COVID-19-associated serum and cerebrospinal fluid cytokines in post- versus para-infectious SARS-CoV-2-related Guillain-Barré syndrome.

INTRODUCTION: Guillain-Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance. MATERIALS AND METHODS: We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7 days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7 days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer's disease (AD; n = 24). RESULTS: Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another. CONCLUSIONS: The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.

Comparing the Impact of COVID-19 on Vaccinated and Unvaccinated Patients Affected by Myasthenia Gravis.

We evaluated 13 patients affected by myasthenia gravis (MG) who had coronavirus disease 2019 (COVID-19) before vaccination and 14 myasthenic patients who contracted severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection after vaccination to evaluate factors related to different COVID-19 outcomes. We compared the two groups' previous stability of MG and the severity of SARS-CoV-2 infection. Vaccinated and non-vaccinated patients were comparable in terms of severity of the previous MG course (mean maximum myasthenia gravis Foundation of America-MGFA-Class III) and during SARS-CoV-2 infection (mean MGFA Class II). In non-vaccinated patients, the hospitalization and severe course percentages were 61.5%, while the mortality reached 30.8%. The hospitalization, severe course, and mortality percentages in vaccinated patients were 7.1%. In deceased, non-vaccinated patients, greater myasthenia severity in the past clinical history, but not at the time of infection, was observed. Similarly, older age at MG onset and at the time of infection correlated with a more severe COVID-19 course in non-vaccinated patients (p = 0.03 and p = 0.04), but not in the group of vaccinated patients. In summary, our data support a protective role of vaccination in myasthenic patients, even if anti-CD20 therapy might be associated with a poor immune response to vaccines.

The importance of thinking about Guillain-Barré syndrome during the COVID-19 pandemic: a case with pure dysautonomic presentation.

Guillain-Barré syndrome (GBS) is a peripheral nervous system disease caused by an immune-mediated inflammatory mechanism, usually triggered by a previous infectious process or vaccine; its typical presentation is a rapid and progressive bilateral limb hyposthenia, associated with sensory deficits and reduction or absence of osteotendinous reflexes. However, also autonomic nervous system can be involved with heart rate fluctuations, blood pressure instability, pupillary dysfunction, and urinary retention. Since the beginning of COVID-19 pandemic, GBS has been reported among neurological complications of SARS-CoV-2 infection, although etiopathological mechanisms still have to be clearly defined. We report the case of a 79-year-old man with multiple comorbidities, including diabetes, who was affected by SARS-CoV-2 interstitial pneumonia and developed dysautonomic symptoms after 10 days of hospitalization. A neurological evaluation was performed, and GBS was considered as a possible cause of the clinical manifestations. This hypothesis was confirmed by electrophysiological study and further supported, ex-juvantibus, by the satisfactory response to immunoglobulin treatment. In our opinion, this case of pure dysautonomic presentation of GBS in a SARS-CoV-2 positive patient is relevant because it suggests to consider GBS upon SARS-CoV-2 infection even if the symptoms have uncommon characteristics (e.g., pure vegetative manifestations) and if there are confounding factors which could lead to a misdiagnosis (e.g., old age, SARS-CoV-2 infection consequences and diabetes).

Myasthenia gravis associated with anti-MuSK antibodies developed after SARS-CoV-2 infection.

INTRODUCTION: Since the onset of the novel coronavirus pandemic, several neurological complications secondary to SARS-CoV-2 infection have been reported, affecting central nervous system, peripheral nervous system and neuromuscular junction. CASE REPORT: We present the case of a 77-year-old man who developed bulbar myasthenia gravis (MG) eight weeks after SARS-CoV-2 infection. The search for serum antibodies against the acetylcholine receptor and the muscle-specific tyrosine kinase (MuSK), performed by radioimmunoassay (RIA), and the search of low-density lipoprotein receptor-related protein 4 antibodies, performed by immunohistochemistry, resulted negative, while anti-MuSK antibodies were detected by cell-based assay (CBA). The patient was treated with pyridostigmine (60 mg four times a day) with unsatisfactory clinical response, followed by immunosuppressive therapy (azathioprine 1.5 mg/kg/day) with improvement of MG symptoms after two months of treatment. DISCUSSION: Several viral diseases have been described as associated with the onset of MG, although the underlying mechanisms are not yet fully understood. Similarly, a growing number of scientific reports suggest a correlation between SARS-CoV-2 infection and autoimmune diseases. The interest of our case lies in the timing of the MG onset (after 2 months from infection), together with the unusual late onset of anti-MuSK MG. These elements suggest that coronavirus infection may act as a trigger of the disease. We confirm the importance of CBA in the serological diagnosis of RIA-negative MG.

