Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Early cortical atrophy in REM sleep behavior disorder. / Atrofia cortical precoz en el trastorno de conducta del sueño REM.

INTRODUCTION: The presence of cortical atrophy (focal or diffuse) prior to the development of symptoms of cognitive impairment could predict the earliest cases of neurodegenerative disease in patients with REM sleep behavior disorder (RSBD). We reviewed the usefulness of cranial CT and MRI as early markers of cortical atrophy in patients with RSBD at our center. PATIENTS AND METHODS: Retrospective observational descriptive analysis of patients diagnosed with RSBD from October 2012 to October 2022. All with cranial CT or MRI, evaluated by a neuroradiologist. RESULTS: 54 patients were included, 21 women (38.88%), 33 men (61.12%), mean age at diagnosis of RSBD: 69.04±12.625 years. Of the 54 patients, 44 (81.48%) had imaging tests consistent with their age, and 10 had atrophy greater than expected for their age. Of the 54 patients, 21 (38.88%) with a diagnosis of neurodegenerative disease, 33 (61.12%) persist as idiopathic, almost all with more than 5years of evolution (range of 1 to 10years of evolution without diagnosis). Of the 10 (18.52%) patients with greater atrophy, all were diagnosed with neurodegenerative disease (8 in 1year, 2 in 8years). CONCLUSIONS: Almost half of our series have developed a neurodegenerative disease in the first 10years of evolution. The majority of them presented global cortical atrophy measured by the GCA scale in the first year of diagnosis, without other neurological symptoms. Patients who did not show cortical atrophy at diagnosis have not yet developed the neurodegenerative disease in 10years of evolution. In our experience, the absence of cortical atrophy on cranial MRI or CT (measured by scales such as GCA) at the diagnosis of RSBD seems to predict slower progression cases. These data should be corroborated with larger series.

Anxiety and depression in patients with narcolepsy.

We analysed the co-existence of psychopathology in patients with narcolepsy at our centre. We performed an observational retrospective descriptive analysis of patients with a diagnosis of narcolepsy, with and without psychopathology, who attended our sleep disorders unit from October 2012 to October 2021. A total of 51patients with narcolepsy (mean [SD] age 41.10 [14.71] years; 23 [45.1%] males and 28 [54.90%] females) were included. In all, 27 patients (52.94%) and 24 patients (47.06%) had narcolepsy with and without cataplexy, respectively. Of the total, 18 (33.33%) had a mood disorder: 18 with anxiety disorder (33.33%). Of these patients 14 (27.45%) had major depression, two (4%) had attempted suicide, one (2%) had manic outbreak, and one (2%) had substance abuse. Of the 18 patients with anxiety and depression, 10 (55.55%) and eight (44.44%) had narcolepsy with and without cataplexy, respectively. In the comparative analysis, a statistically significant relationship was found between younger age and the presence of anxiety. The prevalence of anxiety and depression in patients with narcolepsy was triple that of the general population, especially in younger patients. Psychopathology precedes the diagnosis of narcolepsy in most patients, not being reactive to diagnosis. This high prevalence suggests a possible biological relationship between both disorders, which should be assessed with larger studies.

Saposin C, Key Regulator in the Alpha-Synuclein Degradation Mediated by Lysosome.

