Unveiling the role of subjective cognitive complaints in predicting cognitive impairment in Parkinson´s Disease- A longitudinal study with 4 year of follow up.

BACKGROUND: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). OBJECTIVE: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. METHODS: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. RESULTS: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. CONCLUSION: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints.

The Role of Neurohospitalism in a Specialized Cardiovascular Hospital.

INTRODUCTION: Cardiology and cardiothoracic surgery are among the specialties that most commonly require neurology inpatient consultations. We aimed to study the neurology referrals by the cardiovascular-specialized hospital included in our tertiary hospital center. METHODS: Retrospective study of consecutive patients referred for neurology inpatient consultation between January 1, 2020, and December 31, 2022. We analyzed referrals, patients' characteristics, and the approach taken. A detailed subanalysis was performed for patients diagnosed with acute ischemic stroke (AIS). RESULTS: 143 patients were observed (mean age 67.3 years, 46 [32.2%] females). Most frequent referral reasons were suspected AIS deficits (39.2%), altered mental status (19.6%), suspected seizures (13.3%), and neuroprognostication (11.9%). Mean referral-to-consult time was 2.7 days, and 117 (81.8%) consults were in-person. Additional investigation, treatment changes, and outpatient clinic referral were proposed, respectively, in 79.7%, 60.1%, and 19.6% of patients. Most common diagnoses were AIS (45.5%), hypoxic-ischemic encephalopathy (18.9%), and delirium (7.0%). Regarding patients with AIS (n = 62), most common stroke causes were post-cardiac procedure (44.6%), infective endocarditis (18.5%), aortic dissection (10.8%), acute myocardial infarction (10.8%), and anticoagulant withdrawal in patients with atrial fibrillation (6.2%). Thirty-four AIS patients were diagnosed less than 24 h since last seen well, of which four (6.2%) were treated (three with thrombolysis and one with mechanical thrombectomy). CONCLUSION: AIS is the most common reason for referral in our cardiovascular hospital. Our results highlight the importance of the availability of a neurologist/neurohospitalist with stroke expertise for consultation of inpatients admitted in a specialized cardiovascular hospital.

Parakinesia Brachialis Oscitans in a Patient With a First Manifestation of Multiple Sclerosis.

Objectives: Parakinesia brachialis oscitans (PBO) is the involuntary movement of an otherwise paretic upper limb triggered by yawning. We describe the first case of PBO in a patient with a first manifestation of tumefactive multiple sclerosis (MS). Methods: A 35-year-old man presented to the emergency department with a first episode of generalized seizure. Neurologic examination revealed left-sided spastic hemiparesis, predominantly affecting his upper limb. Brain MRI showed a tumefactive right hemisphere lesion consistent with demyelination. CSF did not document unmatched oligoclonal bands. Results: Two weeks after admission and, despite being unable to voluntarily raise his left arm, the patient noticed a repeated and reproducible involuntary raise of this limb upon yawning, consistent with PBO. In the following weeks, the phenomenon diminished both in frequency and movement amplitude alongside motor recovery. An MRI performed 2 months later showed progression of the demyelinating lesion load and confirmed a diagnosis of MS. Discussion: PBO is an example of autonomic voluntary motor dissociation and reflects the interplay between loss of cortical inhibition of the cerebellum in the setting of functional spinocerebellar pathways. Clinicians should be aware of this transient phenomenon which should not be mistaken as a chronic movement disorder or focal epileptic seizures.

Proteomics to Identify New Blood Biomarkers for Diagnosing Patients With Acute Stroke.

