Refining initial diagnosis of Parkinson's disease after follow-up: A 4-year prospective clinical and magnetic resonance imaging study.

BACKGROUND: No prospective study of patients with Parkinson's disease (PD) has investigated the appearance of vertical gaze abnormalities, a feature suggestive of progressive supranuclear palsy (PSP). OBJECTIVE: To identify, within a cohort of patients with an initial diagnosis of PD, those who developed vertical gaze abnormalities during a 4-year follow-up, and to investigate the performance of new imaging biomarkers in predicting vertical gaze abnormalities. METHODS: A total of 110 patients initially classified as PD and 74 controls were enrolled. All patients underwent clinical assessment at baseline and every year up to the end of the follow-up. The pons/midbrain area ratio 2.0 and the Magnetic Resonance Parkinsonism Index 2.0 were calculated. RESULTS: After 4-year follow-up, 100 of 110 patients maintained the diagnosis of PD, whereas 10 PD patients (9.1%) developed vertical gaze abnormalities, suggesting an alternative diagnosis of PSP-parkinsonism. At baseline, the Magnetic Resonance Parkinsonism Index 2.0 was the most accurate biomarker in differentiating PD patients who developed vertical gaze abnormalities from those who maintained an initial diagnosis of PD. At the end of follow-up, both of these biomarkers accurately distinguished PSP-parkinsonism from PD. CONCLUSIONS: Our results demonstrate that a number of patients with an initial diagnosis of PD developed vertical gaze abnormalities during a 4-year follow-up, and the diagnosis was changed from PD to PSP-parkinsonism. In PD patients, baseline Magnetic Resonance Parkinsonism Index 2.0 showed the best performance in predicting the clinical evolution toward a PSP-parkinsonism phenotype, enabling PSP-parkinsonism patients to be identified at the earliest stage of the disease for promising disease-modifying therapies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The movement time analyser task investigated with functional near infrared spectroscopy: an ecologic approach for measuring hemodynamic response in the motor system.

AIMS: Movement time analyzer (MTA) is an objective instrument to evaluate the degree of motor impairment as well as to investigate the dopaminergic drug effect in Parkinson's disease patients. The aim of this study is to validate a new ecologic neuroimaging tool for quantifying MTA-related hemodynamic response of the cortical motor system by means of functional near-infrared spectroscopy (fNIRS). MATERIALS: 11 right-handed healthy volunteers (six male and five female, age range 27-64 years) were studied with fNIRS and functional magnetic resonance imaging (fMRI) while performing MTA task for each hand. RESULTS: MTA performance was better for the dominant hand and younger participants. Both fNIRS and fMRI analyses revealed MTA-related increase of haemoglobin levels in the primary motor and premotor cortices contralateral to the moving hand. This response progressively increased with aging. CONCLUSION: These findings supported the translation of fNIRS-based MTA behavioural tool in clinical practice.

Breadsticks Flavoured with Olives and Onions: One-Year Shelf Life.

In this work, we compared breadsticks (known as Treccine) flavoured with onions and olives and prepared with olive pomace oil (OPO) or with extra virgin olive oil (EVOO). The effect on one-year shelf life was also studied. The following physical, chemical and sensory analyses were conducted on the breadsticks: water activity, moisture content, colour, texture and sensory analysis (appearance, colour, flavour, taste, texture and overall acceptability). For the oil extracted from the Treccine, we determined acidity, peroxide value, spectrophotometric parameters, ABTS and DPPH assay on the hydrolitic fraction, DPPH on the lipid fraction, and fatty acids. We detected a progressive deterioration in the quality of breadsticks with a decrease in shelf life after 4-6 months in relation to each studied parameter. In the analysed breadsticks, water activity was 0.342 (OPO recipe) and 0.387 (EVOO recipe) after one-year storage; in the same storage period, the moisture content was 6.34 times (OPO) and 5.32 times (EVOO) greater. Appearance and colour were the only two sensory parameters which, after 12 months, remained above or equal to five stated as the minimum quality value. In the extracted oil, Free acidity increased from 0.35 to 0.56% (OPO) and from 0.71 to 0.98% (EVOO); Peroxide value ranged between 6.10 and 102.89 meq/kg oil (OPO) and between 4.41 and 20.91 meq/kg oil (EVOO). K232 was highest in OPO (2.43-3.70) and lowest in EVOO (1.76-2.92), K268 was 1.32-1.580 (OPO recipe) and 0.570-0.640 (EVOO recipe). Treccine prepared with extra virgin olive oil showed better biological properties and longer shelf life.

