Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

Radiologic grading scores enhance clinical model's prognostic ability for Guillain-Barré syndrome.

OBJECTIVE: To assess the value of magnetic resonance imaging (MRI) grading scores based on lumbosacral muscle denervation edema in predicting the course of Guillain-Barré syndrome (GBS). METHODS: We collected data from 354 GBS patients and developed MRI grading criteria (5-point scale) based on the transverse area and longitudinal length of lumbosacral edema. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with GBS prognosis among 12 demographic and radiological features. Clinical models and clinical-MRI models were separately trained and validated by data from Institution 1. External test was performed using data from Institution 2. Differences between the models were assessed using the z-test. RESULTS: Four clinical factors (sex, albumin cytological dissociation in cerebrospinal fluid, medical research council [MRC] sum score at admission, and MRC sum score at discharge [odds ratio, 0.24-5.15; all p < 0.001]) and MRI grading scores (odds ratio, 2.44; p < 0.001) are independent prognostic factors for GBS patients. The shallow neural network achieved the best prognostic performance both clinical model (accuracy of external test cohort, 83.96%) and clinical-MRI model (accuracy of external test cohort, 90.56%). A significant difference between clinical and clinical-MRI model was also found (clinical model vs. clinical-MRI model, area under the receiver operating curve, 0.84 (95% CI: [0.71, 0.91]) vs. 0.97 (95% CI: [0.86, 0.99]), p < 0.001). INTERPRETATION: The MRI grading scores for muscle denervation edema may serve as a potential prognostic risk factor for GBS. Furthermore, they significantly improve the prognostic performance of standalone clinical model in predicting GBS prognosis.

Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay.

Background: Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking. Methods: CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score. Results: In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up. Conclusion: IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.

CSF CXCL13 is elevated in patients with CIDP and may reflect higher disease activity.

To evaluate B-cell involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 11 patients with CIDP, 8 patients with Guillain-Barré syndrome and 13 patients with idiopathic normal pressure hydrocephalus (iNPH) were studied. CSF cytokine and chemokine (IL-10, IL-15, TNF-α, TGF-ß1, GM-CSF, BAFF, CXCL10, and CXCL13) levels were measured by ELISA. The CSF CXCL13 level was significantly higher in patients with CIDP than in those with iNPH. The CSF CXCL13 level was significantly higher in CIDP patients with higher annualized relapse rates and higher modified Rankin scale scores. The CSF CXCL13 level is elevated in CIDP, especially in those with higher disease activity.

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.

Guillain-Barre syndrome in Mexico: clinical features and validation of Brighton Collaboration Group criteria. / Síndrome de Guillain-Barré en México: características clínicas y validación de los criterios de Brighton.

INTRODUCTION: As SARS-CoV-2 vaccination is ongoing in Mexico and Guillain-Barre syndrome (GBS) cases have been reported, validation of Brighton criteria in Mexico is necessary. Moreover, epidemiology of GBS in Mexico differs from European and North American countries. OBJECTIVE: To describe the clinical, cerebrospinal and electrodiagnostic features in Mexican patients diagnosed with GBS and classify them according to the Brighton Collaboration Group diagnostic criteria. Patrients and methods. An ambispective cohort study was conducted. We included patients that fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria for Guillain-Barre syndrome. Patients in this study were classified according to Brighton collaboration group levels of certainty for Guillain-Barre syndrome. RESULTS: Sixty eight percent of patients were male. Of the 248 patients included, 58.4% had history of a precedent infection, mean time from symptom onset to admission was 5 (1-30) days. Mean Medical Research Council sum score 30.3 ± 15.5. Almost 98% of patients had a monophasic course. Level 1 of certainty according to Brighton collaboration group criteria was fulfilled by 54.6% of patients, level 2 by 45% and level 4 by 0.6%. Patients meeting level 2 of certainty were mostly because normal cerebrospinal fluid findings or findings in nerve conduction studies not consistent with any GBS variants. CONCLUSION: GBS is a frequent autoimmune neuropathy that has been associated with preceding infections and with vaccination campaigns. For SARS-CoV-2 vaccination campaign in Mexico, validation of Brighton Criteria is necessary. Although Mexico's GBS epidemiology has been changing throughout recent years, this study provides similar data compared to other countries.