Background Blood biomarkers are a potential tool for early stroke diagnosis. We aimed to perform a pilot and exploratory study on untargeted blood biomarkers in patients with suspected stroke by using mass spectrometry analysis. Methods and Results This was a prospective observational study of consecutive patients with suspected stroke admitted within 6 hours of last being seen well. Blood samples were collected at admission. Patients were divided into 3 groups: ischemic stroke (IS), intracerebral hemorrhage (ICH), and stroke mimics. Quantitative analysis from mass spectrometry data was performed using a supervised approach. Biomarker-based prediction models were developed to differentiate IS from ICH and ICH+stroke mimics. Models were built aiming to minimize misidentification of patients with ICH as having IS. We included 90 patients, one-third within each subgroup. The median age was 71 years (interquartile range, 57-81 years), and 49 participants (54.4%) were women. In quantitative analysis, C3 (complement component 3), ICAM-2 (intercellular adhesion molecule 2), PLGLA (plasminogen like A), STXBP5 (syntaxin-binding protein 5), and IGHV3-64 (immunoglobulin heavy variable 3-64) were the 5 most significantly dysregulated proteins for both comparisons. Biomarker-based models showed 88% sensitivity and 89% negative predictive value for differentiating IS from ICH, and 75% sensitivity and 95% negative predictive value for differentiating IS from ICH+stroke mimics. ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64 displayed the highest importance score in our models, being the most informative for identifying patients with stroke. Conclusions In this proof-of-concept and exploratory study, our biomarker-based prediction models, including ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64, showed 75% to 88% sensitivity for identifying patients with IS, while aiming to minimize misclassification of ICH. Although our methodology provided an internal validation, these results still need validation in other cohorts and with different measurement techniques.

A woman with progressive motor and cognitive complaints.

We describe the case of a 48-year-old woman presenting with a two-year history of progressive left hemibody-weakness associated with frequent falls, speech difficulties and cognitive dysfunction. Her clinical examination was noticeable for subcortical frontal-predominant cognitive impairment, asymmetrical spastic paraparesis, pseudobulbar findings and delayed horizontal saccade initiation with head-trust phenomenon. Apart from brain atrophy in excess for her age group, the patient's initial cranial-spinal MRI appearances were unremarkable.

Discontinuation of disease-modifying therapy in MS patients over 60 years old and its impact on relapse rate and disease progression.

BACKGROUND / AIMS: The benefit of disease-modifying therapy (DMT) is unclear for older patients with multiple sclerosis (MS), namely those who have not experienced clinical disease activity for a prolonged time. We aimed to compare baseline differences and clinical outcomes between DMT discontinuers and continuers in a cohort of MS patients older than 60 years. METHODS: Retrospective, observational study identifying MS patients aged over 60 years, stable on DMT> 24 months. Additional inclusion criteria were a previous diagnosis of relapsing MS and a minimum follow-up period of 24 months. Differences between groups (continuers/discontinuers) were assessed. For risk of relapse and of confirmed disability worsening at follow up, a time to outcome survival model was constructed using Cox proportional hazards regression, testing for possible risk predictors. RESULTS: Thirty-five patients were included (68.6% female), with a mean age at diagnosis of 42.1 ( ± 9.5) years and a median EDSS score of 3 (IQR 2) at the age of 60 years (baseline). Thirteen patients discontinued DMT after baseline, in a mean follow-up time of 77.1 months ( ± 40.2). No differences were found between DMT continuers vs discontinuers. DMT discontinuation did not predict risk to relapse (HR 0.38, 95%CI 0.04-3.80, p = 0.408) or disability worsening at follow-up (HR 0.83, 95%CI 0.31-2.22, p = 0.712). MRI gadolinium-enhancing lesions and EDSS score > 3 at baseline were found to be independent predictors of risk to relapse and disability worsening at follow-up, respectively. CONCLUSION: DMT discontinuation did not seem to influence clinical outcome, equating with the perceived limited effect of continued immunomodulation on older stable and/or progressive patients.

Obstructive Sleep Apnea and Other Vascular Risk factors' Impact on Non-Motor Symptoms in Parkinson's Disease.

