Search

Parkinson's disease is a neurodegenerative disorder and its etiology is unknown, numerous studies show how different environmental factors can influence the development of disease. miRNAs are involved in several pathologies and their dysregulation contribute to different pathologies, also in neurodegenerative such as Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic lateral sclerosis. In this study, we profiled the expression of different candidate miRNAs: miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients and unaffected controls (HCs).We investigated the expression of miRNAs by RT-real time PCR, the results were subjected to statistical analysis. miRNA-155-5p was generally up-regulated in PD patients compared to HCs whereas miRNA-146a-5p was down-regulated in PD patients in comparison to HCs. It is interesting to point out that the expression of miR-155-5p was modified by levodopa treatment, in fact a down-regulation of miR-155-5p in PD patients with the highest dosage was observed. In conclusion, miRNA 155 could not only be a promising target for the anti-inflammatory therapy in PD but also a good candidate as a disease progression biomarker. The role of levodopa in modulating the levels of miRNA 155 requires further studies.•Expression of miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients have been evaluated.•miRNA-155-5p was up-regulated in PD patients compared to HCs, and miRNA-146a-5p was down-regulated in PD patients vs HCs./span•We observed a down-regulation of miR-155-5p in PD patients with the highest dosage was observed./span•miRNA 155 could be a target for the anti-inflammatory therapy in PD, and a good candidate as a disease progression biomarker.

Environmental factors are implicated in the development of Parkinson's disease (PD). The aim of this study is to investigate the role of cell-mediated immunity upon a specific immune-stimulation with HSV-1 and human alpha-synuclein homologues peptides by using the intracellular cytokine method on Parkinson's patients and healthy controls. The study showed, for the first time, a specific response to TNF-α CD8, CD4 and NK cells after stimulation in PD patients. Our data show a possible role of the immune system in the pathogenesis of Parkinson's disease, and that HSV-1 infections may lead to a progression of the disease.

Objective To explore the effects of Dance Therapy (DT) and Traditional Rehabilitation (TR) on both motor and cognitive domains in Parkinson's Disease patients (PD) with postural instability. Methods Sixteen PD patients with recent history of falls were divided in two groups (Dance Therapy, DT and Traditional Rehabilitation, TR); nine patients received 1-hour DT classes twice per week, completing 20 lessons within 10 weeks; seven patients received a similar cycle of 20 group sessions of 60 minutes TR. Motor (Berg Balance Scale - BBS, Gait Dynamic Index - GDI, Timed Up and Go Test - TUG, 4 Square-Step Test - 4SST, 6-Minute Walking Test - 6MWT) and cognitive measures (Frontal Assessment Battery - FAB, Trail Making Test A & B - TMT A&B, Stroop Test) were tested at baseline, after the treatment completion and after 8-week follow-up. Results In the DT group, but not in the TR group, motor and cognitive outcomes significantly improved after treatment and retained after follow-up. Significant changes were found for 6MWT (p = 0.028), TUG (p = 0.007), TMT-A (p = 0.014) and TMT-B (p = 0.036). Conclusions DT is an unconventional physical therapy for PD patients which effectively impacts on motor (endurance and risk of falls) and non-motor functions (executive functions).

In Parkinson's disease (PD) ZnT proteins play an important role. Zinc is a co-factor of numerous enzymes and stabilizes the tertiary structure of several proteins. Nothing is known about previous infections mediated by Mycobacterium avium subsp. paratuberculosis (MAP). We evaluated if a previous infection with MAP could induce the production of antibodies that cross-reacted with the Znt homologous antigenic peptides associated to Parkinson. The humoral response toward MAP3865c peptides, ZnT3 and ZnT10 was evaluated. The hypothesis of cross-reactivity needs to be confirmed; we have observed the presence of MAP in PD patients by PCR, positivity to MAP3865c peptides, therefore MAP infection but not cross-reaction with human homologous Znt proteins.

