Biomedical subjects

Antonio Gambardella

Publications and source records attributed to Antonio Gambardella.

At least 19 recordsLinked to original sources

PubMed2026

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

Humans↗

PubMed2006

Association between the M129V variant allele of PRNP gene and mild temporal lobe epilepsy in women.

Specific variations in the prion protein gene (PRNP) are associated with, and prevalent in patients with intractable temporal lobe epilepsy (TLE) and influence the surgical outcome. We investigated whether or not the PRNP gene is a susceptibility gene in temporal lobe epileptic patients with mild epilepsy. We systematically screened the entire open reading frame of the PRNP gene and evaluated the genetic contribution of the functional PRNP M129V polymorphism in 289 patients with mild TLE compared with a neurologically unaffected age and sex matched control group (n=272). Statistical analysis revealed a moderate difference in the distribution at codon 129 of the PRNP gene between sporadic mild TLE patients and healthy controls (p=0.036; OR=1.30; 95% CI=1.01-1.68). Although, there was no statistically significant difference in the genotype distribution within the study groups (p=0.101), a further analysis showed that the 129V allele was highly represented only in women with TLE compared with control group (p=0.006, OR=1.632; 95%CI=1.15-2.31). This is the first publication of data that support the hypothesis that the common methionine/valine polymorphism at codon 129 of the PRNP gene may modify the susceptibility of women to mild TLE.

Adolescent↗

PubMed2006

Open label, long-term, pragmatic study on levetiracetam in the treatment of juvenile myoclonic epilepsy.

PURPOSE: Patients with juvenile myoclonic epilepsy (JME) may be resistant or show adverse effects to valproate. We present a multicenter, prospective, long-term, open-label study evaluating the efficacy and safety of levetiracetam in JME. METHODS: Patients with newly diagnosed (10) or resistant/intolerant to previous AEDs JME (38) were enrolled. After a 8 week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased up to 3000 mg/day according to the patient's response. Efficacy parameters were: number of seizure-free patients, number of days with myoclonus (DWM), and monthly frequency of generalised tonic-clonic (GTC) seizures. Adverse events were recorded. RESULTS: The overall mean dose of levetiracetam was 2208 mg/day. The mean study period was 19 (range 0.3-38) months. Five patients dropped out. 11/38 (28.9%) patients with add-on treatment and 5/10 (50%) newly diagnosed patients were seizure-free for a mean period of 17.2 (+/-8.8) months. Eighteen patients (37.5%) were without myoclonia, and 35 (72.9%) had no GTC seizures over the study period. The mean monthly frequency of DWM and of GTC seizures in the entire group was significantly reduced after levetiracetam. Five patients complained of side effects. CONCLUSIONS: This open-label study suggests levetiracetam may be effective and well tolerated in resistant cases of JME or may become a reasonable alternative to valproate in newly diagnosed patients.

Adolescent↗

PubMed2006

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia.

Spastic paraplegia type 4 is caused by mutations in the gene that encodes spastin (SPG4), a member of the AAA protein family. A cohort of 34 unrelated Italian patients with pure spastic paraplegia, of which 18 displayed autosomal dominant inheritance and 16 were apparently sporadic, were screened for mutations in the SPG4 gene by denaturing high performance liquid chromatography. We identified a previously reported mutation in a sporadic patient with pure hereditary spastic paraplegia. We also identified eight unrelated patients with pure autosomal dominant hereditary spastic paraplegia carrying five novel mutations in the SPG4 gene (one missense mutation, c.1304 C>T; one nonsense mutation, c.807C>A; two frameshift mutations, c.1281dupT, c.1514_1515insATA; and one splicing mutation, c.1322-2A>C). The frequency for SPG4 mutations detected in autosomal dominant hereditary spastic paraplegia was 44.4%. This study contributes to expand the spectrum of SPG4 mutations in Italian population.

Adenosine Triphosphatases↗

PubMed2006

Reflex periodic spasms induced by eating.

