15-Year Subthalamic Deep Brain Stimulation outcome in a Parkinson's disease patient with Parkin gene mutation: a case report.

INTRODUCTION: Parkinson's Disease (PD) patients with Parkin gene (PRKN) mutations show good response to subthalamic deep brain stimulation (STN-DBS). Currently, the longest follow-up available of these patients is 6 years. We report a very long-term outcome (more than 15 years) of a STN-DBS-treated patient with a compound heterozygous deletion of exons 3 and 11 of the PRKN gene. CASE REPORT: In 1993, a 39-year-old male was diagnosed with PD after the onset of resting tremor. Levodopa was started, and during the following 10 years, he reported good motor symptoms control, with only mild modification of levodopa intake and pramipexole introduction. In 2005, he developed disabling motor fluctuations and dyskinesia. In 2007, he underwent bilateral STN-DBS, with a marked improvement of motor symptoms and fluctuations during the following years. After 6 years, he reported mild motor fluctuations, improved after stimulation and treatment modifications. After 10 years he showed diphasic dyskinesias, feet dystonia, postural instability, and gambling (resolved after pramipexole discontinuation). In 2018, he developed a non-amnestic single-domain mild cognitive impairment (MCI). In 2023, after more than 15 years of STN-DBS, motor symptoms and fluctuations are still well controlled. He reports mild dysphagia, mild depression, and multiple-domain MCI. His quality of life is better than before surgery, and he still reports a subjective significant improvement from STN-DBS. CONCLUSION: Confirming the very long-term efficacy of STN-DBS in PRKN-mutated patients, our case report underlines their peculiar suitability for surgical treatment.

Burden of caregiving for cardiovascular dysautonomia in Parkinson's disease.

PURPOSE: We sought to estimate the impact of cardiovascular autonomic neuropathy (cAN) on informal caregivers of patients with Parkinson's disease (PD), defined as individuals providing regular care to a friend, partner, or family member with PD, and to evaluate the mutual relationship between caregiver burden and patient health-related quality of life (HRQoL). METHODS: We enrolled 36 consecutive patients with PD and their informal caregivers. Patients underwent a detailed motor, autonomic, cognitive, and functional assessment. Caregivers were assessed using the Zarit Burden Interview (ZBI). Differences in caregiver burden, expressed by the ZBI score, and strength of association between caregiver burden, cAN, and HRQoL were assessed using analysis of covariance (ANCOVA), logistic regression, and linear regression analyses. Analyses were adjusted for patients' age, PD duration, and motor and cognitive disability, as well as caregivers' age. RESULTS: Moderate-severe caregiver burden was reported in 41.7% of PDcAN+ versus 8.7% of PDcAN- (p < 0.001). The ZBI score was increased in PDcAN+ versus PDcAN- (31.5 ± 3.4 versus 15.2 ± 2.3; p < 0.001), with tenfold higher odds (p = 0.012) of moderate-severe caregiver burden in PDcAN+, even after adjusting for potential confounders. The ZBI score correlated with cAN severity (p = 0.005), global autonomic impairment (p = 0.012), and HRQoL impairment (p < 0.001). CONCLUSION: These results highlight the significant impact of cAN on PD caregivers and the need for targeted interventions addressing this frequently overlooked and insufficiently treated source of nonmotor disability in PD.

SARS-CoV-2 vaccination, Parkinson's disease, and other movement disorders: case series and short literature review.

BACKGROUND: Several neurological complications have been reported following SARS-Cov-2 vaccination, without a clear causal relationship ever being verified, including some cases of worsening of Parkinson's disease (PD) symptoms and new onset of movement disorders in non-parkinsonian patients. METHODS: We describe two new cases of PD patients treated with device-aided therapy who developed worsening of parkinsonian symptoms after receiving the third vaccine dose (booster). We also conducted a short review of the cases reported in literature of PD symptoms worsening and new onset of movement disorders in non-parkinsonian patients after SARS-Cov-2 vaccination. RESULTS: The first patient, a 46-year-old man implanted with bilateral Subthalamic Deep Brain Stimulation, experienced temporary motor and non-motor symptoms worsening after mRNA-1273 booster, improved after stimulation settings modification. The second patient, a 55-year-old man implanted with percutaneous endoscopic transgastric jejunostomy (PEG-J) for levodopa-carbidopa intestinal gel (LCIG) infusion experienced severe temporary worsening of dyskinesia and managed through temporary LCIG dose reduction. Other seven cases of vaccine-related movement disorder are currently reported in literature, four describing PD symptoms worsening and three the onset of new movement disorders in otherwise healthy people. CONCLUSION: Both our patients and the cases described so far completely recovered after few days with parkinsonian therapy modification, symptomatic treatment, or even spontaneously, underlining the transient and benign nature of side effects from vaccine. Patients should be reassured about these complications, manageable through a prompt evaluation by the reference neurologist.

