Predictors of respiratory failure in Guillain-Barré syndrome: a 22 year cohort study from a single Italian centre.

BACKGROUND AND PURPOSE: The study aimed to identify predictors of respiratory failure leading to mechanical ventilation (MV) and tracheostomy in Guillain-Barré syndrome (GBS). METHODS: Two hundred and thirty adult cases admitted to the Neurology Unit of Modena, Italy, between January 2000 and December 2021 were studied. A cut-off of MV starting within 8 weeks from onset of weakness was used. Univariable, multivariable logistic and Cox regression analyses were used to determine which pre-specified clinical and diagnostic characteristics were capable of predicting MV and tracheostomy, due to weaning failure. The model was internally validated within the full cohort. The Erasmus GBS Respiratory Insufficiency Score was retrospectively applied. RESULTS: One hundred and seventy-six cases (76.5%) were classified as classical sensorimotor GBS and 54 (23.4%) as variants. Thirty-two patients (13.9%) needed MV: 84.3% required respiratory support within 7 days. Independent predictors of respiratory failure and MV were older age, facial, bulbar, neck flexor weakness, dysautonomia, axonal electrophysiological subtype, cardiovascular comorbidities and higher disability score at entry. There was no association with abnormal spinal fluid parameters nor with positive serology for recent infections. Twenty-two patients (68.7%) were ventilated for more than 7 days; 4.7% died within 8 weeks. The patients who required MV were treated more often with plasma exchange. Independent predictors of tracheostomy due to weaning trial failure were facial, bulbar, neck flexor weakness, autonomic dysfunction, associated cardiovascular morbidities and axonal electrophysiological subtype on nerve conduction study. CONCLUSIONS: Our study indicates distinct predictors of MV and tracheostomy in GBS patients.

Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.

BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

Myasthenia Gravis crossing Parkinson's disease: a 20 year study from single Italian center.

PURPOSE: The concomitant diagnosis of Parkinson's disease (PD) and Myasthenia Gravis (MG) is rare. The aim of the study was to report our experience of patients with both diagnoses. MATERIAL AND METHODS: We performed a retrospective analysis of patients with MG and PD, seen at Neurology Department, Modena, Italy from 2000 to 2020. We encountered 12 patients with both diagnoses. All had late onset MG (LOMG) and low Myasthenia Gravis Foundation of America (MGFA) severity scores at baseline. In respect of PD assessement, clinical signs were followed and summarized with modified Hoehn and Yahr staging (mHY). Patients were ranked as progressive or non-progressive, according to any change in mHY staging. We compared characteristics and outcome of the patients with age matched myasthenic subjects without PD. RESULTS: The male gender significantly prevailed (p < 0.01) as well as the presence of multiple comorbidities (p < 0.001) in patients with MG associated with PD. In respect of clinical course, MG was benign as most of cases remained stable (66.7%). Six cases showed worsening of mHY scores; only one subject became wheelchair bound by the end of follow up. This uneven progression, at least in our hands, might suggest that MG and PD can evolve independently. CONCLUSION: Clinicians should be alert about the association of PD and MG since early diagnosis and treatment are essential.

Coincidental Onset of Ocular Myasthenia Gravis Following ChAdOx1 n-CoV-19 Vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The Oxford-AstraZeneca vaccine ChAdOx1 (AZD1222, Vaxzevria) is playing a crucial role in counteracting the coronavirus disease-2019 (COVID-19) pandemic [1]. Since March 2021, reports of unexpected thrombotic events associated with thrombocytopenia and vaccination have been published [2]. To the best of our knowledge there is only one report about vaccination-associated myasthenia gravis (MG) occurring after a second dose of BNT162b2 (Pfizer-BioNTech).

Intravenous immunoglobulin treatment for mild Guillain-Barré syndrome: an international observational study.

OBJECTIVE: To compare the disease course in patients with mild Guillain-Barré syndrome (GBS) who were treated with intravenous immunoglobulin (IVIg) or supportive care only. METHODS: We selected patients from the prospective observational International GBS Outcome Study (IGOS) who were able to walk independently at study entry (mild GBS), treated with one IVIg course or supportive care. The primary endpoint was the GBS disability score four weeks after study entry, assessed by multivariable ordinal regression analysis. RESULTS: Of 188 eligible patients, 148 (79%) were treated with IVIg and 40 (21%) with supportive care. The IVIg group was more disabled at baseline. IVIg treatment was not associated with lower GBS disability scores at 4 weeks (adjusted OR (aOR) 1.62, 95% CI 0.63 to 4.13). Nearly all secondary endpoints showed no benefit from IVIg, although the time to regain full muscle strength was shorter (28 vs 56 days, p=0.03) and reported pain at 26 weeks was lower (n=26/121, 22% vs n=12/30, 40%, p=0.04) in the IVIg treated patients. In the subanalysis with persistent mild GBS in the first 2 weeks, the aOR for a lower GBS disability score at 4 weeks was 2.32 (95% CI 0.76 to 7.13). At 1 year, 40% of all patients had residual symptoms. CONCLUSION: In patients with mild GBS, one course of IVIg did not improve the overall disease course. The certainty of this conclusion is limited by confounding factors, selection bias and wide confidence limits. Residual symptoms were often present after one year, indicating the need for better treatments in mild GBS.

