Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

Transcranial brain parenchyma sonographic findings in patients with myotonic dystrophy type 1 and 2.

Introduction: Myotonic dystrophy type 1 (DM1) and 2 (DM2) are genetically determined progressive muscular disorders with multisystemic affection, including brain involvement. Transcranial sonography (TCS) is a reliable diagnostic tool for the investigation of deep brain structures. We sought to evaluate TCS findings in genetically confirmed DM1 and DM2 patients, and further correlate these results with patients' clinical features. Methods: This cross-sectional study included 163 patients (102 DM1, 61 DM2). Echogenicity of the brainstem raphe (BR) and substantia nigra (SN) as well as the diameter of the third ventricle (DTV) were assessed by TCS. Patients were evaluated using the Hamilton Depression Rating Scale, Fatigue Severity Scale and Daytime Sleepiness Scale. Results: SN hyperechogenicity was observed in 40% of DM1 and 34% of DM2 patients. SN hypoechogenicity was detected in 17% of DM1 and 7% of DM2 patients. BR hypoechogenicity was found in 36% of DM1 and 47% of DM2 subjects. Enlarged DTV was noted in 19% of DM1 and 15% of DM2 patients. Older, weaker, depressive, and fatigued DM1 patients were more likely to have BR hypoechogenicity (p < 0.05). DTV correlated with age and disease duration in DM1 (p < 0.01). In DM2 patients SN hyperechogenicity correlated with fatigue. Excessive daytime sleepiness was associated with hypoechogenic BR (p < 0.05) and enlarged DVT (p < 0.01) in DM2 patients. Conclusions: TCS is an easy applicable and sensitive neuroimaging technique that could offer new information regarding several brainstem structures in DM1 and DM2. This may lead to better understanding of the pathogenesis of the brain involvement in DM with possible clinical implications.

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Cerebral Amyloid Angiopathy-Related Inflammation (CAA-rI): Three Heterogeneous Case Reports and a Focused Literature Review.

Cerebral amyloid angiopathy-related inflammation (CAA-rI) is a largely reversible, subacute encephalopathy, which is considered as a rare variant of cerebral amyloid angiopathy (CAA). Although the diagnosis of this inflammatory vasculopathy is generally clinico-pathologic, a probable or possible diagnosis can often be established based on current clinico-radiological diagnostic criteria. This is important since CAA-rI is considered as a treatable disorder, which most commonly occurs in the elderly population. Behavioral changes and cognitive deterioration are highlighted as the most common clinical signs of CAA-rI, followed by a heterogeneous spectrum of typical and atypical clinical presentations. However, despite the well-established clinical and radiological features incorporated in the current diagnostic criteria for this CAA variant, this rare disorder is still insufficiently recognized and treated. Here, we have shown three patients diagnosed with probable CAA-rI, with significant heterogeneity in the clinical and neuroradiological presentations, followed by different disease courses and outcomes after the introduction of immunosuppressive treatment. Moreover, we have also summarized up-to-date literature data about this rare, yet underdiagnosed, immune-mediated vasculopathy.

Myotonic dystrophy type 1 in the COVID-19 era.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adults. People with DM1 might represent a high-risk population for respiratory infections, including COVID-19. Our aim was to evaluate the characteristics of COVID-19 infection and vaccination rate in DM1 patients. METHODS: This cross-sectional cohort study included 89 patients from the Serbian registry for myotonic dystrophies. Mean age at testing was 48.4 ± 10.4 years with 41 (46.1%) male patients. Mean duration of the disease was 24.0 ± 10.3 years. RESULTS: COVID-19 infection was reported by 36 (40.4%) DM1 patients. Around 14% of patients had a more severe form of COVID-19 requiring hospitalization. The severity of COVID-19 was in accordance with the duration of DM1. A severe form of COVID-19 was reported in 20.8% of patients who were not vaccinated against SARS-CoV-2 and in none of the vaccinated ones. The majority of 89 tested patients (66.3%) were vaccinated against SARS-CoV-2. About half of them (54.2%) received three doses and 35.6% two doses of vaccine. Mild adverse events after vaccination were recorded in 20.3% of patients. CONCLUSIONS: The percentage of DM1 patients who suffered from COVID-19 was like in general population, but with more severe forms in DM1, especially in patients with longer DM1 duration. The study indicated an overall favorable safety profile of COVID-19 vaccines among individuals with DM1 and its ability to protect them from severe COVID-19.

