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Objective: Diabetic osteoporosis (DOP) is a metabolic disease that occurs in patients with diabetes due to insufficient insulin secretion. This condition can lead to sensory neuropathy, nephropathy, retinopathy, and hypoglycemic events, which can increase the risk of fractures. This study aimed to assess the effectiveness of Empagliflozin, a sodium–glucose cotransporter-2 (SGLT-2) inhibitor, in treating diabetic osteoporosis (DOP) and preventing fractures. Methods: This quasi-experimental study enrolled 100 patients with diabetic osteoporosis from February 2023 to February 2024. Participants were randomly assigned to an intervention group (n = 50) and a control group (n = 50). The intervention group received Empagliflozin in combination with symptomatic treatment, while the control group received only symptomatic treatment. The treatment duration was six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin A1c (Hb A1c), bone mineral density (BMD), serum phosphorus and calcium concentration were measured after the intervention and the incidence of fracture was followed up for 12 months. The data were analyzed using SPSS 23. Descriptive statistics (mean, standard deviation, and percentage) and analytical methods (t test, Chi square) were also used to analyze the data. Results: After six months of treatment, the intervention group exhibited significantly lower levels of FBG (P < 0.001), 2 h-PG (P = 0.001), and HbA1c (P < 0.001) than the control group. Additionally, bone mineral density, serum phosphorus, and calcium levels were significantly higher in the intervention group (P < 0.001). After a 12-months follow-up, the incidence of fractures in the intervention group was 2%, while it was 16.33% in the control group (P < 0.05). Conclusion: Empagliflozin, when combined with symptomatic treatment, demonstrates a positive clinical effect in patients with diabetic osteoporosis. The treatment effectively improves blood glucose metabolism, bone mineral density, and phosphorus and calcium metabolism, ultimately leading to a significant reduction in the incidence of fracture. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge. Areas covered: This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024. Expert opinion: Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Using antibiotics in the treatment of acute sore throats has been linked with antimicrobial resistance (AMR) and needs to be addressed. The consensus sought to improve diagnostic accuracy, decrease unwarranted antibiotic prescriptions and enhance patient outcomes. Methods: A multidisciplinary panel of nine experts reviewed published literature and discussed current practices in managing sore throat. Ten evidence-based statements on sore throat and AMR, diagnostic accuracy and antibiotic prescribing, and symptomatic therapy were developed. A modified Delphi exercise was then carried out. A consensus was reached if at least 70% of the group agreed with the statement. Results: All 10 statements for managing acute sore throat achieved consensus. The major concern of AMR caused by improper antibiotic prescribing, particularly in cases of viral sore throat, was recognized. This underscores the need for improved diagnostic tools, such as the McIsaac score, to reduce needless antibiotic prescriptions. To improve patient satisfaction, effective pain management using non-antibiotic alternatives such as paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), and flurbiprofen throat lozenges was recommended. Pain and inflammation can be adequately managed with low-dose NSAIDs. The potential benefits of topical NSAIDs were acknowledged for their milder safety profile than oral formulations. Conclusion: A consensus was achieved on the use of a clinical diagnostic tool, prudent use of antibiotics, and symptomatic therapy in acute sore throat management. The McIsaac score and point-of-care testing (POCT) for the presence of group A beta-hemolytic Streptococcus (GABHS) can aid in the decision-making process for antibiotic use, reducing needless prescriptions. The mainstay of therapy is symptomatic treatment, which includes the use of NSAIDs. [ABSTRACT FROM AUTHOR]

Abstract Objective Diabetic osteoporosis (DOP) is a metabolic disease that occurs in patients with diabetes due to insufficient insulin secretion. This condition can lead to sensory neuropathy, nephropathy, retinopathy, and hypoglycemic events, which can increase the risk of fractures. This study aimed to assess the effectiveness of Empagliflozin, a sodium–glucose cotransporter-2 (SGLT-2) inhibitor, in treating diabetic osteoporosis (DOP) and preventing fractures. Methods This quasi-experimental study enrolled 100 patients with diabetic osteoporosis from February 2023 to February 2024. Participants were randomly assigned to an intervention group (n = 50) and a control group (n = 50). The intervention group received Empagliflozin in combination with symptomatic treatment, while the control group received only symptomatic treatment. The treatment duration was six months. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin A1c (Hb A1c), bone mineral density (BMD), serum phosphorus and calcium concentration were measured after the intervention and the incidence of fracture was followed up for 12 months. The data were analyzed using SPSS 23. Descriptive statistics (mean, standard deviation, and percentage) and analytical methods (t test, Chi square) were also used to analyze the data. Results After six months of treatment, the intervention group exhibited significantly lower levels of FBG (P

amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease with unclear pathophysiology and poor prognosis. Pharmacotherapy in the treatment of ALS is aimed at slowing disease progression and alleviating symptoms. The first and currently only drug that slows disease progression and is available to an unselected population is riluzole. For genetically predisposed patients with a mutation in the gene for superoxide dismutase (SOD1), tofersen is approved by the US Food and Drug Administration and more recently by the European Medicines Agency. European approval is expected soon. Symptomatic pharmacotherapy improves spasticity, sialorrhea, spasms, depression, emotional instability and, in palliative care at the end of life, dyspnea. [ABSTRACT FROM AUTHOR]