Peripheral neuropathy in mixed cryoglobulinaemia: clinical assessment and therapeutic approach.

Peripheral neuropathy (PN) has been detected in up to 69% of patients with mixed cryoglobulinaemic syndrome (MCS). PN should be considered in any patient with sensory and/or motor signs and symptoms in the limbs. Electrodiagnostic tests are mandatory for the diagnosis of PN. Several different sets of diagnostic criteria have been created to assess it. All patients suspected of having neuropathy should undergo a nerve conduction study. A complete neurological evaluation at baseline and periodically should be done possibly by the same neurologists. The authors recommend rigorous scientific evidences that may help to obtain superior tools for accurate diagnosis and management of these conditions. Clinicians, armed with experience and recommendations, can find in this review data-driven guidelines to apply treatments of MCS and closely related disorders.

Regional variation of Guillain-Barré syndrome.

Guillain-Barré syndrome is a heterogeneous disorder regarding the clinical presentation, electrophysiological subtype and outcome. Previous single country reports indicate that Guillain-Barré syndrome may differ among regions, but no systematic comparative studies have been conducted. Comparative studies are required to identify factors determining disease susceptibility, variation and prognosis, and to improve diagnostic criteria. The International Guillain-Barré Syndrome Outcome Study is a prospective, observational cohort study including all patients within the diagnostic spectrum, aiming to describe the heterogeneity of Guillain-Barré syndrome worldwide. The current study was based on the first 1000 inclusions with a follow-up of at least 1 year and confirmed the variation in clinical presentation, course and outcome between patients. The full clinical spectrum of Guillain-Barré syndrome was observed in patients from all countries participating in the International Guillain-Barré Syndrome Outcome Study, but the frequency of variants differed between regions. We compared three regions based on geography, income and previous reports of Guillain-Barré syndrome subtypes: 'Europe/Americas', 'Asia' (without Bangladesh), and 'Bangladesh'. We excluded 75 (8%) patients because of alternative diagnoses, protocol violations, or missing data. The predominant clinical variant was sensorimotor in Europe/Americas (n = 387/562, 69%) and Asia (n = 27/63, 43%), and pure motor in Bangladesh (n = 74/107, 69%). Miller Fisher syndrome and Miller Fisher-Guillain-Barré overlap syndrome were more common in Asia (n = 14/63, 22%) than in the other two regions (Europe/Americas: n = 64/562, 11%; Bangladesh: n = 1/107, 1%) (P < 0.001). The predominant electrophysiological subtype was demyelinating in all regions (Europe/Americas: n = 312/573, 55%; Asia: n = 29/65, 45%; Bangladesh: n = 38/94, 40%). The axonal subtype occurred more often in Bangladesh (n = 34/94, 36%) than in Europe/Americas (n = 33/573, 6%) and other Asian countries (n = 4/65, 6%) (P < 0.001). In all regions, patients with the axonal subtype were younger, had fewer sensory deficits, and showed a trend towards poorer recovery compared to patients with the demyelinating subtype. The proportion of patients able to walk unaided after 1 year varied between Asia (n = 31/34, 91%), Europe/Americas (n = 334/404, 83%) and Bangladesh (n = 67/97, 69%) (P = 0.003). A similar variation was seen for mortality, being higher in Bangladesh (n = 19/114, 17%) than in Europe/Americas (n = 23/486, 5%) and Asia (n = 1/45, 2%) (P < 0.001). This study showed that factors related to geography have a major influence on clinical phenotype, disease severity, electrophysiological subtype, and outcome of Guillain-Barré syndrome.

Factors affecting outcome in ocular myasthenia gravis.