Lysosomal dysfunction has been proposed as one of the most important pathogenic molecular mechanisms in Parkinson disease (PD). The most significant evidence lies in the GBA gene, which encodes for the lysosomal enzyme ß-glucocerebrosidase (ß-GCase), considered the main genetic risk factor for sporadic PD. The loss of ß-GCase activity results in the formation of α-synuclein deposits. The present study was aimed to determine the activity of the main lysosomal enzymes and the cofactors Prosaposin (PSAP) and Saposin C in PD and healthy controls, and their contribution to α-synuclein (α-Syn) aggregation. 42 PD patients and 37 age-matched healthy controls were included in the study. We first analyzed the ß-GCase, ß-galactosidase (ß-gal), ß-hexosaminidase (Hex B) and Cathepsin D (CatD) activities in white blood cells. We also measured the GBA, ß-GAL, ß-HEX, CTSD, PSAP, Saposin C and α-Syn protein levels by Western-blot. We found a 20% reduced ß-GCase and ß-gal activities in PD patients compared to controls. PSAP and Saposin C protein levels were significantly lower in PD patients and correlated with increased levels of α-synuclein. CatD, in contrast, showed significantly increased activity and protein levels in PD patients compared to controls. Increased CTSD protein levels in PD patients correlated, intriguingly, with a higher concentration of α-Syn. Our findings suggest that lysosomal dysfunction in sporadic PD is due, at least in part, to an alteration in Saposin C derived from reduced PSAP levels. That would lead to a significant decrease in the ß-GCase activity, resulting in the accumulation of α-syn. The accumulation of monohexosylceramides might act in favor of CTSD activation and, therefore, increase its enzymatic activity. The evaluation of lysosomal activity in the peripheral blood of patients is expected to be a promising approach to investigate pathological mechanisms and novel therapies aimed to restore the lysosomal function in sporadic PD.

Re-evaluating the accuracy of optimized electrodiagnostic criteria in very early Guillain-Barré syndrome: a sequential study.

Using recent optimized electrodiagnostic criteria sets, we aimed at verifying the accuracy of initial nerve conduction studies (NCS) in classic very early Guillain-Barré syndrome (VEGBS), ≤ 4 days after onset, compared with the results of serial NCS. This is a retrospective study based on unreported and consecutive VEGBS patients admitted to two university hospitals between 2015 and 2019. Each patient had serial NCS in at least four nerves. Initial NCS studies were done within 4 days after onset, and serial ones from days 20 to 94. Electrophysiological recordings were blinded evaluated by four of the authors, GBS subtype being established accordingly. Seven adult classic VEGBS patients were identified with a median age of 58 years. At first NCS, GBS subtyping was only possible in 1 case that exhibited an axonal pattern, the remaining patterns being equivocal in 3, and mixed (combining axonal and demyelinating criteria) in the remaining 3. Upon serial NSC there was a rather intricate evolution of electrophysiological GBS patterns, 3 of them being classified as axonal or demyelinating, and the remaining 4 as equivocal or mixed. NCS in VEGBS systematically allows detection of changes suggestive of peripheral neuropathy, though even after serial studies accurate GBS subtyping was only possible in 43% of cases. We provide new pathophysiological insights for better understanding of the observed electrophysiological changes.

Encephalopathy in severe SARS-CoV2 infection: Inflammatory or infectious?

Concerning the letter by Moriguchi et al., we describe our experience with a case of encephalopathy with and atypical damage on magnetic resonance imaging (MRI) in a patient with severe infection due to the SARS-CoV2 virus. A 56-year-old woman, without previous pathologies, developed cough, fever, and respiratory failure for five days, after returning from a 6-day trip to Venice. Chest radiography shows a large bilateral interstitial infiltrate. In the first 24 hours, she was admitted to the Intensive Care Unit (ICU) for severe respiratory failure and positive protein chain reaction-PCR in nasal exudate. She needed intubation for ten days. In the first 48 hours outside the ICU, she developed an acute confusional syndrome (hyperactive delirium). Neurological examination showed temporal-spatial disorientation and incoherent fluent speech. An electroencephalogram (EEG) showed generalized hypovoltaic activity. Cranial magnetic resonance imaging showed a bilateral and symmetrical increase in the supratentorial white matter's signal intensity, with a discrete thickening of both temporal lobes, with a slight increase in signal intensity and a sequence of normal diffusion. The lumbar puncture showed no changes (glucose 71 mg/dL, protein 30 mg/dL, 1 leukocyte). Within 72 hours of starting symptoms, she was neurologically asymptomatic. Our final diagnosis was an inflammatory encephalopathy related to a SARS-CoV2 infection.

