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Unlabelled: Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson's disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients., Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR)., Results: No G2019S mutations were found in both patients with sporadic PD and controls., Conclusions: Our results may be explained by the relatively small sample size.

Savanna plant communities change considerably across time and space. The processes driving savanna plant species diversity, coexistence and turnover along environmental gradients are still unclear. Understanding how species respond differently to varying environmental conditions during the seedling stage, a critical stage for plant population dynamics, is needed to explain the current composition of plant communities and to enable us to predict their responses to future environmental changes. Here we investigate whether seedling response to changes in resource availability, and to competition with grass, varied between two functional groups of African savanna trees: species with small leaves, spines and N-fixing associations (fine-leaved species), and species with broad leaves, no spines, and lacking N-fixing associations (broad-leaved species). We show that while tree species were strongly suppressed by grass, the effect of resource availability on seedling performance varied considerably between the two functional groups. Nutrient inputs increased stem length only of broad-leaved species and only under an even watering treatment. Low light conditions benefited mostly broad-leaved species' growth. Savannas are susceptible to ongoing global environment changes. Our results suggest that an increase in woody cover is only likely to occur in savannas if grass cover is strongly suppressed (e.g. by fire or overgrazing). However, if woody cover does increase, broad-leaved species will benefit most from the resulting shaded environments, potentially leading to an expansion of the distribution of these species. Eutrophication and changes in rainfall patterns may also affect the balance between fine- and broad-leaved species.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia and postural instability, and is associated with non-motor features, including sleep abnormalities. The high prevalence of excessive daytime sleepiness and snoring in PD patients has led to the suggestion that sleep disordered breathing (SDB) is more common in these individuals than in normal subjects. We aimed to review the literature on SDB prevalence and its clinical repercussions in PD. A PubMed search was performed to identify controlled studies, published from January 1990 through October 2012, which addressed the prevalence of SDB diagnosed by polysomnography in idiopathic PD. From the seven studies included, five reported similar or lower prevalence of SDB in patients when compared to healthy age-matched controls. Two studies reported less oxyhemoglobin desaturation during sleep among patients. These results did not support the idea that PD patients are at increased risk of SDB and indicate that they may not present significant hypoxemia. The prevalence of obstructive sleep apnea syndrome and the long-term outcomes of disordered breathing events during sleep have not been adequately studied in PD., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Changes in land use may lead to increased soil nutrient levels in many ecosystems (e.g. due to intensification of agricultural fertilizer use). Plant species differ widely in their response to differences in soil nutrients, and for savannas it is uncertain how this nutrient enrichment will affect plant community dynamics. We set up a large controlled short-term experiment in a semi-arid savanna to test how water supply (even water supply vs. natural rainfall) and nutrient availability (no fertilisation vs. fertilisation) affects seedlings' above-ground biomass production and leaf-nutrient concentrations (N, P and K) of broad-leafed and fine-leafed tree species. Contrary to expectations, neither changes in water supply nor changes in soil nutrient level affected biomass production of the studied species. By contrast, leaf-nutrient concentration did change significantly. Under regular water supply, soil nutrient addition increased the leaf phosphorus concentration of both fine-leafed and broad-leafed species. However, under uneven water supply, leaf nitrogen and phosphorus concentration declined with soil nutrient supply, this effect being more accentuated in broad-leafed species. Leaf potassium concentration of broad-leafed species was lower when growing under constant water supply, especially when no NPK fertilizer was applied. We found that changes in environmental factors can affect leaf quality, indicating a potential interactive effect between land-use changes and environmental changes on savanna vegetation: under more uneven rainfall patterns within the growing season, leaf quality of tree seedlings for a number of species can change as a response to changes in nutrient levels, even if overall plant biomass does not change. Such changes might affect herbivore pressure on trees and thus savanna plant community dynamics. Although longer term experiments would be essential to test such potential effects of eutrophication via changes in leaf nutrient concentration, our findings provide important insights that can help guide management plans that aim to preserve savanna biodiversity.

