Incidence and mortality rates of Guillain-Barré syndrome in Serbia.

Guillain-Barré syndrome (GBS) is an acute auto-immune polyradiculoneuropathy. A huge variety of GBS incidence and mortality rates has been noted across the world. The objective of the present multi-centric study was to assess the incidence and mortality rates of GBS during a 10-year period in Serbia. We collected data of adult GBS patients who were hospitalized from 2009 to 2018 in all five tertiary healthcare centers in Serbia. The incidence rates per 100 000 inhabitants with 95% confidence intervals (CI) were calculated and further corrected for the estimated number of patients hospitalized in secondary centers. Mortality rates were also assessed. GBS was considered severe if patients were not able to walk at least 10 m without assistance. Six hundred and forty GBS patients were registered in tertiary centers in a 10-year period. The proportion of severe cases was 75% at nadir, and 52% on discharge. GBS incidence rate in Serbia was 1.1 per 100 000 inhabitants, and estimated incidence if patients from secondary centers included 1.2 per 100 000. Peak incidence was observed during the sixth decade of life. During the acute phase, 5.6% of GBS patients died, while overall 9.7% of them died during 6-month period from disease onset. This study contributes to our knowledge about GBS epidemiology. Results will allow us to improve the diagnosis and treatment of GBS patients in Serbia.

Six-month prospective study of quality of life in Guillain-Barre syndrome.

OBJECTIVE: Guillain-Barre syndrome (GBS) is an acute disease of the peripheral nerves and their roots. Quality of life (QoL) in the first year after acute episode of GBS is still underresearched area. The aim of our study was to investigate QoL in GBS patients during a 6-month follow-up period. METHODS: Multicentric, prospective study included 74 adult patients with GBS (54% males). GBS disability scale (GDS) was used to assess functional disability (severe disability GDS > 2), and Individualized Neuromuscular Quality of Life Questionnaire (INQoL) to asses QoL. Patients were tested on day 14, day 28, month 3, and month 6 from symptom onset. RESULTS: Disability as measured by GDS improved during time (P < .01). INQoL scores also improved during time (P < .01) but were not able to differentiate between day 14 and day 28, and some scores also did not make difference between month 3 and 6 (pain, social relations, emotions and total INQoL score; P > .05). Pooled GDS scores correlated with pooled INQoL scores, especially with independence, activities, and weakness subscores (P < .01). Multiple linear regression analysis showed that GDS at day 14 (ß = .52, P < .01) and fatigue score at day 14 (ß = .41, P < .01) were independent predictors of the worse GDS at month 6 (adjusted R2  = .34, P < .01 for overall model). CONCLUSIONS: During a 6-month follow-up period of GBS patients, we observed a gradual recovery of patients' disability and QoL. Our study confirms the importance of patient-reported outcomes and their ability to capture some important issues that are omitted by classic ability measures such as GDS.

Three-Year Follow-Up Study in Patients with Guillain-Barré Syndrome.