Background: Previous studies revealed an association between vascular comorbidities and obstructive sleep apnea (OSA) and the severity of motor and cognitive symptoms in Parkinson's disease (PD). However, there is a lack of studies assessing the entire spectrum of non-motor symptoms (NMS). Objective: To investigate the relationship between vascular comorbidities and NMS in PD patients. Methods: Patients were assessed at baseline and 4 years later with the Non-Motor Symptom Assessment Scale, Parkinson's Psychosis Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Apathy scale. After tetrachoric correlation matrix, we conducted linear regression models (adjusted for age, gender, disease duration, and UPDRS-III) to investigate the relationship between vascular comorbidities and NMS. Results: In 73 PD patients, (mean disease duration 7.1 [5.3]), 57% had hypertension, 44% body mass index >25, 44% elevated cholesterol, 15% diabetes mellitus, 15% OSA, 14% cigarette-smoking history, 8% prior stroke, and 8% coronary disease. Cognition, psychotic symptoms, apathy, urinary function, and miscellaneous domains significantly worsened at the 4-year follow-up. OSA was significantly associated with higher severity of hallucinations/illusions at baseline and with a more severe deterioration of attention/memory, psychotic symptoms, and apathetic mood at the 4-year follow-up. At baseline, but not at follow-up, hypertension was negatively associated with miscellaneous domain scores and coronary disease with autonomic function scores (gastrointestinal tract and urinary function domains). Conclusion: Among PD-associated comorbidities, OSA was the main factor of decline. In addition to cognitive impairment, OSA might also potentially worsen psychotic symptoms and apathy. Treatment of OSA could be a strategy to improve these important NMS.

Clinical pattern and response to treatment of primary stabbing headache: Retrospective case series study from a Portuguese tertiary hospital.

OBJECTIVES: This retrospective case series study aimed to investigate the demographic and clinical patterns of primary stabbing headache (PSH). In addition, we tried to identify subgroups of treatment responses in a neurology outpatient consultation at a Portuguese tertiary hospital. METHODS: Clinical records were retrospectively reviewed and patients meeting the International Classification of Headache Disorders, 3rd edition, criteria for PSH were identified from January 2014 to December 2020. We collected data regarding demographic characteristics, clinical features of the headache, primary headache comorbidities, and information about treatment-related do PSH. RESULTS: Of 1857 patients, 32 (1.7%; mean [SD] age of onset 56 [3.5] years) had the final diagnosis of PSH. Regarding headache characteristics, 20 patients (62.5%) reported episodes of stabbing in fixed locations and 12 (37.5%) in multiple areas; the duration of each attack was between ≤5 s (seven [21.9%]), 5-60 s (20 [62.5%]), and ≥60 s (five [15.6%]). In all, 18 patients (56.3%) had an episodic course (vs. six of 32 [18.8%] an acute course and eight of 32 [25%] a chronic course). In all, 17 patients started medical treatment (53.1%), with total or partial improvement in 10 (58.8%) of them. It was found that patients with pain in fixed locations had a better response to treatment when compared to patients with multiple locations, in a statistically significant way (eight of 11 vs. two of six, p = 0.023). CONCLUSION: In our sample, the mean age of onset of PSH was >50 years and there was a wide range of PSH duration. The duration of each attack (>5 s), the pain in fixed locations, non-daily episodes of the pain in each attack, and the intermittent course of headache were the most prevalent clinical features. Finally, patients with stabbing in localized areas had a better response to treatment.

Trends in online search for multiple sclerosis symptoms - Is pain a hot topic?

Assessing the relative importance among different multiple sclerosis (MS) symptoms could guide the efficient allocation of health care resources. We aimed to evaluate the trends in web search behavior worldwide regarding MS symptoms, by querying Google Trends using search terms related to MS symptoms. The popularity of those symptoms was evaluated worldwide from 16/April/2017 through 3/April/2022. A comparison of all search terms revealed that "multiple sclerosis" pain displayed by far the highest relative search volume. Prompt screening and evidence-based interventions are necessary to evaluate pain and optimize quality of life in MS patients.

Progression in Parkinson's Disease: Variation in Motor and Non-motor Symptoms Severity and Predictors of Decline in Cognition, Motor Function, Disability, and Health-Related Quality of Life as Assessed by Two Different Methods.

