Factors Predicting Prolonged Mechanical Ventilation in Guillain-Barré Syndrome.

BACKGROUND: Up to 30% of patients with Guillain-Barré syndrome require mechanical ventilation and 5% die due to acute complications of mechanical ventilation. There is a considerable group of patients that will need prolonged mechanical ventilation (considered as >14 days) and should be considered for early tracheostomy. The objective of this study is to identify risk factors for prolonged mechanical ventilation. METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with versus without prolonged mechanical ventilation. We considered clinical and electrophysiological characteristics and analyzed factors associated with prolonged mechanical ventilation. RESULTS: Three hundred and three patients were included; 29% required mechanical ventilation. When comparing the groups, patients with prolonged invasive mechanical ventilation (IMV) have a lower score on the Medical Research Council score (19.5 ± 16.2 vs 27.4 ± 17.5, p = 0.03) and a higher frequency of dysautonomia (42.3% vs 19.4%, p = 0.037), as well as lower amplitudes of the distal compound muscle action potential (CMAP) of the median nerve [0.37 (RIQ 0.07-2.25) vs. 3.9 (RIQ1.2-6.4), p = <0.001] and ulnar nerve [0.37 (RIQ0.0-3.72) vs 1.5 (RIQ0.3-6.6), p = <0.001], and higher frequency of severe axonal damage in these nerves (distal CMAP ≤ 1.0 mV). Through binary logistic regression, severe axonal degeneration of the median nerve is an independent risk factor for prolonged IMV OR 4.9 (95%CI 1.1-21.5) p = 0.03, AUC of 0.774, (95%CI 0.66-0.88), p = < 0.001. CONCLUSIONS: Severe median nerve damage is an independent risk factor for prolonged mechanical ventilation.

Uterus infantilis: a novel phenotype associated with AARS2 new genetic variants. A case report.

Objectives: To report the first Mexican case with two novel AARS2 mutations causing primary ovarian failure, uterus infantilis, and early-onset dementia secondary to leukoencephalopathy. Methods: Detailed clinical, clinimetric, neuroimaging features, muscle biopsy with biochemical assays of the main oxidative phosphorylation complexes activities, and molecular studies were performed on samples from a Mexican female. Results: We present a 41-year-old female patient with learning difficulties since childhood and primary amenorrhea who developed severe cognitive, motor, and behavioral impairment in early adulthood. Neuroimaging studies revealed frontal leukoencephalopathy with hypometabolism at the fronto-cerebellar cortex and caudate nucleus. Uterus infantilis was detected on ultrasound study. Clinical exome sequencing identified two novel variants, NM_020745:c.2864G>A (p.W955*) and NM_020745:c.1036C>A (p.P346T, p.P346Wfs*18), in AARS2. Histopathological and biochemical studies on muscle biopsy revealed mitochondrial disorder with cytochrome C oxidase (COX) deficiency. Conclusions: Several adult-onset cases of leukoencephalopathy and ovarian failure associated with AARS2 variants have been reported. To our best knowledge, none of them showed uterus infantilis. Here we enlarge the genetic and phenotypic spectrum of AARS2-related dementia with leukoencephalopathy and ovarian failure and contribute with detailed clinical, clinometric, neuroimaging, and molecular studies to disease and novel molecular variants characterization.

Sural nerve involvement in Guillain-Barré syndrome: Clinical and prognostic implications. A prospective cohort.

BACKGROUND: Sural sparing is common in Guillain-Barré syndrome (GBS). However, one third of patients have sural nerve compromise. Its clinical implications associated factors and short-term prognosis are still unknown. The objective of this study is to identify if sural nerve compromise is associated with a worse prognosis and to describe clinical and electrophysiological characteristics in Guillain-Barré syndrome. MATERIALS AND METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with vs without sural nerve compromise. All patients underwent nerve conduction studies within the first 3 days of hospital admission. Clinical and electrophysiological characteristics were compared between groups. RESULTS: 174 patients were included in this study. Acute inflammatory demyelinating polyneuropathy was the predominant variant (43.7 %). Thirty percent of patients had sural nerve involvement. In the comparative analysis between affected vs unaffected sural groups, age ≥50 years and Guillain-Barré disability score ≥3 demonstrated a statistically significant difference. Regarding short-term recovery period for independent walking, there was no significant difference. In the multivariate analysis, age ≥50 years was identified as independent factors for sural nerve compromise on admission. CONCLUSION: sural nerve compromise occurs in 30 % of patients with GBS and is not associated with a worse functional prognosis. Age ≥50 years was identified as an independent factor for sural nerve compromise.

Deltoid muscle strength and autonomic dysfunction as independent risk factors for invasive mechanical ventilation in patients with Guillain-Barré syndrome.