To contribute to the differentiation of Parkinson's disease (PD) and essential tremor (ET), we compared two different artificial neural network classifiers using (123)I-FP-CIT SPECT data, a probabilistic neural network (PNN) and a classification tree (ClT).(123)I-FP-CIT brain SPECT with semiquantitative analysis was performed in 216 patients: 89 with ET, 64 with PD with a Hoehn and Yahr (HY) score of ≤2 (early PD), and 63 with PD with a HY score of ≥2.5 (advanced PD). For each of the 1,000 experiments carried out, 108 patients were randomly selected as the PNN training set, while the remaining 108 validated the trained PNN, and the percentage of the validation data correctly classified in the three groups of patients was computed. The expected performance of an "average performance PNN" was evaluated. In analogy, for ClT 1,000 classification trees with similar structures were generated.For PNN, the probability of correct classification in patients with early PD was 81.9±8.1% (mean±SD), in patients with advanced PD 78.9±8.1%, and in ET patients 96.6±2.6%. For ClT, the first decision rule gave a mean value for the putamen of 5.99, which resulted in a probability of correct classification of 93.5±3.4%. This means that patients with putamen values5.99 were classified as having ET, while patients with putamen values5.99 were classified as having PD. Furthermore, if the caudate nucleus value was higher than 6.97 patients were classified as having early PD (probability 69.8±5.3%), and if the value was6.97 patients were classified as having advanced PD (probability 88.1%±8.8%).These results confirm that PNN achieved valid classification results. Furthermore, ClT provided reliable cut-off values able to differentiate ET and PD of different severities.

Environmental factors are implicated in the development of Parkinson's disease (PD). We have investigated on the role of molecular mimicry between HSV1 and α-synuclein that could foster the progression of PD. The antibody response against homologous peptides in PD patients and healthy controls was evaluated, showing that these antibodies are highly prevalent among PD patients to healthy controls. The competitive assay demonstrated cross-reactivity between HSV1 and human α-synuclein peptides. The results may suggest the hypothesis of the involvement of HSV1 in stimulating the immune cells against the neurons of the substantia nigra as a consequence of the cross reactivity.

Long-standing overt ventriculomegaly in adults (LOVA) is a clinical entity characterized by chronic hydrocephalus with infant onset, slow evolution and clinical disturbances during adulthood. Few cases are reported in literature describing the evident contrast between the severity of hydrocephalus and the relatively spared neurological functioning and cognitive aspects. The authors describe a 59-year-old man with congenital hydrocephalus complaining of persistent gait impairment. Neurological examination showed a mild paraparesis, severe higher cortical function impairment but relatively sparing of daily living activity. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a very remarkable ventriculomegaly compressing the brain cortex but sparing the cerebellum and the brainstem. Brain Single Photon Emission Computer Tomography (SPECT) showed a prevalent cerebellar perfusion as well. Neuropsychological testing was consistent with severe cognitive deterioration and attention disorders. Language and praxis functions seemed to be preserved. Auditory oddball ERPs (P300) showed morphological abnormalities especially of late components. This case report demonstrates in vivo the level of adaptation to which human brain can reach under chronic mechanic stress conditions. The striking poor cerebral parenchyma representation and the relatively spared language and praxic abilities account for a functional reorganization of residual structures due to the neural plasticity.

To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients.Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills.All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P0.04) and auditory (P0.04) P300 latency and impaired NP tests was found.In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