Effects of Shortening Replacement with Extra Virgin Olive Oil on the Physical-Chemical-Sensory Properties of Italian Cantuccini Biscuits.

Olive oil is recognised for its beneficial effects on human health, mainly due to it containing oleic acid (a monounsaturated fatty acid), whereas fats of animal origin or margarine, which are often used in recipes for biscuit production, contain mainly saturated fatty acids. The aim of this study was to evaluate the shelf-life and physicochemical properties of biscuits and of the fats contained in original recipe Italian Cantuccini biscuits (50% cow's butter and 50% margarine). Additionally, the sensory properties of the biscuits were evaluated, including their colour, appearance, taste, flavour, texture and overall acceptability. At the same time, the fat composition of the original recipe was also modified to contain 30% cow's butter and 70% extra virgin olive oil, in order to replace an aliquot of the saturated fatty acid content with unsaturated fatty acids, in particular with one monounsaturated fatty acid, oleic acid. Colour (CIELab), water activity, relative humidity, hardness and fracturability analyses were conducted on Cantuccini biscuits. Colour (CIELab), free acidity, spectrophotometric characteristics, DPPH assay and fatty acid methyl ester (FAMEs) analyses were conducted on the fat extracted from Cantuccini biscuits prepared from both the original and modified recipes.

Leber's hereditary optic neuropathy associated with a multiple-sclerosis-like picture in a man.

A 35-year-old young man displayed Leber's optic neuropathy (LHON) due to T14484C and multiple sclerosis (MS) phenotype that was dominated by symptoms and signs of spinal cord impairment. Magnetic resonance imaging (MRI) revealed demyelinating lesions extending from D6 to D11 in the spinal cord with gadolinium enhancement, while only three linear demyelinating lesions were seen on brain MRI. In the literature, a major involvement of the spinal cord was already reported in three of four male patients with the 14484 LHON mutation who developed MS, but the reasons of this peculiar association remain unknown, and further research in this area is needed.

Presenilin enhancer-2 gene: identification of a novel promoter mutation in a patient with early-onset familial Alzheimer's disease.

UNLABELLED: γ-Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid-ß (Aß) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer-2 gene (PEN-2) is a necessary component of the γ-Secretase complex. Recently, it has been shown that PEN-2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN-2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty-two subjects (FAD: 97; CONTROLS: 355) were recruited for this study. We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early-FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN-2 gene. Although the effective role of the PEN-2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role.

Magnetic Resonance Parkinsonism Index for evaluating disease progression rate in progressive supranuclear palsy: A longitudinal 2-year study.

INTRODUCTION: We investigated the disease progression rate in patients with progressive supranuclear palsy-Richardson syndrome (PSP-RS) and PSP-parkinsonism (PSP-P) in comparison with Parkinson disease (PD) patients, using MRPI (Magnetic Resonance Parkinsonism Index), and MRPI 2.0. METHODS: Fifteen PSP-RS patients (disease duration, y, mean ± SD: 2.5 ± 1.1), 16 PSP-P patients (disease duration, y, mean ± SD: 6.5 ± 3.2) and 19 PD patients (disease duration, y, mean ± SD: 3.2 ± 2.3) were enrolled. All patients underwent clinical assessment and MRI at baseline, 1-year, and 2-year follow-up. MRPI, MRPI 2.0 and clinical scores over 1 and 2-years were used to evaluate disease progression rate, and to calculate sample sizes required to power placebo-controlled trials. RESULTS: All groups showed increased clinical motor scores over time whereas only PSP groups had increased MRPI and MRPI 2.0 values over T1 and T2 intervals. The percentage increase over 1 and 2-years of MRPI and MRPI 2.0 values was significantly higher in PSP groups than in PD group, and in PSP-RS than in PSP-P patients while no difference between patient groups was observed when clinical motor scores were considered. Sample size estimates showed that MRPI 2.0 performed better than MRPI and clinical scales. Treatment trials with MRPI 2.0 could be performed over 2-years both in PSP-RS and PSP-P with a sample size per treatment arm of 89 and 170 patients, respectively. CONCLUSIONS: Our results demonstrate that MRPI 2.0 was more powerful than MRPI and clinical motor scales in evaluating PSP progression, and in providing the best sample size estimates for clinical trials.