We report on two patients with reflex periodic spasms (PS) triggered by eating. Both patients also had significant cognitive and motor deficits. In both patients, reflex eating PS started during meal and occurred repeatedly at intervals of about 5-30 s, and the whole episode lasted about 10-15 min with 15-20 consecutive PS. Clinically, each PS was characterized by the trunk and head flexion, eyeball elevation, abduction of the upper limbs, and loss of consciousness. Ictal EEG recordings of PS revealed high-voltage sharp slow waves followed by a brief 1-2s voltage attenuation. Simultaneous EMG recording of right and left deltoid muscles revealed an abrupt increase of tone lasting 0.5-1.5s. In two patients, the origins of reflex PS were perirolandic suprasylvian and temporolimbic, respectively, because the first patient had focal epilepsy associated with cortical malformation including bilateral opercular dysplasia and the second one had cryptogenic temporal lobe epilepsy.

Adult↗

PubMed2006

Levetiracetam in patients with generalised epilepsy and myoclonic seizures: an open label study.

PURPOSE: To evaluate the efficacy and tolerability of levetiracetam (LEV) as either 'de novo' (monotherapy) or 'add-on' therapy in patients with different generalised epilepsies characterised by myoclonic seizures from an observational study. METHODS: We evaluated 35 patients (21 female, mean age 24.7 years) with different types of generalised epilepsies (juvenile myoclonic epilepsy (JME), severe myoclonic epilepsy of infancy (SMEI), Lennox-Gastaut syndrome (LGS), myoclonic-astatic epilepsy (MAE), myoclonic absences (MA), benign myoclonic epilepsy in infancy (BMEI) and 4 patients had unspecified epileptic syndromes). Patients received LEV as de novo monotherapy or add-on therapy. Seizure frequency changes and adverse events were observed. Follow-up was conducted for a period of 12 months after treatment. RESULTS: Patients received LEV 2000-3000 mg/day as de novo (n = 8) and as add-on therapy. In total, 29 (82%) of the 35 patients achieved > or = 50% seizure frequency reduction, 15 (42%) patients achieved seizure freedom while a further 14 (40%) patients achieved > or = 50-99% seizure frequency reduction. Six (17%) patients discontinued LEV due to inefficacy or seizure worsening. Not even a single patient discontinued due to adverse effects. CONCLUSIONS: Our results confirm that LEV as de novo (monotherapy) and add-on therapy at doses between 2000 and 3000 mg/day effectively reduces myoclonic seizure frequency in patients with generalised epilepsy. LEV was also well-tolerated.

Adolescent↗

PubMed2006

Genetic heterogeneity in patients with pantothenate kinase-associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern.

We performed a detailed molecular study in two unrelated families with pantothenate kinase-associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye-of-the-tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C-to-T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357. As far as we are aware, this is the first case of classic PKAN with the specific MRI eye-of-the-tiger pattern not carrying a PANK2 mutation. Therefore, the present observation reinforces the notion of the phenotypic and genetic heterogeneity in PKAN.

Adult↗

PubMed2006

Suppressive efficacy by a commercially available blue lens on PPR in 610 photosensitive epilepsy patients.

PURPOSE: Photosensitivity can represent a serious problem in epilepsy patients, also because pharmacologic treatment is often ineffective. Nonpharmacologic treatment using blue sunglasses is effective and safe in controlling photosensitivity, but large series of patients have never been studied. METHODS: This multicenter study was conducted in 12 epilepsy centers in northern, central, southern, and insular Italy. A commercially available lens, named Z1, obtained in a previous trial, was used to test consecutively enrolled pediatric and adult epilepsy patients with photosensitivity. Only type 4 photosensitivity (photoparoxysmal response, PPR) was considered in the study. A standardized method was used for photostimulation. RESULTS: Six hundred ten epilepsy patients were tested. Four hundred (66%) were female patients; 396 (65%) were younger than 14 years. Three hundred eighty-one (62%) subjects were pharmacologically treated at the time of investigation. Z1 lenses made PPR disappear in 463 (75.9%) patients, and PPR was considerably reduced in an additional 109 (17.9%) of them. PPR remained unchanged only in the remaining 38 (6.2%) patients. The response of PPR to Z1 lenses was not significantly influenced by the patients' age, sex, or type of epilepsy. No difference was found between pharmacologically treated and untreated patients. CONCLUSIONS: The Z1 lens is highly effective in controlling PPR in a very large number of photosensitive epilepsy patients irrespective of their epilepsy or antiepileptic drug treatment. The lens might become a valid resource in the daily activity of any clinician who cares for patients with epilepsy.

