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The paper reports some preliminary results concerning the manufacturing process of CuZnSnSe (CZTSe) and CuInGaSe (CIGS) nanowire arrays obtained by one-step electrodeposition for p-n junction fabrication. CZTSe nanowires were obtained through electrodeposition in a polycarbonate membrane by applying a rectangular pulsed current, while their morphology was optimized by appropriately setting the potential and the electrolyte composition. The electrochemical parameters, including pH and composition of the solution, were optimized to obtain a mechanically stable array of nanowires. The samples were characterized by scanning electron microscopy, Raman spectroscopy, and energy-dispersion spectroscopy. The nanostructures obtained showed a cylindrical shape with an average diameter of about 230 nm and a length of about 3 µm, and were interconnected due to the morphology of the polycarbonate membrane. To create the p-n junctions, first a thin film of CZTSe was electrodeposited to avoid direct contact between the ZnS and Mo. Subsequently, an annealing process was carried out at 500 °C in a S atmosphere for 40 min. The ZnS was obtained by chemical bath deposition at 95 °C for 90 min. Finally, to complete the cell, ZnO and ZnO:Al layers were deposited by magnetron-sputtering.

We report on bulk and guided-wave second-harmonic generation via random Quasi-Phase-Matching in Lithium Tantalate. By acquiring the far-field profiles at several wavelengths, we extract statistical information on the distribution of the quadratic nonlinearity as well as its average period, both at the surface and in the bulk of the sample. By investigating the distribution in the two regions we demonstrate a non-invasive approach to the study of poling dynamics.

We observe second harmonic generation via random quasi-phase-matching in a 2.0 mum periodically poled, 1-cm-long, z-cut lithium tantalate. Away from resonance, the harmonic output profiles exhibit a characteristic pattern stemming from a stochastic domain distribution and a quadratic growth with the fundamental excitation, as well as a broadband spectral response. The results are in good agreement with a simple model and numerical simulations in the undepleted regime, assuming an anisotropic spread of the random nonlinear component.

A large three-generation family with autosomal dominant type 1 porencephaly from southern Italy was studied. A high rate of miscarriages was observed. Of the nine affected individuals, four displayed a severe phenotype, and five had slight pyramidal signs or mild cognitive abnormalities. The MRI study disclosed unilateral porencephalic cyst, or colpocephaly. A genome-wide screen resulted in suggestive evidence for linkage to chromosome 13qter with a maximum logarithm-of-the-odds score of 3.16, from multipoint analysis, with marker D13S285.

After West Nile virus (WNV) was first detected in Florida in July 2001, intensive surveillance efforts over the following five months uncovered virus activity in 65 of the state's 67 counties with 1,106 wild birds, 492 horses, 194 sentinel chickens, and 12 people found infected with the virus. Thirteen of 28 mosquito isolations came from Culex mosquitoes. As seen in the northeastern United States, wild bird mortality was the most sensitive surveillance method. However, unlike the predominantly urban 1999 and 2000 epizootics, the Florida transmission foci were rural with most activity detected in the northern part of the state. All human cases were preceded by the detection of WNV in animals; however, only eight of the twelve cases were preceded by reports of WNV activity in the county of residence. West Nile virus-positive animals detected by multiple surveillance systems preceded seven of these cases by two weeks or more.