Anxiety, depression, and worries in advanced Parkinson disease during COVID-19 pandemic.

BACKGROUND: The psychological impact of the COVID-19 outbreak and lockdown on frail populations with advanced Parkinson disease (APD) and their caregivers may present with peculiar features and require specific interventions. METHODS: We enrolled here 100 APD patients and 60 caregivers. Seventy-four patients were treated with device-aided therapies (DAT) and 26 with standard medical treatment (SMT). Through a telephonic interview, subjects underwent the Hospital Anxiety and Depression Scale (HADS-A; HADS-D), and an ad hoc questionnaire to explore thoughts and emotions related to the pandemic. RESULTS: Depression was observed in 35% of APD patients and anxiety in 39%, with a significant reduction of the latter after the lockdown (p= 0.023). We found a significant correlation between the type of therapy and the HADS-A score (p= 0.004). Patients' main worries were as follows: a possible higher risk of COVID-19 infection (25%), interruption of non-pharmacological treatments (35%), interruption of outpatient clinics (38%), PD complications related to COVID-19 (47%). Patients treated with DAT manifested worries about device-related issues and risk for caregivers' infection. The 40% of caregivers showed anxiety, while the 21.7% of them showed depression. CONCLUSION: Our study reveals a higher prevalence of anxiety and the presence of peculiar worries and needs in APD patients during the pandemic alongside psychological sequelae of their caregivers. These findings are important for neurologists and healthcare services to foster strategies for the management of psychological distress in both patients and caregivers.

Efficacy of safinamide as add-on therapy after subthalamic nucleus deep brain stimulation in Parkinson disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson's disease (PD). However, some patients still experience motor fluctuations or dyskinesia after STN-DBS. Safinamide is approved as add-on treatment to levodopa in fluctuating PD patients. In this study, we evaluated the effect of safinamide as adjunctive therapy in PD patients still experiencing motor fluctuations and dyskinesias after STN-DBS. METHODS: PD patients treated for at least 2 years with bilateral STN-DBST and with troublesome motor fluctuation and/or dyskinesias were examined by means of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the quality of life questionnaire Parkinson's Disease Questionnaire-8 (PDQ-8) and the Non-Motor Symptoms Scale (NMSS) at baseline (T0), after 1 month of treatment with safinamide 50 mg daily (T1) and after another month of treatment with safinamide 100 mg daily (T2). RESULTS: Twenty-nine PD patients were examined. An improvement of the MDS-UPDRS IV score (motor complications) was observed between T0 and T1, T0 and T2, and T1 and T2. The time spent in the OFF state, the functional impact and the complexity of motor fluctuations significantly improved between T0 and T1 and T0 and T2. The mean levodopa equivalent daily dose significantly decreased from T0 to T1 and from T0 to T2. Regarding non-motor symptoms, an improvement on mood and pain was observed. CONCLUSIONS: Safinamide seems to be an effective adjunctive treatment in PD patients treated with bilateral STN-DBS, leading to an improvement of motor complications, mood and pain.

Focal seizures with impaired awareness as long-term neurological complication of COVID-19: a case report.

We report here the first case of a young individual otherwise healthy, who presented with frequent focal seizures with impaired awareness as a possible long-term complication of severe acute respiratory syndrome coronavirus-2 infection. Seizures were documented by electroencephalography and responded clinically and neuro-physiologically to antiseizure therapy. The patient underwent an extensive investigation including cerebrospinal fluid examination, conventional and quantitative brain magnetic resonance imaging, and 18-FDG positron emission tomography. Beyond the clinical interest, this case contributes to clarify the possible pathways by which SARS-CoV-2 may enter the central nervous system and cause long-term neurological complications.

Should We Consider Deep Brain Stimulation Discontinuation in Late-Stage Parkinson's Disease?