Adolescent↗

PubMed2006

Clinical and genetic findings in 26 Italian patients with Lafora disease.

PURPOSE: EPM2B mutations have been found in a variable proportion of patients with Lafora disease (LD). Genotype-phenotype correlations suggested that EPM2B patients show a slower course of the disease, with delayed age at death, compared with EPM2A patients. We herein report clinical and genetic findings of 26 Italian LD patients. METHODS: Disease progression was evaluated by means of a disability scale based on residual motor and cognitive functions and daily living and social abilities, at 4 years from the onset. Mutational analysis was performed by sequencing the coding regions of the EPM2A and EPM2B genes. RESULTS: Age at onset ranged from 8.5 to 18.5 years (mean, 13.7+/-2.6). The mean duration of follow-up was 7.1+/-3.9 years. Daily living activities and social interactions were preserved in five of 24 patients. The remaining patients showed moderate to extremely severe limitations of daily living and social abilities. Sixteen (72%) of 22 families showed mutations in the EPM2B gene, and five (22%), in the EPM2A gene. One family showed no mutations. A novel EPM2B mutation also was identified. CONCLUSIONS: In our series, EPM2B mutations occurred in 72% of families, thus indicating that EPM2B is the major gene for LD in the Italian population. Moreover, we found that six of 17 EPM2B patients preserved daily living activities and social interactions at 4 years from onset, suggesting a slow disease progression. Additional clinical and functional studies will clarify whether specific mutations may influence the course of the disease in LD patients.

Activities of Daily Living↗

PubMed2006

Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families.

PURPOSE: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis. METHODS: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models. RESULTS: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity. CONCLUSIONS: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.

Brain↗

PubMed2005

Identification of an Nav1.1 sodium channel (SCN1A) loss-of-function mutation associated with familial simple febrile seizures.

Febrile seizures (FS) affect 5-12% of infants and children up to 6 years of age. There is now epidemiological evidence that FS are associated with subsequent afebrile and unprovoked seizures in approximately 7% of patients, which is 10 times more than in the general population. Extensive genetic studies have demonstrated that various loci are responsible for familial FS, and the FEB3 autosomal-dominant locus has been identified on chromosome 2q23-24, where the SCN1A gene is mapped. However, gene mutations causing simple FS have not been found yet. Here we show that the M145T mutation of a well conserved amino acid in the first transmembrane segment of domain I of the human Na(v)1.1 channel alpha-subunit cosegregates in all 12 individuals of a large Italian family affected by simple FS. Functional studies in mammalian cells demonstrate that the mutation causes a 60% reduction of current density and a 10-mV positive shift of the activation curve. Thus, M145T is a loss-of-function mutant. These results show that monogenic FS should also be considered a channelopathy.

Amino Acid Sequence↗

PubMed2005

Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108.

BACKGROUND: In patients with metastatic colorectal carcinoma (MCC), capecitabine has demonstrated a superior response rate (RR), equivalent disease progression-free (PFS) and overall survival (OS), and an improved overall tolerability profile compared with bolus 5-fluorouracil/leucovorin (5-FU/LV). The FOLFOX4 regimen, combining oxaliplatin with LV and bolus plus infusional 5-FU (LV5FU2), has been shown to improve RR and PFS versus LV5FU2, and it was more effective and less toxic than irinotecan plus bolus 5-FU/LV. Capecitabine (an oral fluoropyrimidine) may be an effective, well tolerated, and more convenient alternative to 5-FU/LV in combination with oxaliplatin, especially in older patients. METHODS: Elderly (> or = 70 years) patients with MCC were treated with a 3-weekly regimen of oxaliplatin at an initial dose of 85 mg/m(2) intravenously on Day 1 plus capecitabine 1000 mg/m(2) orally twice daily from Days 2 to 15 (XELOX regimen). In the absence of Grade > or = 2 hematologic toxicity, oxaliplatin was increased to 100 mg/m(2) in the second cycle, and in the absence of Grade > or = 2 nonhematologic adverse events during Cycle 2, capecitabine was increased to 1250 mg/m(2) twice daily in the third and subsequent cycles. After the first 35 patients (first series), the treatment protocol was amended so that only an oxaliplatin increase to 110 mg/m(2) and 130 mg/m(2) during Cycles 2 and 3, respectively, was planned in the remaining 41 patients (second series). RESULTS: Seventy-six patients with a median age of 75 years (range, 70-82 years) entered the current study. In the first series, the oxaliplatin dose was increased in 18 (51%) patients, and the capecitabine dose was increased in 4 (11%) patients. In the second series, the oxaliplatin dose was increased to 110 mg/m(2) in 26 (63%) patients, and to 130 mg/m(2) in 19 (46%) patients. In all, 2 complete and 29 partial responses were observed, for an overall RR of 41% (95% confidence interval [CI], 30-53%). The median PFS was 8.5 months (95% CI, 6.7-10.3 months), and the median OS was 14.4 months (95% CI, 11.9-16.9 months). In a multivariate analysis, the presence of disease symptoms affected both PFS and OS, whereas OS also was independently affected by male gender and disease spread. Age had no independent effect on PFS or OS. Five percent of patients developed Grade > or = 3 hematologic toxicity during treatment, Grade 3 peripheral neuropathy occurred in 8% of patients, and severe hand-foot syndrome in 13% of patients. CONCLUSIONS: Fit elderly patients with MCC showed a good RR to XELOX with only mild toxicity observed in most patients. XELOX, should, therefore be considered as an important therapeutic option for elderly patients with MCC.

