Biomedical subjects

T Granata

Publications and source records attributed to T Granata.

At least 19 recordsLinked to original sources

PubMed2005

Pathogenesis, diagnosis and treatment of Rasmussen encephalitis: a European consensus statement.

Rasmussen encephalitis (RE) is a rare but severe immune-mediated brain disorder leading to unilateral hemispheric atrophy, associated progressive neurological dysfunction and intractable seizures. Recent data on the pathogenesis of the disease, its clinical and paraclinical presentation, and therapeutic approaches are summarized. Based on these data, we propose formal diagnostic criteria and a therapeutic pathway for the management of RE patients.

Adolescent↗

PubMed2004

Subcortical nodular heterotopia: a functional MRI and somatosensory evoked potentials study.

Subcortical nodular heterotopia (SNH) associated with refractory epilepsy may be surgically treated, and a positive outcome can be expected following the complete excision of the malformed tissue. Recent functional neuroimaging studies have suggested the possible functional relevance of cerebral malformations, and may make it possible to improve presurgical planning, thus allowing extended resections and minimising post-operative deficits. We here report the case of a 19-year-old man with epilepsy and a giant SNH associated with diffused abnormal gyrations of the right temporal-parietal regions. Cortical functional organisation was investigated by means of functional magnetic resonance imaging (MRI) during sensory and motor tasks, and somatosensory evoked potentials. The results revealed enlarged and displaced motor and sensory cortical areas with heterotopic tissue functional activation. The relevance of these findings is discussed in the light of the possible surgical treatment of drug-refractory epilepsy associated with cerebral malformations: surgical treatment based on conventional MRI studies alone, without taking the functional nature of dysplastic tissues into account, may lead to considerable side effects.

Adult↗

PubMed2003

Experience with immunomodulatory treatments in Rasmussen's encephalitis.

The authors investigated immunomodulatory treatments in 15 patients with Rasmussen encephalitis (RE) (14 with childhood and one with adolescent onset RE). Positive time-limited responses were obtained in 11 patients using variable combinations of corticosteroids, apheresis, and high-dose IV immunoglobulins. Although surgical exclusion of the affected hemisphere is the only treatment that halts disease progression, immunomodulation can be considered when early surgery is not feasible, in late-onset patients with slower disease progression, and in the few cases of bilateral disease.

Adolescent↗

PubMed2003

Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy.

OBJECTIVES: SCN1A mutations were recently reported in several patients with severe myoclonic epilepsy in infancy (SMEI). The authors analyzed SCN1A mutations in 93 patients with SMEI and made genotype-phenotype correlation to clarify the role of this gene in the etiology of SMEI. METHODS: All patients fulfilled the criteria for SMEI. The authors analyzed all patients for SCN1A mutations using denaturing high performance liquid chromatography. If a patient's chromatogram was abnormal, the authors sequenced the gene in the patient and both parents. RESULTS: SCN1A mutations were identified in 33 patients (35%). Most mutations were de novo, but were inherited in three patients. Parents carrying the inherited mutations had either no symptoms or a milder form of epilepsy. A greater frequency of unilateral motor seizures was the only clinical difference between patients with SCN1A mutations and those without. Truncating mutations were more frequently associated with such seizures than were missense mutations. The percentage of cases with family history of epilepsy was significantly higher in patients with SCN1A mutations. CONCLUSIONS: Unilateral motor seizures may be a specific clinical characteristic of SMEI caused by SCN1A mutations. Ten percent of SCN1A mutations are inherited from an asymptomatic or mildly affected parent, suggesting that SMEI is genetically heterogeneous. The increased frequency of familial epilepsy indicates that other genetic factors may contribute to this disorder.

Adult↗

PubMed2003

Diagnostic imaging in 13 cases of Rasmussen's encephalitis: can early MRI suggest the diagnosis?