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., Methods: The study group consisted of 72 patients (31 girls and 41 boys; mean age, 12.6 +/- 4.28 years; age at onset, 6.4 +/- 3.7 years) who were observed consecutively over a 5-year period and who received an initial diagnosis of idiopathic CPE. A diagnosis of CD was confirmed by using enzyme-linked immunosorbent assay (ELISA) to assess the presence of antigliadin antibodies and the immunofluorescent undirected test to assess the presence of antiendomysium antibodies., Results: Twenty-five patients had CPEO, whereas the remaining 47 had CPE with centrotemporal spikes (CPEC). None of the patients with CPEC had positive antibody tests. Of the 25 patients with CPEO, two (8%) had antiendomysium immunoglobulin (Ig) A antibodies. In both of these patients, the jejunal biopsy showed atrophy of the villi and hyperplasia of the crypts, consistent with a diagnosis of CD. Brain computed tomography (CT) was normal in one of these patients and revealed occipital corticosubcortical calcifications in the other., Conclusions: Our study indicates that CD screening should be performed routinely only in patients with CPEO.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary syndrome caused by mutations of the Notch3 gene, usually localized to exons 3 and 4., Objectives: To report a novel pathogenetic mutation occurring in exon 6 of the Notch3 gene, a location not previously recognized in patients with CADASIL, and to report the results of magnetic resonance spectroscopy in CADASIL., Methods: Mutation analysis of the Notch3 gene was performed in 2 patients belonging to a large kindred manifesting CADASIL, as well as in 7 clinically unaffected members of the family and 200 control chromosomes. Proton magnetic resonance spectroscopy was used to estimate metabolite resonance intensities in the 2 affected subjects., Results: Sequence analysis of the Notch3 gene showed a new missense mutation CGC-->TGC in codon 332 of exon 6, resulting in the replacement of an arginine residue with a cysteine. This mutation was never observed in the 7 unaffected members of the family and the 200 control chromosomes examined. Proton magnetic resonance spectroscopy showed a diffuse decrease in cerebral N-acetylaspartate, indicating the presence of widespread axonal damage., Conclusions: Our findings emphasize the role of direct DNA sequence analysis for the diagnosis of CADASIL. Moreover, the results of proton magnetic resonance spectroscopy suggest that widespread axonal damage may be an early finding of the 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.

Background: There 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)., Objective: To detect the occurrence of CVT in patients with CDH., Methods: The 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., Results: In 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., Conclusions: CVT, 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.

We investigated the parkin gene in 118 patients with typical Parkinson's disease (PD), i.e. in patients who had an onset of PD after the age of 45 years. The study group included 95 subjects with sporadic PD and 23 subjects from 18 families with autosomal recessive PD. No pathogenetic mutations in the parkin gene were detected either in familial or in sporadic patients. Our findings indicate that the parkin gene is not involved in the pathogenesis of classic late-onset PD.

The authors report a large pedigree from southern Italy with Charcot-Marie-Tooth disease type 2A (CMT2A). The clinical picture was uniform and characterized by distal muscular weakness and atrophy in the lower limbs, reduced or absent tendon reflexes mainly in the lower limbs, and mild sensory impairment in the feet. Significant linkage to the CMT2A locus on chromosome 1p35-p36 was detected. Based on informative recombination in affected individuals, the authors mapped the CMT2A gene between D1S160 and D1S170.

Background: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 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 ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.

The interhemispheric difference of the motor-cortical threshold (IDMT) was studied with focal magnetic transcranial stimulation (TCS) in ten patients with idiopathic generalized epilepsy (IGE) who also displayed versive or circling seizures (IGEvc). The data were compared with those obtained from two control groups; 13 patients with IGE without asymmetrical motor seizures, and 25 normal volunteer subjects. The IDMT, referred to as the percentage of maximum stimulator output, was assessed by focal TCS applied to the hand areas. Seven patients with IGEvc and only one patient with IGE had an interhemispheric motor threshold beyond the normal range. The IDMT in IGEvc patients was significantly higher compared to that of IGE patients and normal individuals. An interhemispheric imbalance of cortical excitability may explain lateralized ictal motor manifestations in patients with IGEvc.

Objective: To investigate the long-duration response (LDR) to L-dopa resulting from different regimens of L-dopa., Background: In clinical practice, L-dopa is usually administered without considering the LDR due to the drug. Moreover, it has not been established whether in early PD a multiple daily intake of small doses of L-dopa may induce a sustained LDR., Methods: Twenty-four patients with early PD underwent a double-blind, crossover trial, comparing three different 15-day treatment periods with L-dopa: treatment A (250 mg every 24 hours); treatment B (250 mg every 8 hours); and treatment C (125 mg every 8 hours). After completion, 20 patients underwent a subsequent open-label randomized trial with prolonged treatments (250 mg every 24 hours or 125 mg every 8 hours) up to 3 months. LDR was measured at the end of each treatment., Results: All patients achieved a sustained LDR after treatments A and B, whereas only 17% of patients reached a sustained LDR after treatment C. Overall, the LDRs resulting from treatments A and B had similar magnitude and were larger than the LDR deriving from treatment C. After 3 months of prolonged treatments, only three of 10 patients treated with 125 mg every 8 hours increased their LDR, whereas all 10 patients treated with 250 mg every 24 hours had a maximal and stable LDR., Conclusions: Sustained LDR to L-dopa is dependent on the amount of the single doses of the drug. A regimen scheduling small, divided doses during the day, as done in clinical practice, is a questionable therapy for the achievement of a sustained LDR.