TITLE: Síndrome de Guillain-Barré en México: características clínicas y validación de los criterios de Brighton.Introducción. Dado que la vacunación contra el SARS-CoV-2 está en curso en México y se han notificado casos de Guillain-Barré, es necesaria la validación de los criterios de Brighton en México. La epidemiología de Guillain-Barré en México difiere de la de los países europeos y norteamericanos. Objetivo. Describir las características clínicas, cerebroespinales y electrodiagnósticas en pacientes mexicanos con diagnóstico de Guillain-Barré y clasificarlos según los criterios diagnósticos del Brighton Collaboration Group. Pacientes y métodos. Se realizó un estudio de cohorte ambispectivo. Se incluyó a pacientes que cumplen con los criterios del National Institute of Neurological Disorders and Stroke para el síndrome de Guillain-Barré (SGB). Se clasificó a los pacientes según los niveles de certeza del Brighton Collaboration Group para el SGB. Resultados. El 68% de los pacientes eran hombres. De los 248 pacientes incluidos, el 58,4% tenía antecedentes de infección previa. La media desde el inicio de los síntomas hasta el ingreso fue de 5 (1-30) días, y la puntuación media de la suma del Medical Research Council, de 30,3 ± 15,5. El nivel 1 de certeza según los criterios del Brighton Collaboration Group se cumplió en el 54,6% de los pacientes; el nivel 2, en el 45%; y el nivel 4, en el 0,6%. Los pacientes que alcanzaron el nivel 2 de certeza se debieron principalmente a hallazgos normales en el líquido cefalorraquídeo o a hallazgos en estudios de neuroconducción que no cumplen los criterios de ninguna variante de SGB. Conclusión. El SGB es una neuropatía autoinmune frecuente que se ha asociado con infecciones previas y con campañas de vacunación. Para la campaña de vacunación contra el SARS-CoV-2 en México es necesaria la validación de los criterios de Brighton. Aunque la epidemiología del SGB en México ha ido cambiando a lo largo de los últimos años, este estudio proporciona datos similares en comparación con otros países.

Elevated blood and cerebrospinal fluid glucose levels affect the severity and short-term prognosis of Guillain-Barré syndrome.

OBJECTIVE: This study aimed to explore the correlation of elevated glucose levels in the blood and cerebrospinal fluid with the progression and short-term prognosis of Guillain-Barré syndrome (GBS). METHODS: The medical records of 982 patients who were diagnosed with GBS in 31 representative tertiary hospitals, located in 14 provinces in southern China, were collected and retrospectively reviewed. Patients were grouped according to the levels of fasting plasma glucose (FPG) and cerebrospinal fluid (CSF) glucose, as well as the concentration of blood hemoglobinAlc (HbA1c). The Hughes grade scale was used to quantify functional outcomes. RESULTS: Compared to patients with normal FPG and CSF glucose levels, those in the high FPG and high CSF glucose groups were characterized by a higher proportion of severe patients (HFGS ≥ 3) at admission (58.8 vs. 73.1, P = 0.000; 57.6 vs. 71.2, P = 0.000), at nadir (67.4 vs. 83.0, P = 0.000; 66.2 vs. 80.4, P = 0.000), and at discharge (29.8 vs. 46.3, P = 0.000; 26.4 vs. 45.0, P = 0.000). Patients in the high HbA1c group also had more severe disability at admission (74.6 vs. 56.1, P = 0.005) and at nadir (80.3 vs. 64.3, P = 0.012) compared to the normal HbA1c group. Moreover, elevated levels of FPG and CSF glucose were significantly correlated with more severe disability at admission, at nadir, and at discharge. CONCLUSIONS: The present study showed that elevated glucose levels in the blood and cerebrospinal fluid were associated with the severity and short-term prognosis of GBS. TRIAL REGISTRATION: chicTR-RRc-17,014,152. ABBREVIATIONS: GBS, Guillain-Barré syndrome; FPG, fasting plasma glucose; CSF, cerebrospinal fluid; HFGS, Hughes Functional Grading Scale; HbA1c, hemoglobin A1c. DM, diabetes mellitus; NCS, nerve conduction study; AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; AMSAN, acute motor sensory axonal neuropathy; MV, mechanical ventilation.