Rasmussen's encephalitis (RE) is a rare, progressive, chronic encephalitis characterised by drug-resistant epilepsy, progressive hemiparesis and mental impairment. It typically involves only one cerebral hemisphere, which becomes atrophic. We present neuroradiological findings in 13 children with RE. MRI was performed in all patients, fluorodeoxyglucose positron-emission tomography (PET) in three, Tc-99m hexamethylpropylenamine oxime single-photon emission computed tomography (SPECT) in two and proton MR spectroscopy ((1)HMRS) in two. MRI showed progression of the hemisphere atrophy, always prevalent in the region primarily involved (13 patients), spread of the abnormal signal in white matter (11) and cortex (10) and progression of atrophy of the head of the caudate nucleus (nine). Associated secondary changes were: atrophy of the contralateral cerebellar hemisphere (in four patients), the ipsilateral hippocampus (in five) and the brain stem (in five). The earliest CT and MRI abnormalities, seen between 1 day and 4 months after the first seizure (in 12 patients examined, nine of whom had MRI) in one cerebral hemisphere included: high signal on T2-weighted images in the cortex (seven patients) and white matter (nine), cortical atrophy usually involving the frontoinsular region, with mild or severe enlargement of the lateral ventricle (eight) and moderate atrophy of the head of the caudate nucleus (seven). Cortical swelling in the early stage of the disease was recognisable only in two patients. PET revealed hypometabolism, SPECT decreased perfusion, and (1)HMRS reduction of N-acetylaspartate in the affected hemisphere. PET and SPECT were usually performed in the late stages and did not provide specific findings. MRI thus demonstrates the progression of RE and may suggest the diagnosis in the early stages, often before the appearance of neurological deficits. Early diagnosis of RE may be crucial for selecting patients for aggressive medical therapy or major surgical interventions such as hemispherectomy.

Atrophy↗

PubMed2003

Rasmussen's encephalitis: early characteristics allow diagnosis.

OBJECTIVE: To identify early manifestations of Rasmussen encephalitis (RE) that can prompt early and reasonably secure diagnosis, allowing medical or surgical therapies at an early stage when they may be more effective in slowing the disease. METHODS: The authors studied 12 patients with clinical and neuropathologic diagnosis of RE, followed from disease onset, assessing clinical history, imaging, and EEG and focusing on early characteristics. Anti-GluR3 antibody assays were also considered in 11 patients. RESULTS: By 4 months from first symptoms, all cases had 1) refractory focal seizures with a predominant motor component, 2) slow focal activity on EEG contralateral to the motor manifestations, and 3) focal contralateral white matter hyperintensity with insular cortical atrophy on neuroimaging. Less constant or later findings were epilepsia partialis continua, oligoclonal bands, and serum anti-GluR3 antibodies. CONCLUSIONS: The association of partial seizures with focal EEG and neuroimaging changes allows a tentative diagnosis of RE 4 to 6 months after first symptoms.

Adolescent↗

PubMed2003

Rasmussen's syndrome.

Rasmussen's encephalitis (RE) is characterized by focal seizures, often associated with epilepsia partialis continua, progressive neurological deterioration, hemispheric atrophy, and inflammatory histopathology. Surgical exclusion of the affected hemisphere is the only treatment that halts progression of the disease. The possible role played by serum antibodies against the glutamate receptor GluR3 in the animal model and in a number of affected patients supports a disimmune component in the pathogenesis of the disease and provides a rational basis for considering the use of immunomodulatory treatments in selected cases. The use of intravenous immunoglobulins has produced encouraging results in adult-onset RE but further studies are needed to assess the effect, dosage, and schedules in childhood-onset RE.

Animals↗

PubMed2002

Similar binding to glutamate receptors by Rasmussen and partial epilepsy patients' sera.

Immunoreactivity of sera from patients with Rasmussen encephalitis (RE) and patients with partial epilepsy (PE) was analyzed by immunohistoblot on rat brain sections and the staining pattern compared with that obtained with antibodies to a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and NMDA receptors. Staining for anti-glutamate receptor 3 (GluR3) was found in 82% of patients with RE and 64% of patients with PE. Histoblot analysis showed a positive staining in GluR3- and NMDA-specific regions of rat brain, providing a comprehensive CNS immunolocalization.

Animals↗

PubMed2001

Labeling of rat neurons by anti-GluR3 IgG from patients with Rasmussen encephalitis.

The authors report the immunocytochemical localization in rat brain of affinity-purified anti-GluR3 (glutamate receptor) antibodies from two patients with Rasmussen encephalitis (RE) and from immunized rabbits. The distribution of immunolabeling was similar using antibodies from rabbits and patients with RE. No electrophysiologic responses were elicited from acutely dissociated kainate-responsive neurons isolated from rat brain when these antibodies were applied. These findings show that anti-GluR3 antibodies purified from patients with RE bind to specific regions of the CNS but do not act through an excitotoxic mechanism.

Animals↗

PubMed2001

Epileptic phenotypes associated with mitochondrial disorders.