The authors report a 44-year-old man with a history of attention deficit and hyperactivity disorder, obsessive compulsive behaviour, vocal tics, depression, and anxiety, in whom a compound heterozygous ATP7B mutation was found, associated with hypoceruloplasminemia, but without clinical or pathological manifestation of Wilson's disease (WD). Genetic testing revealed a compound heterozygous ATP7B mutation already described in WD, p.Met645Arg (C1934TG/c.51+4A→T). Hypoceruloplasminaemia was detected but no clinical manifestations (hepatic or central nervous system) of WD were present. The authors conclude that patients can carry a heterozygous mutation of the ATP7B gene that is associated with hypoceruloplasminaemia and display no overt clinical hepatic and/or central nervous system manifestations of WD., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Few studies have described physical therapy approaches to provide functional independence and reduce pain in individuals with dystonia. This report describes the physical therapy treatment of a 46-year-old woman diagnosed with idiopathic segmental axial dystonia. For two years, the patient was treated with kinesiotherapy (active and resisted movements and stretching of neck and trunk muscles), abdominal taping (kinesiotaping techniques), functional training, and sensory tricks. She was assessed with parts I, II and III of Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-I, TWSTRS-II and TWSTRS-III), Berg Balance Scale (BBS), Six-Minute Walk Test (6-MWT), and the motor domain of Functional Independence Measure (FIM-motor) before and after the two-year treatment and after the one year follow-up. Postural control and symmetry improved (TWSTRS-I: from 30 to 18), functional independence increased (TWSTRS-II: from 27 to 15; BBS: from 36 to 46; 6-MWT: from 0 to 480 meters (m); FIM-motor: from 59 to 81), and the pain diminished (TWSTRS-III: from 12 to 5). The functional improvement was retained after one year (TWSTRS-I: 14/35; TWRTRS-II: 12/30; TWRTRS-III: 5/20; BBS: 48/56; 6-MWT: 450 m; FIM-motor: 81/91). This program showed efficacy on providing a better control of the dystonic muscles and thus the doses of botulinum toxin needed to treat them could be reduced. Outcomes support the therapeutic strategies used to deal with this type of dystonia.

Objectives: To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson's disease., Methods: In a prospective study, 33 consecutive men (mean age 59.2 ± 7.0 years) with Parkinson's disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson's Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated., Results: Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4 ± 7.5 to 11.1 ± 6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8 ± 1.1 to 1.0 ± 1.0 (p<0.001) and the maximum urinary flow varied from 9.3 ± 4.4 to 11.2 ± 4.6 ml/s (p=0.025). The severity of neurological impairment was the only predictor of the clinical response. Additionally, patients with a Unified Parkinson's Disease Rating Scale score lower than 70 had a significantly higher chance of clinical improvement with doxazosin treatment than those with higher Unified Parkinson's Disease Rating Scale scores did (RR=3.10, 95% CI=[1.15 to 5.37], p=0.011)., Conclusions: Doxazosin resulted in the improvement of lower urinary tract symptoms and the maximum flow rate and was well tolerated in men with Parkinson's disease. The response to treatment is dependent on the severity of neurological disability.

Background: It is still unclear whether dopamine (DA) levels correlate with Parkinson's disease (PD) severity or play a role in the mechanisms of high-frequency stimulation (HFS)., Methods: We have used microdialysis to record pallidal DA in 5 patients with PD undergoing microelectrode-guided pallidotomy., Results: We found that patients with more severe disease and, consequently, lower pallidal DA did poorly after pallidal lesions. In the operating room, 4 of 5 patients had a significant increase in DA levels during HFS (600%, on average). To test the hypothesis that DA was important for the effects of stimulation, we correlated the amelioration in rigidity observed in the operating room with pallidal DA release. Though rigidity was 56% better during stimulation, no correlation was found between such an improvement and DA release., Conclusions: These findings suggest that additional mechanisms not directly dependent on pallidal DA release may be involved in the clinical effects of HFS of the globus pallidus internus., (© 2013 Movement Disorder Society.)