Although the landscape of migraine symptomatic treatment has been enriched by novel effective drugs, it is mandatory to critically reappraise older molecules to ascertain whether they could still represent reliable alternatives in specific endophenotypes of patients or migraine attacks. Among these, dihydroergotamine (DHE) nasal spray has been shown to be effective and is characterized by greater tolerability and manageability than the parenteral DHE formulation. In this narrative review, the authors describe the pharmacodynamic and pharmacokinetic properties of DHE nasal spray and explore the results of the trials which explored its efficacy, safety and tolerability as migraine symptomatic treatment. They also discuss the limitations of the classically used device and the attempts that several companies are carrying out to generate devices warranting a more reproducible drug absorption. DHE nasal spray could be considered as rescue treatment in patients who have failed other symptomatic therapeutic strategies. Nevertheless, in the perspective of tailored therapy, the intranasal route of administration and the consequent rapid onset of action may represent benefits putatively making DHE a treatment of choice for challenging migraine attacks such as those with nocturnal onset or quickly reaching the climax of both headache and neurovegetative associated symptoms. [ABSTRACT FROM AUTHOR]

BackgroundExcessive daytime sleepiness (EDS) in multiple sclerosis (MS) can be a significant source of disability. Despite this, its prevalence as a patient-reported outcome in this condition has not been well established, and its causes are not well understood.MethodsWe prospectively assessed EDS as part of an observational study for patients referred for diagnostic neuro-ophthalmological testing. EDS was evaluated by the Epworth Sleepiness Scale (ESS), and visual data were also collected as part of a research protocol. Analysis with patient data was performed following the exclusion of patients with known primary sleep disorders.ResultsA total of 69 patients with MS were included in the analysis. The mean ESS was 6.5 with a SD of 4.3. ESS ≥ 10 was present in 23% of the cohort even in the presence of minimal mean neurological disability (Patient Determined Disease Steps (PDDS) = 1.5). The ESS score was not associated with age, sex, disease-related disability, retinal nerve fiber layer (RNFL), or optic neuritis (ON), but displayed an association with visual dysfunction.ConclusionsThere is an increased prevalence of EDS in MS. The increased values of the ESS are not explained by other sleep disorders, suggesting separate mechanisms. Further study of the underlying mechanisms is warranted.

Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients' satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were "fairly happy", 10.6% were "very happy", and 5.5% were "extremely happy"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsingremitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic. [ABSTRACT FROM AUTHOR]

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors. In this study, we ask whether this negative interaction can also be mimicked in experimental tau models of AD and whether the underlying mechanism can be understood. From a previous age profiling study, 6-month-old line 1 (L1) tau transgenic mice were characterized by a severe reduction in several cholinergic markers. We therefore assessed whether long-term pre-exposure with the acetylcholinesterase inhibitor rivastigmine alone and in conjunction with the tau aggregation inhibitor HMTM can reverse cholinergic deficits in L1. Rivastigmine and HMTM, and combinations of the two compounds were administered orally for 11 weeks to both L1 and wild-type mice. The brains were sectioned with a focus on the basal forebrain, motor cortex and hippocampus. Immunohistochemical staining and quantification of choline acetyltransferase (ChAT), tyrosine kinase A (TrkA)-positive neurons and relative optical intensity (ROI) for vesicular acetylcholine transporter (VAChT), and acetylcholinesterase (AChE) reactivity confirmed reversal of the diminished cholinergic phenotype of interneurons (nucleus accumbens, striatum) and projection neurons (medial septum, nucleus basalis magnocellularis) by HMTM, to a greater extent than by rivastigmine alone in L1 mice. Combined administration did not yield additivity but, in most proxies, led to antagonistic effects in which rivastigmine decreased the benefits shown with HMTM alone. Local markers (VAChT and AChE) in target structures of the basal forebrain, motor cortex and hippocampal CA3 seemed to be normalized by HMTM, but not by rivastigmine or the combination of both drugs. HMTM, which was developed as a tau aggregation inhibitor, strongly decreased the tau load in L1 mice, however, not in combination with rivastigmine. Taken together, these data confirm a cholinergic phenotype in L1 tau transgenic mice that resembles the deficits observed in AD patients. This phenotype is reversible by HMTM, but at the same time appears to be subject to a homeostatic regulation induced by chronic pre-treatment with an acetylcholinesterase inhibitor, which interferes with the efficacy of HMTM. The strongest phenotypic reversal coincided with a normalization of the tau load in the cortex and hippocampus of L1, suggesting that tau accumulation underpins the loss of cholinergic markers in the basal forebrain and its projection targets. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) represents a progressive and painful disease that in time can lead to loss of function and disability. Early diagnosis and correct treatment are essential in preventing the advancement of the condition to a stage where it can affect the quality of life. The development of new imagistic methods and devices can help detect changes in the structure of the join before the onset of symptoms. At the moment there are no diseasemodifying drugs approved, so the current treatment is symptomatic, focusing on pain reduction, improving function and trying to prevent progression towards disability. [ABSTRACT FROM AUTHOR]

Palliative care represents an approach that enhances the quality of life for patients and their families when facing issues associated with a life-threatening illness. Patients are provided with “symptomatic treatment” and “supportive treatment” with the aim of ensuring the highest possible quality of life. Although these terms are often used interchangeably, it’s crucial to remember that there are significant distinctions, particularly regarding therapeutic approaches. The current research employed an online questionnaire to assess the knowledge of the healthcare team and medical students regarding the definitions of symptomatic and supportive treatment. The survey revealed that, despite the clear differences between symptomatic and supportive treatment, 49.6% of respondents experienced confusion about the linguistic overlap between the two concepts, underscoring the need for ongoing medical education. [ABSTRACT FROM AUTHOR]