Chronic inflammatory demyelinating polyradiculoneuropathy: Diagnostic problems in clinical practice in Serbia.

Making diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is challenging since it can mimic a multitude of disorders, and is misdiagnosed in at least 50% of cases. We sought to determine the frequency of CIDP misdiagnosis in clinical practice in Serbia, to uncover CIDP mimics, and to identify factors that may aid in CIDP diagnosis. Our longitudinal retrospective cohort study included 86 eligible adult patients referred to the Neurology Clinic, University Clinical Centre of Serbia, with a diagnosis of CIDP. We also included 15 patients referred to us with different diagnoses that ended up having CIDP as their final diagnosis. Exactly half of patients referred as CIDP failed to meet the established diagnostic criteria (non-CIDP) and were given an alternative diagnosis at the first hospitalization. At the 1-year follow-up, the diagnosis was further revised in four subjects. Confirmed CIDP patients usually had their initial diagnosis based on the nerve conduction studies (NCS), a typical presentation with symmetrical involvement of all four limbs, as well as higher frequencies of elevated protein levels and albuminocytologic dissociation in the cerebrospinal fluid (CSF). CIDP patients also responded better to immune therapy. We found that 52% of the patients initially referred to our Clinic as CIDP were given other diagnoses after a 1-year follow-up. Out of all CIDP cases, 27% had been unrecognized prior to referral to our Center. Utilization of clear and objective indicators - conclusive NCS, improvement on therapy, and elevated CSF proteins may provide greater certainty in diagnosing CIDP.

Clinical score for early diagnosis of myotonic dystrophy type 2.

INTRODUCTION: Myotonic dystrophy type 2 (DM2) is a rare, multisystemic, autosomal dominant disease with highly variable clinical presentation. DM2 is considered to be highly underdiagnosed. OBJECTIVE: The aim of this study was to determine which symptoms, signs, and diagnostic findings in patients referred to neurological outpatient units are the most indicative to arouse suspicion of DM2. We tried to make a useful and easy-to-administer clinical scoring system for early diagnosis of DM2-DM2 early diagnosis score (DM2-EDS). PATIENTS AND METHODS: Two hundred ninety-one patients with a clinical suspicion of DM2 were included: 69 were genetically confirmed to have DM2, and 222 patients were DM2 negative. Relevant history, neurological, and paraclinical data were obtained from the electronic medical records. RESULTS: The following parameters appeared as significant predictors of DM2 diagnosis: cataracts (beta = 0.410, p < 0.001), myotonia on needle EMG (beta = 0.298, p < 0.001), hand tremor (beta = 0.211, p = 0.001), positive family history (beta = 0.171, p = 0.012), and calf hypertrophy (beta = 0.120, p = 0.043). In the final DM2-EDS, based on the beta values, symptoms were associated with the following values: cataracts (present 3.4, absent 0), myotonia (present 2.5, absent 0), tremor (present 1.7, absent 0), family history (positive 1.4, negative 0), and calf hypertrophy (present 1.0, absent 0). A cut-off value on DM2-EDS of 3.25 of maximum 10 points had a sensitivity of 84% and specificity of 81% to diagnose DM2. CONCLUSION: Significant predictors of DM2 diagnosis in the neurology outpatient unit were identified. We made an easy-to-administer DM2-EDS score for early diagnosis of DM2.

