Search

The olfactory bulb (OB) seems to be the first affected structure in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Lewy body dementia (LBD). Deposits of protein aggregates, increased dopaminergic neurons, and decreased cholinergic inputs have all been described in the OB of these diseases. We investigated here the contribution of the activated microglial cells to the increased deposits of protein aggregates. We quantified the number of activated microglial cells and astrocytes in the OB of patients with histological diagnosis of PD (n = 5), AD (n = 13), and LBD (n = 7) and aged-matched controls (n = 8). Specific consensus diagnostic criteria were applied for AD, LBD, and PD. Protein aggregates were scored in the OB as grade 0, none; grade 1, mild; grade 2, moderate; and grade 3, severe. OB sections from the 33 subjects were stained with specific antibodies markers for reactive astrocytes (GFAP) and microglial cells (Iba1 and HLA-DR). The total number of Iba1-ir (Iba-immunoreactive) and HLAD-DR cells was estimated by stereological analysis, while quantification of astrocytes was performed by GFAP optical density. Statistical analysis was done using the Stata 12.0 software. The number of microglia and activated microglia cells (HLA-RD-ir) was increased in patients with neurodegenerative diseases (p < 0.05). Moreover, the density of GFAP-ir cells was higher in the OB of patients. Neither the number of microglia cells nor the density of astrocytes correlated with the number of b-amyloid and alpha-synuclein deposits, but the density of Iba1-ir cells correlated with the number of p-Tau aggregates. Activated microglial cells and reactive astrocytes are present in the OB of patients with neurodegenerative diseases. The lack of correlation between the number of activated microglia cells and protein deposits indicate that they might independently contribute to the degenerative process. The presence of microglia is related to phosphorylated Tau deposits in neurodegenerative diseases.

This study aimed to analyze the association of autonomic dysfunction with cognition, depression, apathy, and fatigue in Lewy body disease (LBD). We included 61 patients [49 with idiopathic Parkinson’s disease, 7 with dementia with Lewy bodies, and 5 E46K-SNCA mutation carriers] and 22 healthy controls. All participants underwent a comprehensive battery of neuropsychological and clinical measures, autonomic symptom assessment with the SCOPA-AUT, analysis of non-invasive hemodynamic parameters during deep breathing, the Valsalva maneuver, and a 20-min tilt test, and electrochemical skin conductance measurement at rest (Sudoscan). Student’s t tests were used to assess group differences, and bivariate correlations and stepwise linear regressions to explore associations between autonomic function, cognition, depression, apathy, and fatigue. Compared to controls, patients who had significant impairment (p

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of dopaminergic neurons and reproduces the motor features of Parkinson disease (PD); however, the effect of MPTP on extranigral structures has been poorly studied. The aim of this research was to study the cardiac sympathetic innervation of control and MPTP-treated monkeys in order to describe the influence of MPTP toxicity on cardiac tissue. Eight monkeys were included in the study and divided into two groups, four monkeys serving as controls and four forming the MPTP group. Sections from the anterior left ventricle were immunohistochemically examined to characterize the sympathetic fibers of cardiac tissue. The intensity of immunoreactivity in the nerve fibers was quantitatively analyzed using ImageJ software. As occurs in PD, the sympathetic peripheral nervous system is affected in MPTP-treated monkeys. The percentage of tyrosine hydroxylase immunoreactive fibers in the entire fascicle area was markedly lower in the MPTP group (24.23%) than the control group (35.27%) (p

Background and objective Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.