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) effects may decrease with Parkinson's disease (PD) progression. There is no indication if, when, and how to consider the interruption of DBS treatment in late-stage PD. The objective of the current study was to investigate the percentage of "poor stimulation responders" among late-stage PD patients for elaborating an algorithm to decide whether and when DBS discontinuation may be considered. METHODS: Late-stage PD patients (Hoehn Yahr stage ≥4 and Schwab and England Scale <50 in medication on/stimulation on condition) treated with STN-DBS for at least 5 years underwent a crossover, double-blind, randomized evaluation of acute effects of stimulation. Physicians, caregivers, and patients were blinded to stimulation conditions. Poor stimulation responders (MDS-UPDRS part III change <10% between stimulation on/medication off and stimulation off/medication off) maintained the stimulation off/medication on condition for 1 month for open-label assessment. RESULTS: Thirty-six patients were included. The acute effect of stimulation was significant (17% MDS-UPDRS part III), with 80% of patients classified as "good responders." Seven patients were classified as "poor stimulation responders," and the stimulation was switched off, but in 4 cases the stimulation was switched back "on" because of worsening of parkinsonism and dysphagia with a variable time delay (up to 10 days). No serious adverse effects occurred. CONCLUSIONS: The vast majority of late-stage PD patients (92%) show a meaningful response to STN-DBS. Effects of stimulation may take days to disappear after its discontinuation. We present a safe and effective decisional algorithm that could guide physicians and caregivers in making challenging therapeutic decisions in late-stage PD. © 2020 International Parkinson and Movement Disorder Society.

Complex therapies for advanced Parkinson's disease: what is the role of doctor-patient communication?

OBJECTIVES: Communication processes play a key role in the patient-doctor relationship. Few studies have considered communicative processes in advanced Parkinson's disease (PD), and in particular in the phase of proposing complex therapies (CT). Therefore, we explored the role of communication and patient-doctor relationship in the transition phase to CT for advanced PD, analysing satisfaction, factors influencing the relationship and patients' unmet needs. MATERIALS AND METHODS: Twenty-four PD patients (mean age 61.7 ± 8.8 years; mean disease duration 12 ± 4.8 years) eligible for deep brain stimulation or infusion therapies were submitted to a semi-structured interview aimed to investigate communication-related cognitions, feelings and behaviours concerning PD and the possible transition towards CT. The Patient-Doctor Relationship Questionnaire (PDRQ-9) was administered along with neuropsychological and behavioural screening tests. RESULTS: All patients discussed the possible transition to CT with a neurologist. A high degree of satisfaction about the relationship with the neurologist was revealed (mean PDRQ-9 score 37.3 ± 7.3). The communication not only aroused feelings of fear (11/24 patients) and concern (15/24 patients), but also fostered the hope for motor improvement (15/24 patients). Half the patients (12/24) wanted to receive more information about CT after communication. CONCLUSIONS: This pilot study highlights the importance of doctor-patient communication in PD when facing the transition to CT. Trust in the physician emerged as a key point in favour of the therapeutic alliance. Neurologists should carefully consider patients' reactions and preferences for eliciting collaboration and treatment adherence, favouring a patient-centred standard of care.

Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different long-term outcome?

OBJECTIVES: Few clinical trials reported the comparative short-term efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) versus medical therapy in advanced Parkinson's disease (PD). However, the comparative efficacy, safety and the potential disease-modifying effect of these treatments have not been investigated over a longer follow-up period. METHODS: In this study, we organised a 'retrospective control group' to compare medical and surgical therapies over a long-term period. We assessed a group of PD patients suitable for STN-DBS but successively treated with medical therapies for reasons not related to PD, and a group of similar consecutive STN-DBS patients. We thus obtained two groups comparable at baseline, which were re-evaluated after an average follow-up of 6 years (range 4-11). RESULTS: Patients treated with STN-DBS showed a long-lasting superior clinical efficacy on motor fluctuations, with a significant reduction in the average percentage of the waking day spent in 'OFF' and in the duration and disability of dyskinesia. Moreover, operated patients showed a better outcome in the activities of daily living in 'Medication-OFF' condition. On the other hand, a similar progression of motor score and cognitive/behavioural alterations was observed between the two groups, apart from phonemic verbal fluency, which significantly worsened in STN-DBS patients. CONCLUSIONS: To our knowledge, this is the first long-term comparison between medical and surgical therapies; a superior efficacy of STN-DBS was observed on motor disability, while no significant differences were observed in the progression of motor symptoms and, apart from phonemic verbal fluency, of neuropsychological alterations.

