Search Results (40)

Sporadic Parkinson’s Disease (PD) affects 3% of people over 65 years of age. People are living longer, thanks in large part to improvements in global health technology and health access for non-neurological diseases. Consequently, neurological diseases of senescence, such as PD, are representing an ever-increasing share of global disease burden. There is an intensifying research focus on the processes that underlie these conditions in the hope that neurological decay may be arrested at the earliest time point. The concept of neuronal death linked to ageing- neural senescence- first emerged in the 1800s. By the late 20th century, it was recognized that neurodegeneration was common to all ageing human brains, but in most cases, this process did not lead to clinical disease during life. Conditions such as PD are the result of accelerated neurodegeneration in particular brain foci. In the case of PD, degeneration of the substantia nigra pars compacta (SNpc) is especially implicated. Why neural degeneration accelerates in these particular regions remains a point of contention, though current evidence implicates a complex interplay between a vast array of neuronal cell functions, bioenergetic failure, and a dysfunctional brain immunological response. Their complexity is a considerable barrier to disease modification trials, which seek to intercept these maladaptive cell processes. This paper reviews current evidence in the domain of neurodegeneration in Parkinson’s disease, focusing on alpha-synuclein accumulation and deposition and the role of oxidative stress and inflammation in progressive brain changes. Recent approaches to disease modification are discussed, including the prevention or reversal of alpha-synuclein accumulation and deposition, modification of oxidative stress, alteration of maladaptive innate immune processes and reactive cascades, and regeneration of lost neurons using stem cells and growth factors. The limitations of past research methodologies are interrogated, including the difficulty of recruiting patients in the clinically quiescent prodromal phase of sporadic Parkinson’s disease. Recommendations are provided for future studies seeking to identify novel therapeutics with disease-modifying properties. Full article

Background: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons, with bulbar dysfunction manifesting in up to 80% of patients. Dysarthria, characterized by impaired speech production, is common in ALS and often correlates with disease severity. Voice analysis has emerged as a promising tool for detecting disease progression and monitoring functional status. Methods: This study investigates acoustic and biomechanical voice alterations in ALS patients and their association with clinical measures of functional independence. A descriptive observational case series study was conducted, involving 43 ALS patients and 43 age and sex matched controls with non-neurological voice disorders. Sustained vowel /a/ recordings were obtained and analyzed using Voice Clinical Systems^® and Praat software (version 6.2.22). Biomechanical and acoustic parameters were correlated with ALS Functional Rating Scale-Revised (ALSFRS-R) and Barthel Index scores. Results: Significant differences were observed between ALS and control groups (elevated muscle force and tension and interedge distance in non-ALS individuals). Between bulbar and spinal ALS subtypes, elevated values were observed in certain parameters in Bulbar ALS patients, indicating irregular vocal fold contact and weakened phonatory control, while spinal ALS exhibited increased values, suggesting higher phonatory muscle tension. Elevated biomechanical parameters were significantly correlated with low ALSFRS-R scores, suggesting a possible relationship between voice measures and functional decline. However, acoustic measurements showed no relationship with performance status. Conclusions: These results highlight the potential of voice analysis as a non-invasive, objective tool for monitoring ALS stage and differentiating between subtypes. Further research is needed to validate these findings and explore their clinical applications. Full article

Multiple sclerosis (MS) is a chronic autoimmune-mediated neurodegenerative disease that affects young adults. The diagnosis of MS currently based on the McDonald criteria, which based on four core principles: the presence of a symptomatic demyelinating syndrome, an objective neurologic finding, the dissemination in space (DIS), and the dissemination in time (DIT). In addition, the diagnosis of MS relies on the exclusion of any alternative diagnosis. This may implicate the absence of systemic non-neurological symptoms and signs, such as rheumatological, cutaneous, or ophthalmological findings. Nevertheless, the non-neurological symptoms are commonly observed in patients with MS either at the onset of MS, which therefore can delay the diagnosis and the incrementation of a disease-modifying therapy, or during the course of the disease progression. The purpose of our review is to highlight non-neurological symptoms of MS that frequently go undiagnosed or mistakenly linked to other conditions, aiming for the more accurate and earlier diagnosis of MS. Full article

