Hyposmia correlates with axial signs and gait disorder in Parkinson's disease: an Italian Olfactory Identification Test study.

BACKGROUND: Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity). METHODS: One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT). RESULTS: Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05). CONCLUSIONS: In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function.

Validation of the Hemifacial Spasm Grading Scale: a clinical tool for hemifacial spasm.

BACKGROUND: To create an objective rating tool for hemifacial spasm (HFS) and validate it on a cohort of patients. METHODS: A panel of movement disorders specialists elaborated, through the Delphi method, the Hemifacial Spasm Grading Scale (HSGS). The validity of the scale was tested in a longitudinal, prospective observational study, with standardized video recording protocol before and after botulinum neurotoxin (BoNT) treatment. The video recordings obtained from each patient were then independently assessed with HSGS by three blinded raters. The scale was compared to patient-reported HFS-7 scale and to the clinical grading of spasm intensity scale. RESULTS: Intra-rater reproducibility ranged between ICC 0.73 (95% CI = 0.54-0.86) and 0.83 (0.68-0.92) and inter-rater reproducibility between 0.62 (95% CI = 0.44-0.77) and 0.82 (0.69-0.90). HSGS scores correlated with clinical grading of spasm intensity scale scores, but not with HFS-7. HSGS confirmed BoNT efficacy, with scores lowering at 1 month from treatment. CONCLUSIONS: HSGS represents an objective, quick and reliable scale for the assessment of HFS, and might be useful to monitor BoNT treatment efficacy over time.

Levodopa-responsive breathing discomfort in Parkinson's disease patients.

In Parkinson's disease (PD), respiratory disturbances have been reported and the effect of levodopa on respiratory function remains controversial. The objective of this study was to evaluate pulmonary function utilizing spirometric and subjective evaluations in mild to moderated PD. Thirty-four consecutive sporadic PD patients (Hoehn and Yahr scale: 1-3) were prospectively evaluated using clinimetric scales, spirometry and modified Borg scale, all in off- and on-conditions. To check the respiratory function, a follow-up was performed at 4 years in a subgroup of these patients. Spirometric results were normal for all patients in both the on- and off-conditions at baseline. After levodopa administration, in addition to a significant improvement in subjective state of breathing discomfort, the mean forced expiratory volume in 1 s (FEV1), vital capacity (VC), forced vital capacity (FVC) values and their mean percentages predicted values (FEV1%, VC%, FVC%) were significantly increased (p < 0.05). Moreover, residual volume, total lung capacity, and the FEV1/FVC ratio were not significantly different for the ON and OFF conditions. At 4-year follow-up no resulting variations in the baseline values for FEV1%, FVC% or VC% were revealed. The results from this prospective study suggest that PD patients report frequently pulmonary discomfort. Levodopa improves respiratory symptoms. Pulmonary restrictive and obstructive dysfunctions, when not present at baseline, might not be present at 4-year follow-up.

The validation of an Italian version of the Freezing of Gait Questionnaire.

Freezing of gait (FOG) is a common and disabling symptom in Parkinson's disease (PD) and its staging is complex because of its episodic nature. Patient-reported assessments are essential in evaluating this disabling symptom. The Freezing of Gait Questionnaire (FOG-Q) is considered a valid and reliable tool for the assessment of FOG severity. The aim of our study was to validate the Italian version of FOG-Q and to investigate for its association with several clinical aspects of PD. Fifty-one PD patients were administered the FOG-Q and the timed up and go test. Moreover, patients were evaluated for the unified PD rating scale (UPDRS), the Hoehn and Yahr Scale (H&Y) and the falls-efficacy scale [FES(S)]. Mean (SD) FOG-Q item scores ranged between 1.5 and 2.7 (1.0-1.4); corrected item-total correlations ranged between 0.63 and 0.86. The total FOG-Q score ranged between 0 and 24, with a mean + SD of 12.6 (6.2) and a median (q1-q3) of 12 (9-17). Reliability was 0.91. FOG-Q correlated with H&Y (0.36, p = 0.0091), UPDRS part III (rS = 0.27, p = 0.054), PD duration (rS = 0.35, p < 0.01), FES(S) (rS = 0.58, p < 0.001) and the timed up and go test (rS = 0.51, p = 0.001). Non-significant positive correlations were observed for dyskinesia and motor fluctuations. Our study validates the Italian version of the FOG-Q, in that it results being a reliable instrument for assessing FOG in PD patients.

Impulse Control Disorders and Levodopa-Induced Dyskinesias in Parkinson's Disease: Pulsatile versus Continuous Dopaminergic Stimulation.

