 69 and a performance IQ of 88. Telemetry and video monitoring recorded 10 seizures during which the EEG showed flattening of ongoing sharp wave activity in the right frontal region. Electrocorticography further identified and localized epileptogenic tissue in the right frontal cortex and surgical removal of involved tissue and the adjacent two tubers was carried out. Twelve months after surgery the patient has had only two brief seizures.     

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.     

Spinal cord lesions in tuberous sclerosis

Spinal cord involvement is not widely recognized as part of the tuberous sclerosis complex. Necropsy study of the spinal cord from 2 patients revealed abnormalities in both. These consisted of clusters of abnormal fiber-forming astrocytes in gray and in white matter, bizarre giant glial forms in white matter in one patient, and neuronal loss. Myelin sheaths in subpial zones were also swollen and slightly fragmented in one patient. Reports of similar studies are sparse. Some investigators have also noted glial proliferation and white matter changes, although the latter most likely represented Wallerian degeneration.