We report on 2 brothers (aged 19 and 12 years) with Marinesco-Sjögren syndrome who also had very low serum vitamin E concentrations with an absence of postprandial chylomicrons. The molecular study ruled out ataxia with isolated vitamin E deficiency, abetalipoproteinemia, and hypobetalipoproteinemia. The electron microscopy of the intestinal mucosa was consistent with a chylomicron retention disease. We speculate that both chylomicron retention disease and Marinesco-Sjögren syndrome are related to defects in a gene crucial for the assembly or secretion of the chylomicron particles, leading to very low serum levels of vitamin E.

To further elucidate the inheritance pattern and range of phenotypic manifestations of benign familial temporal lobe epilepsy (FTLE), we report a large family recently identified in southern Italy. There were 8 patients (4 men), ranging in age from 31 to 68 years in three generations. One affected patient was deceased at the time of the study. Genealogical study strongly supported autosomal dominant inheritance with incomplete penetrance, as three unaffected individuals transmitted the disease. Clinical anticipation could not be assessed because of the ascertainment method. Male to male transmission occurred. Identifiable antecedents for seizures were present in only two patients, who had a simple febrile convulsion and a closed head trauma, respectively. Migraine was overrepresented in this family. Onset of seizures ranged from 17 to 52 years (mean: 27 years). All patients had weekly simple partial seizures suggestive of temporal origin with vegetative or experiential phenomena. Very rare partial complex seizures occurred in 6/7 patients. One had two generalized nocturnal seizures as well. Two had previously been misdiagnosed as having gastritis or panic attacks, and one had not been diagnosed. Interictal anteromesiotemporal spiking was seen in 5/7 patients, and occurred mostly during NREM sleep. Neurological examination, brain CT or MR scans were normal. Antiepileptic medication always controlled the seizures.

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 Parkinson's 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 B 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.

The apolipoprotein E (APOE) gene polymorphism has been studied in Parkinson's disease (PD) with conflicting results. Recently, a newly described functional polymorphism in the regulatory region of the APOE gene, (-491 A/T), has been associated with late-onset Alzheimer's disease. We studied the association between these two polymorphisms of the APOE gene with PD in a sample of 126 PD patients and in 119 controls from the same geographic background. Allelic and genotypic frequencies were not different between PD cases and population controls for either the APOE or -491 A/T polymorphism. The age at onset of the disease was not different according to the specific genotypes of the two polymorphisms of the APOE gene.

Purpose: To evaluate whether the inheritance of the apolipoprotein E (ApoE) epsilon4 allele is a risk factor for nonlesional temporal lobe epilepsy (TLE), and to determine whether the newly described -491 A/T ApoE polymorphism may independently affect the risk of nonlesional TLE., Methods: The study group consisted of 63 patients (35 women and 28 men; age at onset of epilepsy, 30.6 +/- 19.6 years; mean (+/-SD). All of them had received a diagnosis of nonlesional TLE after a detailed clinical, electroencephalographic, and brain magnetic resonance investigation. The ApoE polymorphisms were determined from blood samples by standard methods. The molecular study also was performed in 220 age- and sex-matched normal individuals., Results: There were no differences between TLE patients and controls in either allelic or genotypic frequencies of the ApoE and -491A/T polymorphisms. Moreover, no effect of ApoE or -491A/T polymorphisms was found on the age at onset and severity of epilepsy., Conclusions: The allelic and genotypic frequencies of ApoE polymorphisms in Italian patients with nonlesional TLE are comparable to control values, indicating that ApoE polymorphisms are not a significant genetic risk factor for the occurrence of nonlesional TLE.