Interleukin 8, a Biomarker to Differentiate Guillain-Barré Syndrome From CIDP.

OBJECTIVE: To determine whether CSF interleukin 8 (IL-8) concentration can help to distinguish Guillain-Barré syndrome (GBS) from chronic inflammatory demyelinating polyneuropathy (CIDP) at the initial stage of the disease. METHODS: We performed retrospective immunoassay of IL-8 in CSF, collected at the University Hospitals of Geneva between 2010 and 2018, from patients diagnosed with GBS (n = 45) and with CIDP (n = 30) according to the Brighton and European Federation of Neurological Societies/Peripheral Nerve Society criteria by a physician blinded to biological results. RESULTS: CSF IL-8 was higher in GBS (median: 83.9 pg/mL) than in CIDP (41.0 pg/mL) (p < 0.001). Receiver operating characteristic analyses indicated that the optimal IL-8 cutoff was 70 pg/mL. Above this value, patients were more likely to present GBS than CIDP (specificity 96.7%, sensitivity 64.4%, positive predictive value [PPV] 96.7%, and negative predictive value [NPV] 64.4%). Among GBS subcategories, IL-8 was higher in acute inflammatory demyelinating polyneuropathy (AIDP, median: 101.8 pg/mL) than in other GBS variants (median: 53.7 pg/mL). In addition, with CSF IL-8 above 70 pg/mL, patients were more likely to present AIDP than acute-onset CIDP (p < 0.001; specificity 100%, sensitivity 78.8%, PPV 100%, and NPV 46.2%) or other CIDP with nonacute presentation (p < 0.0001; specificity 95.8%, sensitivity 78.8%, PPV 96.3%, and NPV 76.7%). CONCLUSION: CSF IL-8 levels can help to differentiate AIDP variant of GBS from CIDP, including acute-onset CIDP, with high specificity and PPV. This may improve early and appropriate treatment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that CSF IL-8 levels accurately distinguish patients with GBS from those with CIDP.

COVID-19-associated Guillain-Barre syndrome: Postinfectious alone or neuroinvasive too?

Coronavirus disease 2019 (COVID-19) has been shown to be associated with a lot of neurological complications, of whom Guillain-Barre syndrome (GBS) is an important post-infectious consequentiality. More than 220 patients with GBS have been reported thus far. We intend to share our experience with five patients of GBS where one of them had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the cerebrospinal fluid (CSF). This is the first-ever report demonstrating the presence of SARS-CoV-2 in the CSF of an adult patient; a similar occurrence has recently been described in a pediatric patient. We wish to emphasize the fact that commonly GBS occurs as a result of a post-infectious process but in a few cases where the symptoms of COVID-19 and GBS occur concurrently, corresponding to the viremic phase, separate pathogenesis needs to be thought of. This para-infectious nature is exemplified by the presence of virus in the cerebrospinal fluid of one of our patients. We review the neuroinvasive potential of SARS-Cov-2 in this regard and draw parallels with Cytomegalovirus, Zika virus, and Human Immunodeficiency virus-associated occurrences of GBS.

Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID-19 neuropathy patients.

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.

Oligoclonal IgG bands in chronic inflammatory polyradiculoneuropathies.