COVID-19 infection and vaccination against SARS-CoV-2 in myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction which is typically presented with muscle weakness and excessive fatigability. Majority of MG patients require long-term immune suppression. Our aim was to analyze the frequency and severity of COVID-19 infection in MG patients, as well as the frequency of vaccinated MG patients against SARS-CoV-2. METHODS: We included 125 MG patients from the central Belgrade municipalities-60% females, age at MG onset 50.1 ± 19.7 years, age at testing 61.7 ± 16.8 years, anti-acetylcholine receptor (anti-AChR) positive 78% and muscle specific tyrosine kinase (MuSK) positive 8.6%. RESULTS: One-third of our MG patients had a COVID-19 infection and they were younger compared to those without verified COVID-19. Severe COVID-19 infection was registered in 28% of MG patients, mostly in elder subjects with comorbidities such as cardiac diseases and malignancies. MG worsening was noted in 21% of patients during/after COVID-19 and 42% had COVID-19 sequelae. Majority of MG patients were vaccinated against SARS-CoV-2 (almost 70%). Vaccination was more common among MG patients with diabetes and in those with a milder form of MG. The most common types of vaccines were Sinopharm (42%) and Pfizer-BioNTech (25.6%). Adverse events were observed in 36% of vaccinated patients, with flu-like symptoms (77%) and local reactions (13%) being the most common ones. MG worsening was noticed in 5 (5.8%) patients after vaccination. CONCLUSION: COVID-19 has placed a significant new burden for MG patients. Elder MG patients and patients with comorbidities are in higher risk of having adverse outcome following SARS-CoV-2 infection. Percentage of vaccinated MG patients was higher than in general Serbian population.

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia.

Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region.

Downregulation of LKB1/AMPK Signaling in Blood Mononuclear Cells Is Associated with the Severity of Guillain-Barre Syndrome.

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy.

A longitudinal evaluation of fatigue in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND AIMS: Fatigue is a common but poorly understood complaint in patients with immune-mediated polyneuropathies. We sought to evaluate changes in fatigue over 1 year in a cohort of chronic inflammatory demyelinating polyneuropathy (CIDP) patients and to correlate changes in fatigue with changes in disability and quality of life. Investigation into other factors that may contribute to fatigue with a particular interest in the role other chronic disease states may play was also performed. METHODS: Fifty patients with CIDP who satisfied the 2010 EFNS/PNS diagnostic criteria were followed over the period of 1 year at three tertiary care centers in Serbia. Assessments of disability, quality of life, and patient perception of change and fatigue were collected at two time points 12 months apart. Comorbidities, treatment regimens, and sedating medication use was collected. RESULTS: Disability, quality of life, and patient perception of change showed statistically significant correlations with change in fatigue (p < .01). Increased levels of fatigue were noted in patients who used sedating medications (p = .05) and who had a comorbid chronic medical condition (p = .01). INTERPRETATION: Worsening fatigue correlates over time with increased disability and worse quality of life. Fatigue is not specific to CIDP, but is common in many chronic medical conditions and with the use of sedating medications. Our findings support the importance of identifying and supportively managing fatigue in patients with CIDP, but cautions against considering fatigue as a CIDP diagnostic symptom or using fatigue to justify immunotherapy utilization.

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A.

Introduction: Charcot-Marie-Tooth type 1A (CMT1A) comprises ~50% of all CMT cases. CMT1A is a slowly progressive motor and sensory neuropathy that leads to significant disability. We aimed to investigate the quality of life (QoL) in Serbian patients with CMT1A and to assess sociodemographic and clinical features associated with their QoL. Material and Methods: Forty-five genetically confirmed patients with CMT1A were included -60% women [age 50.4 ± 12.6 years, disease duration 22 (12.5-31.5) years]. SF-36, Medical Research Council (MRC) Sum Score, CMT Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS), Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used in the study. Results: Regarding SF-36, Mental Health and Social Functioning were the scales with the best achievements, whereas Role Physical was the worst domain. Worse QoL in patients with CMT1A was associated with elder age (rho = -0.34, p < 0.05), longer disease duration (rho = -0.31, p < 0.05), more pronounced muscle weakness measured by MRC-SS (rho = 0.43, p < 0.01), presence of tremor (p < 0.05), worse CMTES (rho = -0.68, p < 0.01), more severe disability in upper (rho = -0.70, p < 0.01) and lower limbs (rho = -0.61, p < 0.01) measured by ONLS scores, use of walking aids (p < 0.01), and with depression (p < 0.01) and fatigue (p < 0.01). Worse scores on CMTES (beta = -0.43, p < 0.01), BDI (beta = -0.39, p < 0.01), and FSS (beta = -0.36, p < 0.01) were significant independent predictors of worse QoL in patients with CMT1A (adjusted R 2 = 0.77, p < 0.001). Conclusion: Besides impairment made directly by CMT1A itself, QoL in these patients was also strongly affected by the presence of depression and fatigue. Since CMT1A is still not a curable disease, it is of interest to identify factors associated with QoL that are amenable to treatment.