BACKGROUND: Almost a third of patients with Guillain-Barré Syndrome (GBS) require mechanical ventilation, increasing mortality by 15-30% and proving poor functional outcomes. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is the most frequently used scale to assess probability of respiratory insufficiency within the first week of admission. We aim to determine other clinical and electrophysiological prognostic factors for invasive mechanical ventilation (IMV) in patients with GBS. MATERIAL AND METHODS: A cross-sectional ambispective cohort study was carried out in a referral center in Mexico City, from January 2015 to December 2019. Baseline demographics, MRC score, Hughes scale, EGRIS, dysautonomia and nerve conduction studies were performed on admission in GBS patients that required IMV. A multivariable analysis for IMV and a survival analysis for independent walk in prolonged-IMV (>14 days) were performed. RESULTS: Forty-nine (32%) out of 153 GBS patients required IMV. Statistically significant prognostic factors in multivariable analysis were deltoid muscle strength ≤2 [OR 7.1 (1.6-31.1)], EGRIS [OR 2.5 (1.3-4.6)] and autonomic dysfunction [OR 6.6 (2.0-22.0)]. Electrodecrement <1 mV in the compound muscle action potential (CMAP) of distal motor median nerve was more prevalent in prolonged-IMV patients (44.8% vs. 21%, p = .049). A significant minor prevalence of prolonged-IMV patients regain independent walk at 6 months using the Kaplan-Meier method (log rank test p < .001). CONCLUSIONS: We provide new specific clinical (deltoid muscle strength and autonomic dysfunction) and electrophysiological variables to discriminate GBS patients that will require IMV.

Prognostic Implications of Early Albuminocytological Dissociation in Guillain-Barré Syndrome.

BACKGROUND: Half of Guillain-Barré syndrome (GBS) present elevated cerebrospinal fluid (CSF) protein levels within 1 week since symptom onset and 80% within 2 weeks. Our objective was to determine the clinical and prognostic implication of albuminocytological dissociation in early GBS. METHODS: An ambispective cohort study was conducted. Good outcome was considered if the patient was able to walk unaided (Guillain-Barré disability score [GDS] ≤ 2 points) at 3-month follow-up. Patients were classified into two groups: with and without albuminocytological dissociation; we compared clinical and paraclinic characteristics between the groups. We analyzed clinical and electrophysiological factors related to presenting early dissociation through a multivariate model. RESULTS: We included 240 patients who fulfilled Asbury criteria for GBS. On further selection, only 94 patients fulfilled inclusion. Mean age was 45.94 ± 17.1 years and 67% were male. Median time from symptom onset to admission was 5 days (IQR 3-6). Regarding albuminocytological dissociation and electrophysiological variants, we found a significant difference: acute inflammatory demyelinating polyneuropathy (AIDP) [60.6% vs 26.2%, p = 0.002], acute motor axonal neuropathy (AMAN) [21.2% vs 49.1%, p = 0.009] and acute motor sensory axonal neuropathy (AMSAN) [12.1% vs 1.6%, p = 0.05]. We did not observe significant differences in recovery of independent walking in short term between both groups. The presence of conduction block in any variant (OR 3.21, 95% CI 1.12-9.16, p = 0.02) and absence of sural registration (OR 5.69, 95% CI 1.48-21.83, p = 0.011) were independent factors related to early dissociation. CONCLUSIONS: Early dissociation (<7 days) is not associated with any particular clinical feature or unfavorable outcome. It is more common to see in AIDP rather than axonal variants.

Very low peroneal nerve compound muscle action potential amplitude predicts poor outcome in patients with Guillain-Barré syndrome: a prospective cohort.

INTRODUCTION: Twenty percent of patients with Guillain-Barré syndrome (GBS) have poor outcomes despite proper management. The aim of the study was to characterize electrophysiological factors related to poor outcome in patients with GBS. METHODS: We conducted an observational study from a prospective cohort of 91 patients with GBS in a tertiary healthcare center in Mexico, from 2017 to 2019. Demographics and nerve conduction studies were performed on admission, and a 3-month follow-up for GBS disability score was ensued, allocating patients in good (GBS disability score ≤ 2) and poor outcome (GBS disability score ≥ 3) groups. A logistic regression analysis for independent walk at 3 months was performed. Kaplan-Meier estimator curves for independent walk in very low (< 20% LLN) and low-normal ( ≥20% LLN) peroneal nerve CMAPs are presented. RESULTS: From the 91 GBS patients included, 37 (40.6%) did not regain independent walk at 3 months. Axonal variants were more common in the poor outcome group (31.4% vs 59.4%, p = 0.01) as well as AIDP variants with motor conduction block (6.6% vs 42.4%, p = 0.018). Univariable analysis was statistically significant for very low median, ulnar, tibial, and peroneal CMAP amplitudes in poor outcome patients; however, multivariable analysis was only significant for very low peroneal nerve CMAP amplitude (OR 3.6 [1.1-11.5, p = 0.024]). Conversely, a greater proportion of GBS patients with low-normal CMAPs recovered independent walk at 90 days (75% vs 30%, p < 0.001). CONCLUSION: Severe axonal injury of the peroneal nerve, axonal, and AIDP with motor conduction block variants predicts worse functional outcome regarding independent walk at 3 months.