COVID-19-related and not related Guillain-Barré syndromes share the same management pitfalls during lock down: The experience of Liguria region in Italy.

Recently, during the pandemic infection of the novel SARS-CoV-2, some cases of Guillan-Barré Syndrome (GBS) have been reported. The aim of this work is to report the natural history of patients with GBS, both COVID and not-COVID related, hospitalized in Liguria region, during lock down period, in order to assess clinical features of both groups and possible managements pitfalls due to pandemic emergency. Fifteen GBS patients were admitted to the Hospitals of Liguria, from February 15th to May 3rd 2020, six with SARS-CoV-2 infection and nine without infection. In COVID-19 related GBS five patients presented with classical GBS and one with variant. Two patients presented neurologic symptoms during or shortly after the viral syndrome, suggesting the pattern of a para-infectious profile. Multi-organ involvement, delay in the diagnosis, incomplete work up and start of therapy, were registered in 50% of cases with a GBS-Disability scale ≥4 at follow-up evaluation. In not-COVID-19 related GBS, main problem was diagnostic delay. In three patients the first neurological observation took place after a mean of 33,6 days. Moreover, five patients went to emergency room after an average of 30 days since the onset of neurological symptoms because of fear of contagion. In conclusion, not only SARS-CoV-2 infection can cause GBS, but it can also, due to effects of pandemic on the health organization, affect the outcome of patients with not COVID-19 related GBS.

Impact of quarantine due to COVID infection on migraine: a survey in Genova, Italy.

Quarantine is a well-known risk factor for psychological and psychiatric disturbances. We evaluated burden of migraine during lockdown due to COVID 19 pandemia. Forty-nine subjects followed in our headache clinic for migraine were evaluated for migraine burden by means of global assessment of migraine severity (GAMS) and visual analogue scale (VAS) by phone interview. Moreover, depression and anxiety were quantified by Beck depression inventory (BDI) and Zung Self-Rating Anxiety Scale (SAS). We evaluated changes in the value of migraine score from the 2 months immediately before lockdown (from January 1 to March 9) to the 2 months of quarantine (from March 10 to May 3). Value of GAMS was 5.61 ± 0.76 before and 4.16 ± 1.46 during quarantine (p < .001). VAS was 7.49 ± 1.10 before and 5.47 ± 1.88 during quarantine (p < .001). We also found a time by depression level interaction, F(1,47) = 6.21, p = .016, F(1,47) = 14.52, p < .006, respectively, showing that subjects with lower level of depression had better course of migraine. In conclusion, we showed that, during quarantine due to COVID pandemia, subjects with migraine had fewer migraine attacks and lesser pain and show moderate level of depression, correlated to migraine burden.

Correction to: New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases.

The above article was published online with inverted given and family names. The correct presentation has been corrected above.

Ultrasound versus MRI in common fibular neuropathy.

INTRODUCTION: We prospectively compared ultrasound (US) and MRI in patients with common fibular neuropathy. METHODS: Forty adult patients with clinical suspicion of common fibular neuropathy and 40 healthy controls underwent both US and MRI. US and MRI datasets were randomized for prospective reading. RESULTS: The overall sensitivity of US and MRI for diagnosing fibular neuropathy was 90% (95% confidence interval [CI], 79.7%-97.3%) and 87.5% (95% CI, 71.55%-93.1%), respectively. The overall specificity of US and MRI was 92% (95% CI, 77.45%-96.1%) and 85% (95% CI, 73.3%-94.4%), respectively. The overall sensitivity and specificity of US combined with MRI were 94% (95% CI, 0.80%-0.99%) and 84% (95% CI, 0.70%-0.91%), respectively. Overall intra- and inter-observer agreements among 3 readers were 0.76% (95% CI, 0.62%-0.85%) and 0.74% (95% CI, 0.65%-0.81%). CONCLUSIONS: US diagnostic accuracy for common fibular neuropathy was slightly higher than that of MRI. Muscle Nerve 55: 849-857, 2017.

Fascicular involvement in common fibular neuropathy: Evaluation with ultrasound.