Evidence suggests that isolated intracranial hypertension (iIH) is often associated with cerebral venous thrombosis (CVT). In eight patients referred to our Institution for iIH who were later shown to harbor CVT we have performed a comprehensive coagulation work-up, including genetic tests for inherited predisposition to thrombophilia, to clarify the etiology of sinus venous thrombosis. All subjects were women. All but one were overweight. There were high plasma concentrations of D dimer, thrombin-anti-thrombin complexes or prothrombin fragments 1 and 2, further supporting the neuroimaging diagnosis of CVT. Importantly, seven of eight cases had a raised level of plasminogen activator inhibitor 1, a well known inhibitor of fibrinolysis related to obesity. Tissue plasminogen activator levels were elevated accordingly. Factor V gene mutation was present in one subject, and the 20,210 prothrombin gene mutation was found in another individual. Three patients had elevated plasmatic levels of homocysteine. In conclusion, the present study provides solid evidence that impaired fibrinolysis probably related to overweight, acting in concert with other prothrombotic abnormalities, is involved in the pathogenesis of CVT presenting as iIH.

Objectives: The APOE gene polymorphism and the -491 A/T polymorphism in its regulatory region have been associated with an increased risk for developing Alzheimer's disease. We examined these polymorphisms in multiple sclerosis (MS) patients, to determine if a genetic predisposition may explain the risk for developing cognitive decline in MS., Material and Methods: Eighty-nine relapsing-remitting and secondary progressive MS patients underwent to a full neuropsychological battery as well as to determination of APOE and -491 A/T polymorphisms. Genetic analysis was also performed in 107 population controls., Results: The APOE polymorphism was not associated with the risk of cognitive impairment in MS patients. The AA genotype of the -491 A/T polymorphism in the APOE regulatory region was more frequent in cognitively impaired than in cognitively preserved MS subjects., Conclusion: The AA homozygous state of the -491 A/T polymorphism of the APOE regulatory region is associated with cognitive impairment in patients with MS.

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.

Objective: To determine the latency, magnitude, and duration of the long-duration response (LDR) to levodopa in PD in relationship to the administration of levodopa at different interdose intervals., Methods: In six patients with PD, two different 15-day treatment regimens were used in which the drug was administered with interdose intervals of 24 or 8 hours., Results: The LDR built up within a few days with either regimen, but a faster rate of administering levodopa shortened the latency to the appearance of a sustained LDR. Once a sustained response had been reached, the magnitude of the LDR showed a stable ceiling effect that was independent of the levodopa schedule. After discontinuation of treatment, the decay of the LDR was similar for both regimens., Conclusions: The system underlying the LDR to levodopa may be completely saturated when a sustained response has been fully developed. The intervals between doses of levodopa shorter than the interval effective to reach a sustained LDR should not be used in the clinical management of patients with PD because the antiparkinsonian benefit deriving from the LDR is already maximal and briefer intervals do not provide a greater benefit.

Objectives: To describe a patient with a clinical picture suggestive of idiopathic hyperekplexia (IH), who was later found to harbour a subtle brainstem vascular anomaly., Patient: A 35-year-old man, 4 years earlier, developed sudden jumping and falling in response to unexpected sensory stimuli., Results: Neurological examination was normal. Electromyography showed an excessively large and non-habituating motor startle response. There were no mutations of the alpha1 subunit of the inhibitory glycine receptor which cause hereditary hyperekplexia. Although all these findings were consistent with a diagnosis of IH, a blink reflex study showed an enhanced recovery curve suggestive of a brainstem lesion. A detailed MRI study revealed a subtle vascular anomaly involving the lower brainstem., Conclusion: This is the first report of sporadic hyperekplexia related to a brainstem vascular anomaly. Subtle damage to the brainstem should always be excluded in patients with sporadic hyperekplexia, regardless of the coexistence of additional clear-cut neurological symptoms.