Brainstem degeneration in Parkinson’s disease (PD) may explain the occurrence of many non-motor symptoms in this condition. Purposes of the present work were to investigate brainstem function in PD through a battery of vestibular-evoked myogenic potentials (VEMP) allowing a comprehensive brainstem exploration and to correlate VEMP findings with symptoms related to brainstem involvement. Cervical (cVEMP), masseter (mVEMP) and ocular (oVEMP) VEMPs were investigated in 24 PD patients and compared with those recorded in 24 age-matched controls. Presence of symptoms ascribable to brainstem dysfunction, such as daytime sleepiness, REM sleep behavior disorder and depression, was investigated through Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale, REM Sleep Disorder Screening Questionnaire (RBD-SQ) and Geriatric Depression Scale. Postural instability was additionally assessed through mini-BESTest. The frequency of alteration of VEMPs in patients was 83.3 % when considering the whole set and 41.7 % for cVEMP, 66.7 % for mVEMP and 45.8 % for oVEMP. This was significantly different from controls, with absence being the prevalent alteration in PD. A significant inverse correlation between the number of altered VEMPs and mini-BESTest and a direct correlation with RBD-SQ were found. The VEMP battery under study allowed the identification of brainstem dysfunctions in PD patients, which correlated with clinical tests suggestive of postural and REM sleep disorders. VEMPs might represent a valuable tool of brainstem assessment in PD.

To study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement.Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n=14, disease duration 1.42±0.7years), advanced PD (n=19, disease duration 7.26±2.9years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale.Rate of VEMPs alterations was higher (p0.001) in PD than controls, but similar within PD groups. However, early and advanced PD showed a different pattern of abnormalities (p=0.02), being latency delay prevalent in the former and absence in the latter. VEMP impairment correlated directly with RBD-SQ scores in both PD cohorts and inversely with Mini-BESTest scores in advanced PD.VEMPs displayed progressive severity of alterations at different stages of PD, with remarkable correlations with presence of postural instability and RBD.The combined use of VEMPs may provide interesting insights into the pathophysiological mechanisms of PD at the earliest and prodromal stage of the disease.

Background Recent research has highlighted the role of brainstem (BS) structures in the early spread of Parkinson’s Disease (PD) pathological process. Vestibular Evoked Myogenic Potentials (VEMPs) corresponding to the Vestibulo-Ocular (VOR), Vestibulo-Masseteric (VMR) and Vestibulo-Collic (VCR) reflexes can provide information on BS function. Aims: to test the aforesaid set of VEMPs in a cohort of PD patients and healthy controls and to correlate it with presence of symptoms ascribable to BS dysfunction. Methods 19 PD patients (age 66.9 ± 5.4 years; 12 males; mean disease duration 6.16 ± 3.54 years) and 15 age and sex matched controls underwent bilateral recording of VOR, VMR and VCR from inferior oblique, masseter and sternocleidomastoid active muscles, respectively. PD patients were additionally administered a series of clinical scales used for evaluation of brainstem-integrated activities, namely sleep disorders (Epworth Sleepiness Scale, Parkinson’s Disease Sleep Scale and REM Sleep Behavior Disorder-Screening Questionnaire or RBD-SQ), postural instability (MiniBESTest) and depression (Geriatric Depression Scale). Groups’ comparisons were performed with χ 2 test and Mann–Whitney U-test; Sperman’s rho test was used for correlation analysis. Results VEMPs were significantly impaired in patients compared to controls, absence being the main pattern of alteration. When the set of the 3-VEMP battery was analyzed, both number of altered reflexes ( p = 0.017) and severity of alteration ( p = 0.001) were significantly higher in patients than controls. As for each single VEMP, only the VOR and the VMR were significantly altered (VOR: p = 0.022; VMR: p = 0.005; VCR: p = 0.056). Clinical scales revealed the presence of some degree of depression in 36.8% of patients, sleep disturbances in 68.4%, REM sleep disorder in 26.3% and postural instability in 36.8% of PD patients. A significant correlation with VEMP alterations was found only for high scores on RBD-SQ ( ρ = 0.554; p = 0.014). Conclusions Combined assessment of VOR, VMR and VCR was able to detect BS dysfunction in a rostro-caudal extension in PD. This may prove interesting in the perspective of identifying neurophysiological markers of BS dysfunction in early stages of the disease.