Spanish real-world experience with fingolimod in relapsing-remitting multiple sclerosis patients: MS NEXT study.

PURPOSE: The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice. METHODS: This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months. RESULTS: The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%. CONCLUSIONS: The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting.

Efectividad y seguridad del fingolimod en la práctica clínica habitual en pacientes con esclerosis múltiple remitente recurrente en España: análisis intermedio del estudio MS NEXT / Efficacy and safety of fingolimod in routine clinical practice in patients with relapsing-remitting multiple sclerosis in Spain: an intermediate analysis of the MS NEXT study

Introducción. El fingolimod es un tratamiento modificador de la enfermedad que ha demostrado eficacia y seguridad en ensayos clínicos en pacientes con esclerosis múltiple remitente recurrente (EMRR). Objetivo. Evaluar la efectividad y la seguridad del fingolimod en pacientes con EMRR en la práctica clínica. Pacientes y métodos. Se presentan los resultados del análisis intermedio (julio de 2015) del MS NEXT, un estudio observacional, multicéntrico y retrospectivo. Se incluyó a 442 pacientes (edad media: 41 ± 9 años; escala expandida del estado de discapacidad basal, mediana: 3; 70% mujeres; 284 previamente tratados con tratamientos modificadores de la enfermedad de primera línea, 139 con natalizumab y 19 naïve; media de tratamiento con fingolimod: 25 ± 9 meses) tratados con fingolimod a partir de noviembre de 2011 y con al menos 12 meses de seguimiento. Participaron 56 hospitales españoles. Se recogieron datos demográficos y clínicos (basal y anualmente, número de brotes, puntuación en la escala expandida del estado de discapacidad y actividad radiológica). También se registraron los efectos adversos durante el seguimiento. Resultados. Tras dos años de tratamiento, la tasa anualizada de brotes se redujo un 76%; el 67% de los pacientes estaba libre de brotes; el 91%, libre de progresión de la discapacidad confirmada a los tres meses; el 63%, libre de brotes y progresión de discapacidad; el 50%, libre de actividad radiológica, y el 35%, libre de brotes, progresión de discapacidad y actividad radiológica. Un 3,9% abandonó el fingolimod permanentemente. Conclusiones. En este análisis intermedio, la mayoría de los pacientes tratados con fingolimod en la práctica clínica presenta una actividad clínica controlada y una elevada persistencia al tratamiento

Introduction. Fingolimod is a disease modifying therapies, which has showed clinical efficacy and an acceptable safety profile in clinical trials with relapsing-remitting multiple sclerosis (RRMS) patients. Aim. To assess fingolimod effectiveness and safety in patients with RRMS in clinical practice. Patients and methods. We present an interim analysis (July 2015) of MS NEXT, an observational, retrospective and multicenter study. 442 patients were included (mean age: 41 +/- 9 years; median baseline EDSS: 3.0; 70% female; 284 previously treated with first-line disease modifying therapies, 139 with natalizumab and 19 without a previous treatment; mean fingolimod treatment duration: 25 ± 9 months) treated with fingolimod from November 2011 and with at least 12 months follow-up. 56 neurology-unit Spanish hospitals enrolled patients. Basal clinical and demographic data were recorded. Relapses, EDSS scores and radiological activity were recorded at baseline and annually. Adverse events were also recorded during the follow-up period. Results. After two years of follow-up: annual relapse rates decreased by 76%, the proportion of relapse-free patients was 67%, of disability progression-free patients confirmed at 3 months was 91%, of relapse and disability progression-free patients was 63%, of radiological activity-free patients was 50%, and the proportion of relapse, disability progression and radiological activity-free patients was 35%. Only 3.9% of patients discontinued fingolimod permanently during the first year of treatment. Conclusions. In this interim analysis, most of patients treated with fingolimod in clinical practice had a controlled clinical disease activity, stable disability progression and high persistency

When aphasia is due to aphasic status epilepticus: a diagnostic challenge.