A majority of patients with Guillain-Barré syndrome (GBS) have tendency of a good recovery. Our aim was to evaluate the outcome of the disease 1 and 3 years after GBS symptom onset. METHODS: During 2014, GBS was diagnosed in 82 patients in seven tertiary healthcare centers. Neurological follow-up was conducted in 57 (70%) patients after 1 year, and in 54 (66%) after 3 years. Functional disability was estimated according to the GBS disability scale (GDS), with a score of 0-3 indicating mild disability and a score of 4-6 indicating severe disability during acute phase, whereas a score >1 indicated poor recovery on follow-ups. Visual analog scale was used to assess sensory symptoms and musculoskelatal pain, and Krupp's Fatigue Severity Scale was used to asses fatigue. RESULTS: Poor functional outcome was found in 39% of GBS patients at year 1 and 30% at year 3. Paresthesias/dysesthesias were detected in 60% of patients after 1 year and 43% after 3 years. Musculoskeletal pain was present in 40% of patients at year 1 and 33% at year 3. Significant fatigue after 1 year was found in 21% of subjects and after 3 years in 7%. Parameters associated with poor functional outcome after 1 year were age >55 years (p=0.05), severe disability at admission (p1 indique une récupération difficile au moment des suivis. L'échelle visuelle analogue (EVA) a aussi été utilisée pour évaluer leurs symptômes sensoriels et leurs douleurs musculo-squelettiques. Enfin, l'échelle de gravité de la fatigue de Krupp a été utilisée pour évaluer leur degré de fatigue. Résultats: La première année, on a observé une piètre amélioration des capacités fonctionnelles chez 39% des patients atteints du SGB; pour la troisième année, cette proportion était de 30%. Au bout d'un an, on a aussi détecté la présence de paresthésie/dysesthésie chez 60% des patients; pour la troisième année, cette proportion était de 43%. Des douleurs musculo-squelettiques ont été rapportées chez 40% des patients après un an; deux ans plus tard, ce pourcentage chutait à 33%. Enfin, un état de fatigue important a été noté chez 21% des patients au bout d'un an; ce pourcentage n'était plus que de 7% au bout de trois ans. Les paramètres associés à une piètre amélioration des capacités fonctionnelles au bout d'un an étaient l'âge (>55 ans; p=0,05) ainsi qu'une incapacité sévère au moment de leur admission (p<0,05) et de leur congé (p<0,01). Au bout de trois ans, une piètre amélioration des capacités fonctionnelles était associée au sexe masculin (p<0,05) et à une incapacité sévère au moment d'obtenir un congé (p=0,06). CONCLUSIONS: Un an et trois ans après l'apparition des premiers symptômes du SGB, un nombre important de patients donnaient à voir des séquelles neurologiques, ce qui incluait une forme ou une autre d'incapacité fonctionnelle, des symptômes sensoriels, des douleurs et un état de fatigue.

Guillain-Barré syndrome in the elderly.

The aim of the study was to analyze specific features of Guillain-Barré syndrome (GBS) in old people. The study included 403 GBS patients (62% young [<60 years], 35% young-old [60-80 years], and 3% old-old [>80 years]). Diagnosis of GBS was made according to the National Institute of Neurological Disorders and Stroke (NINDS criteria). Severe disability (GBS disability score of >3) at nadir was more common in old compared with young patients (p = 0.0001) as was mortality (9% vs. 2%, respectively). Acute motor and sensory axonal neuropathy and hyponatremia were more common in old compared with young patients (12% vs. 6% and 27% vs. 18%, respectively, p = 0.04). A positive history for malignancy was more than three times more common in old than young patients (11% vs. 3%, respectively, p = 0.01). Disability on nadir was similar in young-old and old-old subjects with disability on discharge being more severe in old-old (p = 0.04) suggesting slower recovery in this subgroup. Bulbar symptoms were more common in old-old compared with young-old (50% vs. 19%, respectively, p = 0.01). Comorbidities were present in virtually all old-old patients compared with 66% of young-old patients (p = 0.04). In conclusion, Elderly patients, and especially old-old patients, with GBS have more severe disease with slower recovery than do younger patients.

Clinical and epidemiological features of Guillain-Barré syndrome in the Western Balkans.

The aim of this study was to define features of Guillain-Barré syndrome in a large cohort of patients from three Western Balkans countries. Data from adult Guillain-Barré syndrome (GBS) cases from 2009 to 2013 were retrospectively obtained from all tertiary health care centers. During the 5-year period, 327 new cases of GBS were identified with a male to female ratio of 1.7 : 1. The most common GBS variants were demyelinating (65%) and axonal (12%). At nadir 45% of patients were chair-bound, confined to bed, or required assisted ventilation, while 5% died. The crude incidence of GBS in Serbia and Montenegro was 0.93 per 100,000 population, and age-adjusted incidence according to the world standard population was 0.86 per 100,000. Incidence was particularly high in 50- to 80-year-old men. Statistically significant seasonal variations of GBS were not observed. This study of patients with GBS in the Western Balkans allows us to prepare the health system better and to improve the management of patients. This study also opens opportunities for international collaboration and for taking part in the multinational studies on GBS.