Employment status of patients with Charcot-Marie-Tooth type 1A.

Previous studies showed that being unemployed is associated with lower quality of life in patients with Charcot-Marie-Tooth type 1A (CMT1A). The aim of this study was to assess the differences between CMT1A patients capable of working and CMT1A patients incapable of working due to CMT1A. Forty-four patients with genetically confirmed CMT1A were included. Medical Research Council (MRC) Sum Score, Charcot-Marie-Tooth Neuropathy Score (CMTNS), CMT Examination Score (CMTES), Overall Neuropathy Limitations Scale (ONLS), Beck Depression Inventory (BDI), Krupp's Fatigue Severity Scale (FSS), and Falls Efficacy Score (FES) were used. Whole cohort was divided into two groups: 1. CMT1A patients capable of working (employed and unemployed not due to CMT) and 2. CMT1A patients incapable of working due to CMT1A (unemployed due to CMT and retired due to CMT). At time of testing, 38.6% patients were employed, 13.6% were unemployed due to CMT, 6.8% were unemployed but not due to CMT, and 40.9% were retired early due to disability caused by CMT. Patients retired due to CMT1A at the age of 43 ± 10 years. ONLS total score and physical work appeared as significant independent predictors of being incapable of working due to CMT1A. Patients incapable of working were almost four times more likely to have fatigue (OR = 3.7, 95% CI 1.0-13.1, p < 0.05) and 11 times more likely to have fear of falling (OR = 11.0, 95% CI 2.0-59.7, p < 0.01). Patients with more severe functional disability and physical type of job were most likely incapable of working due to CMT1A. Incapability of working was associated with fatigue and fear of falling.

Long-term outcome in patients with myasthenia gravis: one decade longitudinal study.

INTRODUCTION: Even treated, myasthenia gravis (MG) continues to represent a significant burden and might continuously affect patients' quality of life (QoL). The aim of our longitudinal study was to analyze QoL in a large cohort of MG patients after a 10-year follow-up period. METHODS: This study comprised 78 MG patients (60% females, 50 ± 16 years old at baseline, 70% AchR positive) who were retested after 10 years. Disease severity was evaluated by MGFA classification. QoL was assessed using SF-36 questionnaire and Myasthenia Gravis-specific Questionnaire (MGQ). Hamilton rating scales for depression and anxiety (HDRS and HARS), Multidimensional Scale of Perceived Social Support (MSPSS) and Acceptance of Illness Scale (AIS) were also used. RESULTS: Similar percentage of patients was in remission at both time points (42% and 45%). However, at baseline all patients were treated, while 32% were treatment-free at follow-up. SF-36, MGQ, MSPSS and AIS scores were similar at baseline and retest. Mean HDRS and HARS scores worsened during time (p < 0.05), although percentage of patients with depression and anxiety did not change significantly. Significant predictors of worse SF-36 score at retest were depression (ß = - 0.45, p < 0.01), poor disease acceptance (ß = - 0.44, p < 0.01) and older age (ß = - 0.30, p < 0.01). Significant predictors of worse MGQ score at retest were poor disease acceptance (ß = - 0.40, p < 0.01), retirement (ß = - 0.36, p < 0.01), lower education (ß = 0.25, p < 0.01), and depression (ß = - 0.18, p < 0.05). CONCLUSIONS: Although after 10 years, a significant number of MG patients were in remission, their QoL was still reduced. Neurologists should be aware that patients' perception of poor QoL may persist even if MG is well treated from a physician's perspective.

