Peripheral Nervous System Involvement Research Articles

Concomitant Central and Peripheral Nervous System Involvement Associated With Mycoplasma pneumoniae Infection in Pediatric Patients: Two Case Reports and Literature Review.

Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen for community-acquired pneumonia and is also implicated in a broad array of extra-pulmonary manifestations. M. pneumoniae infection is rarely associated with concurrent central nervous system (CNS) and peripheral nervous system (PNS) involvement in children. We report 2 patients who presented with acute encephalitis and polyradiculitis due to M. pneumoniae infection and review the literature to discuss the pathogenesis and treatment of concomitant CNS and PNS involvement associated with M. pneumoniae infection. We report two 6-year-old boys with M. pneumoniae antecedent infection who presented initially with impaired consciousness followed by limb weakness, limb pain and urinary retention, and responded well to immunotherapy. We described 2 patients who presented symptomatic combined CNS and PNS involvement with persistent urinary retention associated with M. pneumoniae infection. We found autoimmunity plays an important role and recommend that antibiotics and immunomodulators should be administered with concurrent CNS and PNS involvement associated with M. pneumoniae.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

Peripheral Nervous System Involvement of Hereditary Transthyretin Amyloidosis in the United States: A Multi-center Perspective (S21.007)

Peripheral Nervous System Involvement of Hereditary Transthyretin Amyloidosis in the United States: A Multi-center Perspective (S21.007)

Clinical characteristics and MRI features of autoimmune glial fibrillary acidic protein astrocytopathy: a case series of 34 patients.

To analyze the clinical and imaging characteristics of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). Forty-three patients diagnosed with GFAP-A between March 2017 and July 2023 were retrospectively recruited. The clinical characteristics and magnetic resonance imaging (MRI) features were collected. Twenty-one patients (61.8%) had a fever and 16 (47.1%) had a headache. Five patients (14.7%) had coexisting neural autoantibodies and one patient (2.9%) had a coexisting neoplasm. The most common presentation was meningoencephalomyelitis (13/34, 38.3%), followed by meningoencephalitis (12/34, 35.3%). The other clinical manifestations included blurred visions (5/34, 14.7%) and peripheral nervous system involvement (4/34, 11.8%). Twenty-six patients (76.5%) had elevated nucleated cell count, predominantly lymphocytes (15/15, 100%), and 27 (79.4%) had elevated protein levels of cerebrospinal fluid. One-half (50%) of the patients presented with hyponatremia. A majority of the patients (30/33, 90.9%) exhibited abnormal hyperintense lesions on T2WI, which were often located in juxtacortical white matter (18/33, 54.5%), followed by periventricular white matter (16/33, 48.5%), basal ganglia (15/ 33, 45.5%), brainstem (11/33, 33.3%), and thalamic lesions (9/33, 27.3%). Twenty-four patients (72.7%) had abnormal brain enhancement, with supratentorial leptomeningeal enhancement being the most frequent enhancement pattern (15/33, 45.5%), followed by linear perivascular radial enhancement (14/33, 42.4%). Nineteen patients (70.4%) had hyperintense intramedullary spinal cord lesions, with long segments (15/27, 55.6%) and transverse lesions (14/27, 51.9%) being the most frequent lesions. Most cases were sensitive to immunotherapy, such as glucocorticoids, intravenous immunoglobulin, and tacrolimus, with three patients (8.8%) experiencing relapses. Patients with brainstem lesions had higher onset modified Rankin scale scores and were more prone to intensive care unit admissions. Linear perivascular radial enhancement was positively associated with poor prognosis (p < 0.05). GFAP-A presented with meningoencephalomyelitis and meningoencephalitis. The brain lesions were often located in juxtacortical white matter, periventricular white matter, basal ganglia, brainstem, and thalamus. Long segments and transverse were the most frequent spine lesions. Leptomeningeal enhancement was the most frequent enhancement pattern, followed by linear perivascular radial enhancement, which may provide new insight into the differential diagnosis of GFAP-A.