OBJECTIVE: To define the clinical and EEG features of the epileptic syndromes occurring in adult and infantile mitochondrial encephalopathies (ME). METHODS: Thirty-one patients with recurrent and apparently unprovoked seizures associated with primary ME were included in the study. Diagnosis of ME was based on the recognition of a morphologic, biochemical, or molecular defect. RESULTS: Epileptic seizures were the first recognized symptom in 53% of the patients. Many adults (43%) and most infants (70%) had nontypical ME phenotypes. Partial seizures, mainly with elementary motor symptoms, and focal or multifocal EEG epileptiform activities characterized the epileptic presentation in 71% of the patients. Generalized myoclonic seizures were an early and consistent symptom only in the five patients with an A8344G mitochondrial DNA point mutation with classic myoclonus epilepsy with ragged red fibers (MERRF) syndrome or "overlapping" characteristics. Photoparoxysmal EEG responses were observed not only in patients with typical MERRF, but also in adult patients with ME with lactic acidosis and strokelike episodes (MELAS), or overlapping phenotypes, and in one child with Leigh syndrome. CONCLUSIONS: Epilepsy is an important sign in the early presentation of ME and may be the most apparent neurologic sign of nontypical ME, often leading to the diagnostic workup. Except for those with an A8344G mitochondrial DNA point mutation, most of our patients had partial seizures or EEG signs indicating a focal origin.

Adolescent↗

PubMed2001

Positive response to immunomodulatory therapy in an adult patient with Rasmussen's encephalitis.

Rasmussen's encephalitis (RE) is a rare and progressive neurologic condition of uncertain etiology that typically has a childhood onset. The authors describe a 45-year-old woman with adult-onset progressive aphasia, right hemiparesis, severe drug refractory epilepsy, and left cerebral hemisphere atrophy. High-dose corticosteroids and plasmapheresis were not effective. She improved with high-dose therapy with human IV immunoglobulin.

Brain↗

PubMed2001

Single-dose pharmacokinetics of lamotrigine in children: influence of age and antiepileptic comedication.

To evaluate the influence of pediatric age and antiepileptic comedication on the single-dose pharmacokinetics of lamotrigine, 19 patients with epilepsy (10 comedicated with enzyme inducers and 9 comedicated with valproic acid) aged 8 months to 30 years received a single oral dose of lamotrigine (0.6 to 2.2 mg/kg) after an overnight fast. Blood samples were collected for at least 36 hours and plasma lamotrigine concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were calculated by noncompartmental analysis. Lamotrigine half-life (T1/2) and oral clearance (Cl/F) values were significantly lower and significantly higher, respectively, in patients comedicated with enzyme inducers than in those receiving valproic acid (T1/2 = 8.1 vs. 41.7 hours respectively, P < 0.001; Cl/F = 0.11 vs. 0.04 L/h per kg respectively, P < 0.005, geometric means), whereas Cmax and Tmax values were comparable in the two groups. The differences in pharmacokinetic parameters persisted when comparisons were made within subgroups stratified according to age. Within groups of patients homogeneous for type of comedication, Cmax and AUC values tended to be lower in children aged less than 12 years than in older patients. There was no significant relationship between half-life values and age. The authors conclude that both age and type of comedication influence lamotrigine pharmacokinetics. The reduction in lamotrigine concentrations caused by enzyme inducers and the elevation caused by valproic acid can be explained by stimulation and inhibition, respectively, of lamotrigine glucuronidation. On the other hand, the lower plasma lamotrigine levels in children than in adolescents and older patients may not be explainable solely by differences in metabolic rate.

Adolescent↗

PubMed2000

Neuromuscular syndrome associated with the 3291T-->C mutation of mitochondrial DNA: a second case.

A mutation was found in an Italian child affecting the gene encoding the mitochondrial transfer RNA for leucine (codon UUR). This mutation (3291T-->C) had previously been reported in a single Japanese patient. In contrast with the original patient, who suffered from early-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), our patient presented an apparently isolated mild myopathy. Mutational analysis in the proband and her family showed that the mutation was heteroplasmic, and that its relative amount was positively correlated with the severity of the phenotype. These findings lead to the definitive confirmation that the 3291T-->C is indeed pathogenic. As commonly found in mitochondrial-DNA related disorders, also for this mutation different clinical manifestations can be associated with the same genetic abnormality.

Biopsy, Needle↗

PubMed1999

Congenital malformations due to antiepileptic drugs.

