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Paolo Curatolo

Publications and source records attributed to Paolo Curatolo.

16 recordsLinked to original sources
PubMed2004

Association between presenilin-1 -48C/T polymorphism and Down's syndrome.

Individuals with Down's syndrome (DS), i.e., trisomy 21, over 40 years of age, are likely to develop neuropathological changes characteristic of Alzheimer's disease (AD). The involvement of chromosome 21 both in DS and AD suggests a shared genetic susceptibility to these disorders, but genetic determinants are still undefined. The -48C/T polymorphism in the PSEN1 promoter is a possible candidate, since it has recently been associated with an increased risk of early onset AD. Based on the assumption that the excess of dementia in DS might be a consequence of a different distribution of the -48C/T polymorphism, we investigated the association between DS and this polymorphism in patients with trisomy 21 and controls. Overall, 260 DS patients and 197 controls were recruited at the Department of Neurosciences, Tor Vergata University of Rome. Cases and controls had similar age and gender distribution. High molecular weight DNA was extracted from whole blood samples collected in EDTANa(2) and -48C/T genotypes were determined. Genotype and allele frequencies were compared between cases and controls. Cases were less likely than controls to have the CC genotype ( P = 0.05). A significant difference for allele distribution between DS cases and controls was found, with DS showing a lower frequency of the allele C compared with the control population (OR: 0.57; 95% CI: 0.35-0.91; P = 0.01). No significant interaction of PSEN1 with age, gender, ApoE and -850 TNF-alpha polymorphisms was found. The association found suggests that the -48C/T polymorphism in the PSN1 gene promoter, which is involved in the modulation of amyloid beta load in human AD, is associated with DS. However, the biological role of this polymorphism in DS-related dementia remains unclear and merits further investigation.

Adolescent↗
PubMed2004

Lamotrigine-induced seizure aggravation and negative myoclonus in idiopathic rolandic epilepsy.

The authors describe a paradoxical reaction to lamotrigine (LTG) treatment in a patient with idiopathic rolandic epilepsy characterized by seizure deterioration, the appearance of new seizure type, and transient cognitive impairment. This phenomenon was present at a low dose after a slow titration and promptly reverted on LTG discontinuation. This rare event may have similarities with carbamazepine-induced seizure worsening caused by the Na++ channel inhibitory effect of the two antiepileptic drugs.

Anticonvulsants↗
PubMed2004

Increased brain apparent diffusion coefficient in tuberous sclerosis.

PURPOSE: To evaluate the water diffusivity of normal-appearing white matter (NAWM) in patients with tuberous sclerosis complex compared with that in control subjects. MATERIALS AND METHODS: Diffusion and conventional magnetic resonance (MR) imaging examinations were performed in 18 patients with clinically established tuberous sclerosis complex (10 male and eight female patients; mean age, 20.1 years; range, 12-30 years), as well as in 18 age-matched control subjects (nine male and nine female; mean age, 20.2 years; range, 11-28 years). Apparent diffusion coefficients (ADCs) were generated, and small elliptic regions of interest were manually placed both in perilesional NAWM and in six anatomic locations of NAWM remote from hamartomatous lesions. Perilesional ADCs were compared with those at the same anatomic site on the contralateral side of the brain (generalized linear regression analysis). ADCs from the predetermined sites in patients were compared with those in control subjects (generalized linear regression analysis). RESULTS: Supratentorial ADCs were higher in patients with tuberous sclerosis complex than in control subjects, and statistically significant differences were observed in the occipital white matter, frontal white matter, centrum semiovale, parietal white matter, and corona radiata (for each location, P <.001). Significant increases were also seen in the perilesional NAWM compared with NAWM at the same anatomic locations on the contralateral side (P <.001). Infratentorial ADCs were normal. CONCLUSION: Significant ADC increases were measured in the supratentorial NAWM.

Adolescent↗
PubMed2004

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.

Autistic Disorder↗
PubMed2004

Epilepsy surgery for tuberous sclerosis.

Tuberous sclerosis complex is often associated with medically refractory epilepsy secondary to cortical tubers. Previous studies have identified an association between early seizure onset, greater seizure burden, and mental retardation in childhood. Early effective seizure control could therefore significantly reduce the adverse developmental effects of chronic epilepsy in tuberous sclerosis complex. In medically intractable epileptic patients, surgical treatment has been demonstrated to reduce or abolish seizures and the associated burden for the child and its environment. Epilepsy surgery has not been widely used in patients with tuberous sclerosis complex thus far, mostly because of the concern that the multifocal nature of the cortical lesions could be associated with the development of independent epileptogenic zones. Advances in electroencephalographic techniques, functional neuroimaging, and invasive cortical mapping are changing this view and allowing an increased number of tuberous sclerosis complex patients to be evaluated for resective surgery. Additional techniques emerging in the neurosurgical field may add further treatment options to the current state of the art.