AIM OF THE STUDY: 50%-60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables. MATERIALS AND METHODS: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients. RESULTS: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL. CONCLUSIONS: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

Varicella zoster virus reactivation antedating ipsilateral brainstem stroke.

itor Title: Varicella zoster virus reactivation antedating ipsilateral brainstem stroke Authors: Giuliana Galassi1, Maurilio Genovese2, Marisa Meacci3, Marcella Malagoli2 Affiliations: 1Department of Biomedical, Metabolic, Neural Sciences, University Hospital of Modena, Italy, 2Neuroradiology Service, University Hospital of Modena, Italy, 3Department of Laboratory Medicine and Patholgy, Microbiology and Virology Unit, University Hospital of Modena, Italy Corresponding Author: Giuliana Galassi, MD, Department of Biomedical, Metabolic, Neural Sciences, University Hospital of Modena, Via P. Giardini 1455, Modena, Italy, Tel: 39-3497325802, Email: giulianagalassi46@gmail.com Abstract: Varicella zoster virus (VZV) infection and reactivation are associated with a number of neurologic conditions. Unifocal large vessel infarcts may follow zoster in the trigeminal or cervical distribution as a result of transaxonal transport of virus from trigeminal or cervical afferent fibers that innervate vessels. Ophthalmic zoster (HZO) might cause ophthalmoplegic syndromes, with secondary optic neuritis. Mechanisms include local orbital muscle inflammation and, viral spread from the ophthalmic branch of the fifth nerve with associated vasculopathy. A 72-year-old man developed a vesicular rash in the territory of C5-T5-6. Within four weeks, the patient developed headache, dysphagia, left facial and extremity ataxic weakness. Magnetic resonance imaging (MRI) revealed a right pontine infarction. A 66-year-old woman presented with right-sided painfull HZO. One week later she developed complete external ophthalmoplegia and blurred vision. MRI showed ill-defined signal alteration in the retrobulbar tissue. Three weeks later, the patient was admitted because of dysarthria, deviated tongue, left-sided limb weakness, and tactile hypoesthesia. Spinal fluid contained 23 lymphocytes/mm3 and increased protein. The serum contained antibodies to VZV IgG and IgM in both cases. The patients received intravenously acyclovir with improvement. This report confirms unusual occurrence of ipsilateral brainstem stroke after VZV reactivation in immunocompetent subjects.

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies.

AIM OF THE STUDY: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. MATERIALS AND METHODS: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. RESULTS: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. CONCLUSIONS: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.

The challenge of diagnosing the acute nontraumatic tetraplegia of a healthy young woman.

Acute nontraumatic myelopathies include vascular etiologies most commonly caused by atherosclerotic vascular disease. Other causes that have been reported to occur with varying frequencies include thrombosis, embolism of thrombi and tumor, arteritis, hypotension, dissecting aortic aneurysm, sickle cell disease, intervertebral disk herniation, vertebral body subluxation and iatrogenic causes, usually angiography or surgery. In case of acutely progressing spinal cord syndromes, the diagnosis often given is of transverse myelitis or unknown cause of infarction. Fibrocartilaginous embolism (FCE) is possible cause of spinal ischemia due to embolization of nucleus pulposus fragments through retrograde spinal artery flow. A young woman after intensive exercise developed profound weakness of her upper extremities, progressing to flaccid quadriplegia with sensory level from C3 dermatome. Magnetic resonance imaging (MRI) showed linear hyperintense intramedullary lesion from C2 to Th2 confined to anterior horn area, with typical"owl's eye" appearance. Although exact mechanism of patient's neurological syndrome remains undetermined, we suspected a cord infarction due to FCE related to her vigorous physical exercise.

Prognostic factors and health-related quality of life in ocular Myasthenia Gravis (OMG).

We evaluate the factors predictive of prognosis in 91 Caucasian patients affected by ocular myasthenia gravis (OMG), followed at our Institution during an observational time, ranging from 12 to 240 months. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was used to grade the disease severity. We considered as outcome measures the variation in two subscores, ocular (O-QMG) and nonocular (NO-QMG); the last one reflected bulbar, neck, extremity functions. None of the independent variables evaluated for association with the outcome, as age of onset, type of therapy, length of interval between first and last examinations, and presence of antibodies to acetylcholine receptors (AChR-Abs) significantly affected the evolution of O-QMG and of NO-QMG. Health-related quality of life (HRQol) was assessed in 63 patients. Variations of diplopia or ptosis did not affect significantly physical (PCS) or mental composite subscores (MCS) of the Short-Form Health Survey (SF-36). Human leukocyte antigen (HLA) genotyping was studied to explore whether HLA class I and II allelic distribution differed among MG patients and controls. None of the studied HLA alleles significantly differed between OMG patients and controls. Similarly, none of the alleles with frequencies higher than 15% either in OMG patients or in controls was significantly associated, after Bonferroni correction, with the presence or absence of anti-AChR-Abs in serum.