The increasing use of immune checkpoint inhibitors (ICI) in cancer therapy has brought attention to their associated neurotoxicities, termed neurological immune-related adverse events (n-irAEs). Despite their relatively rare incidence, n-irAEs pose a significant risk, potentially leading to severe, long-lasting disabilities or even fatal outcomes. This narrative review aims to provide a comprehensive overview of n-irAEs, focusing on their recognition and management. The review addresses a spectrum of n-irAEs, encompassing myositis, myasthenia gravis, various neuropathies, and central nervous system complications, such as encephalitis, meningitis, and demyelinating diseases. The key features of n-irAEs are emphasized in this review, including their early onset after initiation of ICIs, potential association with non-neurological irAEs and/or concurrent oncological response, the significance of ruling out other etiologies, and the expected improvement upon discontinuation of ICIs and/or immunosuppression. Furthermore, this review delves into considerations for ICI re-challenge and the intricate nature of n-irAEs within the context of pre-existing autoimmune and paraneoplastic syndromes. It underscores the importance of a multidisciplinary approach to diagnosis and treatment, highlighting the pivotal role of severity grading in guiding treatment decisions. Full article

Background: Stroke mimics are common in the emergency department (ED) and early detection is important to initiate appropriate treatment and withhold unnecessary procedures. We aimed to compare the frequency, clinical characteristics and predictors of non-neurological and neurological stroke mimics transferred to our ED for suspected stroke. Methods: This was a cross-sectional study of consecutive patients with suspected stroke transported to the ED of the University Hospital Essen between January 2017 and December 2021 by the city’s Emergency Medical Service. We investigated patient characteristics, preclinical data, symptoms and final diagnoses in patients with non-neurological and neurological stroke mimics. Multinominal logistic regression analysis was performed to assess predictors of both etiologic groups. Results: Of 2167 patients with suspected stroke, 762 (35.2%) were diagnosed with a stroke mimic. Etiology was non-neurological in 369 (48.4%) and neurological in 393 (51.6%) cases. The most common diagnoses were seizures (23.2%) and infections (14.7%). Patients with non-neurological mimics were older (78.0 vs. 72.0 y, p < 0.001) and more likely to have chronic kidney disease (17.3% vs. 9.2%, p < 0.001) or heart failure (12.5% vs. 7.1%, p = 0.014). Prevalence of malignancy (8.7% vs. 13.7%, p = 0.031) and focal symptoms (38.8 vs. 57.3%, p < 0.001) was lower in this group. More than two-fifths required hospitalization (39.3 vs. 47.1%, p = 0.034). Adjusted multinominal logistic regression revealed chronic kidney and liver disease as independent positive predictors of stroke mimics regardless of etiology, while atrial fibrillation and hypertension were negative predictors in both groups. Prehospital vital signs were independently associated with non-neurological stroke mimics only, while age was exclusively associated with neurological mimics. Conclusions: Up to half of stroke mimics in the neurological ED are of non-neurological origin. Preclinical identification is challenging and a high proportion requires hospitalization. Awareness of underlying etiologies and differences in clinical characteristics is important to provide optimal care. Full article

Multiple Sclerosis (MS) is a common immune-mediated disorder of the central nervous system that affects young adults and is characterized by demyelination and neurodegeneration. Recent studies have associated C9orf72 intermediate repeat expansions with MS. The objective of this study was to investigate whether C9orf72 repeat length is associated with MS or with a specific disease course in a monocentric Austrian MS cohort. Genotyping of 382 MS patients and 643 non-neurological controls for C9orf72 repeat expansions was performed. The study did not find a difference in the distribution of repeat numbers between controls and MS cases (median repeat units = 2; p = 0.39). Additionally, sub-analysis did not establish a link between intermediate repeats and MS (p = 0.23) and none of the patients with progressive disease course carried an intermediate allele (20–30 repeat units). Exploratory analysis for different cut-offs (of ≥7, ≥17, and ≥24) did not reveal any significant differences in allele frequencies between MS and controls. However, the study did identify a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing behavioral variant frontotemporal dementia (bvFTD) in a retrospective chart review. In conclusion, this study did not find evidence supporting an association between C9orf72 repeat length and MS or a specific disease course in the Austrian MS cohort. However, the identification of a progressive MS patient with a pathogenic C9orf72 expansion and probable co-existing with FTD highlights the complexity and challenges involved in recognizing distinct neurodegenerative diseases that may co-occur in MS patients. Full article