To identify the major risk factors for the increased incidence of congenital malformations in offspring of mothers being treated for epilepsy with antiepileptic drugs (AEDs) during pregnancy and, to determine the relative teratogenic risk of AEDs, we prospectively analyzed 983 offspring born in Japan, Italy, and Canada. The incidence of congenital malformations in offspring without drug exposure was 3.1%, versus an incidence with drug exposure of 9.0%. The highest incidence in offspring exposed to a single AED occurred with primidone (PRM; 14.3%), which was followed by valproate (VPA; 11.1%), phenytoin (PHT; 9.1%), carbamazepine (CBZ; 5.7%), and phenobarbital (PB; 5.1%). The VPA dose and level positively correlated with the incidence of malformations. This study first determined a cut-off value of VPA dose and level at 1000 mg/day and 70 microg/ml, respectively, to avoid the occurrence of malformations. The incidence of malformations increases as the number of drugs increases, and as the total daily dose increases. Specific combinations of AEDs such as VPA + CBZ and PHT + PRM + PB produced a higher incidence of congenital malformations. The incidence of malformations was not associated with any background factors studied except for the presence of malformations in siblings. These results indicate that the increased incidence of congenital malformations was caused primarily by AEDs, suggesting that malformations can be prevented by improvements in drug regimen, and by avoiding polypharmacy and high levels of VPA (more than 70 microg/ml) in the treatment of epileptic women of childbearimg age.

Abnormalities, Drug-Induced↗

PubMed1999

Spectral properties of EEG fast activity ictal discharges associated with infantile spasms.

OBJECTIVE: The aim of this study was to evaluate the characteristics of the ictal EEG event accompanying infantile spasms. METHODS: Quantitative analysis was used, based on the application of a bivariate autoregressive (AR) parametric model; autospectra, coherence, phase functions and inter-hemispheric time differences were estimated on homologous EEG channels in 18 infants presenting with either cryptogenic or symptomatic West syndrome. RESULTS: The AR analysis of the 500 ms EEG epochs preceding spasm onset revealed the presence of a short discharge of fast activity restricted to a narrow frequency band in 13 of the 18 cases included in the study. The fast discharge peaked at 17.5+/-2.1 Hz, with rather low inter-hemispheric coherence values (0.52+/-0.17) and asymmetric amplitude on homologous EEG derivations. It persisted briefly after spasm onset, reaching a higher coherence value (0.71+/-0.16). The inter-hemispheric time difference, estimated in those cases with the coherence values significantly different from zero, ranged from 9.1 to 14.3 ms (11.4+/-1.9) in the epoch preceding spasm onset. CONCLUSION: The data obtained from the analysis of the ictal EEG events, compared with clinical and interictal EEG features, indicate that an asymmetric EEG pattern (mainly consisting of a rhythmic burst of fast activity) consistently preceded both symmetric and asymmetric spasms, thus suggesting a localized cortical origin of the ictal discharge giving rise to the spasms.

Age of Onset↗

PubMed1999

Malformations in offspring of women with epilepsy: a prospective study.

PURPOSE: The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors. METHODS: Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities. RESULTS: The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic-genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients. CONCLUSIONS: The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED-related factors are the primary risk factors for an increased incidence of congenital malformations.

Abnormalities, Drug-Induced↗

PubMed1998

Partial seizures associated with antiphospholipid antibodies in childhood.

We report antiphospholipid antibody positivity in three of a consecutive series of 23 children presenting partial epileptic seizures. There was no clinical or serological evidence of systemic lupus erythematosus or other connective-tissue disease. Neither computed tomography nor magnetic resonance imaging revealed ischemic alteration. The presence of antiphospholipid antibodies in 3/23 children may indicate that immune-mediated neuronal damage could be a pathogenetic mechanism for partial epilepsy.

Adolescent↗

PubMed1998

Long-term selective IgG immuno-adsorption improves Rasmussen's encephalitis.

We report that long-term selective immunoglobulin G immunoadsorption by protein A (PAI) improved seizure frequency and neuropsychological deficits in a 16-year-old patient with severe treatment-resistant Rasmussen's encephalitis (RE). Clinical improvement correlated with reduction of antiglutamate receptor 3 antibodies. The efficacy of PAI in our patient supports the autoimmune hypothesis of RE and suggests its application to avoid, or at least delay, functional hemispherectomy in selected cases.

Adolescent↗