Non-coding 886 (nc886/vtRNA2-1), the epigenetic odd duck - implications for future studies.

Non-coding 886 (nc886, vtRNA2-1) is the only human polymorphically imprinted gene, in which the methylation status is not determined by genetics. Existing literature regarding the establishment, stability and consequences of the methylation pattern, as well as the nature and function of the nc886 RNAs transcribed from the locus, are contradictory. For example, the methylation status of the locus has been reported to be stable through life and across somatic tissues, but also susceptible to environmental effects. The nature of the produced nc886 RNA(s) has been redefined multiple times, and in carcinogenesis, these RNAs have been reported to have conflicting roles. In addition, due to the bimodal methylation pattern of the nc886 locus, traditional genome-wide methylation analyses can lead to false-positive results, especially in smaller datasets. Herein, we aim to summarize the existing literature regarding nc886, discuss how the characteristics of nc886 give rise to contradictory results, as well as to reinterpret, reanalyse and, where possible, replicate the results presented in the current literature. We also introduce novel findings on how the distribution of the nc886 methylation pattern is associated with the geographical origins of the population and describe the methylation changes in a large variety of human tumours. Through the example of this one peculiar genetic locus and RNA, we aim to highlight issues in the analysis of DNA methylation and non-coding RNAs in general and offer our suggestions for what should be taken into consideration in future analyses.

Guillain-Barre Syndrome Followed by Covid-19 Infection, Vaccination and Other Precipitating Factors during the Pandemic.

Background and Aims: Guillain-Barré syndrome (GBS) is usually triggered by an infection. Vaccination is mentioned as a possible trigger in a small number of GBS cases. The aim of this study was to notice GBS distinctness provoked by various triggers during the COVID-19 pandemic. Material and Methods: A total of 109 GBS patients were divided into three groups, respectively: COVID-19 infection associated (19 patients), COVID-19 vaccination associated (16 patients) and precipitated by some other factors (74 patients). We compared the clinical, neurophysiological and laboratory characteristics of these three groups. Results: Neither were differences recorded in the age of the patients of these three groups at the time of illness, nor in the number of days from the precipitating factor to the onset of symptoms. There were no clinical differences between groups related to severity of the disease or patients' recovery. The only clinical difference was observed in relation to facial nerve bilateral affection because it was significantly higher in the post-vaccination group. According to neurophysiological findings, demyelinating form dominated in all three groups. Conclusion: Clinical characteristics, electrophysiological findings and laboratory characteristics did not differ significantly in Guillain-Barre syndrome followed by COVID-19 infection, vaccination and other precipitating factors during the pandemic. The bilateral involvement of facial nerves was significantly higher in the post-vaccination group. Most of these cases had a mild form of the disorder-distal paresthesias GBS variant.

Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues.

Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.

Self-reported autonomic dysfunction in a recovery phase of Guillain-Barré syndrome.

OBJECTIVE: Autonomic dysfunction occurs in approximately two-thirds of Guillain-Barré syndrome (GBS) patients in the acute phase of the disease. Although improving over time, subclinical autonomic involvement may be present for 3-8 years after the GBS episode. The aim of this study was to determine the frequency of self-reported autonomic disorders in GBS patients three and six months after disease onset compared to healthy controls (HCs). METHODS: Our study included adult patients diagnosed with GBS from May 2017 until May 2018 in seven healthcare centers (67.6 % with demyelinating and 13.6 % with axonal syubtype). Functional disability was assessed by the Guillain-Barré syndrome disability scale (GDS). Each subject filled in the Serbian version of the SCOPA-Aut questionnaire. Using GDS and SCOPA-Aut, patients were tested at month 3 (M3) (n = 71) and month 6 (M6) (n = 70) from symptom onset. RESULTS: Dysautonomia was more common in patients with GBS compared to HCs at M3 (p < 0.01), while there was no difference at M6 (p > 0.05). Among autonomic disorders, constipation, complications to pass stool, and orthostatic hypotension were the most frequently reported. Patients with axonal variants had worse total SCOPA-Aut scores at M3 in comparison to AIDP patients (11.7 ± 10.1 vs. 6.1 ± 5.1, p < 0.05). GDS score correlated with the total SCOPA-Aut score. CONCLUSION: Autonomic symptoms are common in GBS patients during the recovery phase. They are more pronounced in patients with axonal forms of GBS and those with a higher degree of functional disability.