Responsiveness of 2 Different Ability Outcome Measures in Guillain-Barré Syndrome.

BACKGROUND: The most frequently used ability outcome measure in Guillain-Barré syndrome (GBS) is the GBS disability scale (GDS). Recently developed inflammatory Rasch-built overall disability (I-RODS) scale has been suggested to be used in inflammatory polyneuropathies. In the present study, we wanted to assess the comparative responsiveness of I-RODS and GDS in subjects who were diagnosed with GBS during a follow-up period of 6 months. METHODS: Our prospective, multicentric study included 72 subjects. Patients were tested, using GDS and I-RODS, on day 14, day 28, month 3, and month 6 from the start of the symptoms. We defined improvement as a reduction for 1 or more points on GDS or improvement on I-RODS as defined by Draak (2014). RESULTS: Between days 14 and 28 there was an improvement in 28% of patients as measured with GDS and only in 10% patients as measured with I-RODS. At month 3 compared with day 14, we noticed an improvement in GDS score in 90% of GBS patients and I-RODS score in 65%. At month 6 improvements were noticed in 94% of patients measured by GDS and 78% according to I-RODS. CONCLUSION: Our findings support the use of GDS in an acute phase of GBS. I-RODS have their role mostly during a longer follow-up period when the majority of patients are ambulant and their other abilities besides walking are also of great importance.

Antecedent infections and vaccinations in chronic inflammatory demyelinating polyneuropathy: A European collaborative study.

INTRODUCTION/AIMS: Chronic inflammatory demyelinating polyneuropathy (CIDP) may be rarely preceded by infection. A causative link remains unproven, in contrast to Guillain-Barré syndrome (GBS), which is commonly postinfectious with well-demonstrated pathophysiological mechanisms of molecular mimicry following Campylobacter jejuni enteritis. Uncommonly, infections are reported before the onset of CIDP. In this study we aimed to determine the frequency and characteristics of CIDP occurring after antecedent infections or vaccinations in two large European cohorts. METHODS: We reviewed the records of 268 subjects with "definite" or "probable" CIDP from the Inflammatory Neuropathy Clinic, Birmingham, UK (129 subjects), and from the Serbian national CIDP database (139 subjects). RESULTS: Twenty-five of 268 (9.3%) subjects had a respiratory or gastrointestinal infection in the 6 weeks preceding CIDP onset, and 3 of 268 (1.1%) had received an influenza vaccination. CIDP disease onset occurred at a younger age (mean [standard deviation], 44.25 [17.36] years vs 54.05 [15.19] years; P < .005) and acute-onset CIDP was more common (42.9% vs 12.1%; odds ratio, 5.46; 95% confidence interval, 2.35-12.68; P < .001) in subjects with preceding infections or vaccinations. No differences in CIDP subtype, rates of cerebrospinal fluid protein level elevation, disability, or likelihood of treatment response, were observed. DISCUSSION: Antecedent infections or vaccinations may precede about 10% of cases of CIDP and are more common in younger subjects. Acute-onset CIDP is more frequent after antecedent events. These findings may suggest specific pathophysiological mechanisms in such cases.

Risk factors for potential drug-drug interactions in patients with myasthenia gravis.