Inpatient Delirium in Guillain-Barré Syndrome: Frequency and Clinical Characteristics in a Mexican Hospital.

Background Delirium has a prevalence of 14%-56% in hospitalized patients. Risk factors include advanced age, invasive mechanical ventilation (IMV), and prolonged intensive care unit stay. Neuropsychiatric symptoms have been reported to be related to autoimmune responses secondary to Guillain-Barré syndrome (GBS) with direct involvement of the central nervous system (CNS) or to delirium. There are few reports of the frequency of delirium in patients with Guillain-Barré syndrome (GBS). Objective To describe the frequency of and the characteristics associated with delirium in patients with GBS. Material and methods A single-center, cross-sectional study was conducted in patients with GBS diagnosis between 2015 and 2019. The diagnosis of delirium was made using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. We compared patients with and without delirium. We performed both univariate and multivariate analyses to identify factors associated with delirium. Results A total of 154 patients with GBS were included, of which 20 (12.9%) fulfilled the DSM-5 criteria for delirium. The mean age was 48 ± 18.2 years, the median Medical Research Council (MRC) sum score was 29.3 ± 21.9 points, 65% had bulbar cranial nerve involvement, 80% presented autonomic dysfunction, 85% had ICU stay, and 90% had mechanical ventilation requirement. In the multivariate analysis, the following were the independent factors for the development of delirium: age ≥ 60 (odds ratio (OR): 5.7; 95% confidence interval (CI): 1.3-23.5), time from symptom onset to admission ≤ 3 days (OR: 4.3; 95% CI: 1.1-16.8), autonomic dysfunction (OR: 13.1; 95% CI: 3-56), and intensive care unit stay (OR: 9.5; 95% CI: 2.1-42.6). Conclusion Delirium is not frequent in patients with Guillain-Barré syndrome. Patients with advanced age, rapid motor progression, bulbar cranial nerve involvement, prolonged intensive care unit stay, and mechanical ventilation need are more likely to present delirium.

Vacuolar Myopathy Associated to CACNA1S Mutation as a Rare Cause of Late-Onset Limb-Girdle Myopathy: A Case Report.

Late-onset limb-girdle myopathies pose a diagnostic challenge. The most common etiologies are inflammatory, followed by genetic and metabolic. Rare cases include limb-girdle dystrophies and permanent myopathies (vacuolar), such as those associated with hypokalemic periodic paralysis (HypoPP). We present the case of a 59-year-old male who initiated with episodic acute severe weakness when he was 11, during which serum potassium levels of <2.5 meq/L were revealed during workup. Potassium reposition reversed these episodes. They occurred every three to five years, and the last episode was five years prior to the current illness. When he was 58, he presented progressive pelvic girdle weakness. On examination, he presented decreased strength in the iliopsoas and quadriceps. The laboratory results showed mildly elevated creatine kinase. Muscle biopsy revealed a vacuolar myopathy, and genetic testing identified a pathogenic variant in the CACNA1S gene, locus 1q32.1 [c.3716G> A (p.Arg1239His), heterozygous state].

Prognostic Factors in Elderly Patients With Guillain-Barré Syndrome: Does Age Matter?

INTRODUCTION: Twenty to 40% of Guillain Barré syndrome (GBS) patients will not be able to walk independently despite effective treatment. Older patients carry additional risks for worse outcomes. METHODS: A single center, ambispective cohort study was performed. Only subjects ≥18 years with a 3-month follow-up were included. Elderly patients were considered as a whole if ≥ 60 years. Demographics, CSF and nerve conduction studies were compared. A binomial logistic regression and Kaplan-Meier analyses were carried out to estimate good prognosis (Hugues ≤2) at 3-month follow-up. RESULTS: From 130 patients recruited, 27.6% were elderly adults. They had a more severe disease, higher mEGOS and more cranial nerve involvement. Age ≥70 years, invasive mechanical ventilation and axonal subtype, portrayed an unfavorable 3-month outcome. Further analysis demonstrated an earlier recovery in independent walk at 3 months for patients <70 years. CONCLUSIONS: Elderly patients with GBS have a more severe disease at admission and encounter worse prognosis at 3-month follow-up, especially those above 70 years.