We report the first instance of restless legs syndrome (RLS) associated with periodic limb movements (PLM) and disruption of sleep architecture occurring in a patient following ischemic infarction in the right lenticulostriate region. Recently, a role for the basal ganglia–brainstem system in the control of motor behaviors and in the regulation of awake–sleep states has been proposed. The purported roles of these structures may be relevant in explaining the occurrence of the RLS in our patient. The discrete brain localization observed in this patient may be a clue to a better understanding of the pathophysiology of RLS and PLM.

Cerebellar pathology commonly shows important motor signs and less evident cognitive dysfunction. The ’cerebellar cognitive affective syndrome’ is characterised by impairment on executive function, spatial cognition, language and behaviour. We report the case of a man with acute onset of transitory motor features and severe mental disorders. Cranial CT and brain MRI revealed extended cerebellar lesions. Neuropsychological assessment disclosed deficits of attention, executive function and memory. Auditory event–related potentials showed abnormal P300. These data suggest a pure “cerebellar cognitive affective syndrome” and strengthen the hypothesis of cerebellar cognitive function modulation.

Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed. Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time. Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions. Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

1. Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Benign Monomelic Amyotrophy (BMA) is a sporadic condition characterized by a neurogenic amyotrophy that affects a single either upper or lower limb; typically the disease is confined to second motoneuron involvement without cerebellar, pyramidal and cognitive signs; extrapyramidal features are not reported in BMA. We describe the case of a patient who experienced weakness and muscle atrophy in the right limb which starts approximately 5 years ago and progressed over the following 4 years. There was no history of poliomyelitis or familial neuromuscolar diseases. He denied any sensory symptoms; neurological examination showed marked amyotrophy of the right calf and mild amyotrophy of the right thigh with mild-to-moderate weakness; cranial nerves, sensory, pyramidal and cerebellar systems were normal. Needle electromyography revealed fibrillation potentials (acute denervation), polyfasic action potential, increased amplitude and long-duration of MUAPs and reduced recruitment pattern (chronic partial denervation and reinnervation). Transcranial magnetic stimulation was normal. MRI of the lower limbs detected severe right leg muscle atrophy and muscular replacement with adipose tissue. After one year extrapyramidal signs were observed as follows: hypomimia, bradykinesia, akinesia, axial and bilateral arm rigidity with decreased arm swing, postural instability, without cerebellar signs or cognitive decline. SPECT DAT SCAN examination showed reduced dopaminergic innervation in the striatum on both sides. We observed improvement of extrapyramidal features with Levodopa replacement therapy. Extrapyramidal dysfunctions are uncommon but recognized feature in motor neuron disease for which the pathological substrate is uncertain. To our knowledge this is the first description of BMA associated with Parkinsonism.

Parkinson’s disease (PD) is one of the most common movement disorders and is characterized by progressive neurodegeneration of the basal ganglia, with tremor, postural instability, rigidity and Akinesia as main clinical features, but also psychiatric symptoms such as depression, anxiety and insomnia are common in PD. Conversion disorder (CD), formerly known as hysteria, is defined as a condition in which patients suffers from neurological symptoms without neurological causes, and is considered a psychiatric disorder according to the DSM-IV. Psychogenic movement disorders (PMD) are characterized by either hyperkinetic or hypokinetic movement disorders, or their combinations not fully explained by organic disease and occurring in association with underlying psychiatric or psychological factors. We present a case of a 60-year old woman with extrapyramidal signs such as tremor, postural instability, and both akinesia and dyskinesia, with acute onset after a psychological traumata. Observed in various movement disorders centers different diagnostic hypotheses were postulated including Huntington’s disease, Parkinson’s disease, distonia, corticobasal degeneration. SPECT DAT-scan evaluation showed reduced dopaminergic innervation in the striatum bilaterally predominantly on the right. No consistent response to dopaminergic replacement therapy was observed. Neuropsychological examination revealed a conversion disorder. We discuss the long diagnositic iter with many clinical evaluations and neuroradiological investigations, their economical burden and the diagnostic difficulties on behalf of literature data.