Wilson's disease (WD) is a potentially treatable, inherited disorder resulting from impaired copper metabolism. Pathological copper accumulation causes a range of symptoms, most commonly hepatic and a wide spectrum of neurological symptoms including tremor, dystonia, chorea, parkinsonism, dysphagia, dysarthria, gait and posture disturbances. To reduce copper overload, anti-copper drugs are used that improve liver function and neurological symptoms in up to 85% of patients. However, in some WD patients, treatment introduction leads to neurological deterioration, and in others, neurological symptoms persist with no improvement or improvement only after several years of treatment, severely affecting the patient's quality of life. This review appraises the evidence on various pharmacological and non-pharmacological therapies, neurosurgical procedures and liver transplantation for the management of neurological WD symptoms. The authors also discuss the neurological symptoms of WD, causes of deterioration and present symptomatic treatment options. Based on case and series reports, current recommendations and expert opinion, WD treatment is focused mainly on drugs leading to negative copper body metabolism (chelators or zinc salts) and copper-restricted diet. Treatment of WD neurological symptoms should follow general recommendations of symptomatic treatment. Patients should be always considered individually, especially in the case of severe, disabling neurological symptoms. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) management in individuals aged 55 and above presents unique challenges due to the complex interaction between aging, comorbidities, immunosenescence, and MS pathophysiology. This comprehensive review explores the evolving landscape of MS in older adults, including the increased incidence and prevalence of MS in this age group, the shift in disease phenotypes from relapsing-remitting to progressive forms, and the presence of multimorbidity and polypharmacy. We aim to provide an updated review of the available evidence of disease-modifying treatments (DMTs) in older patients, including the efficacy and safety of existing therapies, emerging treatments such as Bruton tyrosine kinase (BTKs) inhibitors and those targeting remyelination and neuroprotection, and the critical decisions surrounding the initiation, de-escalation, and discontinuation of DMTs. Non-pharmacologic approaches, including physical therapy, neuromodulation therapies, cognitive rehabilitation, and psychotherapy, are also examined for their role in holistic care. The importance of MS Care Units and advance care planning are explored as a cornerstone in providing patient-centric care, ensuring alignment with patient preferences in the disease trajectory. Finally, the review emphasizes the need for personalized management and continuous monitoring of MS patients, alongside advocating for inclusive study designs in clinical research to improve the management of this growing patient demographic.

Abstract Background Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. Methods The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018–2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. Results Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. Conclusion Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (

BackgroundThe COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made.MethodsWe identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined.ResultsTruncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned.DiscussionThese analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials' validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

Abstract Introduction In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor neuron disorders affect upper motor neurons in the primary motor cortex and/or lower motor neurons in the brain stem and spinal cord. The most frequent motor neuron disease amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease with an average life expectancy of 2–4 years with a yearly incidence of 3.1/100,000 in Central Europe (Rosenbohm et al. in J Neurol 264(4):749–757, 2017. https://doi.org/10.1007/s00415-017-8413-3 ). It is considered a rare disease mainly due to its low prevalence as a consequence of short disease duration. Recommendations These guidelines comprise recommendations regarding differential diagnosis, neuroprotective therapies and multidisciplinary palliative care including management of respiration and nutrition as well as provision of assistive devices and end-of-life situations. Conclusion Diagnostic and therapeutic guidelines are necessary due the comparatively high number of cases and the aggressive disease course. Given the low prevalence and the severe impairment of patients, it is often impossible to generate evidence-based data so that ALS guidelines are partially dependent on expert opinion.

Background: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. Methods: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018–2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. Results: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. Conclusion: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia. [ABSTRACT FROM AUTHOR]

A number of hereditary ataxias are caused by inborn errors of metabolism (IEM), most of which are highly heterogeneous in their clinical presentation. Prompt diagnosis is important because disease-specific therapies may be available. In this review, we offer a comprehensive overview of metabolic ataxias summarized by disease, highlighting novel clinical trials and emerging therapies with a particular emphasis on first-in-human gene therapies. We present disease-specific treatments if they exist and review the current evidence for symptomatic treatments of these highly heterogeneous diseases (where cerebellar ataxia is part of their phenotype) that aim to improve the disease burden and enhance quality of life. In general, a multimodal and holistic approach to the treatment of cerebellar ataxia, irrespective of etiology, is necessary to offer the best medical care. Physical therapy and speech and occupational therapy are obligatory. Genetic counseling is essential for making informed decisions about family planning. [ABSTRACT FROM AUTHOR]

Introduction. The management of respiratory infections in the cold season has been a challenge in recent years due to epidemiological and legislative peculiarities. These medical peculiarities are compounded by campaigns encountered in the media related to symptomatic treatment of acute upper respiratory tract infections. Pseudoephedrine has been a topic of debate at the start of the 2023-2024 cold season, inducing opinions and attitudes from both medical staff and patients. Materials and method. Fifty-five family doctors from Mureș county completed a questionnaire with 10 questions regarding seasonal respiratory infections and their symptomatic treatment, including the place, role and impact of pseudoephedrine. The questionnaire was completed voluntarily, based on personal knowledge and experience. Results. The answers provided by the physicians were centralized and plotted, showing the weight of each answer option in relation to all the answer options provided within a question. Conclusions. The beneficial effects of pseudoephedrine use outweigh the risks that may occur, mainly due to noncompliance with recommended doses and/or the lack of correlation between the treatment benefits and the risks of the coexistence of a decompensated chronic disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: Polypharmacy, the use of ≥ 5 medications, is common in people with multiple sclerosis and is associated with negative outcomes. The use of multiple medications is common for symptom management in people with multiple sclerosis, but risks drug-drug interactions and additive side effects. Multiple sclerosis providers should therefore focus on the appropriateness and risks versus benefits of pharmacotherapy in each patient. This review describes the prevalence and risks associated with polypharmacy in people with multiple sclerosis and offers strategies to identify and mitigate inappropriate polypharmacy. Recent Findings: Research in people with multiple sclerosis has identified risk factors and negative outcomes associated with polypharmacy. Medication class-specific investigations highlight their contribution to potentially inappropriate polypharmacy in people with multiple sclerosis. Summary: People with multiple sclerosis are at risk for inappropriate polypharmacy. Multiple sclerosis providers should review medications and consider their appropriateness and potential for deprescribing within the context of each patient. [ABSTRACT FROM AUTHOR]