Effects of dopaminergic therapy on sleep quality in fluctuating Parkinson's disease patients.

BACKGROUND: Sleep disorders negatively impact quality of life in Parkinson's disease (PD), yet the role of antiparkinsonian drugs on sleep quality is still unclear. We aimed to explore the correlation between sleep dysfunction and dopaminergic therapy in a large cohort of advanced PD patients. METHODS: Patients consecutively evaluated for device-aided therapies eligibility were evaluated by means of the PD Sleep Scale (PDSS-2; score ≥ 18 indicates poor sleep quality), and the Epworth Sleepiness Scale (ESS score ≥ 10 indicates excessive daytime sleepiness-EDS). Binary logistic regression analysis, adjusting for age, sex, disease duration, motor impairment, and sleep drugs, was employed to evaluate the association between dopaminergic therapy and PDSS-2 and ESS scores. Analysis of covariance assessed differences in PDSS-2 and ESS scores between patients without DA, and between patients treated with low or high doses of DA (cut-off: DA-LEDD = 180 mg). RESULTS: In a cohort of 281 patients, 66.2% reported poor sleep quality, and 34.5% reported EDS. DA treatment demonstrated twofold lower odds of reporting relevant sleep disturbances (OR 0.498; p = 0.035), while DA-LEDD, levodopa-LEDD, total LEDD, and extended-release levodopa were not associated with disturbed sleep. EDS was not influenced by dopaminergic therapy. Patients with DA intake reported significant lower PDSS-2 total score (p = 0.027) and "motor symptoms at night" domain score (p = 0.044). Patients with higher doses of DA showed lower PDSS-2 total score (p = 0.043). CONCLUSION: Our study highlights the positive influence of DA add-on treatment on sleep quality in this group of advanced fluctuating PD patients.

Effects of Continuous Dopaminergic Stimulation on Parkinson's Disease Gait: A Longitudinal Prospective Study with Levodopa Intestinal Gel Infusion.

Background: Gait issues, including reduced speed, stride length and freezing of gait (FoG), are disabling in advanced phases of Parkinson's disease (PD), and their treatment is challenging. Levodopa/carbidopa intestinal gel (LCIG) can improve these symptoms in PD patients with suboptimal control of motor fluctuations, but it is unclear if continuous dopaminergic stimulation can further improve gait issues, independently from reducing Off-time. Objective: To analyze before (T0) and after 3 (T1) and 6 (T2) months of LCIG initiation: a) the objective improvement of gait and balance; b) the improvement of FoG severity; c) the improvement of motor complications and their correlation with changes in gait parameters and FoG severity. Methods: This prospective, longitudinal 6-months study analyzed quantitative gait parameters using wearable inertial sensors, FoG with the New Freezing of Gait Questionnaire (NFoG-Q), and motor complications, as per the MDS-UPDRS part IV scores. Results: Gait speed and stride length increased and duration of Timed up and Go and of sit-to-stand transition was significantly reduced comparing T0 with T2, but not between T0-T1. NFoG-Q score decreased significantly from 19.3±4.6 (T0) to 11.8±7.9 (T1) and 8.4±7.6 (T2) (T1-T0 p = 0.018; T2-T0 p < 0.001). Improvement of MDS-UPDRS-IV (T0-T2, p = 0.002, T0-T1 p = 0.024) was not correlated with improvement of gait parameters and NFoG-Q from T0 to T2. LEDD did not change significantly after LCIG initiation. Conclusion: Continuous dopaminergic stimulation provided by LCIG infusion progressively ameliorates gait and alleviates FoG in PD patients over time, independently from improvement of motor fluctuations and without increase of daily dosage of dopaminergic therapy.

Axial symptoms as main predictors of short-term subthalamic stimulation outcome in Parkinson's disease.