Peripheral nervous system manifestations of MOG antibody associated disease.

Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG-IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true-positive MOG-IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

The outcome and risk factors associated with central and peripheral nervous system involvement in hospitalized COVID-19 patients: a retrospective cohort study.

SARS-CoV-2 infection can affect any organ, including both the central nervous system (CNS) and peripheral nervous system (PNS). The aim of this study was to explore the outcome and risk factors associated with the involvement of either CNS or PNS in a cohort of hospitalized COVID-19 patients. We performed a retrospective observational cohort study of hospitalized adult patients with COVID-19, between May 2020 and December 2022, presenting with new onset neurological disabilities any time after admission. We included 115 patients, 72 with CNS manifestations and 43 with PNS involvement. The CNS manifestations were COVID-19-associated encephalopathy, headache, neurovascular events, and seizures in 80.5, 43, 31.9, and 11.1% of patients, respectively. The neurovascular events were ischemic stroke in 17 (23.6%) patients, hemorrhagic stroke in 6 (8.3%) patients, venous thrombosis in 1 (1.4%) patient, and subarachnoid hemorrhage in 1 (1.4%) patient. Cranial nerve involvement was the most frequent PNS manifestation in 34 (79%) cases, followed by mononeuritis in 5 (11.6%) patients and polyneuropathy in 4 (9.3%) patients. The affected cranial nerves were the vestibulocochlear nerve in 26 (60.5%) patients, the olfactory nerve in 24 (55.8%) patients, the oculomotor nerves in 5 (11.6%) patients, and the facial nerve in 1 (2.3%) patient. Two patients (9.3%) presented with polyneuritis cranialis. Older age (HR = 1.02, 95% CI: 1.003-1.037, p = 0.01), COVID severity (HR = 2.53, 95% CI: 1.42-4.5, p = 0.002), ischemic cardiac disease (HR = 2.42, 95% CI: 1.05-5.6, p = 0.03), and increased D-dimers (HR = 1.00, 95% CI: 1.00-1.00, p = 0.02) were independently associated with the development of CNS manifestations. The factors associated with in-hospital mortality were age (HR = 1.059, 95% CI: 1.024-1.096, p = 0.001), C-reactive protein (HR = 1.006, 95% CI: 1.00-1.011, p = 0.03), CNS involvement (HR = 9.155, 95% CI: 1.185-70.74, p = 0.03), and leucocyte number (HR = 1.053, 95% CI: 1.026-1.081, p < 0.001). COVID-19-associated encephalopathy was the most common CNS manifestation in our study, but neurovascular events are also important considering the overlap between inflammatory and prothrombotic pathways, especially in severe cases. CNS involvement was associated with in-hospital all-cause mortality. PNS findings were various, involving mostly the cranial nerves, especially the vestibulocochlear nerve.

Systemic Lupus Erythematosus Patients in the Qassim Region, Saudi Arabia: Insights on Peripheral Nervous System Involvements

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with diverse clinical manifestations. This study aimed to investigate the prevalence, clinical features, and risk factors associated with peripheral nervous system (PNS) involvement in SLE patients. Materials and Methods: This study encompassed a retrospective analysis involving 377 SLE patients diagnosed according to the European Alliance of Associations for Rheumatology/American College of Rheumatology criteria at Qassim region in Saudi Arabia, conducted through a meticulous chart review facilitated by proficient data collectors. A structured data collection form/checklist, incorporating explicit definitions and instructions, was utilized for extracting information from patient files, papers, and databases. Additionally, the SLE Quality of Life Questionnaire was employed to evaluate the quality of life among the participants. A multivariate logistic regression model was employed to identify independent predictors of PNS involvement. Results: Distinct clinical patterns were observed in SLE patients with PNS involvement, including a higher prevalence of nonscarring alopecia, acute cutaneous lesions, oral ulcers, and seizures. Diabetes and chronic kidney disease emerged as significant positive predictors for PNS complications. Hematological abnormalities, renal involvement, and vitamin deficiencies were prevalent, contributing to an overall poor quality of life among these patients. Conclusion: This study underscores the need for heightened clinical awareness of PNS complications in SLE, emphasizing the impact of diabetes and chronic kidney disease as significant risk factors. Early detection and targeted interventions are crucial to improving outcomes and enhancing the overall quality of life for SLE patients with PNS involvement.