Autosomal recessive, early-onset Parkinsonism is clinically and genetically heterogeneous. Here, we report the identification, by homozygosity mapping and exome sequencing, of a SYNJ1 homozygous mutation (p.Arg258Gln) segregating with disease in an Italian consanguineous family with Parkinsonism, dystonia, and cognitive deterioration. Response to levodopa was poor, and limited by side effects. Neuroimaging revealed brain atrophy, nigrostriatal dopaminergic defects, and cerebral hypometabolism. SYNJ1 encodes synaptojanin 1, a phosphoinositide phosphatase protein with essential roles in the postendocytic recycling of synaptic vesicles. The mutation is absent in variation databases and in ethnically matched controls, is damaging according to all prediction programs, and replaces an amino acid that is extremely conserved in the synaptojanin 1 homologues and in SAC1-like domains of other proteins. Sequencing the SYNJ1 ORF in unrelated patients revealed another heterozygous mutation (p.Ser1422Arg), predicted as damaging, in a patient who also carries a heterozygous PINK1 truncating mutation. The SYNJ1 gene is a compelling candidate for Parkinsonism; mutations in the functionally linked protein auxilin cause a similar early-onset phenotype, and other findings implicate endosomal dysfunctions in the pathogenesis. Our data delineate a novel form of human Mendelian Parkinsonism, and provide further evidence for abnormal synaptic vesicle recycling as a central theme in the pathogenesis., (© 2013 WILEY PERIODICALS, INC.)

Objective: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil., Methods: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed., Results: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time., Conclusion: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

Objectives: To evaluate the cognitive performance of a group of patients with Wilson's disease (WD) and to correlate the cognitive findings with changes in magnetic resonance imaging (MRI)., Methods: All patients with WD consecutively attended in a Movement Disorders Clinic between September 2006 and October 2007 were invited to participate in the study, together with a group of matched healthy controls. Patients and controls were submitted to comprehensive neuropsychological assessment. MRI was performed in all patients, and abnormalities (high-intensity signal, low-intensity signal and atrophy) were semi-quantitatively rated. Performance of patients and controls in each cognitive test was compared, and correlations between cognitive scores and MRI changes were investigated within the patients' group., Results: Twenty patients with WD (11 men) and 20 controls (nine men) were evaluated. Mean age in the WD and control groups was 30.05 ± 7.25 and 32.15 ± 5.37 years, respectively. Mean schooling years were 11.15 ± 3.73 among WD cases and 10.08 ± 2.62 among controls. Patients with WD performed significantly worse than controls in the Mini-Mental State Examination, Dementia Rating Scale, phonemic verbal fluency (FAS), verb generation, digit span forward, Stroop test, Frontal Assessment Battery and in the Brief Cognitive Screening Battery. A significant correlation emerged between global cognitive impairment and MRI scale (r = 0.535), being higher for high-intensity signal plus atrophy (r = 0.718)., Conclusion: Patients with WD presented cognitive impairment, especially in executive functions, with good correlation between cognitive abnormalities and MRI changes., (© 2012 John Wiley & Sons A/S.)

Objective: This study investigated whether educational status influenced how people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the Trail Making Test (TMT) and on the Berg Balance Scale (BBS)., Background: Recent studies have shown that educational status may influence cognitive and motor test performance., Methods: We gave the TMT and the BBS to assess executive function and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and 3) and 30 healthy elderly people. Participants reported their number of years of formal education. We divided each group of participants by educational status: low (4 to 10 years of education) or high (≥11 years)., Results: In both the PD (P=0.018) and control (P=0.003) groups, participants with low educational status performed worse on the TMT Part B than did those with high educational status. Within the PD group, the less-educated participants scored worse on the BBS than did the more educated (P<0.001); this difference was not significant between the more- and less-educated controls (P=0.976)., Conclusions: Whether or not they had PD, less-educated people performed worse than more-educated people on the TMT Part B. Educational status affected executive function, but PD status did not. Among individuals with PD, educational status influenced functional balance.

The main clinical manifestations of the spinocerebellar ataxias (SCAs) result from the involvement of the cerebellum and its connections. Cerebellar activity has been consistently observed in functional imaging studies of olfaction, but the anatomical pathways responsible for this connection have not yet been elucidated. Previous studies have demonstrated olfactory deficit in SCA2, Friedreich's ataxia and in small groups of ataxia of diverse aetiology. The authors used a validated version of the 16-item smell identification test from Sniffin' Sticks (SS-16) was used to evaluate 37 patients with genetically determined autosomal dominant ataxia, and 31 with familial ataxia of unknown genetic basis. This data was also compared with results in 106 Parkinson's disease patients and 218 healthy controls. The SS-16 score was significantly lower in ataxia than in the control group (p<0.001, 95% CI for β=0.55 to 1.90) and significantly higher in ataxia than in Parkinson's disease (p<0.001, 95% CI for β=-4.58 to -3.00) when adjusted for age (p=0.001, 95% CI for β=-0.05 to -0.01), gender (p=0.19) and history of tobacco use (p=0.41). When adjusted for general cognitive function, no significant difference was found between the ataxia and control groups. This study confirms previous findings of mild hyposmia in ataxia, and further suggests this may be due to general cognitive deficits rather than specific olfactory problems.