This article provides a review of the current literature on the current principles of symptomatic treatment of lymphovenous insufficiency. Lymphovenous insufficiency is an urgent problem of modern phlebology, the prevalence of this pathology reaches 50% among the world population. Underlying the pathogenesis is venous hypertension, which is caused by venous valve insufficiency, venous outflow obstruction, or combined causes. The use of compression knitwear and symptomatic therapy for lymphovenous insufficiency is an important component of the treatment at the initial stages of the disease — pharmacotherapy based on the use of venoactive drugs. The most promising to date are preparations of the micronized purified flavonide fraction (MPFF) group, which consist of micronized diosmin and flavonides. The use of МОФФ drugs reduces venous hypertension by increasing venous tone, reducing venous capacity, and extensibility of the vessel wall. MPFF also improves lymph conversion by increasing the contractility of the lymphatic capillaries and has an effect on the microcirculation of the vessels of the lower extremities, having an effect on the resistance and permeability of the capillaries. Thus, the use of preparations of the micronized purified fraction of flavonides has a more pronounced effect on the etiology and pathogenesis of the disease, thereby increasing the clinical effect and leading to a more effective result in the treatment of lymphovenous insufficiency. And as presented in this review, drugs containing micronized purified flavonoid fraction are an excellent candidate to be further studied as therapeutic agents for the treatment of lymphovenous insufficiency, because the mechanism of action of the micronized purified flavonoid fraction is directly connected with its pathophysiology and high clinical efficacy.

Abstract Background Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as progressive cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded phase IIb clinical trial. Here, we describe the development of a study protocol (Sponsor Code “IB1001-301”) for the chronic treatment of symptoms in adult and pediatric patients with NPC. Methods This multinational double-blind randomized placebo-controlled crossover phase III study will enroll patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites. Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments. Discussion Pre-clinical as well as observational and phase IIb clinical trials have previously demonstrated that IB1001 rapidly improved symptoms, functioning, and quality of life for pediatric and adult NPC patients and is safe and well tolerated. In this placebo-controlled cross-over trial, the risk/benefit profile of IB1001 for NPC will be evaluated. It will also give information about the applicability of IB1001 as a therapeutic paradigm for other rare and common neurological disorders. Trial registrations The trial (IB1001-301) has been registered at www.clinicaltrials.gov (NCT05163288) and www.clinicaltrialsregister.eu (EudraCT: 2021–005356-10). Registered on 20 December 2021.

BackgroundThere are numerous challenges to treating co-occurring symptoms in multiple sclerosis (MS).ObjectiveTo pilot the feasibility of a novel symptom management platform, CoachMS, to monitor MS symptoms (bladder function, ambulation, and mood: BAM) and respond to changes in real-time.MethodsIn this 12-week randomized controlled pilot trial, participants' symptoms were monitored using weekly questionnaires and remote ambulatory monitoring (Fitbit Flex2®). Behavioral change principles used included shared goal setting at 2 weeks. Between weeks 2-12, the CoachMS group received targeted contact and interventions if symptoms worsened; the control group were treated through usual clinic practice. Our outcomes were feasibility (retention, adherence and acceptability; primary) and proportion of recommended treatments pursued (secondary); efficacy was explored.ResultsOf 21 participants enrolled, 13 (62%) completed the study; protocol adherence was excellent. CoachMS participants demonstrated greater follow-through with clinical recommendations than controls (OR 9.3, 95% CI (0.9, 97.6)). As a cohort, each BAM symptom tended to improve. Suicidality was detected in one control participant, resulting in urgent evaluation and hospitalization.ConclusionsThe innovative CoachMS platform was feasible and acceptable in this cohort with baseline BAM symptoms. It could represent an accessible, cost-effective tool to monitor MS symptoms in real-time; a larger trial is planned.

Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, lysosomal storage disorder. To combat the progressive neurodegeneration in NPC, disease-modifying treatment needs to be introduced early in the course of the disease. The only approved, disease-modifying treatment is a substrate-reduction treatment, miglustat. Given miglustat's limited efficacy, new compounds are under development, including gene therapy; however, many are still far from clinical use. Moreover, the phenotypic heterogeneity and variable course of the disease can impede the development and approval of new agents. Here, we offer an expert review of these therapeutic candidates, with a broad scope not only on the main pharmacotherapies, but also on experimental approaches, gene therapies, and symptomatic strategies. The National Institute of Health (NIH) database PubMed has been searched for the combination of the words 'Niemann-Pick type C'+ 'treatment' or 'therapy' or 'trial.' The website clinicaltrials.gov has also been consulted. We conclude a combination of treatment strategies should be sought, with a holistic approach, to improve the quality of life of affected individuals and their families. [ABSTRACT FROM AUTHOR]