Aphasic status epilepticus is an uncommon entity that should be included in the differential diagnosis of persistent and sudden language disorders. In our study, we describe seven patients admitted with clinical and electroencephalographic diagnosis of aphasic status, who were studied with both neuroimaging and electroencephalogram. The mean age was 65.9 years (range of 39-89). Three of the patients had previously been diagnosed of epilepsy. The aphasia was global in six patients. In one case, we found foci of the left hemorrhagic contusions. The initial electroencephalogram (EEG) was not conclusive of status in two patients. In one patient, neuroimaging showed left hemispheric hypoperfusion, compatible with postictal changes. Six out of seven patients required at least two antiepileptic drugs. Three patients died of systemic complications (infectious causes), whereas the other four cases had a complete recovery. Our study highlights that a second EEG study might be necessary to confirm epileptiform activity, when clinical features and other tests suggest an epileptic origin. An early and specific treatment, avoiding or diminishing comorbidities, might significantly improve the prognosis of these patients.

Structural genomic variations and Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, whose prevalence is projected to be between 8.7 and 9.3 million by 2030. Until about 20 years ago, PD was considered to be the textbook example of a "non-genetic" disorder. Nowadays, PD is generally considered a multifactorial disorder that arises from the combination and complex interaction of genes and environmental factors. To date, a total of 7 genes including SNCA, LRRK2, PARK2, DJ-1, PINK 1, VPS35 and ATP13A2 have been seen to cause unequivocally Mendelian PD. Also, variants with incomplete penetrance in the genes LRRK2 and GBA are considered to be strong risk factors for PD worldwide. Although genetic studies have provided valuable insights into the pathogenic mechanisms underlying PD, the role of structural variation in PD has been understudied in comparison with other genomic variations. Structural genomic variations might substantially account for such genetic substrates yet to be discovered. The present review aims to provide an overview of the structural genomic variants implicated in the pathogenesis of PD.

Genome-wide assessment of Parkinson's disease in a Southern Spanish population.

Here, we set out to study the genetic architecture of Parkinson's disease (PD) through a Genome-Wide Association Study in a Southern Spanish population. About 240 PD cases and 192 controls were genotyped on the NeuroX array. We estimated genetic variation associated with PD risk and age at onset (AAO). Risk profile analyses for PD and AAO were performed using a weighted genetic risk score. Total heritability was estimated by genome-wide complex trait analysis. Rare variants were screened with single-variant and burden tests. We also screened for variation in known PD genes. Finally, we explored runs of homozygosity and structural genomic variations. We replicate PD association (uncorrected p-value < 0.05) at the following loci: ACMSD/TMEM163, MAPT, STK39, MIR4697, and SREBF/RAI1. Subjects in the highest genetic risk score quintile showed significantly increased risk of PD versus the lowest quintile (odds ratio = 3.6, p-value < 4e(-7)), but no significant difference in AAO. We found evidence of runs of homozygosity in 2 PD-associated regions: one intersecting the HLA-DQB1 gene in 6 patients and 1 control; and another intersecting the GBA-SYT11 gene in PD case. The GBA N370S and the LRRK2 G2019S variants were found in 8 and 7 cases, respectively, replicating previous work. A structural variant was found in 1 case in the PARK2 gene locus. This current work represents a comprehensive assessment at a genome-wide level characterizing a novel population in PD genetics.

Analysis of the genetic variability in Parkinson's disease from Southern Spain.