Botulinum toxin (BTX) is the best therapeutic option inpatients with cervical dystonia (CD), but physical therapy (PT) can be added to the treatment to achieve better results. Forty of our 70 patients with CD were en-rolled in a controlled open study. Subjects were divided into two groups: G1 (intervention group comprising patients receiving BTX and PT) and G2 (control group comprising patients receiving BTX only). Both groups were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the 36-Item Short-Form Health Survey (SF-36). On the TWSTRS, significant improvements in disease severity were seen in G1 and G2 but significant improvements on the pain and disability subscales were seen only in G1 patients.There was a significant difference only on the pain sub-scale between G2 and G1 following treatment. An analysis of the physical aspects of SF-36 showed significant improvement in G1 on three subscales. An intergroup difference was also seen on two subscales.Regarding emotional aspects, G1 showed a significant improvement on three subscales. A significant difference on two subscales was also seen between G2 and G1 following treatment. BTX plus PT treatment achieved symptom relief in patients with CD and improved their quality of life.

Language alterations in Huntington's disease (HD) are reported, but their nature and correlation with other cognitive impairments are still under investigation. This study aimed to characterize the language disturbances in HD and to correlate them to motor and cognitive aspects of the disease. We studied 23 HD patients and 23 controls, matched for age and schooling, using the Boston Diagnostic Aphasia Examination, Boston Naming Test, the Token Test, Animal fluency, Action fluency, FAS-COWA, the Symbol Digit Modalities Test, the Stroop Test and the Hooper Visual Organization Test (HVOT). HD patients performed poorer in verbal fluency (p<0.0001), oral comprehension (p<0.0001), repetition (p<0.0001), oral agility (p<0.0001), reading comprehension (p=0.034) and narrative writing (p<0.0001). There was a moderate correlation between the Expressive Component and Language Competency Indexes and the HVOT (r=0.519, p=0.011 and r=0.450, p=0.031, respectively). Language alterations in HD seem to reflect a derangement in both frontostriatal and frontotemporal regions.

Background: Urinary copper excretion higher than 100 μg/24 h is useful for diagnosing Wilson's disease. d-Penicillamine challenge test may produce higher levels than 1400 μg/24 h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering d-penicillamine to the parents of Wilson's disease patients., Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1g d-penicillamine., Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8×27.8 mg%; 71.4×88.0 μg%; p ≤ 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2×18.7 μg/24 h, p=0.01), but did not differ between the genders after d-penicillamine (521.7×525.3, range 31.6-1085.1 μg/24h, p=0.8)., Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after d-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after d-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Transcranial sonography has become a useful tool in the differential diagnosis of parkinsonian syndromes. This is a non-invasive, low cost procedure. The main finding on transcranial sonography in patients with idiopathic Parkinson's disease is an increased echogenicity of the mesencephalic substantia nigra region. This hyperechogenicity is present in more than 90% of cases, and reflects a dysfunction in the dopaminergic nigrostriatal pathway. This study discussed how the hyperechogenicity of the substantia nigra may facilitate the differential diagnosis of parkinsonian syndromes.

Objective: The purpose of this study was to evaluate quality of life (QoL) in a Brazilian population of individuals with cervical dystonia (CD) without effect of botulinum toxin (BTx) or with only residual effect of BTx, and identify possible physical and social aspects that affect their QoL., Method: Sixty five out of sixty seven consecutive patients with CD were assessed with two instruments: Short-form Health Survey with 36 questions (SF-36) and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)., Results: Severity of CD (TWSTRS) correlated moderately with two SF-36 subscale: role-physical (r= -0.42) and body pain (r= -0.43). Women also scored worse in two subscale of SF-36: vitality (p<0.05) and mental-health (p<0.005)., Conclusion: Severity of CD and gender (female) were the main factors related to a worse QoL perception. These findings may help health professionals to predict which characteristics could lead to worse QoL, and therefore, better target their interventions to lessen the burden caused by CD.