BACKGROUND: Cerebrospinal fluid (CSF) albumincytologic dissociation represents a supportive diagnostic criterion of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Few studies have investigated possible systemic or intrathecal humoral immune response activation in CIDP.Aim of our study was to investigate whether the search of oligoclonal IgG bands (OCBs) might provide additional data helpful in CIDP diagnostic work-up. METHODS: Forty-eight consecutive patients with CIDP (34 men, mean age 59.4, range 16-83) were recruited. CSF analysis included nephelometric measurement of albumin and IgG concentrations, calculation of QALB, QAlbLIM and intrathecal IgG synthesis, and OCBs detection with isoelectric focusing. Data were compared with those from CSF and serum of 32 patients with Guillain-Barré syndrome (GBS), 18 patients with anti-myelin associated glycoprotein (MAG) antibody neuropathy, 4 patients with multifocal motor neuropathy and 32 patients with non-inflammatory neuropathies (NINPs). RESULTS: Patients with CIDP and anti-MAG antibody neuropathy had significantly higher CSF albumin concentrations and QALB values than NINPs (p=0.0003 and p=0.0095, respectively). A total of 9 (19%) patients with CIDP presented identical serum and CSF OCBs ('mirror pattern') versus 3 patients (16.6%) with anti-MAG antibody neuropathy, 13 patients (40.6%) with GBS and 12.5% patients with NINPs. Only one patient with CIDP showed unique-to-CSF OCBs. First-line therapy was effective in 80.4% of patients with CIDP, irrespective of CSF findings. CONCLUSIONS: Compared with NINP, CIDP, GBS and anti-MAG antibody neuropathies had a significantly increased CSF protein and blood-spinal nerve root barrier damage. Intrathecal humoral immune response is rare in our patients with CIDP. Systemic oligoclonal activation is more frequent, but not significantly different from what was detected in the control groups.

Cerebrospinal fluid analysis in Guillain-Barré syndrome: value of albumin quotients.

BACKGROUND: Albuminocytologic dissociation in cerebrospinal fluid (CSF) is a diagnostic hallmark of Guillain-Barré syndrome (GBS). Compared to CSF total protein (TP), the CSF/serum albumin quotient (Qalb) has the advantage of method-independent reference ranges. Whether the diagnostic yield differs between Qalb and CSF-TP is currently unknown. METHODS: We retrospectively analyzed the diagnostic yield (i.e., a value above the URL indicating blood-nerve barrier dysfunction) of Qalb and CSF-TP levels in patients with GBS. We evaluated two different equations (Reiber's and Hegen's) for age-adjusted URLs of Qalb and compared results to CSF-TP using the standard URL of 0.45 g/L as well as age-adjusted URLs (by decade of age). Additionally, multivariable logistic regression analysis was used to assess the effect of clinical factors on the diagnostic yield. RESULTS: We analyzed 110 patients [62% males; median age 48 (IQR 35-58)] with sensorimotor (68), motor (16), sensory (12) and localized (8) GBS as well as Miller Fisher syndrome (6). Qalb and CSF-TP were highly correlated (r = 0.95, p < 0.001). The diagnostic yield of Qalb was 65% with Reiber's and 47% with Hegen's age-adjusted URLs compared to 66% with the fixed CSF-TP URL of 0.45 g/L and 49% with age-adjusted CSF-TP URLs. A longer duration from clinical onset to lumbar puncture was associated with a higher diagnostic yield. CONCLUSION: Qalb strongly correlates with CSF-TP in patients with GBS with a similar diagnostic yield for the detection of a blood-nerve barrier dysfunction. However, the diagnostic yield of both values is lower when using more recent age-adjusted URLs and at earlier timepoints.