In vivo evidence for decreased scyllo-inositol levels in the supplementary motor area of patients with Progressive Supranuclear Palsy: A proton MR spectroscopy study.

INTRODUCTION: Several structural and functional neuroimaging studies have shown that the Supplementary Motor Area (SMA) is affected by tau pathology in patients with Progressive Supranuclear Palsy (PSP). The aim of the study was to investigate the biochemical profile of SMA in PSP patients, using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Sixteen PSP patients and 18 healthy controls participated in this study. 1H-MRS was performed by using a Point RESolving Spectroscopy (PRESS) single-voxel sequence implemented on a 3-T scanner. A voxel of 25 × 25 × 15 mm involving the right and left SMA was acquired in all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine with phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), glutamate + glutamine (Glx), glutathione (GSH), myo-Inositol (mI) and Scyllo-Inositol (Scyllo) were calculated using a version 6.3-1K of the fitting program LCModel. Comparative analysis was performed on both absolute concentrations and ratio values relative to Cr. RESULTS: PSP patients showed a significant decrease in Scyllo concentration and Scyllo/Cr ratio values in SMA, compared to controls, whereas no difference between groups was found for the other ratio values. Of note, the attention and working memory functions were positively related to Scyllo and Scyllo/Cr values in PSP patients. CONCLUSIONS: Our study demonstrates that Scyllo and Scyllo/Cr were significantly reduced in the SMA of PSP patients. Because Scyllo seems to be able to protect against formation of toxic fibrils of amyloid-beta fragments and tau oligomers deposition, these preliminary findings may open new perspectives to investigate Scyllo as a new potential disease-modifying therapy for PSP.

Imaging counterpart of postural instability and vertical ocular dysfunction in patients with PSP: A multimodal MRI study.

INTRODUCTION: We investigated the imaging counterpart of two functional domains (ocular motor dysfunction and postural instability) in progressive supranuclear palsy (PSP) patients classified according to the new clinical diagnostic criteria. METHODS: Forty-eight patients with probable PSP-Richardson's syndrome (PSP-RS), 30 with probable PSP-parkinsonism (PSP-P), 37 with Parkinson's disease (PD), and 38 controls were enrolled. For each functional domain, PSP patients were stratified by two certainty levels: vertical supranuclear gaze palsy (O1) and slowness of vertical saccades (O2) for ocular motor dysfunction; early unprovoked falls and tendency to fall on the pull-test for postural instability. Voxel-based morphometry (VBM), whole-brain fractional anisotropy (FA) and MR planimetric measurements were analysed and compared across patient groups. RESULTS: O1 was present in 64%, and O2 in 36% of all PSP patients. All PSP-RS patients showed early unprovoked falls. TBSS whole-brain analysis revealed that superior cerebellar peduncles (SCPs) were the only structures with significantly lower FA values in PSP-RS compared with PSP-P patients. PSP/O1 patients had lower FA values in midbrain than PSP/O2 patients. By contrast, VBM revealed no differences in grey matter volume between PSP patient groups. MR Planimetric measurements confirmed atrophy of midbrain and SCPs, in line with DTI findings. CONCLUSIONS: Our study demonstrates that SCPs were significantly more damaged in patients with PSP-RS in comparison with PSP-P patients, thus suggesting the role of SCPs in developing postural instability. Midbrain damage was less severe in O2 than in O1 patients, suggesting that the degree of vertical ocular dysfunction reflects the severity of midbrain atrophy.