BACKGROUND: Dopaminergic medications in Parkinson's disease (PD) are usually associated with the development of both levodopa-induced dyskinesias (LID) and impulse control and repetitive behavior disorders (ICRB). OBJECTIVE: To assess the prevalence and the severity of ICRB in a cohort of moderate and advanced PD patients and to investigate the potential interplay between ICRB, LID and dopaminergic therapies. METHODS: 117 PD patients were consecutively recruited. LID were assessed by using the Rush Dyskinesia Rating Scale (RDRS). ICRB were tested by means of Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS). RESULTS: 55 patients were affected by LID. Among them, 37 were treated only by oral therapy, OT (LID/OT), while 18 were on treatment with jejunal levodopa infusion, JLI (LID/JLI). 62 patients were not affected by LID (NLID) and all of them were on therapy only with oral drugs. The overall prevalence of clinically significant ICRB was 34% (95% CI = 26% to 43%) and the mean value (±SD) of QUIP-RS total score was 5.4±8.5. Prevalence of clinically significant ICRB, as well as severity of ICRB, was higher in patients with LID compared to NLID patients (p = 0.016 and p < 0.001, respectively). When considering LID/JLI, LID/OT and NLID groups, QUIP-RS total score was significantly higher in LID/OT patients compared to LID/JLI (10.4±11.8 vs. 4.9±6.0, p = 0.019) and NLID (10.4±11.8 vs. 2.5±4.8, p < 0.001) groups. CONCLUSION: PD patients with LID show ICRB more frequently and more severely than patients without LID. Among LID patients, those treated by JLI showed a lower severity of ICRB than those on OT, suggesting a potential protective effect of JLI on ICRB.

T2*-weighted MRI values correlate with motor and cognitive dysfunction in Parkinson's disease.

Brain iron load is one of the main neuropathologic hallmarks of Parkinson's disease (PD). Previous studies indicated that iron in the substantia nigra (SN) is related to disease duration and motor impairment. We explore, through a cross-sectional study, the association between brain iron distribution, evaluated by T2*-weighted magnetic resonance imaging (T2*), and clinical features in a cohort of patients with PD. Thirty-two patients with PD, compared with 10 control subjects, were evaluated for motor and cognitive features (attention and working memory, executive functions, language, memory, and visuospatial function). They underwent a magnetic resonance imaging protocol including T2* analysis of specific brain regions of interest to measure iron load compared with healthy control subjects. We found that iron content of the SN correlated positively with both disease duration and Unified Parkinson's Disease Rating Scale III off score. Montreal Cognitive Assessment, Spatial Span, and Graded Naming Test scores were inversely associated with iron load of the SN, whereas Wechsler Adult Intelligence Scale-IV Similarities score showed an inverse relationship with iron content in all the regions of interest examined. Our findings suggest a relationship between topographic brain iron distribution and cognitive domain impairment.

Stopping Onabotulinum Treatment after the First Two Cycles Might Not Be Justified: Results of a Real-life Monocentric Prospective Study in Chronic Migraine.

INTRODUCTION: Onabotulinum toxin A (OnabotA) cyclic treatment is approved for the prophylactic treatment of chronic migraine (CM), a highly disabling disorder. Although treatment response varies among patients, current guidelines suggest to stop treatment after cycle 2 if no response is achieved. This prospective study aimed to define, in real-life setting, the evolution of the response to OnabotA over five cycles of treatment among patients non-responding to cycle 1. The results of this study might help in decision-making, in particular whether prosecuting OnabotA further or not, when facing a patient not responding to cycle 1. METHODS: Patients failing to respond at cycle 1 were recruited to complete five cycles. Key outcomes were: (i) a ≥50% reduction in headache days, (ii) a ≥50% reduction in total cumulative hours of headache on headache days and (iii) a ≥5-point improvement in Headache Impact Test-6 (HIT-6) scores. RESULTS: Overall, 56 patients were included. Mean age was 45.7 years (female 83.9%). Severe (≥60) HIT-6 score was reported at baseline by 95.8% of patients. Responders (headache days reduction of more than 50%) progressively increased cycle after cycle, doubling from cycle 2 to cycle 5 (from 27 to 48%). In addition, patients regressed from CM to episodic migraine moving on with each cycle, with 78% of them reaching less than nine migraine days/month after cycle 5. The headache days per month decreased significantly from cycle 1 to cycle 5 (overall from 23.3 ± 5.7 to 9.2 ± 3.6; p < 0.001). During 12 months (5 cycles), migraine days per month progressively abated (from 18.5 to 8.7; p < 0.001), days with symptomatic medications intake/month consistently decreased (from 17.4 to 8.1; p < 0.001), and mean HIT-6 score lowered (from 72.4 ± 5.7 to 50.2 ± 4.3; p < 0.001). CONCLUSION: The positive effect of OnabotA treatment spreads over the course of the treatment and might also manifest late in treatment course among patients with no benefit after the first two cycles. Thus, the results of this real-life study suggest to extend OnabotA treatment further, beyond cycle 2, to avoid premature withdrawal in patients who would have become responders at cycle 3, 4, or 5.