Inflammatory Neuropathy Cause and Treatment (INCAT) Scale for the assessment of disability level in patients with chronic inflammatory demyelinating polyneuropathy: linguocultural ratification in Russia

Background. Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable dysimmune polyneuropathy. An objective response for pathogenic therapy is essential in diagnosis and management of CIDP. For proper assessment of patient’s complaints and evaluation of disease progression, it is recommended to use validated scales and questionnaires. The paper presents the results of the first step of Inflammatory Neuropathy Cause and Treatment (INCAT) validation in patients with CIDP.Objective: the development of the Russian version of the INCAT scale and its linguocultural ratification.Materials and methods. 15 patients with definite CIDP (according to EFNS/PNS criteria) were enrolled. Linguocultural ratification was conducted according to the standard protocol.Results. The Russian version of the INCAT scale was developed.Conclusion. We conducted the first stage of INCAT scale validation in patients with CIDP.

Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies

Introduction Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are a consequence of autoimmunity or direct neurotoxicity is unclear. Methods We employed rat dorsal root ganglion (DRG) neurons, Schwann cells (SCs), and human stem cell-derived sensory neurons myelinated with rat SCs as cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in sera of ZIKV patients with and without GBS. In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients, and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Results Overall, IgG antibody reactivity to rat SCs (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequently, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to DRGs (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared to other controls, while IgM reactivity to co-cultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from one patient were confirmed to react with neurofascin-155 and 186. Serum from a ZIKV non-GBS patient displayed strong myelin-binding and anti-lipid antigen reaction characteristics. There was however no significant association of ZIKV-GBS with any anti-glycolipid antibodies. Conclusion Autoantibodies in ZIKV associated GBS patient sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

Reporting of Acute Inflammatory Neuropathies with COVID-19 Vaccines: Subgroup Disproportionality Analyses in VigiBase

Since marketing authorization, cases of neuralgic amyotrophy (NA), facial paralysis/Bell’s palsy (FP/BP), and Guillain-Barré syndrome (GBS) were reported with COVID-19 vaccines of different technologies. This study aimed to assess whether NA, FP/BP, and GBS were more frequently reported in VigiBase with COVID-19 vaccines (of any technologies) than with other viral vaccines, over the full database and across potential risk groups by sex and age. The reporting odds ratio (ROR) with 95% confidence interval (95% CI) was used as the measure of disproportionality and subgroup disproportionality analyses were performed by sex and age. Out of 808,906 safety reports with COVID-19 vaccines, 57 (0.01%) reported NA, 3320 (0.4%) FP/BP, and 632 (0.1%) GBS. There were not signals of disproportionate reporting for NA and GBS with COVID-19 vaccines against other viral vaccines. FP/BP was disproportionately more frequently reported with COVID-19 vaccines than with other viral vaccines over the full database (ROR 1.12, 95%CI 1.07–1.17), in males (ROR 1.65, 95%CI 1.54–1.78) and in age subgroups 65–74 years (ROR 1.21, 95%CI 1.05–1.39) and ≥75 years (ROR 1.84, 95%CI 1.52–2.22). Albeit not proving causation, these findings might support clinicians in decision-making for patients potentially at risk for developing an acute inflammatory neuropathy with COVID-19 vaccines.

Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report

Background Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). Case presentation We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. Conclusions CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

Autoantibody screening in Guillain-Barre Syndrome

Guillain-Barre Syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation and pathogenesis. Serum antibodies against various gangliosides can be found in less than half of all patients in the acute phase of GBS but the target antigens remain unknown for the remaining half. Our work describes a comprehensive screening for serum autoantibodies targeting peripheral nerve tissue, cells, and purified antigens in a prospective GBS cohort including 100 patients. Our study confirms that (1) GBS patients display a very heterogeneous repertoire of autoantibodies targeting nerve cells and structures, (2) gangliosides are the most frequent antigens in GBS patients and have prognostic value, (3) a small subset of patients display antibodies targeting the myelin sheath, and (4) further antigen-discovery experiments are needed to elucidate other potential disease-specific autoantibodies in GBS.

Bilateral form of neuralgic amyotrophy

Neuralgic amyotrophy is an acute painful inflammatory neuropathy involving, as a rule, the trunks of the brachial plexus in one side. A clinical case of a bilateral form of neuralgic amyotrophy is presented with successively involvement of the brachial plexus on both sides in a 62-year-old man and relief of neuropathic pain in response to high doses of glucorticosteroids.

Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study

Background: Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce. Methods: We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS). Results: A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p = 0.04, χ2-test, n = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p = 0.02, t-test, n = 48). Patients with Lewis-Sumner syndrome ( n = 9) and autoantibody mediated neuropathies ( n = 13) had excellent response rates after treatment with RTX (90–100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ. Conclusion: Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.