Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex.

PURPOSE: The aim of the study was to reveal the relationships between the tuber count of the brain found in patients with tuberous sclerosis complex (TSC) and their cognitive outcome. METHODS: A single-center, retrospective analysis was performed of patients with documented TSC seen from 1988 to 2010 at the Children's Memorial Health Institute, Warsaw, Poland. KEY FINDINGS: Sixty-two patients were analyzed, and there was a significant correlation between younger age at the first seizure and developmental delay. The patients who did not develop seizures had normal development, despite some presenting with higher tuber load than those with seizures. There was a statistically significant negative correlation between the number of tubers within the right temporal lobe and cognition. SIGNIFICANCE: Our findings confirm our hypothesis that the cognitive outcome in TSC is more dependent on the age of the seizure onset rather than on the tuber count.

Successful antiepileptic drug withdrawal in infants with epilepsy and cytomegalovirus neuroinfection: longitudinal study.

PURPOSE: A prospective study estimating antiepileptic and antiviral regimens administered to infants with symptomatic epilepsy and human cytomegalovirus (HCMV) neuroinfection followed for at least 4 years. METHODS: Thirty-two infants (19 female, 13 male) with epileptic seizures and HCMV neuroinfection diagnosed during the first year of life. Detection of HCMV DNA by qualitative polymerase chain reaction (PCR) method in cerebrospinal fluid (CSF), blood leukocytes, and urine confirmed the diagnosis. Infants were treated with intravenous ganciclovir (GCV) and different antiepileptic drugs. All had multiple electroencephalographic and neuroimaging examinations. Outcome of seizures was assessed using Engel classification system in the child's fourth year of life. RESULTS: Cessation of seizures was achieved in 19 infants (59.4%). In 11 children (34.4%) it was possible to withdraw administration of AEDs after 30-36 months. No infantile spasms, generalized tonic-clonic seizures, or polymorphic seizures were observed. They remained seizure-free for 1-6 years without relapse and their psychomotor development was normal. Four patients with intractable epilepsy (class V) had the longest GCV treatment (median 8 weeks). GCV treatment was implemented at the time or within 1 month after the onset of epileptic seizures in 10 of 11 infants withdrawn from AEDs. CONCLUSION: Early introduction of antiepileptic and antiviral GCV regimens in epilepsy and CMV neuroinfection may result in discontinuation of antiepileptic treatment and normal psychomotor development in infants.

Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatment.

From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA CMV [corrected] was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA CMV [corrected] and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but one patient [corrected] who required ACTH [corrected] was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures.

Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex.

OBJECTIVE: Tuberous sclerosis complex is an autosomal dominant disorder in which hamartomas occur in several organs. Cardiac rhabdomyomas, the most common heart tumors of childhood, are well known to be associated with tuberous sclerosis complex. Our aim for this study was to characterize the incidence, progression, and clinical consequences of tuberous sclerosis complex-associated rhabdomyomas in a large cohort of patients with TSC1 and TSC2 genotypes. PATIENTS AND METHODS: Patients (154) with tuberous sclerosis complex were evaluated, including clinical assessment, electrocardiography, and echocardiography. Mutations in TSC1 or TSC2 genes were identified in 127 patients. RESULTS: Cardiac rhabdomyomas were found in 74 (48%) patients. Tumors were most frequent in children younger than 2 years (65%). Tumor regression or disappearance was observed in 37 (68%) of 55 children. However, in 6 (3.9%) of them (aged 10-15 years), cardiac rhabdomyomas were noted to either grow (3 cases) or appear de novo (3 cases), such that the frequency of cardiac rhabdomyomas in adolescents was 6 (54%) of 11. Most (61%) tumors were clinically silent. Clinical manifestations included heart failure (5.4%), arrhythmias (23%), and murmurs (14.9%). One child died as a result of cardiac insufficiency. Cardiac rhabdomyomas were more frequent in the TSC2 (54%) than TSC1 (20%) groups. CONCLUSIONS: Cardiac rhabdomyomas are seen in the majority of young children with tuberous sclerosis complex. Most produce no clinical consequences and will spontaneously regress. However, during puberty, cardiac rhabdomyomas may enlarge or appear de novo; thus, attention should be paid to potential clinical signs and monitoring by echocardiography should be performed. Cardiac rhabdomyomas were observed more often in the TSC2 group.

Clinical symptoms of tuberous sclerosis complex in patients with an identical TSC2 mutation.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal, dominantly inherited neurocutaneous syndrome characterized by a wide range of neurological abnormalities, tumors of different organs, and variable clinical symtomatology and severity. TSC is caused by mutations in either of two tumor suppressor genes: TSC1 or TSC2. The aim of this study was to analyze the clinical picture of TSC in patients with an identical TSC2 mutation. We tried to discover to what extent we may expect variability in the clinical set of symptoms in patients with identical mutation of TSC2 gene. MATERIAL/METHODS: Mutations were identified in 100 of 170 cases. There were only 4 patients with the same type of TSC2 mutation: 5238-5255 del 18bp, del 1746 HIKRLR. Their ages were 1.5, 9, 9, and 10 years. A standardized clinical assessment of TSC symptoms was used. RESULTS: Epilepsy, depigmented spots, and periventricular calcification and cortical tubers were diagnosed in all the 4 patients, cardiac rhabdomyoma and angiomyolipoma of the kidneys in 3, and mental retardation and forehead fibroma in 2. Other symptoms occurred rarely or were absent. There was variability in TSC symptoms in patients with the identical type of TSC2 mutation. The main symptoms were present in all or in the majority of patients. Clinical picture also differed with the age of patient. CONCLUSIONS: There are many influencing factors contributing to the diversity of the clinical picture and pathology of TSC. Obviously, a greater number of cases are needed for further analysis and more precise conclusions.