To date, a large spectrum of genetic variants has been related to familial and sporadic Parkinson's disease (PD) in diverse populations worldwide. However, very little is known about the genetic landscape of PD in Southern Spain, despite its particular genetic landscape coming from multiple historical migrations. We included 134 PD patients in this study, of which 97 individuals were diagnosed with late-onset sporadic PD (LOPD), 28 with early-onset sporadic PD (EOPD), and 9 with familial PD (FPD). Genetic analysis was performed through a next-generation sequencing panel to screen 8 PD-related genes (LRRK2, SNCA, PARKIN, PINK1, DJ-1, VPS35, GBA, and GCH1) in EOPD and FPD groups and direct Sanger sequencing of GBA exons 8-11 and LRRK2 exons 31 and 41 in the LOPD group. In the EOPD and FPD groups, we identified 11 known pathogenic mutations among 15 patients (40.5%). GBA (E326K, N370S, D409H, L444P) mutations were identified in 7 patients (18.9%); LRRK2 (p.R1441G and p.G2019S) in 3 patients (8.1%); biallelic PARK2 mutations (p.N52fs, p.V56E, p.C212Y) in 4 cases (10.8%) and PINK1 homozygous p.G309D in 1 patient (2.7%). An EOPD patient carried a single PARK2 heterozygous mutation (p.R402C), and another had a novel heterozygous mutation in VPS35 (p.R32S), both of unknown significance. Moreover, pathogenic mutations in GBA (E326K, T369M, N370S, D409H, L444P) and LRRK2 (p.R1441G and p.G2019S) were identified in 13 patients (13.4%) and 4 patients (4.1%), respectively, in the LOPD group. A large number of known pathogenic mutations related to PD have been identified. In particular, GBA and LRRK2 mutations appear to be considerably frequent in our population, suggesting a strong Jewish influence. Further research is needed to study the contribution of the novel found mutation p.R32S in VPS35 to the pathogenesis of PD.

[Proteomic biomarkers in Parkinson's disease]. / Biomarcadores proteómicos en la enfermedad de Parkinson.

Parkinson's disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature.

TITLE: Biomarcadores proteomicos en la enfermedad de Parkinson.La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo que afecta al movimiento, cuya causa es la muerte de las neuronas dopaminergicas de la parte compacta de la sustancia negra. El diagnostico es fundamentalmente clinico, pero, a pesar de que los signos y sintomas de la EP se conocen bien, el error diagnostico es relativamente alto. Se calcula que un 10-30% de los pacientes inicialmente diagnosticados de EP se reclasifican posteriormente. Esta enfermedad tiene una alta prevalencia a partir de los 60 años, y uno de los mayores problemas que tiene es que su diagnostico se hace cuando el proceso degenerativo esta muy avanzado. Por tanto, es necesaria la busqueda de biomarcadores que permitan un diagnostico precoz de la EP, seguir su progresion, diferenciarla de otras patologias relacionadas (parkinsonismos) y que ayuden a monitorizar el efecto de nuevas terapias. El hecho de que existan mutaciones que conducen a la EP, asi como combinaciones poligenicas que pueden actuar como factores de riesgo, sugiere que es posible analizar las proteinas resultantes de la expresion de estos genes en tejidos perifericos, que, una vez demostrada su sensibilidad y especificidad, podrian utilizarse como biomarcadores de la EP, incluso en fases iniciales de la enfermedad. El objetivo del presente trabajo es centrarse en una revision detallada de los principales biomarcadores proteomicos candidatos investigados hasta el momento, discutiendo la literatura mas reciente.

Biomarcadores proteómicos en la enfermedad de Parkinson / Proteomic biomarkers in Parkinson's disease