X-linked Myotubular Myopathy Manifesting Carrier with Central and Peripheral Nervous System Involvement.

X-linked myotubular myopathy (XLMTM) is a rare genetic disorder caused by X-linked mutations in the MTM1 gene. Although heterozygous females are typically asymptomatic, affected cases have recently been reported. We herein report a case of XLMTM manifesting carrier of the pathogenic c.206dupG mutation in MTM1 with uncommon extramuscular symptoms. She developed gaze nystagmus and cognitive impairment in addition to muscle weakness. Electrophysiological studies and brain magnetic resonance imaging indicated the involvement of the central and peripheral nervous systems. XLMTM manifesting carriers may have a wider spectrum of clinical phenotypes than currently assumed. Appropriate follow-up of extramuscular and conventional muscular manifestations is important in such cases.

A rare neurological complication of COVID-19: Pediatric Miller Fisher Syndrome. A case report

The SARS-CoV-2 pandemic has significantly transformed the world. While it was initially viewed as a respiratory virus, it has now been found to cause cardiovascular, gastrointestinal, and psychological complications. Moreover, the nervous system (NS) is also greatly affected. Research has identified dizziness, headaches, as well as disturbances in one's taste and smell abilities as the most frequent symptoms of NS involvement. Even more significant changes may occur in patients who get infected with SARS CoV-2, such as the development of acute cerebrovascular disorders (stroke), multiple sclerosis, acute disseminated encephalitis, Guillain-Barré syndrome, encephalitis, and myelitis. It is important to note these potential complications and monitor patients closely. A retrospective study conducted in Wuhan, China revealed that CNS (central nervous system) involvement occurred three times more frequently than PNS (peripheral nervous system) involvement. This emphasizes the critical importance of studying and describing CNS manifestations. This case report depicts Miller Fisher syndrome in a 5-month-old infant after SARS CoV-2 infection and explores literature on pediatric cases and potential pathogenic mechanisms.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study

Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively). Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. The Instituto de Salud Carlos III and the European Union.

Long-term results of therapy with sequential use of rituximab and belimumab in patients with systemic lupus erythematosus

Objective: To evaluate the efficacy of combination therapy with rituximab (RTM) and belimumab (BLM) in patients with systemic lupus erythematosus (SLE) during long-term follow-up. Material and methods. Twelve patients with definite high- and moderate activity SLE were included in the study. Nine of them had skin and joint manifestations, and the others had renal, peripheral nervous system involvement, and vasculitis. Patients received RTM at a dose of 500–2000 mg with premedication with 6-methylprednisolone and then BLM according to the standard regimen of 10 mg/kg once a month. Patients were divided into two groups according to the timing of assessment of long-term outcomes. In the 1st group, data were evaluated after 7–9 years (n = 4), and in the 2nd group – after 2–4 years (n = 8) after the prescription of biologic disease-modifying antirheumatic drugs (bDMARDs). Efficacy and tolerability of therapy, SLE activity, and dose of oral glucocorticoids (GC) were evaluated. Results and discussion. Against the background of combination therapy, clinical and immunological response was achieved in 11 of 12 patients after one year (median SLEDAI-2K at baseline – 10 [9.5; 14.5] points, 6 and 12 months after administratrion of BLM – 4 [2; 6] points). When bDMARDs were prescribed in the first two years of the disease, patients responded better to therapy and showed more significant positive dynamics in clinical and laboratory parameters. Subsequently, BLM therapy was limited to an average of 2 years, during which a stable remission was achieved. Prescribing bDMARDs allowed GC to be used as initial therapy in an exacerbation of SLE in medium and low doses (subsequently further reduced). Clinical remission was achieved and maintained in 7 patients, exacerbation at different time points after discontinuation of bDMARDs occurred in 3 patients, efficacy waned in one patient, and no result was achieved with combination therapy in another patient. Conclusion. The most pronounced positive result can be expected when a bDMARDs are prescribed as early as possible after diagnosis of SLE (in the first 2 years of the disease). It is advisable to administer BLM infusions as recommended once a month without long breaks between injections for at least 2 years and to continue until a durable effect is achieved. The use of low-dose GC and its discontinuation is an achievable goal, but careful monitoring of patients is needed to detect early symptoms of exacerbation.