Objectives: To describe the electroclinical features of the idiopathic generalized epilepsies (IGEs) with versive or circling seizures., Methods: Sixteen patients with versive or circling seizures and interictal electroclinical features of IGE were studied. Patients with insufficient clinical or imaging data, with a follow-up period less than 1 year or with partial seizures in addition to the versive or circling ones were excluded from the study. All patients underwent full interictal clinical and neurophysiological studies. The EEG patterns of 13 versive or circling seizures from 4 patients were also analyzed., Results: A specific IGE syndrome was recognized in 9 out of the 16 patients (56%). More specific, 1 patient had childhood absence epilepsy (CAE), 4 had juvenile absence epilepsy (JAE), and 4 had juvenile myoclonic epilepsy (JME). No specific IGE syndrome was recognizable in the remaining 7 patients (44%). These 7 patients had a juvenile epileptic syndrome (mean age at onset of seizures was 15.7 years) characterized by versive or circling seizures followed or not by generalized tonic-clonic fits. Three main EEG patterns were identified during versive or circling seizures: 1) generalized spike-and-wave discharges at 3-4 cps; 2) generalized polyspike-and-wave discharges at 1 to 2.5 cps beginning with generalized fast activity at 12-14 cps, and 3) generalized spike-and-wave discharges at 3-4 cps intermingled with fast activity at 12-14 cps. Most patients had good response to treatment on a single drug regimen (mainly valproic acid)., Conclusions: Versive or circling seizures may occur in the context of an IGE. Although many individuals share the features of different IGE syndromes including CAE, JAE and JME, a consistent number of patients, who show circling or versive seizures solely, remain without a specific syndromic diagnosis. When occurring in the context of IGE, circling or versive seizures do not worsen the prognosis.

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.

Patients with autosomal recessive spinal muscular atrophy (SMA) usually carry a homozygous deletion of exons 7 and 8 of the telomeric survival motor neuron (SMN(T)) gene, although an isolated deletion of SMN(T) exon 8 has never been found. We now report on 2 patients with the typical features of SMA types II and III, who carried a homozygous deletion of SMN(T) exon 8 but retained SMN(T) exon 7. Importantly, to exclude a sequence conversion event of telomeric exon 8, we amplified a fragment that spanned exons 7 and 8 of the SMN gene. The resulting 1,010-base pair (bp) fragments were subjected to nested polymerase chain reaction (PCR) of exon 7. The subsequent restriction analysis failed to show any products of telomeric exon 7, as the site for primer 541C1120 was lost in both alleles. These findings indicate a homozygous deletion of SMN(T) exon 8. Direct sequencing of the cloned 1,010-bp fragment further confirmed that these 2 SMA patients did not possess telomeric exon 8. The more severely affected child also showed a deletion of the neuronal apoptosis inhibitory protein (NAIP) gene. The present findings provide evidence that an isolated deletion of SMN(T) exon 8 is associated with the milder subtypes of SMA. Our data also demonstrate that the additional deletion of the NAIP gene exacerbates the severity of the disease.

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.

A 64-year-old woman, who had no personal or family history of neurologic diseases, had an 18-month history of epilepsia partialis continua (EPC) associated with a moderate intellectual deterioration and subtle extrapyramidal rigidity. There was no photosensitive response. A thorough laboratory investigation was unremarkable. A biopsy of the rectal mucosa revealed abundant fingerprint profiles diagnostic of Kufs' disease (KD). Our case expands the clinical picture of KD and suggests that such a diagnosis should be considered in adult-onset EPC.

We report on the clinical, neuropsychological, neurophysiological, computerized eye movement, magnetic resonance imaging (MRI) and molecular findings from 17 individuals affected with spinocerebellar ataxia type 2 (SCA2) belonging to three families. The average age at onset of the symptoms was 35.6, 11.9 (mean, SD) years. The mean age at onset of the symptoms in the parents was 44.8, 8.2 years, and in the offspring it was 28.7, 7.2 years. In 12 parent-child pairs, the mean anticipation was -15.75, 9.1 years (range -8.1 to -23.3 years, t = -4.9, P = < 0.002). The mutated SCA2 alleles ranged from 38 to 42 CAG repeats, while the normal alleles ranged from 22 to 24 repeats, with 97% of the alleles having 22 repeats. Small differences in the number of CAG repeats influenced the age at onset and rate of progression of the disease considerably. Indeed, patients presenting with their first symptom at an age of 35 years or later with a slower course of the disease harboured between 38 and 39 repeats. In contrast, patients carrying > or = 40 CAG repeats manifested the disease prior to 30 years of age and had a faster disease progression toward incapacity. The presenting symptom was always gait ataxia. Slow saccades occured from the beginning of the disease despite normal delay, accuracy and smooth pursuit eye movements. The neuropsychological study showed early and selective impairment of conceptual reasoning ability, as detected by the Wisconsin Card Sorting Test (WCST). It is noteworthy that a significant mutual relationship was observed between performance on the WCST and saccade velocity. All of these findings favour the hypothesis that the disease process of SCA2 in regions other than the cerebellum and brain stem affects severely and early those cortical structures involved in the control of both visually guided saccades and WCST performance.