Background: Previous studies analyzing short-term outcomes for per-oral endoscopic myotomy (POEM) have shown excellent clinical response rates and shorter operative times compared to laparoscopic Heller myotomy (LHM). Despite this, many payors have been slow to recognize POEM as a valid treatment option. Furthermore, comparative studies analyzing long-term outcomes are limited. This study compares perioperative and long-term outcomes, cost-effectiveness, and reimbursement for POEM and LHM at a single institution. Methods: Adult patients who underwent POEM or LHM between 2014 and 2021 and had complete preoperative data with at least one complete follow up, were retrospectively analyzed. Demographic data, success rate, operative time, myotomy length, length of stay, pre- and postoperative symptom scores, anti-reflux medication use, cost and reimbursement were compared. Results: 58 patients met inclusion with 25 undergoing LHM and 33 undergoing POEM. There were no significant differences in preoperative characteristics. Treatment success (Eckardt ≤ 3) for POEM and LHM was achieved by 88% and 76% of patients, respectively (p = 0.302). POEM patients had a shorter median operative time (106 min. vs. 145 min., p = 0.003) and longer median myotomy length (11 cm vs. 8 cm, p < 0.001). All LHM patients had a length of stay (LOS) ≥ 1 day vs. 51.5% for POEM patients (p < 0.001). Both groups showed improvements in dysphagia, heartburn, regurgitation, Eckardt score, GERD HRQL, RSI, and anti-reflux medication use. The improvement in dysphagia score was greater in patients undergoing POEM (2.30 vs 1.12, p = 0.003). Median hospital reimbursement was dramatically less for POEM ($3,658 vs. $14,152, p = 0.002), despite median hospital costs being significantly lower compared to LHM ($2,420 vs. $3,132, p = 0.029). Results: POEM is associated with a shorter operative time and LOS, longer myotomy length, and greater resolution of dysphagia compared to LHM. POEM costs are significantly less than LHM but is poorly reimbursed. [ABSTRACT FROM AUTHOR]

Background: While intravesical injections of botulinum neurotoxin A (BoNT-A) are currently recommended for patients experiencing refractory neurogenic overactive bladder and/or detrusor overactivity (OAB/DO), it is unclear how much this therapy is effective and sustainable in the long-term in patients with multiple sclerosis (MS). Objectives: To assess the mid-term continuation rate of BoNT-A injections to treat neurogenic OAB/DO in MS patients and to investigate MS-specific risk factors for discontinuation. Methods: This retrospective study involved 11 French university hospital centers. All MS patients who received BoNT-A to treat neurogenic OAB/DO between 2008 and 2013 and were subsequently followed up for at least 5 years were eligible. Results: Of the 196 MS patients included, 159 (81.1%) were still under BoNT-A 5 years after the first injection. The combination of the Expanded Disability Status Scale (EDSS < 6 or ⩾ 6) and of the MS type (relapsing–remitting vs progressive) predicted the risk of discontinuation. This risk was 5.5% for patients with no risk factor, whereas patients presenting with one or two risk factors were 3.3 and 5.7 times more likely to discontinue, respectively. Conclusion: BoNT-A is a satisfying mid-term neurogenic OAB/DO therapy for most MS patients. Combining EDSS and MS type could help predict BoNT-A discontinuation. [ABSTRACT FROM AUTHOR]

Objective: To determine whether administration of antiemetic medication to dogs and cats with gastrointestinal foreign body obstruction (GIFBO) delays time to definitive care (surgery or endoscopy) and increases the risk of complications. Design: Retrospective study (January 2012–July 2020). Setting: Private referral center. Animals: Five hundred and thirty‐seven (440 dogs and 97 cats). Interventions: None. Measurements and Main Results: Medical records of dogs and cats with GIFBO were reviewed for antiemetic administration at the onset of clinical signs, time from onset of clinical signs to first intervention and definitive care, GIFBO‐related complications, and length of hospitalization. Antiemetics were prescribed for 200 of 537 patients (158 dogs, 42 cats). Antiemetic administration was associated with an increased time between the onset of clinical signs and definitive care (3.2 days [95% confidence interval, CI, 2.8–3.5] vs. 1.6 days [95% CI, 1.4–2.0]; P < 0.001) but not with GIFBO‐associated complications (P = 0.45). Antiemetic administration was associated with an increased length of hospitalization (1.6 days [95% CI, 1.4–1.7] vs. 1.1 days [95% CI, 1.1–1.2]; P < 0.001). A longer duration of clinical signs prior to intervention was associated with GIFBO‐related complications (P < 0.001) regardless of antiemetic administration. Conclusions: Antiemetic administration in patients with GIFBO was associated with increased time to definitive care and length of hospitalization but not GIFBO‐associated complications. Antiemetics are not inherently contraindicated in patients for whom GIFBO is a differential, but clients should be counseled to monitor for progression of clinical signs and follow‐up accordingly. [ABSTRACT FROM AUTHOR]

Introduction: In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor neuron disorders affect upper motor neurons in the primary motor cortex and/or lower motor neurons in the brain stem and spinal cord. The most frequent motor neuron disease amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease with an average life expectancy of 2–4 years with a yearly incidence of 3.1/100,000 in Central Europe (Rosenbohm et al. in J Neurol 264(4):749–757, 2017. https://doi.org/10.1007/s00415-017-8413-3). It is considered a rare disease mainly due to its low prevalence as a consequence of short disease duration. Recommendations: These guidelines comprise recommendations regarding differential diagnosis, neuroprotective therapies and multidisciplinary palliative care including management of respiration and nutrition as well as provision of assistive devices and end-of-life situations. Conclusion: Diagnostic and therapeutic guidelines are necessary due the comparatively high number of cases and the aggressive disease course. Given the low prevalence and the severe impairment of patients, it is often impossible to generate evidence-based data so that ALS guidelines are partially dependent on expert opinion. [ABSTRACT FROM AUTHOR]

