Genetic assessment of familial and early-onset Parkinson's disease in a Greek population.

BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. METHODS: A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.

Levetiracetam for the management of levodopa-induced dyskinesias in Parkinson's disease.

The efficacy and safety of levetiracetam (LEV), administered for management of levodopa-induced dyskinesias (LID) in Parkinson's disease (PD), was examined using a multicenter, double-blind, placebo-controlled, parallel groups, crossover trial. Because of having a period effect, data after crossover point was excluded from analysis. Levodopa-treated PD participants with LID (n = 38) received LEV 500 mg/day, were assessed, titrated to 1,000 mg/day and reassessed, before and after crossover. The placebo group followed the same routine. Primary efficacy was defined from percent change in "On with LID" time from patient diaries. Secondary efficacy assessment used "On without LID," "Off" time, unified PD rating scale (UPDRS), clinical global impression (CGI), and Goetz dyskinesia scale after levodopa challenge. Safety measures were also performed. On with LID time decreased 37 minutes (95% confidence interval [CI] 0.59, 7.15; P = 0.02) at 500 mg/day, 7.85% 75 minutes (95% CI 3.3, 12.4; P = 0.002) at 1,000 mg/day. On without LID time increased by 46 minutes (95% CI -1.55, -0.03; P = 0.04) at 500 mg/day and 55 minutes (95% CI -10.39, -1.14; P = 0.018) at 1,000 mg/day. UPDRS 32 showed decreased dyskinesia duration mean change 0.35 (95% CI 0.09, 0.5; P = 0.009) at 1,000 mg/day. CGI showed LID decreased by 0.7 (95% CI 0.21, 1.18; P = 0.006) at 1,000 mg/day. Patient diaries and UPDRS show no increase in Off time. This exploratory trial provides evidence that LEV in 1,000 mg/day, slowly titrated, could be useful in improving LID as was assessed with patient diaries, UPDRS, and CGI scales, safely, with minimal side effects.

Octreotide: a therapeutic option for idiopathic intracranial hypertension.

PURPOSE: To study the effects of octreotide, a somatostatin analogue, in patients with Idiopathic Intracranial Hypertension (IIH). METHODS: We performed a prospective, open-label study of the effect of Octreotide on 26 patients with symptoms and signs of IIH, investigated by brain MRI and lumbar puncture. Octreotide was administered subcutaneously, at an initial dose of 0.3 mg/day; and was gradually increased until headache was relieved (upper-dose limit: 1 mg/day). Treatment with octreotide at 1 mg/day was administered for a maximum of six to eight months and afterwards the dose was gradually tapered. Patients were followed prospectively every month for three years. CSF opening pressure was measured before the treatment was started and again in the first follow-up examination, on month one. In all follow-up visits the presence of papilledema was evaluated by fundoscopy; visual fields and visual acuity were also examined. RESULTS: Overall 24/26 patients improved significantly (92%). Headache was relieved within days (1-10, median 7 days). Papilledema subsided in all 24 patients, in up to two months (35 to 68, median 45 days). Visual disturbances, initially presenting in 20 of our patients, improved in 18 (90%). The mean reduction in CSF pressure after treatment was 20.72A+/-10.7 cmH2O (range 2 to 48). Patients were followed for three years after cessation of treatment. No recurrence of papilledema, or any other symptoms, has been observed. CONCLUSIONS: Octreotide resulted in a significant and sustained improvement of IIH in our patients. These results suggest that it may be an effective alternative to existing treatments for IIH.

Technical aspects and considerations of deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) represents one of the more recent advancements in Neurosurgery. Even though its most successful applications evolved in movement disorders (MDs), indications now include pain, psychiatric disorders, epilepsy, cluster headaches and Tourette syndrome. As this type of surgery gains popularity and the indications for DBS surgery increase, so it will certainly increase the number of neurosurgeons who will use this neuromodulatory technique. A detailed description of the technical aspects of the DBS procedure, as it is performed in our department, is presented. In our opinion, our method is a good combination of all the well-established necessary techniques in a cost-effective way. This technical article may be helpful to neurosurgeons considering to start performing this type of surgery. It could also prompt others who perform DBS regularly to express their views, and hence, lead to further refinement of this demanding procedure.

Methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin as a cause of acute osteomyelitis in children.

Staphylococcus aureus was identified as the cause of acute childhood osteomyelitis in 19 patients. A single clone of community-acquired methicillin-resistant S. aureus (MRSA) carrying the type IV mecA staphylococcal cassette chromosome and the Panton-Valentine leukocidin (PVL) genes was isolated from five patients. Among the remaining 14 patients, two methicillin-sensitive S. aureus (MSSA) isolates were PVL-positive. The maximal erythrocyte sedimentation rate and C-reactive protein values, and the time required for normalisation, were significantly different in patients with PVL-positive strains (MRSA and MSSA), suggesting that the production of PVL is an important factor that contributes to the course of the disease.