Objective This study was undertaken to analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson's disease (iPD). Methods Patients with Lewy body diseases were enrolled and prospectively evaluated at 3 years, including patients with iPD (n = 42), dementia with Lewy bodies (n = 4), E46K-SNCA mutation carriers (n = 4), and controls (n = 17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment, and Unified Parkinson's Disease Rating Scale score was obtained in patients. Macular ganglion cell-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thicknesses and the risk of subsequent cognitive and motor worsening, using clinically meaningful cutoffs. Results GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63 mu m in iPD patients and 0.23 mu m in controls (p < 0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (relative risk [RR] = 3.49, 95% confidence interval [CI] = 1.10-11.1, p = 0.03 and RR = 3.28, 95% CI = 1.03-10.45, p = 0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. Interpretation Our results provide evidence of the potential use of optical coherence tomography-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD This study was cofunded by the Michael J. Fox Foundation (RRIA [Rapid Response Innovation Awards] 2014 Program, grant ID: 10189), the Carlos III Health Institute, and the European Union (ERDF/ESF, "A Way to Make Europe"/"Investing in Your Future") through the projects PI14/00679 and PI16/00005; the Juan Rodes grant JR15/00008 (I.G.); and the Department of Health of the Basque Government through the projects 2016111009 and 2020333033. We thank all the patients and participants involved in the study.

For many years the subthalamic nucleus had a poor reputation among neurosurgeons as a result of the acute movement disorders that develop after its lesion or manipulation through different surgical procedures. However, this nucleus is now considered a key structure in relation to parkinsonism, and it is currently one of the preferred therapeutic targets for Parkinson's disease. The implication of the subthalamic nucleus in the pathophysiology of chorea and in the parkinsonian state is thought to be related to its role in modulating the basal ganglia, a fundamental circuit in movement control. Indeed, recent findings have renewed interest in this anatomical structure. Accordingly, this review aims to present a history of the subthalamic nucleus, evolving from the classic surgical concepts associated with the avoidance of this structure, to our current understanding of its importance based on findings from more recent models. Future developments regarding the relationship of the subthalamic nucleus to neuroprotection are also discussed in this review. © 2018 International Parkinson and Movement Disorder Society.

• Feeding dystonia, trunk spasms, head-drops and orolingual mutilations are distinctive features of ChAc.

Background Deep brain stimulation electrodes can record oscillatory activity from deep brain structures, known as local field potentials. The authors’ objective was to evaluate and quantify the effects of dexmedetomidine (0.2 μg·kg-1·h-1) on local field potentials in patients with Parkinson disease undergoing deep brain stimulation surgery compared with control recording (primary outcome), as well as the effect of propofol at different estimated peak effect site concentrations (0.5, 1.0, 1.5, 2.0, and 2.5 μg/ml) from control recording. Methods A nonrandomized, nonblinded controlled clinical trial was carried out to assess the change in local field potentials activity over time in 10 patients with Parkinson disease who underwent deep brain stimulation placement surgery (18 subthalamic nuclei). The relationship was assessed between the activity in nuclei in the same patient at a given time and repeated measures from the same nucleus over time. Results No significant difference was observed between the relative beta power of local field potentials in dexmedetomidine and control recordings (−7.7; 95% CI, −18.9 to 7.6). By contrast, there was a significant decline of 12.7% (95% CI, −21.3 to −4.7) in the relative beta power of the local field potentials for each increment in the estimated peak propofol concentrations at the effect site relative to the control recordings. Conclusions Dexmedetomidine (0.2 μg·kg-1·h-1) did not show effect on local field potentials compared with control recording. A significant deep brain activity decline from control recording was observed with incremental doses of propofol.

Gastrointestinal (GI) symptoms can precede by many years the motor symptoms of Parkinson's disease (PD) and these patients can show some degree of inflammation associated with abnormal aggregates of alpha-synuclein in the GI tract. The abnormal accumulation of alpha-synuclein and the spreading of the aggregates from the gut to the brain might be promoted by inflammation, rising the hypothesis of a possible relationship between inflammatory bowel disease and PD. Many population-based studies have explored this association, but they have found conflicting results. It is essential to clarify this hypothesis and to try to elucidate the milestones of this relationship. There is no clear concordance between the results and the interpretation of different previous findings, probably due to many confounding factors such as drugs with anti-inflammatory activity, surgery, genetic predisposition and also selection bias. If there is a real association between both diseases, gastroenterologists and neurologists should be able to detect possible triggers of the disease or on the other hand, protective factors, that may be considered in clinical practice.

