Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ...‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.
Lateral elbow tendinopathy (LET) seems to be the most appropriate term to use in clinical practice because previous terms such as lateral epicondylitis, tennis elbow, lateral epicondylalgia, ...epicondylosis, enthesopathy, Father of the Bride's Elbow, lateral elbow or extensor tendonitis, lateral elbow or extensor tendinosis, and extensor tendinopathy make reference to inappropriate aetiological, anatomical, and pathophysiological terms ....
Background and purpose
Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and ...parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS‐related PN.
Methods
A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta‐analysis.
Results
The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%–20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS‐related PN. The commonest type of pSS‐related PN is distal axonal polyneuropathy (80% of patients with pSS‐related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies—particularly trigeminal—are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune‐mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS‐related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin.
Conclusions
PN is very common in pSS patients. Evidence on long‐term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.
The pooled prevalence of peripheral neuropathy in primary Sjögren syndrome (pSS) is estimated to be 15% (95% confidence interval = 11%–21%). pSS‐related neuropathy usually manifests in the 6th decade of life. The commonest type is distal axonal polyneuropathy, followed by sensory ganglionopathy.
Background: Fabry disease (FD) is an inherited lysosomal storage disorder, leading to multisystemic manifestations and causing significant morbidity and mortality. Objective: The aim of this ...narrative review is to present the current and novel therapeutic strategies in FD, including symptomatic and specific treatment options. Methods: A systematic literature search was conducted to identify relevant studies, including completed and ongoing randomized-controlled clinical trials (RCTs), prospective or retrospective cohort studies, case series and case reports that provided clinical data regarding FD treatment. Results: A multidisciplinary symptomatic treatment is recommended for FD patients, personalized according to disease manifestations and their severity. During the last two decades, FD-specific treatments, including two enzyme-replacement-therapies (agalsidase alfa and agalsidase beta) and chaperone treatment with migalastat have been approved for use and allowed for symptoms’ stabilization or even disease burden reduction. More therapeutic agents are currently under investigation. Substrate reduction therapies, including lucerastat and venglustat, have shown promising results in RCTs and may be used either as monotherapy or as complementary therapy to established enzymereplacement- therapies. More stable enzyme-replacement-therapy molecules that are associated with less adverse events and lower likelihood of neutralizing antibodies formation have also been developed. Ex-vivo and in-vivo gene therapy is being tested in animal models and pilot human clinical trials, with preliminary results showing a favorable safety and efficacy profile. Conclusion: The therapeutic landscape in FD appears to be actively expanding with more treatment options expected to become available in the near future, allowing for a more personalized approach in FD patients.
Background
Fibromyalgia (FM) and generalized anxiety disorder (GAD) share common clinical features: they both affect women more than men, their diagnosis is based solely on clinical criteria, and ...some of the symptoms such as anxiety, aches and muscle tension, sleep disorders, and cognitive dysfunction occur in both diseases. For both conditions, an underlying dysregulation of the autonomic nervous system (ANS) has been proposed.
Objective
The aims of this study were to investigate ANS dysfunction in FM and GAD and compare them with controls.
Methods
Sympathetic skin response (SSR) from palm and sole and cross-sectional area (CSA) of bilateral vagus nerves (VN) were measured in 28 healthy controls, 21 FM patients, and 24 GAD patients.
Results
CSA of VN was significantly smaller in FM patients (right: 1.97 ± 0.74mm
2
, left: 1.75 ± 0.65 mm2) and GAD patients (right: 2.12 ± 0.97mm
2
, left: 1.71 ± 0.86 mm
2
) compared to controls (right: 3.21 ± 0.75 mm
2
, left: 2.65 ± 1.13 mm
2
,
p
< 0.001, but did not differ between the two patient groups. SSR parameters were similar between patients and controls. SSR latency correlated to clinical scales (FM Widespread Pain Index) in the FM group (
r
= 0.515,
p
= 0.02 and
r
= 0.447,
p
= 0.05) for the upper and lower limbs respectively, but no other correlation between clinical and neurophysiological parameters was identified.
Conclusion
This study confirms similar ANS abnormalities in FM and GAD that fairly distinguish them from controls and support the hypothesis of a common pathophysiological substrate underlying both conditions.
Muscle-specific kinase (MuSK) Myasthenia Gravis (MG) represents a prototypical antibody-mediated disease characterized by predominantly focal muscle weakness (neck, facial, and bulbar muscles) and ...fatigability. The pathogenic antibodies mostly belong to the immunoglobulin subclass (Ig)G4, a feature which attributes them their specific properties and pathogenic profile. On the other hand, acetylcholine receptor (AChR) MG, the most prevalent form of MG, is characterized by immunoglobulin (Ig)G1 and IgG3 antibodies to the AChR. IgG4 class autoantibodies are impotent to fix complement and only weakly bind Fc-receptors expressed on immune cells and exert their pathogenicity
interfering with the interaction between their targets and binding partners (e.g. between MuSK and LRP4). Cardinal differences between AChR and MuSK-MG are the thymus involvement (not prominent in MuSK-MG), the distinct HLA alleles, and core immunopathological patterns of pathology in neuromuscular junction, structure, and function. In MuSK-MG, classical treatment options are usually less effective (e.g. IVIG) with the need for prolonged and high doses of steroids difficult to be tapered to control symptoms. Exceptional clinical response to plasmapheresis and rituximab has been particularly observed in these patients. Reduction of antibody titers follows the clinical efficacy of anti-CD20 therapies, a feature implying the role of short-lived plasma cells (SLPB) in autoantibody production. Novel therapeutic monoclonal against B cells at different stages of their maturation (like plasmablasts), or against molecules involved in B cell activation, represent promising therapeutic targets. A revolution in autoantibody-mediated diseases is pharmacological interference with the neonatal Fc receptor, leading to a rapid reduction of circulating IgGs (including autoantibodies), an approach already suitable for AChR-MG and promising for MuSK-MG. New precision medicine approaches involve Chimeric autoantibody receptor T (CAAR-T) cells that are engineered to target antigen-specific B cells in MuSK-MG and represent a milestone in the development of targeted immunotherapies. This review aims to provide a detailed update on the pathomechanisms involved in MuSK-MG (cellular and humoral aberrations), fostering the understanding of the latest indications regarding the efficacy of different treatment strategies.