Functional magnetic resonance imaging of visual object construction and shape discrimination : relations among task, hemispheric lateralization, and gender.

We studied the brain activation patterns in two visual image processing tasks requiring judgements on object construction (FIT task) or object sameness (SAME task). Eight right-handed healthy human subjects (four women and four men) performed the two tasks in a randomized block design while 5-mm, multislice functional images of the whole brain were acquired using a 4-tesla system using blood oxygenation dependent (BOLD) activation. Pairs of objects were picked randomly from a set of 25 oriented fragments of a square and presented to the subjects approximately every 5 sec. In the FIT task, subjects had to indicate, by pushing one of two buttons, whether the two fragments could match to form a perfect square, whereas in the SAME task they had to decide whether they were the same or not. In a control task, preceding and following each of the two tasks above, a single square was presented at the same rate and subjects pushed any of the two keys at random. Functional activation maps were constructed based on a combination of conservative criteria. The areas with activated pixels were identified using Talairach coordinates and anatomical landmarks, and the number of activated pixels was determined for each area. Altogether, 379 pixels were activated. The counts of activated pixels did not differ significantly between the two tasks or between the two genders. However, there were significantly more activated pixels in the left (n = 218) than the right side of the brain (n = 161). Of the 379 activated pixels, 371 were located in the cerebral cortex. The Talairach coordinates of these pixels were analyzed with respect to their overall distribution in the two tasks. These distributions differed significantly between the two tasks. With respect to individual dimensions, the two tasks differed significantly in the anterior--posterior and superior--inferior distributions but not in the left--right (including mediolateral, within the left or right side) distribution. Specifically, the FIT distribution was, overall, more anterior and inferior than that of the SAME task. A detailed analysis of the counts and spatial distributions of activated pixels was carried out for 15 brain areas (all in the cerebral cortex) in which a consistent activation (in > or = 3 subjects) was observed (n = 323 activated pixels). We found the following. Except for the inferior temporal gyrus, which was activated exclusively in the FIT task, all other areas showed activation in both tasks but to different extents. Based on the extent of activation, areas fell within two distinct groups (FIT or SAME) depending on which pixel count (i.e., FIT or SAME) was greater. The FIT group consisted of the following areas, in decreasing FIT/SAME order (brackets indicate ties): GTi, GTs, GC, GFi, GFd, [GTm, GF], GO. The SAME group consisted of the following areas, in decreasing SAME/FIT order : GOi, LPs, Sca, GPrC, GPoC, [GFs, GFm]. These results indicate that there are distributed, graded, and partially overlapping patterns of activation during performance of the two tasks. We attribute these overlapping patterns of activation to the engagement of partially shared processes. Activated pixels clustered to three types of clusters : FIT-only (111 pixels), SAME-only (97 pixels), and FIT + SAME (115 pixels). Pixels contained in FIT-only and SAME-only clusters were distributed approximately equally between the left and right hemispheres, whereas pixels in the SAME + FIT clusters were located mostly in the left hemisphere. With respect to gender, the left-right distribution of activated pixels was very similar in women and men for the SAME-only and FIT + SAME clusters but differed for the FIT-only case in which there was a prominent left side preponderance for women, in contrast to a right side preponderance for men. We conclude that (a) cortical mechanisms common for processing visual object construction and discrimination involve mostly the left hemisphere, (b) cortical mechanisms specific for these tasks engage both hemispheres, and (c) in object construction only, men engage predominantly the right hemisphere whereas women show a left-hemisphere preponderance.

Acupuncture in headache: a critical review.

Twenty-seven clinical trials that evaluated the efficacy of acupuncture in the treat ment of primary headaches (migraine headache, tension-type headache, and mixed forms) were reviewed. In the majority of the trials (23 of the 27 trials), it was concluded that acupuncture offers benefits in the treatment of headaches. Conversely, the evaluation of physical forms of treatment, including acupuncture, has special difficulties, and certain parameters in the study design need consideration. Acupuncture methods need individualization, a carefully selected placebo ("minimal acupuncture" seems to be best), and the crossover design must have adequate time between the two treatment periods. Clinical trials that evaluate acupuncture frequently are characterized by several inadequacies (including some from these evaluating headaches), but it seems that additional clinical research is necessary to confirm its efficacy and to clarify its indications.

Auditory event related potentials in patients with epilepsy on sodium valproate monotherapy.

