Guillain-Barré syndrome and COVID-19: A 1-year observational multicenter study.

BACKGROUND AND PURPOSE: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported during the coronavirus disease 19 (COVID-19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID-19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID-19. METHODS: Guillain-Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID-19-positive and COVID-19-negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered. RESULTS: The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18-1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71-1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020-March 2021 and, most importantly, COVID-19-positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID-19-negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019-February 2020. CONCLUSIONS: Other than showing an increase of GBS in northern Italy in the "COVID-19 era" compared to the previous year, this study emphasizes how GBS cases related to COVID-19 represent a significant part of the total, thus suggesting a relation between COVID-19 and GBS.

Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study.

BACKGROUND: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. METHODS: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)). RESULTS: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1). CONCLUSION: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.

Botulinum neurotoxin-A does not spread to distant muscles after intragastric injection: A double-blind single-fiber electromyography study.

The purpose of this study was to perform a careful neurophysiological examination to identify subclinical signs of botulinum toxin spread distant to the injection site following intragastric injection for obesity treatment. Single-fiber electromyography of extensor digitorum communis and repetitive stimulation of abductor digiti minimi were performed before and 8 days after multiple intragastric injections of botulinum toxin A (Botox, 200 U per patient) or placebo. The study was performed in a randomized double-blind fashion. No patient in either group displayed results indicative of neuromuscular dysfunction either before or after the treatment. No significant change in muscle jitter was observed when comparing baseline with the after-treatment evaluation in either group, and no significant differences between groups were observed. After intragastric botulinum toxin injection no subclinical sign of distant spread was observed.

Defective Fas-mediated T-cell apoptosis predicts acute onset CIDP.

Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies. GBS is characterized by acute onset and subsequent remission of symptoms, whereas CIDP displays slow progression over at least 2 months. However, a small proportion of CIDP patients display acute onset CIDP (a-CIDP) resembling that of GBS. The Fas receptor is involved in shutting off the immune response and its defective function predisposes to auto-immune diseases. In CIDP patients, Fas function is lower than in GBS patients and healthy controls. This study is aimed at assessing whether evaluation of T-cell Fas function helps in early discrimination between GBS and a-CIDP. Fas function was evaluated in patients with acute onset polyneuropathy: 55 retrospective patients analyzed after development of GBS or a-CIDP before year 2005; 50 prospective patients analyzed at onset after year 2005 and followed up for development of GBS or a-CIDP. In both groups, a-CIDP patients displayed defective Fas function, whereas GBS patients displayed normal function. These findings suggest that the evaluation of Fas function in acute onset polyneuropathy helps in early prediction of long-term outcome.

Overview on pathophysiology and newer approaches to treatment of peripheral neuropathies.

Peripheral neuropathies are extremely heterogeneous nosological entities. One of the most common symptoms is pain, the underlying mechanisms of which are numerous and complex. Inflammation, reparative processes, and anatomical and gene expression alterations lead to chronic pain, the persistence of which is sustained by peripheral and central sensitisation mechanisms. Treatment of peripheral neuropathies is targeted to its symptomatic and aetiological features. For pain relief, several types of drugs may be used, notably antidepressants (e.g. tricyclic antidepressants, selective serotonin reuptake inhibitors, and both serotonin and noradrenaline [norepinephrine] reuptake inhibitors), antiepileptic drugs (e.g. carbamazepine, phenytoin, lamotrigine, valproic acid, gabapentin, topiramate and pregabalin), NSAIDs and opioid analgesics. Aetiological therapy is aimed at modifying the pathophysiological mechanisms underlying the neuropathy, some of which are common in different neuropathic conditions. Certain drugs are known to exert more than one action on different pathophysiological mechanisms. This is the case with acetyl-L-carnitine (ALC), which can be considered both a symptomatic therapy that can be used in any kind of painful neuropathy, and an aetiological therapy, at least in diabetic neuropathy and neuropathies induced by nucleoside reverse transcriptase inhibitors and cancer chemotherapeutic agents. ALC acts via several mechanisms, inducing regeneration of injured nerve fibres, reducing oxidative stress, supporting DNA synthesis in mitochondria, and enhancing nerve growth factor concentrations in neurons.

Foxp3 expressing CD4+ CD25+ and CD8+CD28- T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma.

The role of T regulatory (Treg) cells in human cancer has not yet been clarified. We assessed the presence and function of CD4+ and CD8+ Treg cell subsets in the peripheral blood of patients with lung cancer (LC) and pleural mesothelioma (PM). We found a low but significant increase in the number of CD4+ T cells with phenotype and functional features of Treg cells in LC patients compared to normal healthy controls (NHC). Furthermore, total CD4+ T cells from LC patients proliferated less than cells from controls, suggesting that the increase in the CD4+ Treg cell pool has functional importance. LC patients also showed an expansion of the CD8+CD28- T cell subset and these cells expressed Foxp3 mRNA, as recently observed in alloantigen-specific CD8+CD28- T suppressor cells. No variation of peripheral Treg cell subsets was found in patients with PM, a disease with a predominantly localized nature. However, the lack of correlation between cancer stage and the number or the function of peripheral Treg cells in LC patients refuted the hypothesis that these cells are involved in tumor spreading. A possible involvement of the peripheral Treg cell pool in cancer development and/or in inducing systemic immunosuppression in LC patients can be hypothesized.

Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label study.

Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus (HIV) patients under dideoxynucleoside therapy, benefits only partially from medical therapy, and often leads to drug discontinuation. Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism, eventually related to a reduction of mitochondrial DNA content, and interference with nerve growth factor activity. Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions. Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation. The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients. Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period. Efficacy was evaluated by means of the modified Short Form McGill Pain Questionnaire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit. Mean pain intensity score was significantly reduced during the study, changing from 7.35 +/- 1.98 (mean +/- SD) at baseline to 5.80 +/- 2.63 at week 4 (p = 0.0001). Electrophysiological parameters did not significantly change between baseline and week 4. In this study, acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity. On the contrary, no effect was noted on neurophysiological parameters.

Neuroglial activation and neuroinflammation in the brain of patients with autism.

Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.