This study is to test the technologies related to natural language processing (NLP) and text analysis to solve the problem of symptom analysis and symptomatic treatment for healthcare workers and patients after large-scale outbreaks of infectious diseases. Using the keyword extraction tool based on NLP technology combined with text analysis, the symptom description of the infected population obtained from the questionnaire survey was analyzed, and the efficacy of the symptomatic treatment drug was analyzed, and finally a pre-experimental system of online symptomatic treatment support drug selection system was produced. Through natural language processing (NLP) and text analysis of the symptoms of infected people, we found that high-frequency symptoms were mainly reflected in: nasal congestion, sore throat, fever and other high-frequency keywords, and through the analysis of alternative drug libraries, we also found that the drugs were mainly concentrated in: cold medicines, antipyretic drugs, and traditional Chinese medicines. In the early stage of infectious disease outbreak, it is difficult to use the existing drug library to make a prompt system under the premise of insufficient data collection, and a relatively complete symptomatic treatment support medication system can be formed after accumulating certain samples. [ABSTRACT FROM AUTHOR]

Without any disease-modifying treatment strategy for multiple system atrophy (MSA), the therapeutic management of MSA patients focuses on a multidisciplinary strategy of symptom control. In the present review, we will focus on state of the art treatment in MSA and additionally give a short overview about ongoing randomized controlled trials in this field. [ABSTRACT FROM AUTHOR]

The worldwide prevalence of Parkinson's disease (PD) has been constantly increasing in the last decades. With rising life expectancy, a longer disease duration in PD patients is observed, further increasing the need and socioeconomic importance of adequate PD treatment. Today, PD is exclusively treated symptomatically, mainly by dopaminergic stimulation, while efforts to modify disease progression could not yet be translated to the clinics. New formulations of approved drugs and treatment options of motor fluctuations in advanced stages accompanied by telehealth monitoring have improved PD patients care. In addition, continuous improvement in the understanding of PD disease mechanisms resulted in the identification of new pharmacological targets. Applying novel trial designs, targeting of pre-symptomatic disease stages, and the acknowledgment of PD heterogeneity raise hopes to overcome past failures in the development of drugs for disease modification. In this review, we address these recent developments and venture a glimpse into the future of PD therapy in the years to come. [ABSTRACT FROM AUTHOR]

Objectives Symptomatic treatment is an essential component in the overall treatment of multiple sclerosis (MS). However, knowledge in this regard is confusing and scattered. Physicians also have challenges in choosing symptomatic treatment based on the patient’s condition. To share, update, and reuse this knowledge, the aim of this study was to provide an ontology for MS symptomatic treatment. Methods The Symptomatic Treatment of Multiple Sclerosis Ontology (STMSO) was developed according to Ontology Development 101 and a guideline for developing good ontologies in the biomedical domain. We obtained knowledge and rules through a systematic review and entered this knowledge in the form of classes and subclasses in the ontology. We then mapped the ontology using the Basic Formal Ontology (BFO) and Ontology for General Medical Sciences (OGMS) as reference ontologies. The ontology was built using Protégé Editor in the Web Ontology Language format. Finally, an evaluation was done by experts using criterion-based approaches in terms of accuracy, clarity, consistency, and completeness. Results The knowledge extraction phase identified 110 articles related to the ontology in the form of 626 classes, 40 object properties, and 139 rules. Five general classes included “patient,” “symptoms,” “pharmacological treatment,” “treatment plan,” and “measurement index.” The evaluation in terms of standards for biomedical ontology showed that STMSO was accurate, clear, consistent, and complete. Conclusions STMSO is the first comprehensive semantic representation of the symptomatic treatment of MS and provides a major step toward the development of intelligent clinical decision support systems for symptomatic MS treatment.

Zuzanna Cyske,1 Paulina Anikiej-Wiczenbach,2 Karolina Wisniewska,1 Lidia Gaffke,1 Karolina Pierzynowska,1 Arkadiusz Ma&nacute;ski,2 Grzegorz Wegrzyn1 1Department of Molecular Biology, Faculty of Biology, University of Gdansk, Gdansk, 80-308, Poland; 2Psychological Counselling Centre of Rare Genetic Diseases, University of Gdansk, Gdansk, 80-309, PolandCorrespondence: Grzegorz Wegrzyn, Department of Molecular Biology, Faculty of Biology, University of Gda&nacute;sk, Wita Stwosza 59, Gda&nacute;sk, 80-308, Poland, Tel +48 58 523 6024, Fax +48 58 523 5501, Email grzegorz.wegrzyn@ug.edu.plAbstract: Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disease grouping five genetic disorders, four of them occurring in humans and one known to date only in a mouse model. In every subtype of MPS III (designed A, B, C, D or E), a lack or drastically decreased activity of an enzyme involved in the degradation of heparan sulfate (HS) (a compound from the group of glycosaminoglycans (GAGs)) arises from a genetic defect. This leads to primary accumulation of HS, and secondary storage of other compounds, combined with changes in expressions of hundreds of genes and many defects in organelles and various biochemical processes in the cell. As a result, dysfunctions of tissues and organs occur, leading to severe symptoms in patients. Although changes in somatic organs are considerable, the central nervous system is especially severely affected, and neurological, cognitive and behavioral disorders are the most significant changes, making the disease enormously burdensome for patients and their families. In the light of the current lack of any registered therapy for Sanfilippo syndrome (despite various attempts of many research groups to develop effective treatment, still no specific drug or procedure is available for MPS III), optimizing care with a multidisciplinary approach is crucial for managing this disease and making quality of patients’ life passable. This includes efforts to make/organize (i) accurate diagnosis as early as possible (which is not easy due to various possible misdiagnosis events caused by similarity of MPS III symptoms to those of other diseases and variability of patients), (ii) optimized symptomatic treatment (which is challenging because of complexity of symptoms and often untypical responses of MPS III patients to various drugs), and (iii) psychological care (for both patients and family members and/or caregivers). In this review article, we focus on these approaches, summarizing and discussing them.Keywords: mucopolysaccharidosis type III, accurate diagnosis, symptomatic treatment, psychological care