OBJECTIVES: The effects of antiepileptic drugs on event related potentials (ERPs) have been studied, but with contradictory results. In this study we examine the effect of sodium valproate (VPA) on ERPs in patients with epilepsy. MATERIALS AND METHODS: Auditory event related potentials were recorded in 40 patients with idiopathic generalized epilepsy, 20 on monotherapy with sodium valproate (VPA), 20 on monotherapy with carbamazepine and 20 age and sex matched controls. All subjects performed a simple auditory discrimination task in which a target tone was presented on 20% of the trials. RESULTS: Mean P3 latency of the VPA group was significantly prolonged but not in carbamazepine group and healthy controls. CONCLUSION: We conclude that VPA monotherapy has an effect on P300 latency in patients with epilepsy. This difference might be attributed to effects of treatment with VPA and may clarify in the future the mechanism of P300.

Box-Jenkins intervention analysis of functional magnetic resonance imaging data.

Data obtained in functional magnetic resonance imaging (fMRI) typically form a time series of MRI signal collected over a period of time at constant intervals. These data are potentially autocorrelated and may contain time trends. Therefore, any assessment of significant changes in the MRI signal over a certain period of time requires the use of specific statistical techniques. For that purpose we used the Box-Jenkins intervention time series analysis to determine brain activation during task performance. We found that for a substantial number of pixels there was significant autocorrelation and, occasionally, time trends. In these cases, use of the classical t-test would not be appropriate. In contrast, Box-Jenkins intervention analysis, by detrending the series and by explicitly taking into account the correlation structure, provides a more appropriate method to determine the presence of significant activation during the task period in fMRI data.

Mental rotation studied by functional magnetic resonance imaging at high field (4 tesla): performance and cortical activation.

We studied the performance and cortical activation patterns during a mental rotation task (Shepard & Metzler, 1971) using functional magnetic resonance imaging (fMlU) at high field (4 Tesla). Twenty-four human subjects were imaged (fMRI group), whereas six additional subjects performed the task without being imaged (control group). All subjects were shown pairs of perspective drawings of 31, objects and asked to judge whether they were the same or mirror images. The measures of performance examined included (1) the percentage of errors, (2) the speed of performance, calculated as the inverse of the average response time, and (3) the rate of rotation for those object pairs correctly identified as "same." We found the following: (1) Subjects in the fMRI group performed well outside and inside the magnet, and, in the latter case, before and during data acquisition. Moreover, performance over time improved in the same manner as in the control group. These findings indicate that exposure to high magnetic fields does not impair performance in mental rotation. (2) Functional activation data were analyzed from 16 subjects of the fMRI goup. Several cortical areas were activated during task performance. The relations between the measures of performance above and the magnitude of activation of specific cortical areas were investigated by anatomically demarcating these areas of interest and calculating a normalized activation for each one of them. (3) We used the multivariate technique of hierarchical tree modeling to determine functional clustering among areas of interest and performance measures. Two main branches were distinguished: One comprised areas in the right hemisphere and the extrastriate and superior parietal lobules bilaterally, whereas the other comprised areas of the left hemisphere and the frontal pole bilaterally; all three performance measures above clustered with the former branch. Specifically, performance outcome ("percentage of errors") clustered with the parieto-occipital subcluster, whereas both the speed of performance and the rate of mental rotation clustered with the right precentral gyms. We conclude that the mental rotation paradigm used involves the cooperative interaction of functional groups of cortical areas of which some are probably more specifically associated with performance, whereas others may serve a more general function within the task constraints.

EEG and topographic frequency analysis in migraine attack before and after sumatriptan infusion.

Electroencephalographic changes occurring in patients with migraine have received much attention. Although in migraineurs a number of studies have been done after nitroglycerin-induced attacks, there is no reported EEG study before and after nitroglycerin-induced sumatriptan-treated attacks. We, therefore, studied the EEG topographic frequency analysis in 19 symptom-free, otherwise healthy, unmedicated patients with common migraine and in 19 age- and sex-matched controls before nitroglycerin, at the time of maximum pain, and 30 minutes after sumatriptan. During headache attacks, an increase of slow rhythmic activity of the theta and delta range and a decrease of activity in the alpha and beta range were observed. These abnormalities disappeared 30 minutes after a sumatriptan injection. This suggests that common migraine is associated with disturbances of cortical electrogenesis and may provide insight into the causes of migraine and aid in the development of effective therapies.

Quantitative relations between parietal activation and performance in mental rotation.

The quantitative relationships between functional activation of the superior parietal lobule (SPL) and performance in the Shepard-Metzler mental rotation task were investigated in 16 human subjects using magnetic resonance (MR) imaging at high field (4 Tesla). Subjects were shown pairs of perspective drawings of three-dimensional objects and asked to judge whether they were the same or mirror images. Increased SPL activation was associated with a higher proportion of errors in performance. The increase in errors, and the concomitant increase in SPL activation, could be due to an increased difficulty in, and therefore increased demands for, information processing at several stages involved in making a decision, including encoding of the visual images shown, mentally rotating them, and judging whether they are the same or mirror images.