BACKGROUND: Parkinson's disease (PD) is multi-symptom disease with variable progression. OBJECTIVES: We performed a longitudinal study to address the evolution of motor symptoms (MS) and non-motor symptoms (NMS), predictors of motor-, cognitive-, disability-, and health-related quality of life (HRQL) status and the relative usefullness of a battery of separate NMS scales (BSS) versus the Non-Motor Symptom Scale (NMSS). METHODS: Seventy-two patients were assessed at baseline and 4 years later with the NMSS and BSS. We assessed the following outcomes: cognition (Montreal Cognitive Assessment scale [MoCA]), disability (Unified Parkinson's Disease Rating Scale Part II [UPDRS II], Schwab and England [S&E]), motor dysfunction (Unified Parkinson's Disease Rating Scale Part III [UPDRS III], Hoehn and Yahr [HY]), and HRQL (EuroQol [EQ] EQ-vertical visual analogue scale [VAS] and EQ-Index). Statistical analysis included a comparison between scales scores at both time points and multivariate regression analysis to calculate the impact of each baseline symptom in outcomes. NMSS and BSS were introduced in separate models. RESULTS: NMSS Domain 4: perception/hallucinations, Parkinson's Psychosis Questionnaire, Apathy Scale, NMSS Domain 7: urinary, S&E, UPDRS II, HY, and MoCA scores worsened significantly. Dementia increased to a 4-year prevalence of 39.8%. In the multivariate model using BSS, cognitive state variation was significantly predicted by baseline HY, EQ-Index, and S&E. Using the NMSS, MoCA change was significantly associated with NMSS Domain 4: perceptions/hallucination score, cognitive status with UPDRS III score, HRQL with NMSS Domain 4: perception/hallucinations score, and S&E. CONCLUSION: Our study suggests that NMS progress heterogeneously, BSS approach being more sensitive to change than NMSS. The multivariate analysis has shown that S&E and NMSS Domain 4: perception/hallucinations scores are the stronger predictors of HRQL and cognitive dysfunction variation, favoring NMSS over the BSS approach.

Willingness to be vaccinated against COVID-19: An exploratory online survey in a Portuguese cohort of multiple sclerosis patients.

BACKGROUND: Little is known about MS patients' acceptability of a COVID-19 vaccine. OBJECTIVE AND METHODS: An online survey was conducted among MS patients to study COVID-19 vaccine acceptability and its associated factors. RESULTS AND CONCLUSION: Among 256 participants, 80.9% of the patients were either definitely or probably willing to receive a COVID-19 vaccine. Most hesitant patients would consider being vaccinated under physician recommendation. Older patients and those with comorbidities seem to be more willing to get vaccinated. Moreover, vaccine acceptability was associated with participants' convictions and concerns about COVID-19, as well as previous vaccination practices.

REM sleep absence in patients referred to polysomnography for REM sleep behavior disorder.

Detection of REM sleep behavior disorder (RBD) with polysomnography (PSG) is relevant for the diagnosis of α-synucleinopathies. However, some patients referred for suspicion of RBD do not present REM sleep at PSG (NoREMSusRBD), rendering the study inconclusive. Our objective was to investigate disorders possibility associated with REM sleep absence in patients referred to PSG for investigation of RBD, in particular α-synucleinopathies. A sleep-lab database was revised to select NoREMSusRBD (n = 15) and patients: with no REM sleep referred for suspicion of other sleep disorder (NoREMSusOther, n = 28); referred for RBD suspicion with negative PSG (NegativeRBD, n = 24); α-synucleinopathies with no REM sleep (NoREMα, n = 23) and idiopathic RBD (iRBD, n = 26). NoREMSusRBD patients were compared with the other groups regarding PSG data and the emergence of prodromal features or established criteria for α-synucleinopathy. Severe Obstructive Sleep Apnea (OSA) was significantly more frequent in the NoREMsusRBD compared to the NoREMα and iRBD groups. No patient in the NoREMSusRBD developed a α-synucleinopathy (2 cases on the iRBD group). The prevalence of prodromal features in NoREMSusRBD (n = 7, 46.7%) was similar to that of iRBD (n = 18, 69.2%) and significantly higher than in the other groups. Apnea-Hypopnea Indices (AHI) were significantly higher in the NoREMSusRBD compared with iRBD and NoREMα. Our study suggests that the absence of REM sleep in NoREMSusRBD could be caused by OSA but does not exclude the possibility of underlying α- synucleinopathy, suggested by an increased prevalence of prodromal features. These data support the need for excluding OSA in patients suspected for RBD and recommends follow-up of NoREMSusRBD patients to uncover a possible α- synucleinopathy.