OBJECTIVES: Our aim was to determine risk factors for and frequency of potential drug-drug interactions (pDDIs) among hospitalized patients with myasthenia gravis (MG). METHODS: This was a retrospective cross-sectional study of the-first time hospitalized MG patients or patients hospitalized because of the exacerbation of MG at the Neurology Clinic of the Clinical Center of Serbia, Belgrade. Medical records and discharge summaries of hospitalized MG patients over a 10-year period were reviewed. The pDDIs were identified by means of Micromedex, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. RESULTS: The study included 687 patients with MG. In total, 2041 pDDIs were detected in 608 (88.5%) patients. Among the discovered pDDIs, 329 different pDDIs were observed. The most frequent pDDIs were pyridostigmine-prednisone (487patients/70.9%) and aspirin-prednisone (90 patients/13.1%) classified as moderate, and enalapril-potassium chloride (71patients/10.3%) classified as major pDDI. Five drugs (aspirin, insulin, prednisone, cyclosporine, metformin) were responsible for 22.6% of different pDDIs. Dyspnea, generalized form of MG, diabetes mellitus, hypertension, total number of drugs-used, use of antiplatelets were identified as the relevant risk factors for total number of pDDIs (R2 = 0.626,F = 73.797, p < 0.001), while age of patients and history of cancer were inversely correlated with such an outcome. CONCLUSION: The frequency of the pDDIs in hospitalized MG patients is high, and adversely influenced by dyspnea, generalized MG, diabetes mellitus, hypertension, total number of drugs-used and use of antiplatelets.

The influence of the COVID-19 pandemic on patients with chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVES: At a time of global health crisis, fear, anxiety, and stress levels increase. The effects of protracted social isolation, and media related misinformation's about the coronavirus disease 2019 (COVID-19) resulting in increased fear/stress related to the insufficiently known illness. The aim was to assess the influence of the COVID-19 health crisis on patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A cross-sectional study on 29 adult CIDP patients was performed. The Medical Research Council scale was used to evaluate muscle strength. The degree of functional disability was measured using the Inflammatory Neuropathy Cause and Treatment disability scale. The overall quality of life (QoL) was self-estimated on a 0-100 numeric rating scale. We also used a specifically designed 22-question-survey about COVID-19. RESULTS: Regarding the COVID-19 pandemic, 62% of CIDP patients were concerned. The daily activities of 55% of patients were negatively influenced by the pandemic. During the COVID-19 outbreak, 21% of patients reported their CIDP got worse. In 39% of CIDP patients, the influence of the pandemic on CIDP therapy was reported (reducing the dose or time interval or even discontinuation). The mean value of the self-estimated QoL was 64 ± 19. Independent predictors of worse QoL were age of patients (beta = -0.35, p < 0.05) and fear of the COVID-19 (beta = -0.34, p < 0.05). CONCLUSION: The COVID-19 pandemic has a significant impact on CIDP patients. Besides the direct influence of the virus and fear of the virus, restrictive measures can indirectly harm the patients with CIDP.

Prospective analysis of disability and quality of life in patients with chronic inflammatory demyelinating polyradiculoneuropathy.

PURPOSE: Even treated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) continues to pose a significant burden in patients' everyday functioning and may continuously affect their quality of life (QoL). The aims of our prospective study were to analyze health-related QoL in CIDP patients during a 1-year follow-up period in real-life settings and to compare QoL changes with changes in disability and with patient impression of change. METHODS: The study comprised 59 patients diagnosed with CIDP. SF-36 questionnaire was applied in order to evaluate patients' QoL. Inflammatory neuropathy cause and treatment (INCAT) disability scale was used to assess patients' functionality. The second question from the SF-36 questionnaire was used as an estimation of the patient impression of change (PIC) after 1 year. RESULTS: SF-36 scores did not change over time in the group as a whole. According to INCAT disability scores, worsening was registered in 24 (40%) patients and improvement in 8 (14%). Fifteen (25%) patients reported worsening and the same number reported improvement, according to PIC. Concordant results on INCAT and PIC were registered in 49% of patients. Pooled SF-36 scores moderately correlated with pooled INCAT disability scores (rho = - 0.27 to - 0.59, p < 0.01). One-year changes of SF-36 scores did not differ when compared to different INCAT outcomes (worsening, stable, improvement). On the other hand, significant changes of SF-36 scores in different outcome groups according to PIC (worsening, stable, improvement) were noted (p < 0.01). CONCLUSION: INCAT, PIC, and SF-36 are complementary outcome measures that provide neurologists with useful items of information. We propose complementary use of these scales in CIDP patients in everyday clinical practice in order to detect worsening of the disease and/or of related symptoms on time.