La enfermedad de Parkinson (EP) es un trastorno neurodegenerativo que afecta al movimiento, cuya causa es la muerte de las neuronas dopaminérgicas de la parte compacta de la sustancia negra. El diagnóstico es fundamentalmente clínico, pero, a pesar de que los signos y síntomas de la EP se conocen bien, el error diagnóstico es relativamente alto. Se calcula que un 10-30% de los pacientes inicialmente diagnosticados de EP se reclasifican posteriormente. Esta enfermedad tiene una alta prevalencia a partir de los 60 años, y uno de los mayores problemas que tiene es que su diagnóstico se hace cuando el proceso degenerativo está muy avanzado. Por tanto, es necesaria la búsqueda de biomarcadores que permitan un diagnóstico precoz de la EP, seguir su progresión, diferenciarla de otras patologías relacionadas (parkinsonismos) y que ayuden a monitorizar el efecto de nuevas terapias. El hecho de que existan mutaciones que conducen a la EP, así como combinaciones poligénicas que pueden actuar como factores de riesgo, sugiere que es posible analizar las proteínas resultantes de la expresión de estos genes en tejidos periféricos, que, una vez demostrada su sensibilidad y especificidad, podrían utilizarse como biomarcadores de la EP, incluso en fases iniciales de la enfermedad. El objetivo del presente trabajo es centrarse en una revisión detallada de los principales biomarcadores proteómicos candidatos investigados hasta el momento, discutiendo la literatura más reciente (AU)

Parkinson’s disease (PD) is a neurodegenerative disorder that affects movement and is caused by the death of the dopaminergic neurons in the compact part of the substantia nigra. Its diagnosis is essentially clinical, but although the signs and symptoms of PD are well known, the rate of diagnostic error is relatively high. It is estimated that 10-30% of patients initially diagnosed with PD are later reclassified. This disease has a high prevalence beyond the age of 60, and one of its biggest problems is that it is diagnosed when the degenerative process is already at a very advanced stage. Therefore, it is necessary to look for other biomarkers that make it possible to carry out an early diagnosis of PD, follow up its development, distinguish it from other related pathologies (parkinsonisms) and help monitor the effect of novel therapies. The fact that there are mutations that lead to PD, as well as polygenetic combinations that can act as risk factors, suggests the possibility of measuring the proteins resulting from the expression of these genes in peripheral tissues. And once their sensitivity and specificity have been proved they could be used as biomarkers for PD, even in the early phases of the disease. The aim of this work is to focus on a detailed review of the main candidate proteomic biomarkers researched to date by discussing the most recent literature (AU)

Neurophysiological study in cerebrotendinous xanthomatosis.

INTRODUCTION: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal-recessive disease due to mutations of the 27α-hydroxylase. It is characterized by cataracts, xanthomas, and neurological manifestations. Polyneuropathy has been reported, although it is unclear whether it is axonal or demyelinating. METHODS: We report clinical and neurophysiological results of 13 patients with CTX diagnosed in Spain. RESULTS: In 8 patients (62%), peripheral neuropathy was demonstrated (4 demyelinating, 3 axonal, and 1 mixed; 3 predominantly motor and 5 sensorimotor). All patients had clinical signs/symptoms of peripheral neuropathy. Upper limb somatosensory evoked potentials (SSEPs) were affected in 38% of patients, and lower limb SSEPs in 67%. Fifty percent of patients had delayed brainstem auditory evoked potentials, and 43% had affected visual evoked potentials. DISCUSSION: In this series, polyneuropathy was predominantly sensorimotor and demyelinating. Neurophysiological studies correlated only partially with clinical follow-up. Therefore, we recommend neurophysiological follow-up studies only if clinical symptoms are present.

Oxidative stress and aminopeptidases in Parkinson's disease patients with and without treatment.