Aged↗

PubMed2005

Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.

BACKGROUND: Several factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD. OBJECTIVE: To examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease. DESIGN: Cohort study. SETTING: Referral center for Parkinson disease in Calabria, southern Italy. Patients Two hundred fifty patients with Parkinson disease were screened for the presence or absence of PDD following a short-term levodopa administration, and 215 subjects were available for further evaluations, including genotypic analysis of the CA dinucleotide short tandem repeat (CAn-STR) polymorphism located in the dopamine receptor D2 gene (DRD2). RESULTS: One hundred five patients (48.8%) exhibited PDD following short-term levodopa administration, and 110 patients (51.2%) did not. Multivariate logistic regression analysis showed that independent predictors for the occurrence of PDD were female sex, earlier age at onset of Parkinson disease, longer duration of treatment, and higher dose of levodopa. Genetic factors related to the DRD2 CAn-STR polymorphism were not independent predictors for PDD in the total population, but they had a strong protective effect on the appearance of PDD when the multivariate analysis was performed in men (odds ratio, 0.34 [95% confidence interval, 0.14-0.84]). In women, a genetic protective effect on PDD was not evident. CONCLUSIONS: Risk factors for PDD, both clinical and genetic, act in different ways for men and women. Genetic factors related to the DRD2 polymorphic status have a protective effect on PDD development in men but not in women. A female sex-related effect for the risk of PDD may be so strong that it overcomes any protective effect due to genetic factors.

Age of Onset↗

PubMed2005

Movement time and aging: a normative study in healthy subjects with the "Movement Time Analyzer".

BACKGROUND AND AIMS: Parkinson's disease (PD) is one of the most frequent neurodegenerative disorders characterized by bradykinesia, tremor at rest, and rigidity. Movement Time (MT) has been investigated in PD to evaluate bradykinesia and its levodopa-induced modifications. The Movement Time Analyzer (MTA) is a simple, objective and reliable instrument to study MT, but no normative study has been reported to date. METHODS: In a sample of normal subjects (n = 68), we studied MT detected by MTA in order to assess normative values, so that the MTA could be used to evaluate patients with PD in daily clinical practice. RESULTS: In normal subjects, MT progressively increased with aging, and was slower on the non-dominant side than on the dominant side. No differences were found between men or women. CONCLUSION: Our data provide further information about normative values on MT detected by MTA, and indicate that age and handedness are the main variables influencing motor task performance.

Adolescent↗

PubMed2005

A tailored regimen including capecitabine and oxaliplatin for treating elderly patients with metastatic colorectal carcinoma Southern Italy Cooperative Oncology Group trial 0108.