Objectives: The use of latero-orbital (Lo) electrodes is a routine practice in any EEG laboratory to evaluate eye motion, but there are no data about their usefulness in revealing interictal epileptiform abnormalities., Methods: In 60 consecutive patients (27 men, 33 women, mean age 36.8 years, range 17-72) with complex partial seizures, we prospectively evaluated the utility of Lo electrodes in comparison with anterior temporal (AT) electrodes, for the detection of interictal epileptiform discharges (SW)., Results: No epileptiform abnormality was seen in 4/60 patients. Both AT and Lo electrodes were significantly superior to 10-20 electrodes for detection of both patients and foci. Indeed, the standard 10-20 system alone allowed the detection of only 39 independent epileptiform foci in 35/56 (63%) patients, while AT and Lo electrodes were necessary for detection of 23 epileptiform foci in the remaining 21/56 (37%) patients. Importantly, there was no statistically significant difference in detection between AT and Lo electrodes., Conclusions: Recordings from Lo electrodes are comparable to those from AT electrodes and are useful for localizing interictal temporal spiking activity. Lo electrodes may be substituted for basal electrodes in the day-to-day evaluation of patients with complex partial seizures.

Objective: To assess the efficacy of two different high doses of intravenous methylprednisolone (IVMP) for the treatment of relapses in MS., Background: IVMP 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.

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.

Hereditary motor and sensory neuropathy with focally folded myelin sheaths, or Charcot-Marie-Tooth disease neuropathy type 4B (CMT4B), is a distinct clinical and genetic entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies. We previously described a large pedigree with CMT4B and found evidence of linkage to chromosome 11q23. We now describe a second, unrelated family in which two individuals were affected with CMT4B. We exclude the disease locus segregating in this smaller pedigree from the 11q23 region as well as from most of the regions where other CMT loci have been mapped. We thus provide evidence for a second locus causing the CMT4B phenotype.

Periodic sharp wave complexes (PSWC) are sensitive and specific of Creutzfeldt-Jakob disease (CJD). Once they have emerged, PSWC may exceptionally disappear in the terminal stage of the disease, as a consequence of the flattening of scalp electroencephalogram (EEG). We document the disappearance of PSWC in serial EEG during the clinical course in two women (57 and 70 years of age) with pathologically proven CJD. Despite PSWC disappearance, diffuse theta-delta activity was still well recognizable. Moreover, external stimuli failed to trigger PSWC. The absence of PSWC in CJD might be due to the timing and frequency of EEG recordings. PSWC disappearance should not be interpretated as evidence against the diagnosis of CJD.

Childhood-onset partial epilepsy caused by focal cortical dysplastic lesions (FCDLs) is often severe. A few patients reported with a favorable outcome had a normal neuropsychological examination, and FCDLs were always localized around the opercular region, suggesting that extent and location of the lesion may account for the favorable outcome. We report two patients with extraopercular FCDLs, who had a spontaneous remission of their childhood-onset epilepsy, despite a severe neurological deficit. A 22-year-old girl (patient 1) and a 16-year-old boy (patient 2), began to have partial seizures at the age of 9 years and 1 year respectively. On neurological examination, patient 1 had left hemiparesis and patient 2 had low IQ. Interictal EEG recordings revealed repetitive epileptiform discharges involving the right temporo-parietal or frontal areas in patients 1 and 2 respectively. MRI study showed focal cortical thickening or abnormal gyration located over the right parietal and frontal region respectively in patients 1 and 2, but failed to evidence T2 prolongation in the white matter beneath the dysplastic cortex. Optimal antiepileptic regimen always stopped seizures. Their long-term course was favorable, with remission of the seizures and normalization of EEG recordings, even 4-5 years after medication withdrawal. In conclusion, FCDLs may cause epilepsy with a benign course even in patient with mental retardation or neurological abnormalities. This may be related to a morphologically milder dysplastic lesion than found in patients with FCDLs and severe epilepsy.