The authors present a historical review of the seminal clinical contribution of Professor Américo Negrette, a Venezuelan neurologist, to the evolution of scientific knowledge about Huntington's disease.

Objective: To evaluate the initial results of a surgical team in the hormonal control of secreting pituitary adenomas., Materials and Methods: In five years 51 functioning adenomas were operated (31 GH-secreting, 14 ACTH-secreting, 5 PRL-secreting and 1 TSH-secreting). Hormonal control was defined as GH < 2,5 ng/mL, normal free-urinary cortisol, lower prolactin and normal T3 and FT4., Results: Control rates were 36% in acromegaly, and 57% in Cushing's disease. Two prolactinomas normalized prolactin levels. Thyroid hormone levels were normalized in the TSH-secreting adenoma. Control of hypercortisolism was positively correlated with years of experience (p = 0.01)., Conclusion: Our results, although restricted to the beginning of our experience, lie below the reported range of other surgical series with much longer experience. During these years, there was a significant improvement in initial post surgery urinary cortisol levels in Cushing's disease as a function of surgical experience.

The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus. The spatial distribution and organization of axonal projections from each of these four terminal fields were analyzed and compared systematically with the anterograde pathway tracer PHAL in rats where the terminal fields had been labeled with intravitreal injections of a different anterograde pathway tracer, CTb. First, the well-known projections of two medial retinohypothalamic tract targets (the ventrolateral suprachiasmatic nucleus and perisuprachiasmatic region) were confirmed and extended. They share qualitatively similar projections to a well-known set of brain regions thought to control circadian rhythms. Second, the projections of a third medial tract target, the ventromedial part of the anterior hypothalamic nucleus, were analyzed for the first time and shown to resemble qualitatively those from the suprachiasmatic nucleus and perisuprachiasmatic region. And third, projections from the major lateral retinohypothalamic tract target were analyzed for the first time and shown to be quite different from those associated with medial tract targets. This target is a distinct core part of the ventral zone of the anterior group of the lateral hypothalamic area that lies just dorsal to the caudal two-thirds of the supraoptic nucleus. Its axonal projections are to neural networks that control a range of specific goal-oriented behaviors (especially drinking, reproductive, and defensive) along with adaptively appropriate and complementary visceral responses and adjustments to behavioral state., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Cervical dystonia (CD) is a prevalent and incapacitating movement disorder which needs a thorough clinical evaluation of every patient to better tailor treatment strategies. In Brazil, there are no validated CD scales that measure the burden of dystonia. The aim of our study was to translate and adapt the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) to Brazilian Portuguese. After translation and back-translation according to international methods, a pre-test was carried out with 30 patients. Patients under 8 years of formal schooling had severe difficulty in understanding the whole scale. The scale went through a remodeling process, without loss of its conceptual and semantic properties. The new scale was tested in 15 patients, with good understanding scores. We are now in the process of validation of the adapted scale.

Background: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period., Methods: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome., Results: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%., Conclusion: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.

LRRK2 mutations can cause familial and sporadic Parkinson's disease (PD) with Lewy-body pathology at post-mortem. Studies of olfaction in LRRK2 are sparse and incongruent. We applied a previously validated translation of the 16 item smell identification test from Sniffin' Sticks (SS-16) to 14 parkinsonian carriers of heterozygous G2019S LRRK2 mutation and compared with 106 PD patients and 118 healthy controls. The mean SS-16 score in LRRK2 was higher than in PD (p < 0.001, 95% CI for β = -4.7 to -1.7) and lower than in controls (p = 0.007, 95% CI for β = +0.6 to +3.6). In the LRRK2 group, subjects with low scores had significantly more dyskinesia. They also had younger age of onset, longer disease duration, and reported less frequently a family history of PD, but none of these other differences reached significance. Odor identification is diminished in LRRK2 parkinsonism but not to the same extent as in idiopathic PD., (© 2010 Movement Disorder Society.)

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.