BACKGROUND/OBJECTIVE: Mitochondrial dysfunction, oxidative stress and protein metabolism impairment are the main molecular events underlying the pathogenesis of Parkinson's disease (PD). However, only few studies have addressed the changes produced by these phenomena in the blood of PD patients. Our purpose was to compare oxidative stress between newly diagnosed PD patients (ntPD) and PD patients under treatment (tPD). We also analyzed changes in plasma activity of several aminopeptidases (AP) involved in the metabolism of various active peptides. METHODS: Plasma lipid peroxide (LPO) and lactate (LAC) concentrations were measured by colorimetric methods, and plasma AP activities were determined by fluorometric assay. RESULTS: LPO and LAC concentrations were significantly elevated in ntPD and tPD patients versus controls, but there were no differences between the PD groups. Alanine-, cystine- and aspartate-AP activities were significantly lower in tPD versus ntPD patients. Nondenaturing electrophoresis and Western blot results confirmed these findings. CONCLUSIONS: The plasma LPO and LAC levels were high in both PD groups, indicating that they are elevated at an early stage of PD and are not affected by anti-PD treatment. The higher AP activities in ntPD versus tPD patients suggest that anti-PD treatment may improve protein metabolism while not altering oxidative stress. A therapy directed to reduce oxidative stress and normalize AP activity may be useful in the treatment of PD.

Plasma alpha-synuclein in patients with Parkinson's disease with and without treatment.

Alpha-synuclein (alpha-syn) is an intracellular protein with a high tendency to aggregation. It is the major component of Lewy bodies and may play a key role in the pathogenesis of Parkinson's disease (PD). alpha-Syn is also released by neurons and can be detected in biological fluids, such as plasma. The purpose of this study was to determine whether plasma alpha-syn concentrations are elevated in newly diagnosed PD patients before treatment (nontreated PD group, ntPD; n = 53) and to compare them with concentrations in PD patients with at least 1 year of specific treatment (tPD; n = 42) and in healthy controls (n = 60). Plasma alpha-syn concentrations in the ntPD and tPD groups were similar and significantly higher than in healthy controls. In conclusion, alpha-syn was elevated early in the development of PD and specific PD treatment did not change plasma alpha-syn levels.

Oxidative stress and plasma aminopeptidase activity in Huntington's disease.

Huntington's disease (HD) is a genetic neurodegenerative disorder. Oxidative stress, mitochondrial dysfunction, and protein metabolism impairment have been implicated in its pathogenesis. However, the contribution of these phenomena to HD onset or progression is not well known, and they have been less studied in peripheral blood. We analyzed plasma lipid peroxide (LPO) and lactate (LAC) concentrations as indicators of oxidative stress and mitochondrial dysfunction in symptomatic HD patients (sHD) and asymptomatic HD gene carriers (aHD). We also measured the plasma activity of aminopeptidases (APs), an important group of proteolytic enzymes. LPO and LAC concentrations were significantly elevated in sHD patients but not in aHD carriers. Aspartate and glutamate AP activities were significantly reduced in sHD patients and aHD carriers. These findings demonstrate that sHD patients are under oxidative stress, which may favor progression of the disease. Plasma AP activity was decreased before the appearance of HD symptoms and oxidative stress and may be related to protein metabolism impairment. These results indicate that therapy directed to improve oxidative stress and normalize AP activity may be useful in the treatment of HD. They also suggest that decreased plasma AP activity in aHD carriers may predict the future onset of HD symptoms.

Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa.

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). There are several methods to measure oxidative stress, being lipid peroxidation (LPO) one of the most frequently used. Endogenous plasma LPO was determined by a spectrofluorimetric method in fifty two patients with sporadic PD and in forty controls. To know the maximum capacity of lipids to peroxidate, LPO was also measured after co-incubation with Fe2+/H2O2 (exogenous LPO). All PD patients were taken L-dopa and the effect of this treatment on LPO levels was additionally studied. Urine catecholamines and their main metabolites were also analyzed, and their possible correlation to LPO statistically studied. Endogenous plasma LPO levels were 33% higher in PD group than in control group (P<0.001). Exogenous plasma or oxidizability was also higher in PD patients compared to controls (20%, P<0.05). The intake of L-dopa was negatively dose-related to endogenous and exogenous plasma LPO. In conclusion, plasma of PD patients has elevated levels of LPO and also is more prone to peroxidation than that in the control group. The results also suggest an antioxidant effect of L-dopa.