The long-duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.

Purpose: Epileptic negative myoclonus (ENM) has been increasingly recognized in different epilepsies, but the reasons for its appearance and prognosis remain uncertain. We report 3 patients who developed de novo, almost continuous ENM, triggered by antiepileptic drug (AED) tapering, that resolved with treatment., Methods: Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures recurred. The patient also began to report repetitive postural lapses of one or more limbs that interfered with eating or writing. At this time, each patient underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid, biceps, and triceps muscles and of the wrist extensor and flexor bilaterally., Results: In all patients, EEGs demonstrated almost continuous epileptiform discharges whose spatial distribution was similar to that observed before ENM appearance. Polygraphic recordings showed repetitive loss of postural EMG activity in one or more limbs, 100-400 ms in duration, which occurred in conjunction with the spike-waves. One milligram of clonazepam intravenously always terminated ENM status, which has not recurred in the ensuing 9-36 months., Conclusions: ENM may emerge as a new type of seizure due to tapering of AED therapy. This effect is possibly related to the great activation of epileptiform activity with consequent interference with cortical activity.

We present the first documented case of photic-induced epileptic negative myoclonus. A 17-year-old girl had experienced two generalized tonic-clonic seizures (GTCS) while watching television. The only EEG abnormality was a photoparoxysmal response (PPR), which was sometimes accompanied by loss of postural tone in both arms. Valproate was effective in abolishing photosensitivity. Negative myoclonus should be included among the ictal phenomena accompanying PPR.

We describe 10 patients from a large family with early onset motor and sensory neuropathy. Six were still living at the time of the study. In all cases, early motor milestones had been achieved. Mean age at onset of symptoms was 34 months; these included progressive distal and proximal muscle weakness of lower limbs. Pes equinovarus developed in all patients during childhood. Slight facial weakness was present in four patients, and one of them also had bilateral facial synkinesia. Intellectual function was normal in all cases. There was no evidence of thickened peripheral nerves. All three adult patients (mean age, 27 years) were seriously handicapped and wheelchair-bound. Death occurred in the fourth to fifth decade of life and the duration of the illness varied from 27 to 39 years. Motor nerve conduction velocities ranged from 15 to 17 m/sec in the upper limbs of the youngest patients, and were undetectable in the adult patients. Sensitive action potentials were almost always absent. In all patients, auditory evoked potentials showed abnormally delayed interpeak I-III latencies. The most prominent pathologic finding was a highly unusual myelin abnormality consisting of irregular redundant loops and folding of the myelin sheath. The genealogic study gave strong evidence of autosomal-recessive inheritance. The molecular analysis failed to demonstrate either duplication in the chromosome 17p11.2-12, point mutations in the four exons of the PMP-22 (17p11.2) and the six exons of the Po (1q21-q25) genes, or linkage to chromosome 8q13-21.1.

Vertical and horizontal saccadic (SEMv, SEMh) and smooth pursuit eye movements (SPEM) were recorded in 66 normal subjects of different ages using a computerized system. No difference was found in SEMh recordings for the right versus the left eye or for gaze direction. In contrast, SEMv recordings of upgaze vs. downgaze showed a significant difference in performance index (peak velocity) and delay. SEMh and SEMv performance index and delay were significantly slowed in elderly subjects, although accuracy was not affected. SPEM analysis also revealed a decrease in velocity in elderly people indicating diminished tracking ability as a result of the aging process. These data suggest that senescence may influence some SEM and SPEM parameters. We thus emphasize the usefulness of having reliable normative data corrected for age.