Increased glutamate + glutamine levels in the thalamus of patients with essential tremor: A preliminary proton MR spectroscopic study.

INTRODUCTION: The aim of this study was to investigate the thalamic biochemical profile in patients with essential tremor (ET), using proton magnetic resonance spectroscopy (1H-MRS), and to explore the correlations between clinical and biochemical data. METHODS: Sixteen patients with ET and 14 healthy controls participated in this study. After conventional MR imaging, single-voxel 1H-MRS (TR = 2000 ms; TE = 28 ms) was performed by using a PROBE-SV system implemented on a 3-T scanner. A voxel of 10 × 10 × 15 mm involving the ventrointermediate (Vim) nucleus was acquired in each thalamus of all subjects. Peak areas of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (NAA), creatine + phosphocreatine (Cr), glycerophosphocholine + phosphocholine (Cho), and glutamate + glutamine (Glx) were calculated using a version 6.3-1 K of the fitting program LCModel for each voxel. Comparative and correlation analyses were performed on the NAA, Cr, Cho, and Glx concentrations, as well as on the values of the NAA/Cr, a neural density marker, Cho/Cr, a membrane marker, and Glx/Cr, an intracellular neurotransmitter marker. RESULTS: Patients with ET showed a significant increase in Glx concentration and Glx/Cr ratio values in both thalami, compared to healthy controls, whereas no difference inter-group was found for the other metabolites and NAA/Cr and Cho/Cr ratio values. Of note, the tremor severity was positively related to increased Glx concentrations and Glx/Cr ratio values in ET group. CONCLUSIONS: Our study shows that 1H-MRS can highlight in vivo metabolic abnormalities in the thalami of ET patients, supporting the evidence that the increase of thalamic glutamatergic transmission can play a role in developing of tremor in ET.

A new MR imaging index for differentiation of progressive supranuclear palsy-parkinsonism from Parkinson's disease.

INTRODUCTION: Differentiating clinically progressive supranuclear palsy-parkinsonism (PSP-P) from Parkinson's disease (PD) may be challenging, especially in the absence of vertical supranuclear gaze palsy (VSGP). The Magnetic Resonance Parkinsonism Index (MRPI) has been reported to accurately distinguish between PSP and PD, yet few data exist on the usefulness of this biomarker for the differentiation of PSP-P from PD. METHODS: Thirty-four patients with PSP-P, 46 with PSP-Richardson's syndrome (PSP-RS), 53 with PD, and 53 controls were enrolled. New consensus criteria for the clinical diagnosis of PSP were used as the reference standard. The MRPI, and a new index termed MRPI 2.0 including the measurement of the third ventricle width (MRPI multiplied by third ventricle width/frontal horns width ratio), were calculated on T1-weighted MR images. RESULTS: The MRPI differentiated patients with PSP-P from those with PD with sensitivity and specificity of 73.5% and 98.1%, respectively, while the MRPI 2.0 showed higher sensitivity (100%) and similar specificity (94.3%) in differentiating between these two groups. Both biomarkers showed excellent performance in differentiating PSP-P patients with VSGP from those with PD, but the MRPI 2.0 was much more accurate (95.8%) than MRPI in differentiating PSP-P patients with slowness of vertical saccades from PD patients. CONCLUSION: The MRPI 2.0 accurately differentiated PSP-P patients from those with PD. This new index was more powerful than MRPI in differentiating PSP patients in the early stage of the disease with slowness of vertical saccades from patients with PD, thus helping clinicians to consolidate the diagnosis based on clinical features, in vivo.

Increased cerebellar gray matter volume in head chefs.

