Dihydropyridines (DHPs) may have neuroprotective effects against Parkinson's disease (PD).
More than 50% of stroke patients have sleep-disordered breathing (SDB), mostly in the form of obstructive sleep apnea (OSA). SDB represents both a risk factor and a consequence of stroke. The presence of SDB has been linked with poorer long-term outcome and increased long-term stroke mortality. Continuous positive airway presure is the treatment of choice for OSA. Oxygen and other forms of ventilation may be helpful in other (e.g., central) forms of SDB. SDB can improve spontaneously after stroke. About 20 to 40% of stroke patients have sleep-wake disorders (SWD), mostly in form of insomnia, excessive daytime sleepiness/fatigue, or hypersomnia (increased sleep needs). Depression, anxiety, SDB, stroke complications, and medications may contribute to SWD and should be addressed first therapeutically. Brain damage per se, often at thalamic or brainstem level, can be also a cause of persisting SWD. In these patients, hypnotics, dopeminergic agents, and stimulants (e.g., modafinil) can be attempted.
Background: Cerebral small vessel disease (CSVD) as measured by cortical atrophy and white matter hyper -intensities [leukoaraiosis], captured via magnetic resonance imaging (MRI) are increasing in prevalence due to the growth of the aging population and an increase in cardiovascular risk factors in the population. CSVD impacts cognitive function and mobility, but it is unclear if it affects complex, functional activities like driving.Methods: In a cohort of 163 cognitively normal, community-dwelling older adults (age >= 65), we compared naturalistic driving behavior with mild/moderate leukoaraiosis, cortical atrophy, or their combined rating in a clinical composite termed, aging-related changes to those without any, over a two-and-a-half-year period. Results: Older drivers with mild or moderate cortical atrophy and aging-related changes (composite) experienced a greater decrease in the number of monthly trips which was due to a decrease in the number of trips made within a one-to-five-mile diameter from their residence. Older drivers with CSVD experience a larger reduction in daily driving behaviors than drivers without CSVD, which may serve as an early neurobehavioral marker for functional decline. Conclusions: As CSVD markers, leukoaraiosis and cortical atrophy are standard MRI metrics that are widely available and can be used for screening individuals at higher risk for driving safety risk and decline in community mobility.
The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.
While neural antibody testing can be instrumental to diagnosing autoimmune encephalitis, concerns have been raised surrounding test overutilization [ 1 Budhram A. Dubey D. Sechi E. Flanagan E.P. Yang L. Bhayana V. et al. Neural antibody testing in patients with suspected autoimmune encephalitis. Clin. Chem. 2020; 66: 1496-1509 Crossref PubMed Scopus (27) Google Scholar , 2 Zidan A. Fein A. Zuchowski K. The use, misuse and abuse of paraneoplastic panels in neurological disorders. A retrospective study. Clin. Neurol. Neurosurg. 2019; 186105545 Crossref PubMed Scopus (7) Google Scholar , 3 Fredrich S.E. Vernino S. Blackburn K.M. Antibody testing for neurological autoimmune disorders: evaluation of best practices at a tertiary referral center. Front. Neurol. 2021; 12690415 Crossref PubMed Scopus (1) Google Scholar ]. In addition to placing strain on health care systems due to costliness, test overutilization can increase the proportion of false-positive antibody results and contribute to patient misdiagnosis [ 4 Budhram A. Yang L. Bhayana V. Mills J.R. Dubey D. Clinical sensitivity, specificity, and predictive value of neural antibody testing for autoimmune encephalitis. J. Appl. Lab. Med. 2022; 7: 350-356 Crossref PubMed Scopus (9) Google Scholar , 5 Flanagan E.P. Geschwind M.D. Lopez-Chiriboga A.S. Blackburn K.M. Turaga S. Binks S. et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023; 80: 30-39 Crossref PubMed Scopus (15) Google Scholar , 6 Dinoto A. Zara P. Mariotto S. Ferrari S. Flanagan E.P. Budhram A. et al. Autoimmune encephalitis misdiagnosis and mimics. J. Neuroimmunol. 2023; 378578071 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ]. Despite these adverse impacts, no interventions aimed at improving utilization of neural antibody testing for autoimmune encephalitis have been examined. We developed an Autoimmune Neurology approval process for this testing to improve utilization at our centre, and herein examine test volume and yield following its implementation.