Background and objective In 2004 we described the E46K mutation in alpha-synuclein gene (E46K-SNCA), a rare point mutation causing an aggressive Lewy body disease with early prominent non-motor features and small fiber denervation of myocardium. Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls. Patients and methods We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.5/UCHL-1, TH and p-synuclein) and sudomotor function with electrochemical skin conductance (ESC) (SudoScan). Results All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers. The severity of the latter skin abnormalities in E46K-SNCA were correlated with sudomotor dysfunction (lower ESC) in hands (p = 0.035). Interpretation These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.

(1) Background: Both cerebral vascular disorders and cognitive decline increase in incidence with age. The role of cerebral vascular disease and hemodynamic changes in the development of cognitive deficits is controversial. The objective of this study was to assess the cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed cognitive impairment several years after previous cardiac stress testing. (2) Methods: This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed up until May 2015, and we selected those who developed cognitive dysfunction including dementia, mild cognitive impairment, and subjective cognitive decline, after the stress test. Heart rate and blood pressure both at rest and at peak exercise, and the mean R-R interval at rest were recorded. For each patient who developed cognitive impairment, we selected one matched control who did not show cognitive decline by the end of the follow-up period. (3) Results: From the cohort of 7224 patients, 371 developed cognitive impairment, of these, 186 (124 men) met the inclusion criteria, and 186 of the other patients were selected as matched controls. During follow-up, cognitive impairment appeared 6.2 ± 4.7 years after the cardiac stress test. These patients who had subsequently developed cognitive impairment had significantly lower at-rest systolic, diastolic, and mean blood pressure than controls (p &lt, 0.05). Further, compared with controls, their maximum heart rate was significantly higher at peak exercise. (4) Conclusion: The results from this study suggest that differences in cardiovascular response to stress might be present in individuals who develop cognitive decline. These findings challenge the possibility of assessing blood pressure and heart rate variability at rest and during cardiac stress as potential risk factors associated with cognitive impairment.

The objective of this study was to assess cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed motor features of Parkinson's disease several years after the cardiac stress testing. This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed until May 2012 to select those who developed Parkinson's disease. Heart rate and blood pressure both at rest and at peak exercise and heart rate variability at rest were recorded. For each patient who developed Parkinson's disease, 2 matched controls who did not develop Parkinson's disease at the end of the follow-up period were selected. Patients who were diagnosed with Parkinson's disease the same day of cardiac stress testing also were selected for comparison purposes. After excluding participants who were lost to follow-up, 2739 patients remained. From this cohort, 18 (11 men) had developed Parkinson's disease 4.27 ± 2.56 years after the cardiac stress test. Thirty-six matched controls were selected. At peak exercise, the maximum heart rate and the percentage of theoretical maximum heart rate were significantly lower in patients who developed Parkinson's disease after cardiac stress testing compared with controls. The sensitivity of a maximum heart rate ≤ 143 beats per minute to predict a diagnosis of Parkinson's disease after a mean of 4.27 years was 83%, and the specificity was 62%. The results from this exploratory study demonstrate that chronotropic insufficiency may constitute an early sign of Parkinson's disease during the premotor phase, serving as potential risk factor for its diagnosis. Further investigations are needed in larger populations. © 2013 Movement Disorder Society.