Guillain-Barre syndrome associated to COVID-19 infection: a review of published case reports. / Síndrome de Guillain-Barré asociado a infección por COVID-19: revisión de casos publicados.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic is a major worldwide health disorder. There is an increasing number of neurological complications recognized with COVID-19 including patients with GBS and its variants. DEVELOPMENT: A review of the clinical cases of GBS associated to COVID-19 infection published in the last months has been developed. We included 48 patients (31 men, mean age 56.4 years). The most common COVID-19 symptoms were cough (60.4%) and fever (56.3%). Mean time from COVID-19 symptoms to neurologic manifestations was 12.1 days, but in nine patients (18.8%) developed GBS within seven days. Eleven patients (22.9%) presented cranial nerve involvement in the absence of muscle weakness; 36 presented the classic sensory motor variant (75%) and one had a pure motor variant (2.1%). The electrodiagnostic pattern was considered demyelinating in 82.4% of the generalized variants. The presence of hyposmia/dysgeusia was associated with a latency shorter than seven days to GBS onset of symptoms (30% vs 15.6%), and cranial nerve involvement in the absence of weakness (30.8% vs 17.1%). Most patients (87.5%) were treated with intravenous immunoglobulin. Neurological outcome was favorable in 64.6%; 29.2% had respiratory failure and 4.2% died shortly after being admitted. CONCLUSIONS: GBS in patients with SARS-CoV-2 infection resembles clinically and electrophysiology the classical forms. Further studies are necessary to understand whether GBS frequency is actually increased due to SARS-CoV-2 infection and explore pathogenic mechanisms.

TITLE: Síndrome de Guillain-Barré asociado a infección por COVID-19: revisión de casos publicados.Introducción. La pandemia por la enfermedad por coronavirus 2019 (COVID-19) es un importante problema para la salud mundial. Hay un incremento en las complicaciones neurológicas reconocidas por la COVID-19, incluyendo el síndrome de Guillain-Barré (SGB) y sus variantes. Desarrollo. Se realizó una revisión de los casos publicados en los últimos meses de SGB asociado a infección por COVID-19. Incluimos a 48 pacientes (31 hombres; edad media: 56,4 años). Los síntomas de COVID-19 más comunes fueron tos (60,4%) y fiebre (56,3%). El tiempo promedio entre los síntomas de COVID-19 y el SGB fue de 12,1 días, pero nueve pacientes (18,8%) desarrollaron SGB en menos de siete días. Once pacientes (22,9%) presentaron afectación de los nervios craneales en ausencia de debilidad muscular, 36 presentaron la variante clásica sensitivomotora (75%) y uno tuvo una variante motora pura (2,1%). El patrón electrofisiológico se consideró desmielinizante en el 82,4% de las variantes generalizadas. La presencia de hiposmia/disgeusia estuvo asociada con una latencia menor a los siete días hasta el inicio de los síntomas del SGB (30 frente a 15,6%) y a la afectación de los nervios craneales en ausencia de debilidad (30,8 frente a 17,1%). La mayoría de los pacientes (87,5%) fueron tratados con inmunoglobulina endovenosa. La evolución neurológica fue favorable en el 64,6%, el 29,2% tuvo insuficiencia respiratoria y hubo un 4,2% de muertes. Conclusiones. El SGB en pacientes con infección por SARS-CoV-2 es similar clínica y electrofisiológicamente a las formas clásicas. Se requieren más estudios para comprender si la frecuencia del SGB realmente aumentó debido a la pandemia por COVID-19 y explorar los mecanismos patógenos involucrados.

Cerebrospinal Fluid Protein Level and Mechanical Ventilation in Guillain-Barré Syndrome patients.

The prognostic value of cerebrospinal fluid (CSF) protein in Guillain Barré Syndrome (GBS) is unclear. We aimed to explore the potential association between CSF protein level and mechanical ventilation in GBS. We undertook a retrospective study of GBS patients from January 2000 to November 2019 at the University of Michigan. 94 patients were ultimately included for evaluation. After adjusting for the Erasmus GBS Respiratory Insufficiency Scale (EGRIS), we did not find a significant difference in CSF protein between ventilated and non-ventilated patients. Elevated CSF protein level does not appear to portend an increased likelihood of mechanical ventilation in GBS patients.

Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients.

INTRODUCTION: Polymerase chain reaction (PCR)-based testing of cerebrospinal fluid (CSF) samples has greatly facilitated the diagnosis of central nervous system (CNS) infections. However, the clinical significance of Epstein-Barr virus (EBV) DNA in CSF of individuals with suspected CNS infection remains unclear. We wanted to gain a better understanding of EBV as an infectious agent in immunocompetent patients with CNS disorders. METHODS: We identified cases of EBV-associated CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with EBV PCR positivity in CSF who visited Pusan National University Hospital between 2010 and 2019. RESULTS: Of the 780 CSF samples examined during the 10-year study period, 42 (5.4 %) were positive for EBV DNA; 9 of the patients (21.4 %) were diagnosed with non-CNS infectious diseases, such as optic neuritis, Guillain-Barré syndrome, and idiopathic intracranial hypotension, and the other 33 cases were classified as CNS infections (22 as encephalitis and 11 as meningitis). Intensive care unit admission (13/33 patients, 39.3 %) and presence of severe neurological sequelae at discharge (8/33 patients, 24.2 %) were relatively frequent. In 10 patients (30.3 %), the following pathogens were detected in CSF in addition to EBV: varicella-zoster virus (n = 3), cytomegalovirus (n = 2), herpes simplex virus 1 (n = 1), herpes simplex virus 2 (n = 1), Streptococcus pneumomiae (n = 2), and Enterococcus faecalis (n = 1). The EBV-only group (n = 23) and the co-infection group (n = 10) did not differ in age, gender, laboratory data, results of brain imaging studies, clinical manifestations, or prognosis; however, the co-infected patients had higher CSF protein levels. CONCLUSION: EBV DNA in CSF is occasionally found in the immunocompetent population; the virus was commonly associated with encephalitis and poor prognosis, and frequently found together with other microbes in CSF.

CSF sphingomyelin: a new biomarker of demyelination in the diagnosis and management of CIDP and GBS.

OBJECTIVE: To validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker. METHODS: We prospectively enrolled 184 patients from six Italian referral centres, in whom CSF SM levels were quantified by a fluorescence-based assay optimised and patented in our laboratory. RESULTS: We confirmed increased levels of SM in the CSF of patients affected by typical CIDP (n=35), atypical CIDP (n=18) and acute inflammatory demyelinating polyradiculoneuropathy, AIDP (n=12) compared with patients affected by non-demyelinating neurological diseases, used as controls (n=85) (p<0.0001, p=0.0065 and p<0.0001, respectively). In patients with CIDP classified for disease stage, SM was higher in active CIDP compared with both controls and stable CIDP (p<0.0001), applying for a selective tool to treatment tailoring or withdrawal. SM was also increased in AIDP compared with axonal GBS, discerning the demyelinating from axonal variant of the disease. SM did not correlate with CSF protein levels, stratifying patients independently from commonly used CSF indexes, and displaying high specificity to avoid potential misdiagnosis. Finally, SM correlated with the main clinical scores and some neurophysiological parameters in patients with CIDP and AIDP. CONCLUSIONS: CSF SM is a diagnostic and staging wet biomarker for acquired demyelinating neuropathies and may effectively improve the management of patients affected by GBS and CIDP.

Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series.

We report a case series of five patients affected by SARS-CoV-2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID-19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain-Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right-sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin-8. Peripheral nervous system involvement after infection with COVID-19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.

Cerebrospinal fluid lipidomic biomarker signatures of demyelination for multiple sclerosis and Guillain-Barré syndrome.