Background: Niemann-Pick disease type C (NPC) is a rare autosomal recessive neurodegenerative lysosomal disease characterized by multiple symptoms such as progressive cerebellar ataxia and cognitive decline. The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies, including animal models of NPC, observational clinical case studies, and a multinational, rater-blinded phase IIb clinical trial. Here, we describe the development of a study protocol (Sponsor Code "IB1001-301") for the chronic treatment of symptoms in adult and pediatric patients with NPC. Methods: This multinational double-blind randomized placebo-controlled crossover phase III study will enroll patients with a genetically confirmed diagnosis of NPC patients aged 4 years and older across 16 trial sites. Patients are assessed during a baseline period and then randomized (1:1) to one of two treatment sequences: IB1001 followed by placebo or vice versa. Each sequence consists of a 12-week treatment period. The primary efficacy endpoint is based on the Scale for the Assessment and Rating of Ataxia, and secondary outcomes include cerebellar functional rating scales, clinical global impression, and quality of life assessments. Discussion: Pre-clinical as well as observational and phase IIb clinical trials have previously demonstrated that IB1001 rapidly improved symptoms, functioning, and quality of life for pediatric and adult NPC patients and is safe and well tolerated. In this placebo-controlled cross-over trial, the risk/benefit profile of IB1001 for NPC will be evaluated. It will also give information about the applicability of IB1001 as a therapeutic paradigm for other rare and common neurological disorders. Trial registrations: The trial (IB1001-301) has been registered at www.clinicaltrials.gov (NCT05163288) and www.clinicaltrialsregister.eu (EudraCT: 2021–005356-10). Registered on 20 December 2021. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is frequently diagnosed in people of reproductive age, many of whom will become pregnant following diagnosis. Although many women report an improvement in symptoms and relapses during pregnancy, symptoms such as fatigue and spasticity are commonly reported and can worsen. Prescribing medications during pregnancy and breastfeeding presents unique challenges and guidance on the use of symptomatic therapies is limited. Objectives: This paper aims to provide a consensus on the current evidence base to facilitate informed decision-making and optimise pre-conception counselling. Methods: A list of most commonly prescribed medications for symptom management in MS was created using pregnancy and MS-related READ codes in the Welsh GP Dataset, followed by a review by MS neurologists. Results: A final list of 24 medications was generated for review. Searches were performed on each medication, and evidence graded using standardised criteria. Evidence-based recommendations were developed and distributed to experts in the field and revised according to feedback using modified Delphi criteria. Conclusions: Our guidelines provide evidence-based recommendations on the safety of symptomatic therapies during pregnancy and breastfeeding for general practitioners and specialist teams working with people with MS who are hoping to embark on pregnancy or are currently pregnant. Individual risk–benefit ratios should be considered during pre-conception counselling to optimise symptom burden and minimise harm to both parent and child. [ABSTRACT FROM AUTHOR]

Nivik grass (Arum maculatum), which belongs to the Araceae family, is also known as snake's pillow, bear's ear, shadbush and kabargan. In the international literature, it is known as bobbins snakeshead, Adam and Eve, lords-andladies, arum, naked girls, soldiers diddies and wake robin. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) frequently affects women of childbearing age, and an increasing number of disease-modifying therapies are available. However, a consequence of this is that women and clinicians face complex shared decisions surrounding disease-modifying therapy use in pregnancy and postpartum. It has been suggested that there are both knowledge and communication gaps that need to be addressed in order to improve outcomes for women with MS desiring a pregnancy. Existing pregnancy studies are subject to limitations including selection bias and missing data; however, when these are combined with clinical expertise, consensus guidelines can be developed and used as a framework to support this complex decision-making process. This commentary paper aims to provide a practical and evidence-based overview of the safety of disease-modifying therapies and symptomatic drug therapies during pregnancy and breastfeeding, along with highlighting where insufficient data exist to guide practice. Plain Language Summary: Multiple sclerosis is more common in women than men, and many women with multiple sclerosis have not completed their families when they are diagnosed. This means that they face complicated decisions around using disease-modifying therapies, many of which have limited evidence for use in pregnancy. Conversations between clinicians and women with multiple sclerosis around pregnancy do not always address all of the issues that women face, partly because not all of the needed information is available. Consensus guidelines have recently been developed, and both experience and opinion have been used to inform these. This paper provides a practical overview of the use of treatments for MS and its symptoms. [ABSTRACT FROM AUTHOR]