Anticonvulsants↗
PubMed2004

Pharmacologic treatment of autism.

Autism is a chronic and lifelong pervasive developmental disorder for which there is yet no effective cure, and medical management remains a major challenge for clinicians. In spite of the possible similarities with conditions that have an established pharmacotherapy, and despite improvements in some associated "problematic behaviors" following the use of available medications, effective medical treatment for the core symptoms involving language and social cognition remains elusive. The purpose of the present article is to review current biologic knowledge about autism in an attempt to correlate clinical trials with known mechanisms of disease. In addition, the need for controlled studies and for the creation of homogeneous subgroups of patients based on clinical and genetic characteristics is emphasized. The application of molecular genetic investigations and pharmacogenetics in the diagnostic work-up of autistic patients can lead to more effective individualized medical care.

Anticonvulsants↗
PubMed2004

A neurocutaneous disorder with a severe course: Wyburn-Mason's syndrome.

Wyburn-Mason's syndrome is a rare neurocutaneous disorder consisting mainly of unilateral arteriovenous malformations of the midbrain and retina with multiple cutaneous nevi. The authors report on the clinical presentation, neurologic phenotype, and long-term neurologic follow-up of two unrelated children. The first patient had recurrent epistaxis during early childhood. At the age of 7 years, he developed acute hemianopsia and right hemiplegia. Angiography revealed large bilateral arteriovenous malformations involving the midbrain thalamic area and the right optic nerve. During the following years, he had recurrent episodes of headache, right hemiplegia, and cognitive deterioration. The second patient had some episodes of epistaxis in the first years of life. At the age of 5 years, he presented with sudden onset of headache, followed by a loss of consciousness, vomiting, and, subsequently, visual disturbances. Angiography revealed deeply located arteriovenous malformations involving the right temporal, frontobasal, capsulonuclear, insular, and parietal areas and the right optic nerve. During the following years, he had an acute strokelike episode followed by transient hemiplegia and slow progressive signs, with mild worsening of cognitive abilities. Early onset of neurologic manifestations is a poor prognostic factor for long-term outcome.

Adolescent↗
PubMed2003

The role of -850 tumor necrosis factor-alpha and apolipoprotein E genetic polymorphism in patients with Down's syndrome-related dementia.

Down's syndrome (DS) is a disease with a complex etiology. It is likely that other factors besides genes located on chromosome 21 may play a role in clinical features of affected patients. Tumor necrosis factor-alpha (TNF-alpha) (6p21.3) and apolipoprotein E (APOE) (19q13.2) are candidate genes as they interact with the brain deposition of Abeta, one of the neuropathological hallmarks in DS. We examined 136 DS patients and 113 controls for -850 TNF-alpha and APOE polymorphisms. The -850T frequency in DS was significantly higher than in controls (P<0.005, OR 2.05, 95% CI 1.22-3.49) while the APOE E4 allele was negatively selected in patients compared to normal subjects (P<0.005, OR 0.38, 95% CI 0.20-0.71). Our findings suggest that the -850T allele, which is more common among patients at high risk of dementia such as those with DS, might eventually play a role in the development of dementia; no inference on the role of the allele APOE E4 in DS-related dementia may be derived from our results.

Adolescent↗
PubMed2003

Neurologic aspects of 49,XXXXY syndrome.

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome characterized by mental retardation, severe speech impairment, craniofacial abnormalities, multiple skeletal defects, and genital abnormalities. We describe a 13-year-old boy with 49,XXXXY syndrome, language impairment, seizures, and left-hemisphere magnetic resonance imaging abnormalities and review the distinctive neurologic, cognitive, and behavioral phenotypes associated with this disorder. Finally, we discuss testosterone supplementation in the treatment of this syndrome.

Abnormalities, Multiple↗
PubMed2002

Convulsive disorder and the genetics of signal transduction; a study of a low molecular weight protein tyrosine phosphatase in a pediatric sample.

Recent studies point to an involvement of kinases and phosphatases in ionic channel regulation and in physiopathologic mechanisms leading to convulsive disorders. Acid phosphatase locus 1 (ACP1), also named cytosolic low molecular weight phosphotyrosine phosphatase, is a highly polymorphic phosphatase that is especially abundant in the central nervous system and is known to be involved in several signal transduction pathways. We studied ACP1 in 122 children with idiopathic generalized tonic-clonic seizures, 80 children with febrile convulsions, and 417 controls from the population of Rome. Low activity phenotypes of ACP1 (*A/*A and *A/*B) were found to be over-represented while high activity phenotypes (*C/*C and *B/*C) were under-represented in generalized seizures cases compared to controls (P < 0.005). No significant difference was observed between febrile convulsion cases and controls. These observations suggest a protective role of the high activity ACP1 phenotypes against seizures in children.

Adult↗
PubMed2002

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.

Anticonvulsants↗