OBJECTIVE: Chefs exert expert motor and cognitive performances on a daily basis. Neuroimaging has clearly shown that that long-term skill learning (i.e., athletes, musicians, chess player or sommeliers) induces plastic changes in the brain thus enabling tasks to be performed faster and more accurately. How a chef's expertise is embodied in a specific neural network has never been investigated. METHODS: Eleven Italian head chefs with long-term brigade management expertise and 11 demographically-/ psychologically- matched non-experts underwent morphological evaluations. RESULTS: Voxel-based analysis performed with SUIT, as well as, automated volumetric measurement assessed with Freesurfer, revealed increased gray matter volume in the cerebellum in chefs compared to non-experts. The most significant changes were detected in the anterior vermis and the posterior cerebellar lobule. The magnitude of the brigade staff and the higher performance in the Tower of London test correlated with these specific gray matter increases, respectively. CONCLUSIONS: We found that chefs are characterized by an anatomical variability involving the cerebellum. This confirms the role of this region in the development of similar expert brains characterized by learning dexterous skills, such as pianists, rock climbers and basketball players. However, the nature of the cellular events underlying the detected morphological differences remains an open question.

Thalamic neurometabolic alterations in tremulous Parkinson's disease: A preliminary proton MR spectroscopy study.

INTRODUCTION: The objective of this study was to investigate the thalamic biochemical changes in tremor-dominant Parkinson's disease (tPD) patients in comparison with essential tremor with resting tremor (rET) patients, by using proton MR spectroscopy (1H-MRS). METHODS: Fourteen tPD patients, 12 rET patients and 10 controls participated in this study. All patients underwent dopamine transporter single-photon emission computed tomography (DAT-SPECT) with 123I-ioflupane, and a short-echo single-voxel 1H-MRS on a 3T scanner. A voxel of 10 × 15 × 10 mm involving the Vim nucleus was acquired in both thalami of all subjects. Peak areas of N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (Cho), and glutamate (Glu) were measured for each voxel using LCModel. The NAA/Cr, Cho/Cr, and Glu/Cr ratios were then calculated. RESULTS: DAT-SPECT was abnormal in tPD patients, whereas it was normal in rET patients. Patients with tPD showed a significant reduction of NAA/Cr and Cho/Cr in the thalami compared to rET and healthy controls; whereas there were no significant differences between rET patients and controls. The combination of thalamic NAA/Cr and Cho/Cr ratios showed a 100% accuracy in distinguishing tPD patients from rET patients and controls. CONCLUSIONS: This study provides preliminary evidence that thalamic neurometabolic abnormalities occur in tremor-dominant phenotype of PD, and suggests that 1H-MRS can help differentiate patients with tPD from those with rET.

MR parkinsonism index predicts vertical supranuclear gaze palsy in patients with PSP-parkinsonism.

OBJECTIVE: To identify a biomarker for predicting the appearance of vertical supranuclear gaze palsy (VSGP) in patients affected by progressive supranuclear palsy-parkinsonism (PSP-P). METHODS: Twenty-four patients with PSP-P were enrolled in the current study. Patients were clinically followed up every 6 months until the appearance of VSGP or the end of the follow-up (4 years). Participants underwent MRI at baseline and at the end of follow-up. Magnetic resonance parkinsonism index (MRPI), an imaging measure useful for diagnosing PSP, was calculated. RESULTS: Twenty-one patients with PSP-P completed follow-up, and 3 patients dropped out. Eleven of 21 patients with PSP-P developed VSGP after a mean follow-up period of 28.5 months (range 6-48 months), while the remaining 10 patients with PSP-P did not develop VSGP during the 4-year follow-up period. At baseline, patients with PSP-P who later developed VSGP had MRPI values significantly higher than those of patients not developing VSGP without overlapping values between the 2 groups. MRPI showed a higher accuracy (100%) in predicting VSGP than vertical ocular slowness (accuracy 33.3%) or postural instability with or without vertical ocular slowness (accuracy 71.4% and 42.9%, respectively). CONCLUSIONS: Our study demonstrates that MRPI accurately predicted, on an individual basis, the appearance of VSGP in patients with PSP-P, thus confirming clinical diagnosis in vivo.

Further evidence of genetic heterogeneity in autosomal dominant distal motor neuronopathy.