During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. Axonal damage includes swelling, defects in transport, and failure to clear damaged intracellular proteins, all of which affect recovery and compromise neuronal integrity. The clearance of damaged cell components is important to maintain normal turnover and restore homeostasis. In this study, we used mass spectrometry to identify insoluble proteins within high-speed/mercaptoethanol/sarcosyl-insoluble pellets from purified white matter plaques isolated from the brains of individuals with relapsing–remitting MS (RRMS). We determined that the transmembrane protein 106B (TMEM106B), normally lysosome-associated, is insoluble in RRMS plaques relative to normal-appearing white matter from individuals with Alzheimer’s disease and non-neurologic controls. Relative to wild-type mice, hypomorphic mice with a reduction in TMEM106B have increased axonal damage and lipid droplet accumulation in the spinal cord following myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis. Additionally, the corpora callosa from cuprizone-challenged hypomorphic mice fail to clear lipid droplets efficiently during remyelination, suggesting that when TMEM106B is compromised, protein and lipid clearance by the lysosome is delayed. As TMEM106B contains putative lipid- and LC3-binding sites, further exploration of these sites is warranted. Full article

Our aim was to determine the frequency and characteristics of neurological post-COVID-19 syndrome and the diagnostic and therapeutic measures that were used for the treatment of these patients. Data were collected for 243 patients examined during the period of 11 May 2021 to 22 June 2022. The inclusion criteria were COVID-19 illness and neurological symptoms associated with COVID-19. The exclusion criteria were non-neurological symptoms, patients who did not suffer from COVID-19, and symptoms that occurred after vaccination against the SARS-CoV-2 virus. Data for 227 patients with neurological post-COVID-19 symptoms were analyzed. Most patients presented with multiple symptoms, most often headache, cognitive impairment, loss of smell, paresthesia, fatigue, dizziness, and insomnia. Patients were most often referred for consultative examinations, neuroradiological imaging, and EEG. The therapy was mostly symptomatic. Most patients had no change in their symptoms on follow-up visits (53.21%), while positive outcome was found in 44.95% of patients. This study found that neurological post-COVID-19 syndrome appears to be more common in women, and generally, the most common symptoms are headache and cognitive impairment. The gender distribution of symptoms was clearly visible and should be further investigated. There is a need for longitudinal follow-up studies to better understand the disease dynamic. Full article

Parkinson’s disease (PD) is a chronic, progressive neurological disorder and the second most common neurodegenerative condition. We report three common but overlooked symptoms in PD—hiccups, hypersalivation, and hallucinations—in terms of their prevalence, pathophysiology, and up-to-date evidence-based treatment strategies. Whilst all these three symptoms do occur in many other neurological and non-neurological conditions, early recognition and treatment are paramount. Whilst hiccups affect 3% of healthy people, their rate of occurrence is higher (20%) in patients with PD. Hypersalivation (Sialorrhea) is another common neurological manifestation of many neurological and other neurodegenerative conditions such as motor neuron disease (MND), with a median prevalence rate of 56% (range: 32–74%). A 42% prevalence of sialorrhea is also reported in sub-optimally treated patients with PD. Hallucinations, especially visual hallucinations, are commonly reported, with a prevalence of 32–63% in PD, and a 55–78% prevalence is noted in patients with dementia with Lewy bodies (DLB), followed by tactile hallucinations, which are indicated by a sensation of crawling bugs or imaginary creatures across the skin surface. Whilst mainstay and primary management strategies for all these three symptoms are carried out through history taking, it is also essential to identify and treat possible potential triggers such as infection, minimise or avoid causative (such as drug-induced) factors, and especially carry out patient education before considering more definitive treatment strategies, such as botulinum toxin therapies for hypersalivation, to improve the quality of life of patients. This original review paper aims to provide a comprehensive overview of the disease mechanisms, pathophysiology, and management of hiccups, hypersalivation, and hallucinations in Parkinson’s disease. Full article