Rituximab in Refractory Myasthenia Gravis: Experience in a Single Healthcare Center in Mexico.

BACKGROUND: Ten to fifteen percent of patients with myasthenia gravis (MG) have treatment-refractory disease. In short series and case reports, rituximab has proven to be effective in refractory MG. METHODS: A retrospective, longitudinal study was conducted. Recruitment was performed in an MG cohort from a single third-level healthcare center in Mexico. The selection included refractory MG patients that were treated with rituximab. Response after rituximab therapy was assessed with MG composite score (MGCS) and prednisone dose reduction at 6, 12, and 18 months after initiation. Wilcoxon signed-rank test was used to evaluate differences between related groups for non-continual variables. P<0.05 was considered statistically significant. RESULTS: Ten patients (7%) fulfilled criteria for refractory MG, and eight of them were treated with rituximab. The mean age at MG diagnosis was 25.5 (±2) years, with a female predominance (75%). All our patients (100%) had positive acetylcholine receptor (AchR) antibodies. The median MG duration was six years (interquartile range [IQR] 4.2-6) before rituximab initiation. All patients were previously treated with azathioprine and 50% additionally with cyclophosphamide. The median prednisone doses before rituximab treatment and 18-month follow-up were 50 mg (IQR 30-50 mg) and 10 mg (IQR 0-20 mg), respectively (p=0.011). The median baseline MGCS and at 18-month follow-up were 19.5 (IQR 11-31) and 6 (IQR0-16), respectively (p = 0.012). CONCLUSION: Rituximab appears to be associated with clinical improvement and prednisone dose reduction in Latin-American patients diagnosed with anti-AchR MG. Our findings need to be interpreted in light of the limitations mentioned.

Electrophysiological subtypes and associated prognosis factors of Mexican adults diagnosed with Guillain-Barré syndrome, a single center experience.

BACKGROUND: The clinical characteristics of electrophysiological subtypes and prognostic factors of Mexican adults diagnosed with Guillain-Barré Syndrome (GBS) have not been described. MATERIALS AND METHODS: A single center, ambispective, cohort study was performed (2015-2019). GBS was defined following the Asbury and Cornblath criteria. Electrodiagnosis was made according to Hadden criteria. Clinical, biochemical and electrodiagnostic parameters were described, compared and analyzed using a multivariate model. Only patients who completed a 3-month follow-up were included. RESULTS: 137 GBS patients (92 males; mean age 46.6 ± 16.6).132 (96.3%) underwent an electrodiagnostic assessment.68 (51.5%) were classified as axonal GBS, with further classified into two groups: acute motor axonal neuropathy (AMAN) 45.4%, and acute motor and sensory axonal neuropathy (AMSAN) 8,6%. The following characteristics were lower in the AMAN group: Medical Research Counsel sumscore (MRC) 30.1 ± 16.3 vs 36.4 ± 14.4, unilateral facial palsy 10% vs 25.9% and albuminocytologic dissociation 41.3% vs. 71.7%.Multivariate analysis found AMAN as an independent predictor of an unfavorable outcome OR: 3.34 (p = 0.03) CONCLUSIONS: AMAN subtype is the most frequent presentation of GBS in Mexican adult patients and an independent predictor of inability to walk independently at 3 months after discharge.

Guillain-Barré Syndrome Associated With Zika Virus Infection: A Prospective Case Series From Mexico.

Background: On May 2016, anticipating the rainy season from June to October in Mexico, we expected an increase in cases of Zika virus (ZIKV) infections. With the goal of identifying cases of GBS associated with ZIKV infection, a prospective joint study was conducted by a reference center for neurological patients and the Secretary of Health in Mexico City from July 2016 to November 2016. Methods: Serum, cerebrospinal fluid, urine, and saliva were tested by RT-PCR for ZIKV, dengue virus, and chikungunya virus in patients referred from states with reported transmissions of ZIKV infection, and with clinical symptoms of GBS according to the Brighton Collaboration criteria. Clinical, electrophysiological, and long-term disability data were collected. Results: In the year 2016 twenty-eight patients with GBS were diagnosed at our institute. In five hospitalized patients with GBS, RT-PCR was positive to ZIKV in any collected specimen. Dengue and chikungunya RT-PCR results were negative. All five patients had areflexic flaccid weakness, and cranial nerves affected in three. Electrophysiological patterns were demyelinating in two patients and axonal in three. Three patients were discharged improved in 10 days or less, and two patients required intensive care unit admission, and completely recovered during follow-up. Conclusion: Our results are similar to those reported from the state of Veracruz, Mexico, in which out of 33 samples of urine of patients with GBS two had a positive RT-PCR for ZIKV. Simultaneous processing of serum, CSF, urine, and saliva by RT-PCR may increase the success of diagnosis of GBS associated to ZIKV.