Deep brain stimulation (DBS) is an established therapeutic option for Parkinson's disease (PD) patients; however, a clear-cut definition of subthalamic (STN) DBS predictors in PD is lacking. We analyzed a cohort of 181 STN-treated PD patients and compared pre- vs. 1-year post-surgical motor, dyskinesia, Off time, and daily-life activities (ADL) scores. A multivariate linear regression analysis was used to evaluate the association between clinical/demographic characteristics and the extent of STN-DBS response for outcomes proving a significant change after surgery. After STN-DBS, we observed a significant improvement of motor symptoms (P < 0.001), dyskinesia (P < 0.001), and daily Off time (P < 0.001). Sex, PD duration, cognitive status, and the motor and axial response to levodopa significantly explained the motor improvement (R = 0.360, P = 0.002), with presurgical response of axial symptoms (Beta = 0.203, P = 0.025) and disease duration (Beta = 0.205, P = 0.013) being the strongest predictors. Considering the daily Off time improvement, motor and axial response at the levodopa challenge test and disease duration explained 10.6% of variance (R = 0.326, p < 0.001), with disease duration being the strongest predictor of improvement (Beta = 0.253, p: 0.001) and axial levodopa response showing a trend of significance in explaining the change (Beta = 0.173, p: 0.056). Dyskinesia improvement was not significantly explained by the model. Our findings highlight the emerging role of axial symptoms in PD and their response to levodopa as potentially pivotal also in the DBS selection process.

Visuospatial Deficits Are Associated with Pisa Syndrome and not Camptocormia in Parkinson's Disease.

Background: Pisa syndrome (PS) and camptocormia (CC) are postural abnormalities frequently associated with Parkinson's disease (PD). Their pathophysiology remains unclear, but the role of cognitive deficits has been postulated. Objectives: To identify differences in the neuropsychological functioning of patients with PD with PS or CC compared with matched patients with PD without postural abnormalities. Methods: We performed a case-control study including 57 patients with PD with PS (PS+) or CC (CC+) and 57 PD controls without postural abnormalities matched for sex, age, PD duration, phenotype, and stage. Patients were divided into four groups: PS+ (n = 32), PS+ controls (PS-, n = 32), CC+ (n = 25), and CC+ controls (CC-, n = 25). We compared PS+ versus PS- and CC+ versus CC- using a neuropsychological battery assessing memory, attention, executive functions, visuospatial abilities, and language. Subjective visual vertical (SVV) perception was assessed by the Bucket test as a sign of vestibular function; the misperception of trunk position, defined as a mismatch between the objective versus subjective evaluation of the trunk bending angle >5°, was evaluated in PS+ and CC+. Results: PS+ showed significantly worse visuospatial performances (P = 0.025) and SVV perception (P = 0.038) than their controls, whereas CC+ did not show significant differences compared with their control group. Reduced awareness of postural abnormality was observed in >60% of patients with PS or CC. Conclusions: Low visuospatial performances and vestibular tone imbalance are significantly associated with PS but not with CC. These findings suggest different pathophysiology for the two main postural abnormalities associated with PD and can foster adequate therapeutic and prevention strategies.

Association between sleep disorders and cognitive dysfunctions in non-demented patients with advanced Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is increasingly recognized as a multidimensional disorder, characterized by several non-motor symptoms, including disturbances of sleep and cognition. Current studies on the relationship between sleep problems and neuropsychological functions, mainly conducted in early to moderate PD patients, outline mixed results. In this study, we analysed the relationship between subjectively reported sleep alterations and cognitive functions in a large cohort of 181 advanced PD patients. METHODS: All consecutive, non-demented, advanced PD patients candidates for device-aided therapy completed two self-administered sleep questionnaires-the Parkinson's Disease Sleep Scale (PDSS-2) and the Epworth Sleepiness Scale (ESS)-and underwent a comprehensive battery of neuropsychological tests encompassing five cognitive domains (reasoning, memory, attention, frontal executive functions, and language). RESULTS: Patients showed mild to moderate sleep problems (PDSS-2 score: 23.4 ± 1.2) and mild daytime sleepiness (ESS 8.6 ± 5.1). A significant correlation was found between PDSS-2 total score and non-verbal reasoning, as well as attentive skills, executive functions, and language abilities. No correlations were found between sleep measures and memory tests scores. Patients with clinically relevant sleep disturbances performed worse on attention, executive functions, and language. No significant correlations were found between daytime sleepiness and any neuropsychological test. CONCLUSIONS: In advanced PD patients, sleep disturbances selectively correlate with specific neuropsychological functions and not with short-term memory and consolidation. Even if confirmations by means of longitudinal studies are needed, our observations suggest the importance of considering treatment of sleep disturbances to minimize their potential impact on cognition.