Dopamine (DA), its derivatives, and dopaminergic drugs are compounds widely used in the management of diseases related to the nervous system. However, DA receptors have been identified in nonneuronal tissues, which has been related to their therapeutic potential in pathologies such as sepsis or septic shock, blood pressure, renal failure, diabetes, and obesity, among others. In addition, DA and dopaminergic drugs have shown anti-inflammatory and antioxidant properties in different kinds of cells. Aim: To compile the mechanism of action of DA and the main dopaminergic drugs and show the findings that support the therapeutic potential of these molecules for the treatment of neurological and non-neurological diseases considering their antioxidant and anti-inflammatory actions. Method: We performed a review article. An exhaustive search for information was carried out in specialized databases such as PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, Bookshelf, DrugBank, Livertox, and Clinical Trials. Results: We showed that DA and dopaminergic drugs have emerged for the management of neuronal and nonneuronal diseases with important therapeutic potential as anti-inflammatories and antioxidants. Conclusions: DA and DA derivatives can be an attractive treatment strategy and a promising approach to slowing the progression of disorders through repositioning. Full article

Human organoids are small, self-organized, three-dimensional (3D) tissue cultures that have started to revolutionize medical science in terms of understanding disease, testing pharmacologically active compounds, and offering novel ways to treat disease. Organoids of the liver, kidney, intestine, lung, and brain have been developed in recent years. Human brain organoids are used for understanding pathogenesis and investigating therapeutic options for neurodevelopmental, neuropsychiatric, neurodegenerative, and neurological disorders. Theoretically, several brain disorders can be modeled with the aid of human brain organoids, and hence the potential exists for understanding migraine pathogenesis and its treatment with the aid of brain organoids. Migraine is considered a brain disorder with neurological and non-neurological abnormalities and symptoms. Both genetic and environmental factors play essential roles in migraine pathogenesis and its clinical manifestations. Several types of migraines are classified, for example, migraines with and without aura, and human brain organoids can be developed from patients with these types of migraines to study genetic factors (e.g., channelopathy in calcium channels) and environmental stressors (e.g., chemical and mechanical). In these models, drug candidates for therapeutic purposes can also be tested. Here, the potential and limitations of human brain organoids for studying migraine pathogenesis and its treatment are communicated to generate motivation and stimulate curiosity for further research. This must, however, be considered alongside the complexity of the concept of brain organoids and the neuroethical aspects of the topic. Interested researchers are invited to join the network for protocol development and testing the hypothesis presented here. Full article

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or “long COVID”), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms. Full article

Objective: The aim of this study was to describe the presentation and outcomes of patients with granulomatosis with polyangiitis (GPA) presenting with neurologic involvement according to ACR criteria. Methods: Consecutive newly diagnosed GPA patients who had undergone follow-up for at least six months between 2013 and 2018 at Amir-A’lam hospital, Tehran University of Medical Sciences, were retrospectively analyzed. Results: Patients were divided into two groups: those with nervous system involvement at either disease diagnosis or follow-up (89 patients) and those without neurological symptoms until the last follow-up (131 patients). From all patients reviewed in this study, 68 (30.9%) patients died during the follow-up period. Among the deceased patients, 18 (20.2%) were in the non-neurologic group, and 50 (38.2%) were in the neurologic group. The median (IQR) of BVAS in 220 patients was 11.0 (18.0-8.0) in total: 10.0 (14.5-7.50) and 12.0 (21.0-8.0) in the non-neurologic and the neurologic groups, respectively. The score of BVAS in the neurologic group was significantly higher than in the non-neurologic group (p = 0.039). Of 131 patients, sensory neuropathy was found in 99 patients (75.5%). In total, 95 patients (72.5%) complained of hearing loss, which was diagnosed as sensory–neural hearing loss; 27 patients (20.6%) complained of headache; 13 (9.9%) had a history of cerebrovascular events; 5 (3.8%) had an episode of seizure or loss of consciousness (LOC); and 3 (2.3%) had mononeuritis multiplex. Two patients (1.5%) were diagnosed with meningitis and two (1.7%) with encephalitis. Conclusion: According to this study, neurological symptoms are an undeniable part of the disease course for GPA patients, and these symptoms are associated with disease severity, prognosis, and response to treatment. Full article