Outcome after intravenous thrombolysis in embolic stroke of undetermined source compared to cardioembolic stroke.

BACKGROUND: It is assumed that most cases of embolic stroke of undetermined source (ESUS) are of cardioembolic origin. The data about outcome after the treatment with intravenous thrombolysis (IVT) for this type of acute ischemic stroke (AIS) are limited. We aimed to compare clinical characteristics and outcomes after IVT for AIS between patients with ESUS and cardioembolic stroke (CS). METHODS: This study was a single center retrospective analysis of stroke patients treated with IVT. The Trial of ORG 10172 in Acute Stroke Treatment criteria were used to establish stroke etiology subtype at 3 months, while ESUS was considered a subset of stroke of undetermined etiology, defined according to 2014 international criteria. Functional outcome was assessed at 3 months and defined as excellent (modified Rankin scale 0-1) and favorable (modified Rankin scale 0-2). RESULTS: Total of 394 patients were treated with IVT; 113 had a cardioembolism, 88 had undetermined stroke subtype, of which 62 met the ESUS criteria. Patients with ESUS were on average younger (63.7 years versus 69.7 years, p = 0.001), had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission (12 versus 15, p = 0.002) and lower prevalence of antiplatelets use (27.4% versus 42.5%, p = 0.04) compared with CS patients. Favorable outcome was more likely in ESUS patients, at discharge (48.4% versus 24.0%, p = 0.002) and after 3 months (71.0% versus 37.2%, p < 0.001). Hemorrhagic transformation was less frequent (17.7% versus 33.6%, p = 0.03) in ESUS patients. Independent predictors of 3­month favorable outcome were ESUS, the absence of leukoaraiosis on computed tomography (CT) and absence of diabetes as a risk factor. CONCLUSION: Patients with ESUS had better outcome after IVT than patients with CS, which can be attributed to younger age and milder strokes in these patients.

Recurrent Guillain-Barré Syndrome - Case Series.

Recurrent Guillain-Barré syndrome (RGBS) episodes appear in up to 6% of Guillain-Barré syndrome (GBS) patients. The purpose of this study was to identify patients with previous episodes of GBS and to assess their clinical features in a large cohort of adult GBS patients. GBS patients hospitalized at tertiary centers in three Balkan countries were included in the study (n = 404). We identified 13 (3.2%) patients with recurrent GBS (RGBS). The male to female ratio was 3: 1. All RGBS patients had two episodes of the disease. The most common GBS subtype in both episodes of the disease was acute inflammatory demyelinating polyradiculoneuropathy (AIDP) (77%, first episode; 85%, second episode). Around 23% of patients presented with a different variant during the second GBS attack. Disability seems to be equally severe at both episodes (P > 0.05). Recurrent GBS was registered in 3% of our GBS patients. The majority of them were younger males. Different GBS subtypes were found to recur.

A CASE OF PROBABLE NEUROSARCOIDOSIS PRESENTING AS UNILATERAL OPHTHALMOPLEGIA.

Sarcoidosis is a multisystem disease of unknown etiology, characterized by the presence of noncaseating epithelioid granulomas and accumulation of T lymphocytes and mononuclear phagocytes, which damages the normal structure of tissues. Isolated form of neurosarcoidosis is very rare and difficult to diagnose and requires histologic confirmation of noncaseating granulomas in the nervous tissue. We report a case of a 55-year-old female who had probable isolated neurosarcoidosis based on magnetic resonance imaging findings of relapsing pachymeningitis with an inflammatory process in the apex of the right orbit and pseudotumor inflammation of the superior and lateral recti of the right eye. Diagnosis was further verified by positive response to dual corticosteroid and immunosuppressive therapy. Our case demonstrates the importance of considering isolated neurosarcoidosis as a potential underlying etiology of painful ophthalmoplegia, even without systemic manifestation of the disease.