R. L. Oliveri

Randomized trial comparing two different high doses of methylprednisolone in MS : A clinical and MRI study

Objective To assess the efficacy of two different high doses of intravenous methylprednisolone (IVMP) for the treatment of relapses in MS. Background NMP is the treatment of choice for MS relapses, but it is unknown whether its effects are dose related. Methods We conducted a double-blind, randomized study. Follow-up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and 60 days after the beginning of treatment. Outcome measures were the number of brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded Disability Status Scale score. Results Both treatment regimens improved clinical scores and reduced the number of MRI enhancing lesions during the follow-up period. The higher dose of IVMP was significantly more effective than the lower dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days, mainly by decreasing the rate of new lesion formation. Conclusions The higher dosage of IVMP has a more powerful and prolonged action in maintaining blood-brain barrier integrity after a clinical relapse.

Dopamine D2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD.

OBJECTIVE To investigate whether polymorphisms in the genes for dopamine receptors D1 and D2 are associated with the risk of developing peak-dose dyskinesias in PD. BACKGROUND Peak-dose dyskinesias are the most common side effects of levodopa therapy for PD. The identified predictors may only partially account for the risk of developing peak-dose dyskinesias because a substantial proportion of patients never develop peak-dose dyskinesias. Genetic factors could play a role in determining the occurrence of peak-dose dyskinesias. METHODS A case-control study of 136 subjects with sporadic PD and 224 population control subjects. We studied three polymorphisms involving the dopamine receptor D1 gene and one intronic short tandem repeat polymorphism of the dopamine receptor D2 gene. RESULTS The polymorphisms of the dopamine receptor D1 gene were not associated with the risk of developing PD or peak-dose dyskinesias. The 15 allele of the polymorphism of the dopamine receptor D2 gene was more frequent in parkinsonian subjects than in control subjects. More important, the frequency of both the 13 allele and the 14 allele of the dopamine receptor D2 gene polymorphism was higher in nondyskinetic than in the dyskinetic PD subjects. The risk reduction of developing peak-dose dyskinesias for PD subjects carrying at least 1 of the 13 or 14 alleles was 72% with respect to the PD subjects who did not carry these alleles. CONCLUSIONS Certain alleles of the short tandem repeat polymorphism of the dopamine receptor D2 gene reduce the risk of developing peak-dose dyskinesias and could contribute to varying susceptibility to develop peak-dose dyskinesias during levodopa therapy.

A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1

Background: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the α4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24. Objective: To report a new third ADNFLE locus on chromosome 1 in a large Italian family. Methods: The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers. Results: The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE—ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24—was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1. Conclusions: The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the β2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.

Silent Celiac Disease in Patients with Childhood Localization-Related Epilepsies

Summary:  Purpose: To evaluate how many patients with a clinical picture of idiopathic childhood localization‐related epilepsies may also have silent celiac disease (CD). This will help determine whether investigation for CD should be restricted to those patients with childhood partial epilepsy with occipital paroxysms (CPEO) or should be extended to all patients with childhood partial epilepsy (CPE) regardless of seizure type and electroencephalographic (EEG) paroxysms.

Loss of long-duration response to levodopa over time in PD: Implications for wearing-off

Objective: To determine the modifications of the long-duration response to levodopa in PD over a 1-year period. Background: The development of predictable motor fluctuations in PD has been attributed mainly to modifications over time of the short-duration response to levodopa, whereas the role of the long-duration response has not been widely investigated. Methods: In 17 patients with PD the authors examined prospectively both the short-duration response and the long-duration response to levodopa under standardized conditions on two different occasions separated by a period of approximately 1 year (11.7 ± 3.6 months). Results: At the end of the follow-up period, the short-duration response increased in magnitude but did not change significantly in duration. A total of 24% of patients lost the long-duration response 1 year after their first examination, but a sustained long-duration response could be reestablished by shortening the interdose interval for levodopa intake. Moreover, the duration of the long-duration response after discontinuation of treatment became significantly shorter during 1 year. Conclusion: Modifications of the long-duration response may have a pivotal role in generating a fluctuating response, and suggest that therapeutic strategies based on maintenance of the long-duration response should be sought to avoid the appearance of motor fluctuations.

The parkin gene is not involved in late-onset Parkinson’s disease

Mutations in the parkin gene have been reported in patients with early onset PD. The authors investigated the parkin gene in 118 patients who had an onset of PD after age 45 years: 95 subjects were sporadic patients and 23 subjects were from 18 families with a probable autosomal recessive inheritance. No pathogenetic mutations in the parkin gene were detected either in familial or in sporadic patients. Moreover, no differences were found between patients and 100 age-matched normal controls in the allele and genotype frequencies of four exonic parkin polymorphisms.

Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDH

BackgroundThere is evidence that patients with chronic daily headache (CDH) may have isolated intracranial hypertension without papilledema (IHWOP). Recent studies have emphasized that isolated IH may be due to cerebral venous thrombosis (CVT). ObjectiveTo detect the occurrence of CVT in patients with CDH. MethodsThe authors investigated the occurrence of CVT in 114 consecutive patients with CDH by using MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age-matched control subjects. ResultsIn all the control subjects, both MRV and CSF pressure were normal. One hundred three of the 114 patients with CDH had normal MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of one or both transverse sinuses. Six of these 11 patients had flowing abnormalities of one transverse sinus (Group 2), whereas the remaining five patients showed involvement of both transverse sinuses (Group 3). The CSF pressure of Group 2 was higher than that of either Group 1 or the control subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3 displayed the highest CSF pressure, and four of five had isolated IHWOP. The headache profiles of patients with CDH and CVT did not differ from those of patients with CDH but normal MRV. ConclusionsCVT, as detected by MRV, occurred in 9.6% of patients who presented with CDH. Almost half of the patients with CVT had isolated IHWOP. These results suggest that MRV may be a useful tool for selecting patients with CDH who should have LP to exclude isolated IHWOP.

The dopamine D2 receptor gene is a susceptibility locus for Parkinson's disease

The dopamine D2 receptor (DRD2) gene has been proposed as a candidate gene underlying several psychiatric and neurologic disorders. The aim of the present study was to examine if selected polymorphisms in the DRD2 gene are associated with Parkinsons disease (PD). We determined the allelic frequencies for four polymorphisms located in the DRD2 gene in a sample of 135 patients with PD and 202 normal control subjects. No significant difference was observed in the allelic frequencies between patients with PD and control subjects with regard to the ‐141C Ins/Del and the Ser311/Cys311 variants. On the contrary, the A1 allele of the TaqIA polymorphism and the B1 allele of the TaqIB polymorphism were more frequent in patients with PD than in control subjects (control subjects: TaqIA A1 = 14.6%, TaqIB B1 = 10.6%; patients with PD: TaqIA A1 = 20.7%, TaqIB B1 = 17.4%). Patients carrying the A1 allele or the B1 allele had an increased risk of developing PD (TaqIA, odds ratio: 1.71, 95% confidence intervals: 1.08–2.73; TaqIB, odds ratio: 1.83, 95% confidence intervals: 1.12–3.02). The TaqIA and TaqIB polymorphisms were in strong linkage disequilibrium, suggesting that these two polymorphisms convey the same information about the risk of presenting with PD. Genetic variation in the DRD2 gene may influence the risk of developing PD, thus confirming that the DRD2 gene is a susceptibility locus for PD.

Mild non-lesional temporal lobe epilepsy : a common, unrecognized disorder with onset in adulthood

OBJECTIVE To compare mild vs. severe non-lesional temporal lobe epilepsy (TLE). METHODS Data from 104 consecutive patients with non-lesional TLE were reviewed. Seventy-three of the 104 fulfilled the criteria for inclusion in this study of a follow-up period longer than three years at our Institute. Patients were considered to have a mild TLE if they were seizure free for at least three years after appropriate antiepileptic medication, or had rare (< or = 2/year) complex partial or secondarily generalized seizures for at least three years with or without appropriate antiepileptic therapy. Clinical, EEG and MRI data of mild vs. severe non-lesional TLE patients were compared on the basis of a cross-sectional study design. RESULTS Of the 73 patients with non-lesional TLE included in the study, 43 (59%) had mild TLE, and 30 (41%) had severe TLE. Duration of epilepsy was significantly shorter (mean 15.2 +/- 10.5 years vs. 26.4 +/- 13.2 years) and age at onset was significantly higher (mean 34.3 +/- 15.3 years vs. 7.8 +/- 6.8 years) in mild than in severe TLE group. Patients with mild TLE had also a significantly higher prevalence of positive family history of epilepsy (37.2% vs. 10%), and a significantly lower occurrence rate of febrile convulsions (FC) (4.7% vs. 33.3%), mesial temporal sclerosis (MTS) (6.9% vs. 36.7%), and intelligence deficiency (0% vs. 20%). In mild TLE there was also a significantly high rate (58.1 vs. 0%) of delayed diagnosis (from 1 to 28 years), because of misdiagnosis (39.5%) or no medical counseling (18.6%). CONCLUSIONS Mild non-lesional TLE is a common, unrecognized disorder mainly characterized by both onset in adulthood and high prevalence of familial history of epilepsy. The present findings suggest that mild non-lesional TLE may represent a clinical entity different from severe non-lesional TLE.

Pulsed methylprednisolone induces a reversible impairment of memory in patients with relapsing-remitting multiple sclerosis.

Objective – Chronic administration of corticosteroids has been reported to selectively impair explicit memory in systemic diseases without central nervous system involvement. Our aim was to verify that a short course of pulsed intravenous methylprednisolone (IVMP) administered for the treatment of a relapse impairs cognitive functions in relapsing‐remitting multiple sclerosis (RRMS) patients and to determine whether this impairment is reversible. Material and methods – Neuropsychological evaluations were made before the start of treatment, and 7 and 60 days after the end of treatment in 14 RRMS patients. The neuropsychological battery was also administered to 12 controls matched for age, sex and years of education. Results – RRMS patients performed worse than the controls at their baseline evaluation for a variety of neuropsychological tasks. IVMP administration induced a selective impairment of explicit memory which completely recovered 60 days after treatment. Conclusions – In RRMS patients, IVMP induces a selective and reversible impairment of explicit memory.