Sensory disturbances in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

Neurolymphomatosis in Non-Hodgkin's Lymphoma

non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of hematopoietic puffins, with diphun B-velicocyclotinous lymphoma accounting for 25% of all NHLs and having the greatest midline to axis growth (Leeuwenуе et al., 2014). Of all NHLs, the central and peripheral nervous systems are most often affected in diphytic B-lycocytic lymphoma (Padala, &amp; Kallam, 2022. Liu, &amp; Barta, 2019). In NHL, infiltration of cranial and peripheral nerves can be detected - neurolymphomatosis (NL) emerges. NL is a very rare condition and occurs in about 0.2% of patients with NHL (Baehring, Damek, Martin, Betensky &amp; Hochberg, 2003). These infiltrations can manifest with detection of mononeuropathy, multiple neuropathy, symmetric neuropathy or plexopathy (Grisold W., Grisold A., Marosi, Meng, &amp; Briani, 2015). The aim of the work was to study the features of the clinical course, diagnosis and treatment of neurolymphomatosis in the form of lesions of the trigeminal, facial cranial nerve and the left ulnar nerve in diffuse B-bollichelial non-Hodgkin lymphoma based on a clinical case. We present a review of a clinical case of peripheral nervous system involvement in a patient born in 1977 with diffuse B-cell non-Hodgkin's lymphoma. The diagnosis was established on the basis of clinical manifestations of lesions of the branches of the trigeminal and left facial nerves, the left ulnar nerve, magnetic resonance imaging of the head and brain, electroneuromyography, and immunohistochemical examination of the infiltrate biopsy from the affected buccal branch of the left facial nerve. In March 2022, the patient developed moderate peripheral paresis of the mimic muscles on the left side, burning pain with impaired tactile and pain sensitivity of the dorsum, wing of the nose, and left instep. A week later there was a decrease in the strength, tactile and pain sensitivity, and patience of the fourth and fifth fingers of the left hand. Within a month, the burning pain had spread to the left cheek, periorbital, and chin areas of the face. In 2021, the patient was diagnosed with B-bollichelial non-Hodgkin's lymphoma with involvement of the right axillary, supraclavicular lymph nodes, left breast, followed by chemotherapy and clinical remission. Magnetic resonance imaging of the head revealed a perineural lesion of the third branch of the right trigeminal nerve, the second branch of the left trigeminal nerve, and the cheek branch of the left facial nerve. Electroneuromyography revealed an axonal lesion of the left ulnar nerve. The results of examination of the infiltrate biopsy from the affected buccal branch of the facial nerve specimens confirmed non-Hodgkin's diffuse B-cell lymphoma, GCB-phenotype and nerve damage due to NHL. Treatment of multiple neuropathy with glucocorticosteroids, nonsteroidal anti-inflammatory drugs, acelicholinesterase inhibitors, and specific chemotherapy resulted in limited therapeutic effect. Prescribing pregabalin resulted in decreased reduction of neuropathic facial pain. Thus, neurolymphomatosis is a rather rare manifestation of non-Hodgkin's lymphomas, the use of magnetic resonance imaging of the head and brain as well as immunohistochemical examination of the affected nerve infiltrate biopsy is important to confirm the diagnosis.&#x0D; In the Ukrainian scientific medical literature, there are few descriptions of cases of neurolymphomatosis in NHL, although they occur in patients, and it is necessary to describe in more detail the peculiarities of the collicular course of the diagenesis and treatment in these cases.