In previous studies, we demonstrated that the benzodiazepine (BZP) receptors of the visual system are functionally preserved in Creutzfeldt-Jakob disease (CJD). We hypothesized that such a functional preservation is not confined to the visual system. In a 74-year-old woman suffering from CJD, three consecutive recording sessions of somatosensory cortical evoked potentials (SEPs) by right median nerve stimulation were carried out: (a) basal condition, without any pharmacologic treatment; (b) 1 min after i.v. administration of 10 mg diazepam (DZP); (c) 2.5 min after i.v. administration of 3 mg FMZ, a high-affinity receptor benzodiazepine antagonist. DZP greatly decreased the amplitude of SEP early components, whereas flumazenil (FMZ) reversed such an effect. The results of this study, paralleling our previous findings on the visual system in CJD, demonstrated functional preservation of BZP receptors in the somatosensory pathways as well.

A 80-year-old man with cobalamin deficiency and no history of epilepsy developed a partial complex epileptic confusional status (ECS) unresponsive to acute i.v. diazepam. Brain CT scan and MRI investigation ruled out a focal cerebral lesion. Therapy with high doses (10,000 micrograms i.m. daily) of cobalamin alone was started, and the patient fully recovered in the following 72-hour. Control EEGs repeatedly performed days and weeks later showed progressive disappearance of the frontal interictal spiking, while the patient was on monotherapy with cobalamin (5,000 micrograms i.m. weekly). A month later the patient unfortunately discontinued replacement therapy and 13 weeks later he developed a fatal convulsive epileptic status. To our knowledge the association of ECS and cobalamin deficiency has not been previously reported.

We evaluated the effects of flumazenil (FMZ), a high-affinity benzodiazepine receptor antagonist, on flash-evoked visual potentials (FEPs) in a patient with Creutzfeldt-Jacob disease (CJD). FEPs were recorded in three different consecutive sessions: (1) basal condition, without any pharmacological treatment; (2) 3.5 min after i.v. administration of 5 mg FMZ; (3) 1 min after i.v. administration of 10 mg diazepam (DZP). FMZ provoked a marked increase in the amplitude as well as evident shortening of the latency of early FEP components. DZP reversed these effects. These results are in agreement with our previous findings of anatomical and functional integrity of the geniculo-striate pathways in human CJD and demonstrate functional integrity of benzodiazepine receptors in this visual system in CJD.

Two more patients with triphasic waves (TW) on their EEGs in the absence of metabolic disturbances are described. One patient had coma associated with cerebellar hematoma, the other had mild dementia associated with idiopathic calcifications of the basal ganglia and normal auditory brainstem responses, subcortical and cortical somatosensory evoked potentials. Neurologic examination failed to show asterixis in both patients. The literature on nonmetabolic causes of TW was also reviewed, and the clinical and anatomic reports of 10 patients have been analyzed: 7 patients had focal brainstem-diencephalic lesions (craniopharyngioma: 2 patients; thalamic gliomas: 3 patients; pontine stroke: 2 patients), and 3 patients suffered from diffuse subcortical or multifocal encephalopathies (Binswanger's encephalopathy: 1 patient; cerebral carcinomatosis: 1 patient; multifocal cerebral lymphoma: 1 patient). From the clinical point of view, patients with nonmetabolic diseases causing TW presented either disturbance of higher cerebral functions with no asterixis or sudden onset of coma. It is concluded that TW may result from focal brainstem/diencephalic lesions or from diffuse subcortical or multifocal encephalopathies in the absence of concomitant metabolic abnormalities. Nonmetabolic causes of TW should be suspected in patients presenting with neurologic disturbances not associated with asterixis.

Eight patients presenting with intermediate or terminal evolution of Creutzfeldt-Jakob disease (CJD) were investigated by means of evoked potentials. Fifteen age-matched healthy subjects served as controls. The 8 patients had well-recognizable but simplified flash evoked potentials (FEPs) consisting of P1 and N2 waves followed by a single late positive (P2) deflection. Enlarged FEPs were found in 2 of the 8 patients. The somatosensory central conduction time was normal in 3 of 5 patients, and it resulted in upper normal limits or was moderately slowed in 2 patients. No enlarged somatosensory scalp potentials were recorded. Cortical somatosensory responses were characterized by an unrecognizable (4 patients) or delayed (2 patients) N33 wave. Brainstem auditory evoked responses, recorded in 6 patients, were normal. In CJD very important functional impairment of the sensory cortical areas is associated with absent or mild dysfunction of the subcortical sensory pathways.