From September 2001 to November 2002, 35 patients aged 70-81 (median, 75) years, with measurable metastatic lesions from colorectal carcinoma, were treated with a combination of oxaliplatin (OXA) infused i.v. over 2 h on day 1, and capecitabine, assumed orally twice a day (12-h apart) from day 2 to day 15. An alternated dose escalation for both drugs was planned over the first three cycles for each patient, in the absence of WHO grade > or =2 toxicity on previous cycle: starting doses were 85 mg/m2 for OXA, and 2000 mg/m2 (day) for capecitabine on first cycle; on second cycle, OXA was planned at 100mg/m2, while capecitabine was planned at 2500 mg/(m2 day) on third cycle. Treatment was repeated every 3 weeks until progression, or for a maximum of 12 cycles. A total of 212 cycles were administered, with a median of 6 (range, 1-12) cycles/patient. Dose escalation was performed in 18 (51%) patients for OXA, and in 4 (11%) patients for capecitabine. No grade 4, and 10 (29%) cases of grade 3 toxicity of any type were reported. Abdominal symptoms (pain, nausea, or vomiting) affected 66% of patients, but they were of grade 3 in only 2 (6%) patients. Grade 3 diarrhoea occurred in 3 (9%) patients. Two complete and 12 partial responses (PR) were reported, for an overall response rate of 40% (95% CI, 24-58%). Progression of disease occurred in 23 (66%) patients, and 18 (51%) died. The actuarial median progression-free and survival time were 6.9 and 14.1 months, respectively.

Aged↗

PubMed2005

ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy.

PURPOSE: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.

Adolescent↗

PubMed2004

Increased risk for Alzheimer disease with the interaction of MPO and A2M polymorphisms.

BACKGROUND: The genes encoding myeloperoxidase (MPO) and alpha(2)-macroglobulin (A2M) are involved in molecular pathways leading to beta-amyloid deposition. Two polymorphic sites in these genes (MPO-G/A and A2M-Ile/Val) have been associated with Alzheimer disease (AD), but conflicting findings have been reported in populations with different ethnic backgrounds. OBJECTIVES: To study the association of MPO-G/A and A2M-Ile/Val polymorphisms with sporadic AD and to investigate the interactions among the MPO, A2M, and apolipoprotein E (APOE) gene polymorphisms in determining the risk of the development of AD. DESIGN: Case-control study. SETTING: Referral center for AD in Calabria, southern Italy. PARTICIPANTS: One hundred forty-eight patients with sporadic AD and 158 healthy control subjects. RESULTS: The MPO-G and A2M-Val alleles were found more frequently in cases than in controls, as were the MPO-G/G and A2M-Val/Val genotypes. The odds ratio (OR) for the MPO-G/G genotype was 1.78 (95% confidence interval [CI], 1.13-2.80); for the A2M-Val/Val genotype, 3.81 (95% CI, 1.66-8.75). The presence of MPO-G/G and A2M-Val/Val genotypes synergistically increased the risk of AD (OR, 25.5; 95% CI, 4.65-139.75). Stratification of cases by sex, age at onset of AD, and APOE-epsilon 4 status did not show significant differences in the distribution of MPO or A2M polymorphisms. CONCLUSIONS: The MPO and A2M polymorphisms are associated with sporadic AD in southern Italy. Moreover, a genomic interaction between these polymorphisms increases the risk of the development of AD.

Age of Onset↗

PubMed2004

Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy.

We recently reported mutations in the sodium channel gene SCN2A in two families with benign familial neonatal-infantile seizures (BFNISs). Here, we aimed to refine the molecular-clinical correlation of SCN2A mutations in early childhood epilepsies. SCN2A was analyzed in 2 families with probable BFNIS, 9 with possible BFNIS, 10 with benign familial infantile seizures, and in 93 additional families with various early childhood epilepsies. Mutations effecting changes in conserved amino acids were found in two of two probable BFNIS families, in four of nine possible BFNIS families, and in none of the others. Our eight families had six different SCN2A mutations; one mutation (R1319Q) occurred in three families. BFNIS is an autosomal dominant disorder presenting between day 2 and 7 months (mean, 11.2 +/- 9.2 weeks) with afebrile secondarily generalized partial seizures; neonatal seizures were not seen in all families. The frequency of seizures varied; some individuals had only a few attacks without treatment and others had clusters of many per day. Febrile seizures were rare. All cases remitted by 12 months. Ictal recordings in four subjects showed onset in the posterior quadrants. SCN2A mutations appear specific for BFNIS; the disorder can now be strongly suspected clinically and the families can be given an excellent prognosis.

Adolescent↗