Giulia Di Lazzaro

Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers. However, neuropathology of iNPH is so rich and heterogeneous that many processes can be tracked in CSF, including Alzheimer’s disease core pathology, subcortical degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has not been provided yet. In this brief survey, we thus attempted to summarize the main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic model. Although defined cut-off values for biomarkers are not available, a better knowledge of CSF characteristics may definitely assist in diagnosing the disease.

Rotigotine may control drooling in patients with Parkinson's Disease: Preliminary findings

OBJECTIVE To evaluate the efficacy of rotigotine in controlling the drooling of Parkinsons Disease (PD) patients. PATIENTS AND METHODS We assessed 7 PD patients (Hoehn and Yahr scale >2.5) with three different clinical scores (Drooling Severity and Frequency Scale - DSFS, Drooling Rating Scale - DRS and Sialorrhea Clinical Scale for PD - SCS) before and after 4 weeks of therapy. Statistical differences were analyzed with Wilcoxon signed-rank test. RESULTS We observed that rotigotine significantly improves drooling as measured by the lowering of the three scores (p<0.05). CONCLUSIONS Among non-motor symptoms of PD, drooling is one of the most embarrassing and disabling for patients. Current treatments are unsatisfactory and novel approaches are thus desirable. In this open-label pilot study we demonstrated on a small sample of patients that up to 4mg/24h of rotigotine, a non-ergolinic dopamine agonist with continuous transdermal delivery, may be helpful in the management of drooling in advanced PD.

Does Pisa syndrome affect upper limb function in patients with Parkinson's disease? An observational cross-sectional study

BACKGROUND Trunk alignment is thought to contribute to upper limb (UL) function. However, this common assumption is not clear in patients with Parkinsons Disease (PD) suffering from Pisa syndrome (PS). PS is a postural abnormality, characterized by revisable lateral trunk flexion more than 10 degrees. OBJECTIVE To investigate the UL functioning and activities of daily living in PD patients with PS. METHODS Forty-five participants distributed equally in three groups PD patients with PS, PD patients without PS and age/sex matched healthy controls (HC). The function and disability of UL was assessed by Arm Shoulder and Hand (DASH) questionnaire for all groups. PD groups then completed clinical assessments by the Unified Parkinsons Disease Rating Scale (UPDRS) part II-III, Modified Hoenh & Yahr (mH&Y) staging and the Levodopa Equivalent Daily Dose (LEDD). RESULTS Three groups showed significant differences in DASH questionnaire (p < 0.001) with higher scores for PS group, intermediate for PD group and lower for HC group. PS group also showed higher score in UPDRS-II and mH&Y (p = 0.019), while no differences emerged between PD and PS in UPDRS-III score and LEDD. CONCLUSION Our results demonstrated that PS is associated with major impairment of both UL functioning and activities of daily living in PD patients.

Outlining a Population “at Risk” of Parkinson's Disease: Evidence from a Case-Control Study

The multifactorial pathogenesis of Parkinsons Disease (PD) requires a careful identification of populations “at risk” of developing the disease. In this case-control study we analyzed a large Italian population, in an attempt to outline general criteria to define a population “at risk” of PD. We enrolled 300 PD patients and 300 controls, gender and age matched, from the same urban geographical area. All subjects were interviewed on demographics, family history of PD, occupational and environmental toxicants exposure, smoking status, and alcohol consumption. A sample of 65 patients and 65 controls also underwent serum dosing of iron, copper, mercury, and manganese by means of Inductively Coupled-Plasma-Mass-Spectrometry (ICP-MS). Positive family history, toxicants exposure, non-current-smoker, and alcohol nonconsumer status occurred as significant risk factors in our population. The number of concurring risk factors overlapping in the same subject impressively increased the overall risk. No significant differences were measured in the metal serum levels. Our findings indicate that combination of three to four concurrent PD-risk factors defines a condition “at risk” of PD. A simple stratification, based on these questionnaires, might be of help in identifying subjects suitable for neuroprotective strategies.

CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients

INTRODUCTION Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD. METHODS CSF levels of 42-amyloid-β, total and phosphorylated tau, α-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features. RESULTS We observed that α-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively). CONCLUSIONS Our findings suggest that the reduction of CSF α-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF α-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.

Pisa Syndrome in Parkinson’s Disease: Evidence for Bilateral Vestibulospinal Dysfunction

Introduction Pisa syndrome (PS) is a postural complication of Parkinsons disease (PD). Yet, its pathophysiology remains unclear, although a multifactorial component is probable. Cervical vestibular evoked myogenic potentials (cVEMPs) explore vestibulospinal pathway, but they have not been measured yet in PD patients with PS (PDPS) to assess a potential vestibular impairment. Materials and Methods We enrolled 15 PD patients, 15 PDPS patients, and 30 healthy controls (HCs). They underwent neurological examination and were examined with Unified Parkinsons Disease Rating Scale II-III (UPDRSII-III), audiovestibular workup, and cVEMP recordings. Data were analysed with Chi-square, one-way ANOVA, multinomial regression, nonparametric, and Spearmans tests. Results cVEMPs were significantly impaired in both PD and PDPS compared with HCs. PDPS exhibited more severe cVEMP abnormalities with prevalent bilateral loss of potentials, compared with the PD group, in which a prevalent unilateral loss was instead observed. No clinical-neurophysiological correlations emerged. Conclusions Differently from HC, cVEMPs are altered in PD. Severity of cVEMPs alterations increases from PD without PS to PDPS, suggesting an involvement of vestibulospinal pathway in the pathophysiology of PS. Our results provide evidence for a significant impairment of cVEMPs in PDPS patients and encourage further studies to test validity of cVEMPs as diagnostic and prognostic biomarkers of PD progression.

Dopaminergic involvement in a drummer with focal dystonia: A case study

Musicians Dystonia (MD) represents an intriguing disorder with rich phenomenology and unclear pathophysiology. We observed a MD affecting left upper limb in a professional drummer. DaT-Scan revealed slight reduced uptake in the right putamen; no extrapyramidal or other neurological signs emerged in 2.5 years of follow up. The case offers insight on dopaminergic involvement in MD.

Assessment of Hearing Impairment in Parkinson's Disease: Implications for Differential Diagnosis and Disease Progression

Background and objective: Non-motor symptoms (NMS) of Parkinsons disease (PD) are still underestimated and causative of disability and poor quality of life. Recently, it has been suggested that hearing impairment could be included into the spectrum of NMS, although both mechanisms and phenomenology are unclear. In this study we investigated the peripheral auditory pathway of PD, in patients with asymmetric rest tremor (ART) without dopaminergic denervation, and comparison with healthy controls (HC), aiming to detect differential alterations of cochlear functioning and medial olivocochlear system (MOC).Methods: 23 PD patients, 9 with ART and 19 HC were assessed for auditory functions with clinical examination and Transient-evoked otoacoustic emissions (TEOAEs). PD and ART groups were also evaluated with Unified Parkinsons Disease Rating Scale (UPDRS) II-III and Hoehn and Yahr scale. One-way ANOVA analysis and Pearsons test were performed to measure differences between groups and correlations.Results: TEOAE responses in PD patients were significantly lower compared to HC at 3 and 4 kHz, bilaterally. PD patients showed statistically significant lower TEOAEs at the same frequencies compared to ARTs. In addition, a MOC dysfunction in PD patients was observed. Conversely, no difference was found between ART and HC in all tests performed.Conclusion: PD patients, differently from both ART patients and HC, show abnormalities of basal TEOAEs at the highest frequencies. Auditory dysfunction correlates to motor disturbances, suggesting an underlying dopaminergic pathogenic mechanism. Early recognition of hearing impairment may represent a tool for patient assessment and help in the differential diagnosis in ART patients.