Dementia causes deterioration in cognitive and physical functions. The scope of this study is to investigate the effect of different exercise programs on cognitive functions and functionality of ...persons suffering from mild Alzheimer's disease (AD) by generating information on the exercise types and their parameters. A randomized controlled trial (RCT) will be performed involving aerobic and resistance exercise interventions, taking place both at the sample collection center and at home. Participants will be randomly divided into two different intervention groups and a control group. All groups will be assessed twice; once at baseline and once after 12 weeks. The primary outcome shall comprise the effect of exercise programs on cognitive functions using cognitive testing, such as Addenbrooke's Cognitive Examination-Revisited (ACE-R), Mini Mental State Examination (MMSE), Trail Making Test A-Β (TMT A-B), and Digit Span Test (DST): Digit Span Forward (DSF) and Digit Span Backward (DSB). The effect on functionality will be assessed using the Senior Fitness Test (SFT), Berg Balance Scale (BBS), and Instrumental Activities of Daily Living Scale (IADL) questionnaire. Secondary outcomes include the effect of exercise on depression using the Geriatric Depression Scale-15 (GDS-15), on physical activity using the International Physical Activity Questionnaire (IPAQ), as well as the participants' compliance with the intervention. This study will investigate the possible effect of intervention of different exercise types and the comparison between them. Exercise forms a low-cost and reduced-risk intervention.
To explore the psychometric properties of the Greek version of the World Health Organization Disability Assessment Schedule (WHODAS 2.0–12 item) in adult patients suffering from motor disabilities. ...The questionnaire of WHODAS 2.0–12 item was officially translated and cross-culturally adapted into Greek (WHODAS 2.0–12Gr).136 adult patients with motor disabilities included in the present observational study. A reliability study was carried out to explore WHODAS 2.0–12Gr’s internal consistency (Cronbach’s
a
), repeatability (Pearson’s
r
) and test retest test-retest reliability between the WHODAS 2.0–12Gr outcomes of day-1 and day-8 intra-class correlation coefficients with 95% confidence intervals (ICC 95%CI), and the convergent validity (item-total correlation) of the questionnaire. Exploratory factor analysis (EFA) was used to explore the construct validity of the WHODAS 2.0–12Gr, while the concurrent validity of the questionnaire was testing against the Greek Medical Outcomes Study 36-item Short Form Health Survey version 1.0 (SF-36v1.0-Gr).
Reliability properties:
WHODAS 2.0–12Gr Cronbach’s
a
was 0.814 (
p
< 0.001), Pearson’s
r
value was 0.980 (p < 0.001) and ICC (95%CI) was 0.990 (0.985–0.993) (p < 0.001).
Validity properties:
Pearson
’s r
values of item-total correlation were ranged from 0.376 to 0.736. EFA extracted a 3-factor model. Regarding concurrent validity, the significant correlations between the WHODAS 2.0–12Gr and the SF36v1.0-Gr ranged from −0.169 to −0.720. WHODAS 2.0–12Gr showed significant high to excellent reliability and significant weak to strong validity properties. Overall, it can be suggested that WHODAS 2.0–12Gr could be a reliable and valid tool for assessing patients with motor disabilities.
Stroke is a cerebrovascular disorder characterized by the sudden onset of symptoms and clinical signs caused by either vascular infraction or hemorrhage. One of the main symptoms in the majority of ...post-stroke patients is spasticity. The main therapeutic options of spasticity in post-stroke patients include pharmacological interventions, rehabilitation techniques, and surgery. This review aims to explore the effectiveness of Neuromuscular Electrical Stimulation (NMES) for post-stroke spastic hemiparetic limb (upper and lower). Thorough research of the PubMed Medline database was performed. Records were limited to clinical studies published between 01/01/2010 and 01/01/2022. The results were screened by the authors in pairs. The search identified 26 records. After screening, nine records met the inclusion-exclusion criteria and were assessed. There were seven studies for spastic upper limbs and two for spastic lower limbs. The approaches investigated the effectiveness of electrical stimulation on post-stroke spastic upper or lower limb. Spasticity was measured through the modified Ashworth scale (MAS) and electromyographic recordings (EMG). In most cases, spasticity was decreased for at least two weeks post-intervention. In conclusion, NMES can be used either solo or in combination with different physical therapy modalities in order to produce optimal results, taking into consideration the specific needs and limitations of each individual patient. Based on the existing literature, as well as the limitations of the included studies, the authors believe that future studies on the subject of NMES in the management of post-stroke spasticity should focus on carefully examining each electrical parameter.
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