Robot-assisted gait training (RAGT) is a promising therapeutic vehicle to maximize active participation and enhance functional neuroplasticity in patients with central nervous system pathology by adequately adjusting gait speed, body weight support (BWS) level, and impedance provided by the exoskeleton. The aim of the present study was to determine the relationship between RAGT training parameters (BWS and speed) and electromyography (EMG) muscle activity torques in the knee and hip joint during RAGT. To analyze the correlation between the joint torques measured in the Walkbot gait rehabilitation system and the EMG signal of the lower limbs (vastus lateralis oblique, biceps femoris, tibialis anterior, and gastrocnemius) and understand the real-time state of the lower limb an experiment involving 20 subjects was conducted. The EMG–torque relationship was evaluated in a general rehabilitation training setting to overcome the limitations of in vivo settings. Pearson correlation coefficient analysis was performed at p < 0.05. Moderate relationships between biceps femoris activation data and hip and knee torques were statistically significant, ranging from r = 0.412 to −0.590, p < 0.05). Importantly, inverse relationships existed between hip torques and vastus lateralis oblique, biceps femoris, and tibialis anterior activation, respectively. The present results demonstrated the association between EMG locomotor control patterns and torque generation in the hip and knee joints during RAGT-treadmill under the different BWS and walking speed settings while adjusting the impedance mode parameters in non-neurological adults. Additionally, the EMG locomotor control patterns, concurrent torque generation in the hip and knee joints, and application of different BWS and walking speed parameters in the RAGT were linked to the gait speed and BWS. The outcomes also showed that the amount of BWS supplied had an impact on the effects of treadmill speed on muscle activity and temporal step control. It is essential to adjust RAGT parameters precisely in order to maximize training session efficiency and quality. The results of this study nevertheless call for more investigation into the relationship between muscle activity and torque outcomes in diseased populations with gait impairment. Full article

Canine distemper is caused by canine distemper virus (CDV), a multisystemic infectious disease with a high morbidity and mortality rate in dogs. Nanotechnology represents a development opportunity for new molecules with antiviral effects that may become effective treatments in veterinary medicine. This study evaluated the efficacy and safety of silver nanoparticles (AgNPs) in 207 CDV, naturally infected, mixed-breed dogs exhibiting clinical signs of the non-neurological and neurological phases of the disease. Group 1a included 52 dogs (experimental group) diagnosed with non-neurologic distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 1b included 46 dogs (control group) diagnosed with non-neurological distemper treated with supportive therapy only. Group 2a included 58 dogs with clinical signs of neurological distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 2b included 51 dogs (control group) diagnosed with clinical signs of neurological distemper treated with supportive therapy only. Efficacy was measured by the difference in survival rates: in Group 1a, the survival rate was 44/52 (84.6%), versus 7/46 in Group 1b (15.2%), while both showed clinical signs of non-neurological distemper. The survival rate of dogs with clinical signs of neurological distemper in Group 2a (38/58; 65.6%) was significantly higher than those in Control Group 2b (0/51; 0%). No adverse reactions were detected in experimental groups treated with AgNPs. AgNPs significantly improved survival in dogs with clinical signs of neurological and non-neurological distemper. The use of AgNPs in the treatment of neurological distemper led to a drastic increase in the proportion of dogs recovered without sequels compared to dogs treated without AgNPs. The evidence demonstrates that AgNP therapy can be considered as a targeted treatment in dogs severely affected by canine distemper virus. Full article