Low frequency subthalamic stimulation and event-related potentials in Parkinson disease.

BACKGROUND: High frequency (130 Hz) subthalamic Deep-Brain-Stimulation (STN-DBS) optimally improves cardinal motor symptoms in Parkinson disease (PD). Low stimulation frequencies (60-80 Hz) improve axial symptoms in some patients and, according to preliminary evidences, may also have a beneficial effect on the cognitive component of motor planning. OBJECTIVE: To analyze the configuration of the P300 component of cortical event-related auditory potentials (ERPs), a reliable index of attentive cognitive functions, at different stimulation frequencies in STN-DBS in PD patients. METHODS: 12 PD patients underwent ERPs recordings using a standard oddball auditory paradigm with STN-DBS at 60 Hz, 80 Hz, 130 Hz, and OFF-stimulation, applied in a randomized double-blind sequence. ERPs analysis considered the peak amplitude and latency of the P300 components at midline electrode positions (Fz, Cz, Pz). RESULTS: P300 latency over Cz and Pz electrodes significantly increased with STN-DBS at 130 Hz compared to OFF-stimulation. P300 latency was also significantly increased, though to a lesser degree, over Pz electrode with stimulation at 80 Hz. No significant P300 latency modifications were detected at 60 Hz stimulation compared to OFF-stimulation condition. P300 amplitude did not change significantly for any of the stimulation conditions tested. CONCLUSIONS: Low frequency STN-DBS is associated with minor modifications of P300 latency compared to conventional stimulation at 130 Hz, possibly suggesting that 60 and 80 Hz may have less interference with attentive and cognitive processes in PD patients.

COVID-19 and Parkinson's Disease: What Do We Know So Far?

BACKGROUND: Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected patients enrolled in most studies did not allow to draw robust conclusions on the COVID-19 impact in PD. OBJECTIVE: We aimed to assess whether the prevalence and outcome of COVID-19 in PD patients are different from those observed in the general population. METHODS: We conducted a systematic review of studies reporting data on PD patients with a diagnosis of COVID-19 (PD-COVID+). We extracted prevalence, clinical-demographic data, outcome, and mortality. We also analyzed risk or protective factors based on comparisons between PD-COVID+ and control populations with PD without COVID-19 or without PD with COVID-19. RESULTS: We included 16 studies reporting on a total of 11,325 PD patients, 1,061 with a confirmed diagnosis of COVID-19. The median infection prevalence ranged from 0.6% to 8.5%. PD-COVID+ patients had a median age of 74 and a disease duration of 9.4 years. Pooling all PD-COVID+ patients from included studies, 28.6% required hospitalization, 37.1% required levodopa dose increasing, and 18.9% died. The case fatality was higher in PD-COVID+ patients than the general population, with longer PD duration as a possible risk factor for worse outcome. Amantadine and vitamin D were proposed as potential protective factors. CONCLUSION: Available studies indicate a higher case fatality in PD patients affected by COVID-19 than the general population. Conversely, current literature does not definitively clarify whether PD patients are more susceptible to get infected. The potential protective role of vitamin D and amantadine is intriguing but deserves further investigation.

Deep brain stimulation outcomes in the malignant end of Parkinson's disease spectrum.

BACKGROUND: Heterogeneity of Parkinson's Disease (PD) phenotype may influence deep brain stimulation (DBS) outcome. However, DBS response in the malignant end of the PD spectrum has been poorly investigated. OBJECTIVE: To evaluate and compare DBS outcomes in malignant and benign PD patients, defined according to motor and non-motor symptom presentation at the presurgical selection. METHODS: We categorized a cohort of 154 parkinsonian patients fulfilling criteria for subthalamic nucleus (STN)-DBS into malignant, benign, and intermediate subtypes, according to a recently validated clinical PD classification. DBS efficacy on daily living independence (Schwab and England -S&E-score ≥70%), motor symptoms, and motor fluctuations (Unified Parkinson's Disease Rating Scale -UPDRS- part-III and -IV, and Ambulatory Capacity Measure) were compared between malignant and benign patients, using corrected binary logistic regressions and repeated measure general linear model. RESULTS: One year after surgery, the probability of losing daily life independence was 16-fold higher in malignant patients, even after adjusting for age at PD onset, PD duration, and percentage of motor improvement after STN-DBS (OR: 16.233; p: 0.035). Conversely, malignant and benign patients showed a similar extent of improvement after STN-DBS (p > 0.05) in motor symptoms, motor fluctuations, and ambulatory capacity, both in medication-ON and medication-OFF conditions. CONCLUSION: DBS candidates in the malignant end of the PD spectrum may profit from a similar improvement of motor symptoms and fluctuations after STN-DBS when compared to benign PD. However, patients of the malignant group have a lower probability of maintaining independence in daily life early after surgery.