P06.14.A DIAGNOSIS AND MANAGEMENT OF NEUROPATHIES RELATED TO IMMUNE CHECKPOINT INHIBITORS: A CASE SERIES

Abstract BACKGROUND Immune checkpoint inhibitors (ICIs) are associated with a wide range of neurotoxicities. Several types of neuropathies have been associated to immune checkpoint inhibitors (ICIs), from length-dependent sensory neuropathies to radiculoneuropathies similar to Guillain-Barré syndromes, with an overall incidence estimated to be between 0.1-1.2% of patients. Guidelines recommend prompt ICI discontinuation and the INTRODUCTION of steroids depending on the severity of the adverse event. However, the usage of IVIG or plasmapheresis (alternatively or in addition to steroids) has been reported in cases of Guillain-Barré-like syndromes. MATERIAL AND METHODS In this study, we report a retrospective consecutive series of patients with an ICI-related neuropathy referred to our department between 2016 and 2021, with the intent to describe their clinical and para-clinical features and the outcome after ICI discontinuation and steroids. RESULTS We identified 12 cases of acute peripheral nervous system involvement, with a predominant sensory pattern. The median onset of symptoms from ICI initiation was 18 weeks, and the median number of ICIs doses was 3. Electrophysiological studies, done in 11 patients, showed a radiculopathy in 9 cases, associated with an axonal neuropathy in 3, and a demyelinating neuropathy in 2 cases. Altogether, these findings are consistent with Guillain-Barré-like syndrome. ICIs were stopped in all patients and steroids started in 7 patients, leading to a favourable outcome (complete recovery =7, partial recovery =4, stability =1). CONCLUSION This consecutive retrospective series identifies Guillain-Barré-like syndrome as the main clinical pattern of immune related neuropathies. We did not observe any case of length-dependent axonal neuropathy without an associated root involvement. Our systematic management, consisting of ICI discontinuation in all patients and steroids in more severe cases, seems a valid strategy. On the other hand, our results do not support the use of IVIG or other treatments.

CORRECTION & REPLACEMENT, Prevalence of Peripheral Nervous System Involvement in Adult Leukodystrophies (P2-5.031).

CORRECTION & REPLACEMENT, Prevalence of Peripheral Nervous System Involvement in Adult Leukodystrophies (P2-5.031).

Isolated Sixth Nerve Palsy and COVID-19: A Recurrent Case in a 7-Month-Old Child and Analysis of Reported Cases.

With the SARS-CoV-2 pandemic (COVID-19), data on central and peripheral nervous system involvement, including those causing cranial nerve 6 (CN6) palsy, have been limited to case reports. To extract clinically relevant features of COVID-19-related CN6 palsy, we report on a recurrent pediatric case and analysis of reported cases associated with infection or immunization. A PubMed search revealed 18 cases of isolated CN6 palsy in addition to the index case (n = 19). Clinical characteristics, workup, and temporal associations between systemic symptoms onset or vaccination, symptoms onset, and resolution were compiled and analyzed. The median age of CN6 onset was 43 years (interquartile range [IQR]: 28-52). Sixteen cases (84.2%) were associated with COVID-19 illness and 3 (15.8%) were associated with COVID-19 vaccination. Four cases (23.5%) had positive neuroimaging findings. The median latency from first COVID-19 symptoms or vaccination to onset of CN6 palsy was 6 days (IQR: 2.3-16), and the median time from onset to resolution was 30 days (IQR: 14-60). Latency to onset of CN6 palsy was significantly and directly associated with time to resolution (R2 = 0.401, P = 0.010). Patients who had a positive SARS-CoV-2 antibody test had significantly longer days from symptoms to onset (6.0 vs 24.5, P = 0.030), and patients with a positive SARS-CoV-2 polymerase chain reaction test had a significantly shorter time to resolution (17.50 vs 90, P = 0.042). Isolated CN6 palsy from COVID-19 is rare, can occur in infants as young as 7 months, and can be recurrent. Longer latency from systemic symptoms onset portends greater recovery times, and this relationship may reflect multiple mechanisms by which COVID-19 (and/or an immune response thereto) causes cranial neuropathies with direct clinical relevance.