REM sleep behaviour disorder in essential tremor: A polysomnographic study.

Our objectives were to assess the prevalence of REM sleep behaviour disorder in patients with Essential Tremor, using video-polysomnography and to compare REM sleep behaviour disorder features in essential tremor with those of patients with alpha-synucleinopathies. Forty-nine patients with essential tremor were screened with the REM Sleep Behaviour Disorder Screening Questionnaire. Patients scoring positive and those with spontaneous complaints of REM sleep behaviour disorder (n = 6) underwent video-polysomnography. The clinical features of essential tremor were compared between patients with and without REM sleep behaviour disorder. Video-polysomnography data were compared between patients who had essential tremor and Parkinson's disease with REM sleep behaviour disorder and those with idiopathic REM sleep behaviour disorder. Fourteen patients (23.5%) screened positive for REM sleep behaviour disorder, confirmed by video-polysomnography in five (11.6%). All patients with essential tremor and REM sleep behaviour disorder had rest tremor, compared with 13 (34.2%) in the group with essential tremor but without REM sleep behaviour disorder (p = .009). In video-polysomnography, patients with essential tremor and REM sleep behaviour disorder were similar to patients with Parkinson's disease with REM sleep behaviour disorder and presented worse sleep dysfunction and lower severity of REM sleep behaviour disorder compared to those with idiopathic REM sleep behaviour disorder. We found a high prevalence of REM sleep behaviour disorder in patients with essential tremor, associated with a predominance of rest tremor. Polysomnography data from patients with essential tremor and REM sleep behaviour disorder were similar to those in patients with Parkinson's disease. This suggests a relation between this subgroup of patients with essential tremor and the alpha-synucleinopathies.

Polysomnographic predictors of sleep, motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study.

OBJECTIVE: To assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients. METHODS: PD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores. RESULTS: We included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase. CONCLUSIONS: The present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.

Do dreams tell the future? Dream content as a predictor of cognitive deterioration in Parkinson's disease.

Cross-sectional studies suggest a correlation between alterations in dream content reports and executive dysfunction tests in Parkinson's disease (PD), but this has not been assessed in longitudinal studies. Our objective was to assess the predictive value of dream content for progression of cognitive dysfunction in PD. We prospectively addressed all consecutive, non-demented patients with PD attending an outpatient clinic during a 1-year period. Dream reports were collected at baseline by means of a dream diary and analysed according to the Hall and Van de Castle system. Patients were assessed at baseline for rapid eye movement sleep behaviour disorder, motor stage, mood disorder and psychosis. The Montreal Cognitive Assessment (MoCA) was applied at baseline and 4 years later. Linear regression analysis was used to the test the relation between each dream index (predictors), demographic and other motor and non-motor variables (covariates), and change in MoCA scores (dependent variable). In all, 58 patients were assessed at both time points and 23 reported at least one dream (range 1-27, total 148). Aggression, physical activities, and negatively toned content predominated in dream reports. The MoCA scores decreased significantly from baseline to follow-up. In the multivariate model, negative emotion index was the strongest predictor of cognitive decline. We found a significant positive association between negative emotions in dreams at baseline and subsequent reduction in MoCA scores. These findings suggest that some dream content in patients with PD could be considered a predictor of cognitive decline, independent of other factors known to influence either dream content or cognitive deterioration.

Prognostic value of kappa free light chains determination in first-ever multiple sclerosis relapse.

Given its highly variable clinical course, an unmet need for objective prognostic assessment in Multiple Sclerosis (MS) persists. In this work, we suggest that CSF kappa free light chains (KFLC) determination at first relapse may provide insight into future disease activity and disability worsening. We quantified KFLC by nephelometry in paired CSF/serum samples of 28 patients, collected within one month of first-ever MS relapse, and explored correlations with clinical data on disease activity, retrospectively registered across a median follow-up time of 79 months. We documented KFLC ratio (CSF-FKLC/Serum-KFLC) as an independent predictor of second relapse occurrence and disability worsening at follow-up, in this cohort.