Multiple sclerosis (MS) and Guillain-Barré syndrome (GBS) are demyelinating disorders affecting the central nervous system and peripheral nervous system (PNS), respectively. Cerebrospinal fluid (CSF) is one of the most valuable sources of diagnostic biomarkers in neurological diseases. In the present study high sensitivity shotgun mass spectrometry was used to characterise the CSF lipidome of patients with MS, GBS and controls with non-demyelinating diseases. The quantification of 222 CSF lipid molecular species revealed characteristic changes in the absolute and relative lipid concentrations in MS and GBS compared to the controls. For the GBS group, the fourfold elevation in the total lipid content was a discriminatory and a newly identified feature of PNS demyelination. In contrast, in MS, the accumulation of the myelin-derived cerebrosides represented a specific feature of demyelination. As a common feature of demyelination, we identified upregulated levels of lipid metabolic intermediates. We found strong positive correlation between total protein content and lipid concentrations in both diseases. By exploring the CSF lipidome we demonstrate usefulness of broad-range shotgun lipidomic analysis as a fast and reliable method of biomarker discovery in patients with demyelinating neurological disorders that might be a valuable diagnostic complement to existing examinations.

Central diabetes insipidus unveiled by glucocorticoid therapy in a patient with an empty sella: A case report and literature review.

RATIONALE: Some diseases contribute to hypopituitarism without clinical manifestations and the glucocorticoid therapy may unveil central diabetes insipidus. The condition is rare and usually causes problems for clinical physicians. PATIENT CONCERNS: A 59-year-old woman presented to our hospital due to facial numbness and persistent eyelid heaviness. DIAGNOSIS: Physical examination and cerebrospinal fluid examination supported a diagnosis of Guillain-Barre[Combining Acute Accent] syndrome. Magnetic resonance imaging showed an empty sella. Hormone test indicated hypopituitarism. INTERVENTIONS: The patient received intravenous immunoglobulin and glucocorticoid. Central diabetes insipidus appeared after 20 days. Subsequently, the patient was prescribed 1-desamino-8-D-arginine vasopressin and prednisone. OUTCOMES: During 6 months' follow-up, the patient's urine output was gradually reduced to normal level. LESSONS: This case indicated that hypopituitarism may be caused by an empty sella and be masked by adrenal insufficiency. Central diabetes insipidus may present after glucocorticoid therapy.

Ratio and index of Neurofilament light chain indicate its origin in Guillain-Barré Syndrome.

OBJECTIVE: Neurofilament light chain (NfL) has been established as a biomarker of axonal damage in many diseases of the central nervous system (CNS). Increased levels of serum NfL (sNfL) can derive as well from damage in the peripheral nervous system (PNS) as from CNS, but little is known about the quantities contributing to sNfL. Peripheral nerve damage may be reflected by an increase in sNfL levels, while the NfL CSF/serum ratio and NfL index decreases. METHODS: We collected serum and cerebrospinal fluid (CSF) from 21 Guillain-Barré Syndrome (GBS) patients and measured NfL in serum and CSF and compared them with 19 neurologically healthy controls. RESULTS: In general, NfL in CSF and serum was significantly higher in GBS patients. Serum NfL was higher in GBS patients admitted to the intensive care unit (P = 0.02). Controls had a mean CSF/serum NfL ratio of 26.7 (ranging from 5.8 to 69.5) indicating a central origin of NfL. Three GBS patients had a similar range (23.9 to 42.7, mean 33.3) all of them with demyelinating pathology in the PNS. Eighteen GBS patients with axonal or mixed axonal-demyelinating pathology showed significantly lower CSF/serum ratios (0.02-12.2, mean 4.4), indicative of a peripheral origin of NfL. When applying the NfL index subdivisions remain the same. INTERPRETATION: These results demonstrate that the PNS is a relevant contributor to sNfL levels and that the distribution can be identified by a lowered NfL CSF/serum ratio of NfL index. Furthermore, acute or subacute polyneuropathies are likely confounding factors in interpreting sNfL levels in CNS diseases.