Objectives Study the differences in the oscillatory activity of the internal globus pallidus (GPi) in Parkisnon’s disease, dystonia, chorea and Tourette’s sindrome Methods 13 patients with Deep Brain Stimulation (DBS) of the GPi were studied by means of local field potential (LFP) recordings through the stimulation electrode. Seven patients had dystonia, and two patients had Parkinson’s disease, chorea and Tourette’s syndrome, respectively. Long segments (>5 min) of GPi-LFP recordings at rest were selected from each patient (in PD patients, “on” and “off” medication). Results The two PD patients had low-beta, high-beta and HFO peaks in the “off” power spectrum. In the “on” state, the low-beta peak attenuated and the HFO peaks changed in frequency and power, as expected. The patients with dystonia showed theta and high-beta peaks. However, either no HFO peak or a much smaller one (in only two patients) was observed. The two patients with chorea had high-beta and HFO peaks only. The patients with Tourette’s sindrome had no evident beta peaks, but HFO activity was very evident. Conclusions The activity observed in PD patients in the GPi is similar to that observed in the STN, including the presence of HFOs. HFOs are also observed in patients with chorea or Tourette’s syndrome, but might be absent or smaller in patients with dystonia. Beta peaks were absent in the two patients with Tourette’s syndrome. Significance The GPi and STN show similar oscillatory activity in PD, including HFOs. Different neurologic diseases are associtated with different oscillatory activities in the GPi.

The objective of this study was to assess cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed motor features of Parkinson's disease several years after the cardiac stress testing. This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed until May 2012 to select those who developed Parkinson's disease. Heart rate and blood pressure both at rest and at peak exercise and heart rate variability at rest were recorded. For each patient who developed Parkinson's disease, 2 matched controls who did not develop Parkinson's disease at the end of the follow-up period were selected. Patients who were diagnosed with Parkinson's disease the same day of cardiac stress testing also were selected for comparison purposes. After excluding participants who were lost to follow-up, 2739 patients remained. From this cohort, 18 (11 men) had developed Parkinson's disease 4.27 ± 2.56 years after the cardiac stress test. Thirty-six matched controls were selected. At peak exercise, the maximum heart rate and the percentage of theoretical maximum heart rate were significantly lower in patients who developed Parkinson's disease after cardiac stress testing compared with controls. The sensitivity of a maximum heart rate ≤ 143 beats per minute to predict a diagnosis of Parkinson's disease after a mean of 4.27 years was 83%, and the specificity was 62%. The results from this exploratory study demonstrate that chronotropic insufficiency may constitute an early sign of Parkinson's disease during the premotor phase, serving as potential risk factor for its diagnosis. Further investigations are needed in larger populations. © 2013 Movement Disorder Society.

La degeneración lobar frontotemporal engloba tres síndromes diferentes, que comparten características clínicas y patológicas comunes, dificultando así su diagnóstico en estadios iniciales. Se incluyen en este grupo las tres variantes de la demencia frontotemporal, el síndrome corticobasal y el síndrome de parálisis supranuclear progresiva. Se ha llevado a cabo una revisión del perfil neuropsicológico de cada uno de los síndromes, que permita clarificar las características fundamentales que los definen y ayudar a diferenciarlos de otras demencias. Se ha hecho una revisión de los diferentes trabajos publicados en la literatura al respecto, describiendo las características clínicas, patológicas y los hallazgos de imagen fundamentales de cada entidad para describir de manera exhaustiva los hallazgos en los diferentes dominios neuropsicológicos y su progresión. Aunque existe un solapamiento entre los síndromes que conforman la degeneración lobar frontotemporal, la comparación del perfil neuropsicológico de las mismas entre sí y frente a otras demencias permite establecer características propias de su perfil neuropsicológico para llevar a cabo un diagnóstico diferencial. Frontotemporal lobar degeneration encompasses three different syndromes, with clinical and pathologic commonalities, making diagnosis difficult in early stages. Three subtypes are recognized: frontotemporal dementia and its three variants, corticobasal syndrome and supranuclear palsy syndrome. The objective of this study is to review the neuropsychological features of each syndrome in order to differentiate amongst subtypes as well as from other forms of dementia. We review multiple studies from the literature, highlighting the main clinical features, neuropathology and changes in brain imaging of each syndrome. Subsequently, we describe the neuropsychological profile compared to other dementias, and how it progresses over time. Although there is an overlap amongst the different subtypes of frontotemporal lobar degeneration, neuropsychological profiles can help identify subtypes and discriminate frontotemporal lobar degeneration from other forms of dementia.