Background/Purpose: This study aimed to investigate the association between the time course of type 2 diabetes mellitus (DM) and the development of optic neuritis (ON) in the Korean population aged 20 years and older. Methods A total of 10,069,044 subjects were included in this study, which utilized stratified random sampling from the national cohort. The hazard ratios (HRs) for incident ON were compared between subjects with normal fasting glucose (NFG) levels, impaired fasting glucose (IFG) levels, patients with new-onset DM, diabetes duration of fewer than 5 years (early DM), and diabetes duration of 5 years or more (late DM). In addition, the HR for incident ON was assessed and stratified into 20 fasting glucose levels. Results The cumulative incidence and HR for ON demonstrated a significant increase across the time course of diabetes (adjusted hazard ratio [aHR] = 1.05, 95% confidence interval [CI]: 1.00 to 1.10 for IFG; aHR = 1.31, 95% CI: 1.19 to 1.44 for new-onset DM; aHR = 1.46, 95% CI: 1.32 to 1.60 for early DM; and aHR = 1.92, 95% CI: 1.77 to 2.08 for late DM). Moreover, the HR for ON was 1.71-fold higher in individuals with fasting glucose levels of 132 mg/dL or more compared to those with levels below 75 mg/dL. Conclusion In this nationwide cohort study, the risk of ON was found to increase with the time course of diabetes and elevated glucose levels. These results suggest that efforts to regulate glucose levels and prevent DM progression could reduce the risk of ON.
Although clinical studies have demonstrated that prior use of antiplatelets was associated with decreased blood viscosity (BV) in patients with acute ischemic stroke, the impact of previous anticoagulant use on blood viscosity in cardioembolic stroke with non-valvular AF (NVAF) has not yet been clearly studied. This single-center retrospective observational study aimed to determine the impact of prior antithrombotic (antiplatelet and anticoagulant) use on BV in patients with cardioembolic stroke (CES) due to NVAF. Patients with CES and NVAF were analyzed with the following inclusion criteria: (1) patients over 20 years of age admitted within five days of stroke onset; (2) ischemic stroke presumably due to an NVAF-derived embolus; (3) compatible cortical/subcortical lesion on brain computed tomography or magnetic resonance imaging; (4) hemoglobin level of 10–18 mg/dL; and (5) receiving antiplatelets within five days or anticoagulants within two days if previously medicated. From the screening of 195 patients (22% of the total stroke population during the study period) who had experienced ischemic stroke with AF, 160 were included for the final analysis. Eighty-nine patients (56%) were taking antithrombotics (antiplatelet, 57%; warfarin, 13%; NOACs, 30%) regularly. Compared to patients without previous antithrombotic use, those with previous antithrombotic use (antiplatelets, warfarin, and NOACs) were significantly associated with decreased systolic BV (SBV) and diastolic BV (DBV) (p < 0.036). In multiple linear regression analysis, hematocrit (Hct) level and prior antithrombotic use were significantly associated with decreased SBV and DBV. Hct was positively correlated with increased SBV and DBV. In Hct-adjusted partial correlation analysis, prior uses of any antithrombotic agents were associated with decreased SBV (r < −0.270, p < 0.015) and DBV (r < −0.183, p < 0.044). In conclusion, this study showed that prior antithrombotic use (antiplatelets, VKAs, and NOACs) was associated with decreased SBV and DBV in patients presenting with acute CES secondary to NVAF. Our results indicated that previous use of NOACs may be a useful hemorheological parameter in patients with acute CES due to NVAF. Accumulation of clinical data from a large number of patients with the risk of stroke occurrence, initial stroke severity, and functional outcome is necessary to assess the usefulness of BV.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that progressively affects bulbar and limb function. Despite increasing recognition of the disease as a multinetwork disorder characterized by aberrant structural and functional connectivity, its integrity agreement and its predictive value for disease diagnosis remain to be fully elucidated. In this study, we recruited 37 ALS patients and 25 healthy controls (HCs). High-resolution 3D T1-weighted imaging and resting-state functional magnetic resonance imaging were, respectively, applied to construct multimodal connectomes. Following strict neuroimaging selection criteria, 18 ALS and 25 HC patients were included. Network-based statistic (NBS) and the coupling of grey matter structural-functional connectivity (SC-FC coupling) were performed. Finally, the support vector machine (SVM) method was used to distinguish the ALS patients from HCs. Results showed that, compared with HCs, ALS individuals exhibited a significantly increased functional network, predominantly encompassing the connections between the default mode network (DMN) and the frontoparietal network (FPN). The increased structural connections predominantly involved the inter-regional connections between the limbic network (LN) and the DMN, the salience/ventral attention network (SVAN) and FPN, while the decreased structural connections mainly involved connections between the LN and the subcortical network (SN). We also found increased SC-FC coupling in DMN-related brain regions and decoupling in LN-related brain regions in ALS, which could differentiate ALS from HCs with promising capacity based on SVM. Our findings highlight that DMN and LN may play a vital role in the pathophysiological mechanism of ALS. Additionally, SC-FC coupling could be regarded as a promising neuroimaging biomarker for ALS and shows important clinical potential for early recognition of ALS individuals.