Background and Objectives: The Greek Society of Migraine and Headache Patients conducted, in 2020, its second online survey, titled "Migraine in Greece—2020", after publication of the first similar online survey conducted in 2018. To compare the current findings with the corresponding data obtained in 2018, we herein release the second part of results obtained from the 2020 survey on the efficacy of preventive and symptomatic anti-migraine medications and the patients' reported satisfaction with these treatments. Materials and Methods: We surveyed 2105 migraine patients from all over Greece with the use of a 151-questions specific migraine-focused questionnaire in Greek language, which was distributed through the online research software "SurveyMonkey". Results: Triptans were mostly used with efficacy for the symptomatic relief of migraine attacks. About 2 of 3 surveyed patients had received various prophylactic oral medications and the majority of them discontinued these prophylactic medications as a result of inefficacy/safety issues. BoNTA was reported to be effective only when administration was commenced by a trained neurologist/headache specialist, while our current findings are generally comparable to those obtained in our 2018 pre-COVID-19 survey and the pandemic has not imposed any significant attitudes on migraine therapies and corresponding patients' satisfaction. Conclusion: Although a market change is anticipated with the evolving widespread use of anti-CGRPs monoclonal antibodies or gepants in the symptomatic and prophylactic treatment of migraine, it is of great interest to review published results of larger longitudinal population-based studies to further ascertain the satisfaction of patients to migraine therapies. [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) is a rare and rapidly-progressive neurodegenerative disorder, characterized by the combination of dysautonomia, poor levodopa responsive parkinsonism, cerebellar ataxia, and pyramidal tract signs. Insidious onset, clinical heterogeneity and progression of the disease complicate the difficulty of early diagnosis and challenge, the development of neuroprotective drugs. In order to improve the knowledge of diagnosis and treatment of the disease, this paper reviews advances in its diagnostic criteria, biomarkers of early diagnosis and management of the disease.

A number of hereditary ataxias are caused by inborn errors of metabolism (IEM), most of which are highly heterogeneous in their clinical presentation. Prompt diagnosis is important because disease-specific therapies may be available. In this review, we offer a comprehensive overview of metabolic ataxias summarized by disease, highlighting novel clinical trials and emerging therapies with a particular emphasis on first-in-human gene therapies. We present disease-specific treatments if they exist and review the current evidence for symptomatic treatments of these highly heterogeneous diseases (where cerebellar ataxia is part of their phenotype) that aim to improve the disease burden and enhance quality of life. In general, a multimodal and holistic approach to the treatment of cerebellar ataxia, irrespective of etiology, is necessary to offer the best medical care. Physical therapy and speech and occupational therapy are obligatory. Genetic counseling is essential for making informed decisions about family planning.

Vertigo is a fairly common complaint with which patients present to physicians of various profiles, and especially to general practitioners, neurologists, and otorhinolaryngologists. Vertigo is a condition where a person has the illusion of movement or of surrounding objects moving when they are not. Vertigo is a symptom of a wide range of diseases, both benign and life-threatening. Vertigo can have a variety of causes, and the suggested treatment should depend on the cause. Due to the multifactorial etiology of medical care, many patients receive inadequate treatment under the primary healthcare scheme, especially during initial presentation. The main causes of vertigo are benign paroxysmal positional vertigo, Meniere’s disease, vestibular neuritis, vestibular migraine, and cerebrovascular diseases. Patients with other disorders, such as depression and hyperventilation syndrome, may present with complaints of nonrotary vertigo. Differential diagnosis of vertigo can be made using easy-to-perform tests during physical examination, including assessment of nystagmus, Dix-Hallpike maneuver, and blood pressure measurements with head-up tilt table tests. Treatment of patients with complaints of vertigo includes drug and non-drug therapy, depending on the established nosological form. However, due to the multifactorial etiology, many patients receive inadequate treatment under the primary healthcare scheme, especially during initial presentation. The dimensionhydrinate/cinnarizine combination is one of the drugs for the symptomatic treatment of vertigo of various origins in adults.

• The net benefit and effectiveness of pyridostigmine are moderate. • A quarter of all patients report side effects as the main reason to discontinue pyridostigmine. • The most common side effects of pyridostigmine are flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. • The results of this study can be used to better inform patients about the effectiveness and side effects of pyridostigmine and guide in shared decision making. Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG. [ABSTRACT FROM AUTHOR]

La maladie de Sjögren ou syndrome de Sjögren primitif (SSp) est caractérisée par l'association d'une triade symptomatique (douleur, sécheresse, fatigue) à des manifestations systémiques variées. Alors que les atteintes systémiques touchent environ 30 % des patients, le syndrome sec, principalement oculaire et buccal, est présent chez la quasi-totalité des patients. Ce symptôme est à l'origine d'une altération marquée de la qualité de vie et il ne doit pas être négligé. L'objectif de cette mise au point est d'offrir un rappel sur les mécanismes à l'origine du syndrome sec au cours du SSp, de rappeler quelles sont les conséquences potentielles de ce symptôme et de donner aux lecteurs des outils pratiques pour guider la prise en charge de nos patients atteints de SSp. Enfin, cet article fait le point sur l'impact sur le syndrome sec des traitements ciblés en développement dans le SSp. Sjögren's disease or primary Sjögren's syndrome (pSS) is characterized by the association of a symptomatic triad (dryness, pain and fatigue) with various systemic manifestations. While systemic involvement affects about 30% of patients, sicca, mainly ocular and oral, is present in almost all patients. This symptom causes high burden of the disease and a marked deterioration in quality of life. It should not be neglected in the management of pSS patients. The purpose of this update is to provide a review of the mechanisms that cause dry syndrome in pSS, to outline the potential consequences of this symptom, and to give practical tools to guide the management of our pSS patients. Finally, this article reviews the impact of targeted therapies in development in pSS on dryness. [ABSTRACT FROM AUTHOR]