Distal hereditary motor neuronopathy is a genetically and clinically heterogeneous disorder. To date, five loci, and their relative genes, have been mapped on chromosomes 7p14, 7q11, 9q34, 11q12 and 12q24, respectively. We describe an Italian family with autosomal dominant distal HMN starting at around 30 years of age with weakness and atrophy of distal leg muscles and pyramidal features. We performed genetic linkage analysis on chromosomes 7p14, 9q34, 11q12 and 12q24. Moreover we sequenced the genes mapped to 7q11 and 12q24. Negative LOD scores excluded linkage to 7p14, 9q34, and 11q12 chromosomes in our family. No mutations were found in genes mapped to 7q11 and 12q24. In addition, because of pyramidal features, we performed the linkage analysis to all the known loci for autosomal dominant hereditary spastic paraparesis. The analysis was negative thus excluding a complicated form of autosomal dominant hereditary spastic paraparesis. These data further confirm a genetic heterogeneity within inherited motor neuronopathy.

A large family with pure autosomal dominant hereditary spastic paraplegia from southern Italy mapping to chromosome 14q11.2-q24.3.

A large Italian pedigree from southern Italy with autosomal dominant uncomplicated spastic paraplegia is reported. The clinical picture was uniform and characterized by insidiously progressive lower extremity weakness and spasticity. The mean age at onset of symptoms was 8.3 years. Significant linkage to the SPG3 locus on chromosome 14 was detected. The authors also report their search for mutations in a gene located in the region and its exclusion as a candidate for SPG3.

No evidence of association between the alpha-2 macroglobulin gene and Parkinson's disease in a case-control sample.

Alpha-2 macroglobulin (A2M) is a component of Lewy bodies, a hallmark of Parkinson's disease (PD). In 159 PD patients and 190 normal controls, we studied two A2M polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism method: a five-nucleotide deletion at the 5' splice site of exon 18; and a valine to isoleucine exchange in amino acid position 1000 near the thiolester active site. No significant differences in allelic and genotypic distribution were found between cases and controls or between early and late-onset PD patients. The present data suggest that these polymorphisms do not represent a risk factor for PD and do not modulate the age at onset of PD.

FRAXE intermediate alleles are associated with Parkinson's disease.

There is evidence that male subjects with a clinical picture of action tremor, Parkinsonism, and cerebellar ataxia may have Fragile X premutations (FRAXA). We analyzed FRAXA and FRAXE triplet repeats in 203 male subjects with Parkinson's disease (PD) and 370 healthy controls. No full mutations or premutations at the FRAXA and FRAXE loci were found in the subjects with PD or in the controls. FRAXA allele distribution was similar in patients and controls. FRAXE intermediate alleles (31-60 repeats CCG) were found in 13 of 203 (6.4%) subjects with PD and in only one of the 370 (0.27%) healthy controls (P < 0.001), thus indicating that these relatively large alleles may be associated with PD.

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.

Body weight influences pharmacokinetics of levodopa in Parkinson's disease.

Changes in body weight may induce substantial variations in peripheral pharmacokinetics of drugs, but the relation between body weight and levodopa (LD) pharmacokinetics has never been investigated in Parkinson's disease. To address this issue, we conducted a pharmacokinetic study with 164 patients with sporadic Parkinson's disease. Patients underwent an oral acute LD test with 250 mg of LD, and pharmacokinetic variables were assessed at baseline and at 30, 60, 120, and 240 minutes after LD administration. Plasmatic-LD areas under the curve and body weight were significantly and inversely correlated as well as the elimination of the half-life of LD and body weight. In our sample, women were significantly lighter and had a significantly greater area under the curve than men. Moreover, a greater percentage of women showed LD peak-dose dyskinesias compared with men. Our findings suggest that lighter patients with Parkinson's disease probably receive a greater cumulative dosage of LD per kilogram of body weight during long-term treatment, because in clinical practice, LD is administered without any adjustment of the dose to body weight. This could explain gender differences for the development of LD-induced peak-dose dyskinesias observed during the course of the disease.