Objective: To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease -tracking biomarker for amyotrophic lateral sclerosis (ALS).Methods: In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. Results: The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/pre-cuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04).Interpretation: The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.
Background/objective: The aim of this study is to identify frequencies of various neurological disorders (NDs) and associated disability in patients attending neurologic clinics in rural and urban centers in Pakistan. Methods: This is an observational study conducted in 39 neurological centers in both rural and urban areas, public and private health sectors all over Pakistan. This study was conducted between august 2017 to December 2019. Results: A total of 28,845 adults were enrolled. Mean age of the study participants was 46.2 +/- 17.2 years, 15,252 (52.9%) were men and 13,593 (47.1%) were women. Most common comorbid medical condition was hypertension 7622(26.4%) followed by Diabetes 3409(11.8%). Among neurological diagnoses, vascular diseases (20%) were the most common followed by Headache disorders (18.6%), Epilepsy (12.5%), nerve and root diseases (12.4%), Psychiatric diseases (10%), Dementias (8%) and movement disorders (7.9%). Half of the patients 15,503(53.7%) had no neurological disability, while minor disability was present in 10,442(36.2%) of cases. Moderate to severe disability was present in 2876(10%) cases. Headache disorders, psychiatric diseases, muscle pain/muscle related disorders and demyelinating diseases were more common in women. Vascular diseases, movement disorders and Dementias were more common in 46 years and above age group whereas headache disorders, Epilepsy and Psychiatric disorders were more prevalent in <46 years age groups. Conclusion: Vascular diseases are the most common presentation of patients in neurology clinics followed by headache disorders and epilepsies. Minor disability was present in 36% while moderate to severe disability was present in 10% cases.
Glaucoma is one of the most devastating eye diseases, since the disease can develop into blindness and no effective therapeutics are available. Although the exact mechanisms and causes of glaucoma are unknown, increased intraocular pressure (IOP) has been demonstrated to be an important risk factor. Exosomes are lipid nanoparticles secreted from functional cells, including stem cells, and have been found to contain diverse functional molecules that control body function, inhibit inflammation, protect and regenerate cells, and restore damaged tissues. In the present study, exosome-rich conditioned media (ERCMs) were attained via hypoxic culture (2% O2) of human amniotic membrane mesenchymal stem cells (AMMSCs) and amniotic membrane epithelial stem cells (AMESCs) containing 50 times more exosome particles than normoxic culture (20% O2) medium (NCM). The exosome particles in ERCM were confirmed to be 77 nm in mean size and contain much greater amounts of growth factors (GFs) and neurotrophic factors (NFs) than those in NCM. The glaucoma-therapeutic effects of ERCMs were assessed in retinal cells and a hypertonic (1.8 M) saline-induced high-IOP animal model. CM-DiI-labeled AMMSC exosomes were found to readily penetrate the normal and H2O2-damaged retinal ganglion cells (RGCs), and AMMSC-ERCM not only facilitated retinal pigment epithelial cell (RPEC) proliferation but also protected against H2O2- and hypoxia-induced RPEC insults. The IOP of rats challenged with 1.8 M saline increased twice the normal IOP (12–17 mmHg) in a week. However, intravitreal injection of AMMSC-ERCM or AMESC-ERCM (3.9–4.5 × 108 exosomes in 10 μL/eye) markedly recovered the IOP to normal level in 2 weeks, similar to the effect achieved with platelet-derived growth factor-AB (PDGF-AB, 1.5 μg), a reference material. In addition, AMMSC-ERCM, AMESC-ERCM, and PDGF-AB significantly reversed the shrinkage of retinal layers, preserved RGCs, and prevented neural injury in the glaucoma eyes. It was confirmed that stem cell ERCMs containing large numbers of functional molecules such as GFs and NFs improved glaucoma by protecting retinal cells against oxidative and hypoxic injuries in vitro and by recovering IOP and retinal degeneration in vivo. Therefore, it is suggested that stem cell ERCMs could be a promising candidate for the therapy of glaucoma.