Standardized olfactory tests are now available to quantitatively assess disorders of olfaction. A Brazilian-Portuguese version of the University of Pennsylvania Smell Identification Test (UPSIT) is currently being developed specifically for the Brazilian population. The most recent Brazilian-Portuguese version of the UPSIT (UPSIT-Br2) was administered to 88 Brazilian subjects who had no history of neurological or otorhinolaryngological disease. UPSIT-Br2 scores decreased with age, were lower in men than in women, and were lower in subjects with lower income. The degree to which the poorer performance of subjects with lower socio-economic status reflects lack of familiarity with test items is not known. Although this version of the UPSIT provides a sensitive and useful test of smell function for the Brazilian population, a revision of some test items is needed to achieve comparable norms to those found using the North American UPSIT in the United States.

Among nonmotor symptoms observed in Parkinson's disease (PD) dysfunction in the visual system, including hallucinations, has a significant impact in their quality of life. To further explore the visual system in PD patients we designed two fMRI experiments comparing 18 healthy volunteers with 16 PD patients without visual complaints in two visual fMRI paradigms: the flickering checkerboard task and a facial perception paradigm. PD patients displayed a decreased activity in the primary visual cortex (Broadmann area 17) bilaterally as compared to healthy volunteers during flickering checkerboard task and increased activity in fusiform gyrus (Broadmann area 37) during facial perception paradigm. Our findings confirm the notion that PD patients show significant changes in the visual cortex system even before the visual symptoms are clinically evident. Further studies are necessary to evaluate the contribution of these abnormalities to the development visual symptoms in PD.

This study had the objective to verify if the presence of wearing-off phenomenon in patients with Parkinson's disease (PD) could be better identified by the administration of the "Wearing-off Questionnaire Card" (QC). The participant patients were first evaluated by resident doctors in neurology and then invited to answer the QC for detection of motor and nonmotor wearing-off manifestations. Seventy and nine patients were enclosed in the study. The questionnaire revealed that 63 patients (80%) presented wearing-off, whereas the consultation by the resident doctors only identified 33 subjects (41%) with this phenomenon. The motor wearing-off manifestations were more frequent then the nonmotor. We conclude that the administration of the QC in patients with PD may be a useful tool for the diagnosis of wearing-off phenomena.

In order to evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment of hemifacial spasm (HFS), a retrospective analysis of patients treated at the Movement Disorders Unit of the Division of Neurology, Clinical Hospital, University of São Paulo, School of Medicine from 1993 to 2004 was made. A total of 808 injections with BTX were administered to 54 patients with HFS. The mean duration of improvement per application was 3.46 months and the mean rate of improvement using subjective judgement by the patient was of 83%. Adverse effects, mostly minor, were observed in 64.8% of patients at least once along the period of follow-up and the most frequent of them was orbicularis oris paralysis (38.8%). There was no decrement in response when compared the first and the last injection recorded.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a cause of movement disorders and cognitive decline which has probably been underdiagnosed, especially if its prevalence proves similar to those of progressive supranuclear palsy and amyotrophic lateral sclerosis. We report a case of a 74-year-old man who presented with action tremor, gait ataxia and forgetfulness. There was a family history of tremor and dementia, and one of the patient's grandsons was mentally deficient. Neuropsychological evaluation disclosed a frontal network syndrome. MRI showed hyperintensity of both middle cerebellar peduncles, a major diagnostic hallmark of FXTAS. Genetic testing revealed premutation of the FMR1 gene with an expanded (CGG) 90 repeat. The diagnosis of FXTAS is important for genetic counseling because the daughters of the affected individuals are at high risk of having offspring with fragile X syndrome. Tremors and cognitive decline should raise the diagnostic hypothesis of FXTAS, which MRI may subsequently reinforce, while the detection of the FMR1 premutation can confirm the condition., Competing Interests: Disclosure: The authors report no conflicts of interest.

Cervical dystonia (CD) is a complex disorder but the response to long-term botulinum toxin (BTX) therapy is satisfactory in most cases. Bad results are attributed by some authors to changes in muscle activation. Our purpose is to verify if the change in head deviation affects negatively the response to BTX therapy in a long-term follow-up, and if there are any differences in clinical parameters of these patients in comparison to those with stable pattern. From a total of 88 patients evaluated at the Movement Disorders Clinics of Hospital das Clinicas - University of São Paulo School of Medicine between January 1993 and December 2005, 67 were included. In 24 (35.8%) change in pattern of CD was observed, in a medium follow-up period of 80 months. The time between onset of dystonia and the diagnosis of pattern change was 9.7 years. Comparing with patients with no changes in CD pattern, there were no significant statistical differences. Improvement of symptoms around 60% was reported in both groups. In conclusion, the change in head deviation observed in CD was not responsible for bad response to therapy with BTX and there were no significant differences between both groups.