INTRODUCTION: The aim of this study was to demonstrate single fascicular involvement in common fibular (CF) neuropathy using high-resolution ultrasound (US). METHODS: We prospectively enrolled 40 adult patients with clinical and electrodiagnostic suspected CF neuropathy between April 2012 and December 2014. Two musculoskeletal radiologists used high-resolution US probes to prospectively and independently evaluate the CF nerve bilaterally in these patients. The presence of single fascicular involvement (increased cross-sectional area and loss of fascicular echotexture) was recorded. RESULTS: US revealed involvement of only 1 fascicular component of the CF nerve in 7 patients. In all these patients, US revealed involvement of the anterior fascicles corresponding to fibers for the deep fibular nerve. CONCLUSIONS: High-resolution US allowed identification of single fascicular involvement in CF neuropathy. Anterior fascicular involvement was present in up to 17% of patients with suspected CF neuropathy.

MR Imaging of total hip arthroplasty: comparison among sequences to study the sciatic nerve at 1.5 T.

PURPOSE: This study was done to test a series of MR sequences for evaluating the sciatic nerve after total hip arthroplasty (THA). MATERIAL AND METHODS: The study protocol was approved by the institutional review board. Informed consent was obtained from all patients. Twenty-five patients (11 men and 14 women mean age: 62.3±5.7 years) with THA were included in this prospective study. MRI protocol included sequences that were preliminarily tailored for nerve imaging in patients with THA: proton density (PD)-weighted turbo SE, T1-weighted turbo SE (TSE) 3 mm thickness, T1-weighted turbo SE (TSE) 6 mm thickness, T1-weighted turbo SE with high bandwidth (TSE hBW), T2- weighted TSE, T2-weighted with fat saturation and short-tau inversion recovery (STIR). For each sequence, we evaluated the visibility of the sciatic nerve using a semiquantitative score (0=total masking; 1=insufficient visibility; 2=sufficient visibility; 3=optimal visibility). The sum of the scores given to each sequence was divided by the maximal sum, obtaining a percentage visibility index. Friedman and sign tests were used for statistical analysis. RESULTS: MR examination time was approximately 40 min. No patients reported pain, heat or symptoms related to nerve stimulation. The visibility index ranged between 88% and 70% for the first four sequences. The T1-weighted TSE hBW sequence had the best visibility index (P<.05). The visibility indexes of the first four sequences were significantly higher (P<.004, sign test) than those of the remaining three sequences. CONCLUSION: The sciatic nerve could be studied at 1.5 T in patients following THA. The nerve is better visualized with T1-weighted TSE hBW sequences. On T2-weighted sequences and STIR, the visibility of the nerve is low.

Plasma levels of insulin and amyloid beta 42 are correlated in patients with amnestic Mild Cognitive Impairment.

Epidemiological and experimental data suggest that type 2 diabetes (DM2) and sporadic late-onset Alzheimer's disease (AD) share a common mechanism, that is able to produce accumulation of insulin and amyloid beta 42 (Abeta42), the major pathogenic events respectively of the two conditions. In 71 non diabetic patients with amnestic mild cognitive impairment we found a significant linear correlation between fasting plasma levels of insulin and Abeta42 (R = +0.25, P < 0.05). The levels of both peptides were elevated in comparison to 48 age-matched cognitively normal controls. The correlation of insulin and Abeta42 plasma levels suggests a pathogenic link between DM2 and sporadic AD.

Protein misfolding in Alzheimer's and Parkinson's disease: genetics and molecular mechanisms.

The accumulation of altered proteins is a common pathogenic mechanism in several neurodegenerative disorders. A causal role of protein aggregation was originally proposed in Alzheimer's disease (AD) where extracellular deposition of beta-amyloid (Abeta) is the main neuropathological feature. It is now believed that intracellular deposition of aggregated proteins may be relevant in Parkinson's disease (PD), amyotrophic lateral sclerosis and polyglutamine disorders. An impairment of ubiquitin-proteasome system (UPS) appears directly involved in these disorders. We reviewed the results on the role of protein misfolding in AD and PD and the influence of mutations associated with these diseases on the expression of amyloidogenic proteins. Results of genetic screening of familial cases of AD and PD are summarized. In the familial AD population (70 subjects) we found several mutations of the presenilin 1 (PS1) gene with a frequency of 12.8% and one mutation in the gene encoding the protein precursor of amyloid (APP) (1.4%). One mutation of Parkin in the homozygous form and two in the heterozygous form were identified in our PD population. We also reported data obtained with synthetic peptides and other experimental models, for evaluation of the pathogenic role of mutations in terms of protein misfolding.