Background: Levodopa, a common drug that improves symptoms of Parkinson's disease (PD), can induce a reduction in blood pressure (BP); however, the effect of levodopa on cerebral blood flow (CBF) remains unclear.Objectives: To observe the changes in BP and CBF during active standing before and after the acute levodopa challenge test (ALCT) and analyse the influencing factors of CBF in patients with PD.Methods: BP and CBF velocity were simultaneously recorded by continuous beat-to-beat non-invasive BP monitoring and transcranial Doppler at supine and orthostatic positions twice, before and after ALCT. The pa-tients were divided into two groups according to those with increased and decreased CBF at baseline after ALCT to analyse the influencing factors.Results: We examined 64 patients with PD (59.2 +/- 11.6 years, 33 males). BP decreased at all timepoints after ALCT, while there was no significant change in the magnitude of the drop in BP induced by standing. CBF was reduced after ALCT, especially within 15 s to 1 min of standing (15 s: 48.95 +/- 13.50 vs. 44.93 +/- 13.26, p < 0.001; 30 s: 52.46 +/- 12.06 vs. 50.11 +/- 12.56, p = 0.033; 1 min: 52.19 +/- 11.83 vs. 50.17 +/- 13.21, p = 0.044). Lower body mass index (beta = -0.280, p = 0.027) was an independent factor associated with CBF reduction after ALCT.Conclusions: Additional attention should be paid to changes in CBF and BP within 1 min after standing in patients with PD taking levodopa, especially in those with low bodyweight.
BACKGROUND:Anhedonia, the inability to feel pleasure or motivation for reward, is a core feature of depression in epilepsy, but can occur independent from depression. It is reported in over a third of people with epilepsy and has a significant impact on quality of life. OBJECTIVES:This study determined whether specific features of medication refractory epilepsy are predictive of anhedonia. DESIGN:We assessed 267 patients with medication refractory epilepsy for anhedonia, primarily using the clinically validated Snaith-Hamilton Pleasure Scale (SHAPS) scale. METHODS:Patients with clinically significant anhedonia were compared with those without for key demographics, epilepsy characteristics and medication using a logistic regression analysis. RESULTS:We found that seizure frequency (p < 0.01) but not duration of epilepsy was significantly associated with anhedonia. We also found that benzodiazepine use was significantly associated (p = 0.01) with anhedonia, and levetiracetam/brivaracetam and sodium valproate were significantly negatively associated with anhedonia (0.01 and 0.03 respectively). CONCLUSION:High seizure burden in medication refractory epilepsy is significantly associated with anhedonia. Specific antiseizure medications are also associated with the development of anhedonia, but it is unclear whether their use is causative or influenced by the presence of anhedonia.
Background: Tuberculous meningitis (TBM) causes high mortality and morbidity, in part due to raised intracranial pressure (ICP). Automated pupillometry (NPi) and optic nerve sheath diameter (ONSD) are both low-cost, easy-to-use and non-invasive techniques that correlate with ICP and neurological status. However, it is uncertain how to apply these techniques in the management of TBM.Methods: We conducted a pilot study enrolling 20 adults with TBM in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Our objective was to investigate the relationships between baseline and serial measurements of NPi and ONSD and disease severity and outcome. Serial NPi and ONSD were performed for 30 days, at discharge, and at 3-months, with measurements correlated with clinical progression and outcomes.Results: ONSD and NPi measurements had an inverse relationship. Higher ONSD and lower NPi values were associated with lower Glasgow coma score. Baseline NPi was a strong predictor 3-month outcome (median NPi 4.55, interquartile range 4.35-4.65 for good outcomes versus 2.60, IQR 0.65-3.95 for poor outcomes, p = 0.002). Pupil inequality (NPi >= 0.7) was also strongly associated with poor 3-month outcomes (p = 0.006). Individual participants' serial NPi and ONSD were variable during initial treatment and correlated with clinical condition and outcome.Conclusion: Pupillometry and ONSD may be used to predict clinical deterioration and outcome from TBM. Future, larger studies are need explore the optimal timing of measurements and to define how they might be used to optimise treatments and improve outcomes from TBM.