Mutations in the Grb10-interacting GYF protein 2 (GIGYF2) gene, within the PARK11 locus, have been nominated as a cause of Parkinson's disease in Italian and French populations. By sequencing the whole GIGYF2 coding region in forty-six probands (thirty-seven Italians) with familial Parkinson's disease compatible with an autosomal dominant inheritance, we identified no mutations. Our data add to a growing body of evidence suggesting that GIGYF2 mutations are not a frequent cause of PD.

Introduction: Brain magnetic resonance imaging (MRI) studies on Wilson's disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce., Methods: Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: D: -penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P., Results: MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis., Conclusions: From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.

Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.

The authors provide an historical review of restless legs syndrome, emphasizing the contribution of Professor Karl-Axel Ekbom, the Swedish neurologist who made the first detailed clinical description of this disease.

Aims: We assessed the lower urinary tract symptoms (LUTS) of patients with Parkinson's disease (PD) and their association with different clinical parameters., Methods: We prospectively evaluated 110 patients (84 men), with a mean age of 61.8 +/- 9.6 years. Mean duration of the disease was 12.3 +/- 7.2 years. Neurological impairment was assessed by the Hoehn-Yahr and the Unified Parkinson Disease Rating scales. LUTS were assessed by the International Continence Society questionnaire. We evaluated the impact of age, PD duration, neurological impairment, gender, and use of anti-Parkinsonian drugs on the voiding function., Results: On multivariate analysis, voiding dysfunction increased with the neurological impairment, but not with patient's age or disease duration. Quality of life (QOL) was affected by the severity of LUTS, and the symptoms with the worst impact were frequency and nocturia. Sixty-three (57.2%) patients were symptomatic. They did not differ with the asymptomatic as to age and disease duration, but had more severe neurological impairment. No impact on LUTS was associated with the use of levodopa, anticholinergics, and dopamine receptor agonists. Men and women were similarly affected by urinary symptoms., Conclusions: The severity of the neurological disease is the only predictive factor for the occurrence of voiding dysfunction, which affects men and women alike., ((c) 2009 Wiley-Liss, Inc.)

Wilson's disease (WD) or hepatolenticular degeneration is a rare, genetic and systemic disease, caused by a deficit in the metabolism of copper, leading to its accumulation in different organs, mainly the liver, followed by the central nervous system, especially the basal ganglia. When symptoms begin between the second and third decades of life, approximately 50% of the patients show neurological symptoms. Although dystonia and dysarthria are the most common neurological signs, cognitive changes have been reported since the first cases were described in 1912. Memory change is one of the most common impairments, but other cognitive changes have been reported, including dementia in untreated cases. In this article we review the cognitive changes in WD patients and the occurrence of dementia., Competing Interests: Disclosure: The authors reports no conflicts of interest.

Smell identification tests may be of routine clinical value in the differential diagnosis of PD but are subject to cultural variation and have not been systematically evaluated in the Brazilian population. We have applied culturally adapted translations of the University of Pennsylvania 40-item smell identification test (UPSIT-40) and the 16-item identification test from Sniffin' Sticks (SS-16) to nondemented Brazilian PD patients and controls. Pearson's correlation coefficient between the test scores was 0.76 (95% CI 0.70-0.81, n = 204, P < 0.001). To calculate reliability measures for each test we used the diagnosis (either PD or control) as outcome variable for separate logistic regression analyses using the score in the UPSIT-40 or the SS-16 as a covariate. The SS-16 specificity was 89.0% with a sensitivity of 81.1% (106 PD and 118 controls). The UPSIT-40 specificity was 83.5% and its sensitivity 82.1% (95 PD and 109 controls). Regression curves were used to associate an individual's smell test score with the probability of belonging to the PD, as opposed to the control group. Our data provide support for the use of the UPSIT-40 and SS-16 to help distinguish early PD from controls., ((c) 2008 Movement Disorder Society.)

We review the history of Tourette syndrome, emphasizing the contribution of Jean-Martin Charcot.