Clinical and immunologic features of the phenotype of systemic lupus erythematosus combined with Sjögren's syndrome

The problem of clinical and immunological heterogeneity of systemic lupus erythematosus (SLE) is of great interest, especially the combination of SLE and Sjögren's syndrome (SjS) determines a more favorable prognosis and specifics of therapy.Objective: to characterize the clinical and immunological features of SLE combined with SjS.Material and methods. The retrospective study included 44 patients with SLE combined with SjS and 356 patients with SLE without SjS, hospitalized at the V.A. Nasonova Research Institute of Rheumatology between 2013 and 2021. The two groups of patients were compared in terms of life expectancy, clinical manifestations, laboratory parameters and therapy.Results and discussion. The following phenotypic features of the clinical and immunological variant of SLE combined with SjS were found: significantly longer duration of SLE (p&lt;0.01); higher incidence of polyarthritis (p=0.01) and Raynaud's syndrome (p&lt;0.003) at disease onset. Subacute cutaneous lupus erythematosus, Raynaud's syndrome, peripheral nervous system involvement (sensory polyneuropathy and distal sensory-motor polyneuropathy) were found more frequently in SLE combined with SjS than in SLE without SjS, p&lt;0.0001. Among laboratory abnormalities in SLE patients with SjS, leukopenia (p&lt;0.0001), antibodies to SSA/Ro, SSB/La, and rheumatoid factor (p&lt;0.0001) were observed in a greater number of cases. In the group of SLE combined with SjS, the chronic variant of SLE course according to the classification of V.A. Nasonova, and lower activity were observed, which didn't not require therapy with high doses of glucocorticoids; in this group, rituximab (p&lt;0.01), cyclophosphamide and methotrexate were used significantly more often.Conclusion. Thus, significant clinical and laboratory differences were found between SLE with SjS and without SjS. They determine prognosis, approaches to pathogenetic therapy and monitoring.

Peripheral Polyneuropathy in Children and Young Adults with Ataxia-Telangiectasia.

Ataxia-telangiectasia (A-T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A-T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive & systemic therapies. The aim was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age-dependent neuropathy in A-T. In this prospective study 42 classical A-T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data was compared to published standard values and a healthy age-gender-matched control group of 23 participants. Ataxia scores (Klockgether, SARA) were also assessed. In A-T neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy were predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p<0.001). In A-T, polyneuropathy occurs mostly subclinical as early as the first year of life. The current study of a large national A-T cohort demonstrates that development of neuropathy in A-T differs in the upper and lower extremities.

Miller Fisher Syndrome Associated With COVID-19: A History of Molecular Mimicry and an Up-to-Date Review of the Literature.

Miller Fisher syndrome (MFS) was first recognized by Collier in 1932 as a clinical triad of ataxia, areflexia, and ophthalmoplegia. In 1956, three cases with this triad were published by Miller Fisher as a limited variant of Guillian-Barré syndrome (GBS), and the disease started to be called by his name. Since the beginning of the SARS-CoV-2 pandemic, there have been many reports of peripheral and central nervous system involvement. Until December 2022, a total of 24 cases, including four children associated with MFS, had been reported. This current review aimed to present the basic clinical and laboratory characteristics of patients with MFS and coronavirus disease-2019 (COVID-19). Since 2020, cases with different age and gender characteristics have been reported from eight different countries. Most cases were reported from Europe. SARS-CoV-2 infection was confirmed in seven of the cases.The youngest case reported was a 6-year-old boy from Turkey, while the oldest case was a 70-year-old female from Spain. All these reported cases and our past medical knowledge of MFS suggest that molecular mimicry is the main immunological mechanism. Despite all these data, more case reports, cohorts, and case-control studies will be needed to clarify the relationship between MFS and COVID-19.

Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease.

Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.