Neurological comorbidities and COVID-19-related case fatality: A cohort study.

BACKGROUND: Neurological involvement in Coronavirus disease-2019 (COVID-19) is widely recognized. However, the role of pre-existing neurological comorbidities in modulating COVID-19-related mortality still remains unclear. This cohort study evaluates the COVID-19-related case fatality rate (CFR) of patients with pre-existing neurological diseases. METHODS: We retrospectively evaluated all patients consecutively admitted to our hospital with a diagnosis of COVID-19 between March and April 2020. We used a multivariate regression analysis to estimate the association between pre-existing neurological diseases and COVID-19-related mortality. Then, we compared the CFR and survival curves of two cohorts (patients suffering vs. those not suffering from pre-existing neurological disease), matched trough the propensity score (PS). Age and other comorbidities were considered for PS calculation. We applied a 1:1 matching for the entire neurological cohort and, separately, for cerebrovascular, neurodegenerative, and other neurological diseases. RESULTS: Among 332 patients, 75 (22.6%) were affected by pre-existing neurological disease (n = 29 cerebrovascular, n = 26 neurodegenerative, n = 20 others). From the multivariate regression analysis, they resulted with a significant increase of COVID-19-related mortality (OR:2.559; 95%CI 1.181-5.545; p < 0.017). From the cohort analysis, CFR resulted 2-fold higher in patients with neurological disease (48.0% vs. 24.0%; p = 0.002). CFR was significantly higher in patients with neurodegenerative diseases compared to matched individuals (73.9% vs. 39.1%; p = 0.017), while CFR increase in patients with cerebrovascular diseases did not reach statistical significance (48.3% vs. 41.4%; p = 0.597). CONCLUSIONS: Pre-existing neurological comorbidities, in particular neurodegenerative diseases, increase significantly COVID-19-related case fatality, indicating a clear priority for viral screening, access to care facilities and vaccination in these populations.

Neurological comorbidity and severity of COVID-19.

OBJECTIVE: Neurological symptoms of COVID-19 patients have been recently described. However, no comprehensive data have been reported on pre-existing neurological comorbidities and COVID-19. This study aims at evaluating the prevalence of neurological comorbidities, and their association with COVID-19 severity. METHODS: We evaluated all consecutive patients admitted to the Emergency Room (ER) of our hospital between the 3rd March and the 14th April 2020, and diagnosed with COVID-19. Data on neurological and non-neurological diseases were extracted, as well as data on demographic characteristics and on severity degree of COVID-19. The prevalence of neurological comorbidities was calculated, and multivariate binary logistic regression analyses were used to estimate the association between neurological diseases and COVID-19 severity. RESULTS: We included 344 patients. Neurological comorbidities accounted for 22.4% of cases, with cerebrovascular diseases and cognitive impairment being the most frequent. Neurological comorbidity resulted independently associated with severe COVID-19 (OR 2.305; p = 0.012), as well as male gender (p = 0.001), older age (p = 0.001), neoplastic diseases (p = 0.039), and arterial hypertension (p = 0.045). When neurological comorbidity was associated with non-neurological comorbidities, the OR for severe COVID-19 rose to 7.394 (p = 0.005). Neurological patients, in particular cerebrovascular and cognitively impaired ones, received more respiratory support indication. CONCLUSION: Neurological comorbidities represent a significant determinant of COVID-19 severity, deserving a thorough evaluation since the earliest phases of infection. The vulnerability of patients affected by neurological diseases should suggest a greater attention in targeting this population for proactive viral screening.

Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders.

OBJECTIVE: To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: Supine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales. RESULTS: A total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72). CONCLUSIONS: OH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.