Peripheral Nervous System Involvement Research Articles

Oral and gut microbiome profiles in people with early idiopathic Parkinson’s disease

BackgroundEarly detection of Parkinson’s disease (PD), a neurodegenerative disease with central and peripheral nerve involvement, ensures timely treatment access. Microbes influence nervous system health and are altered in PD.MethodsWe examined gut and mouth microbiomes from recently diagnosed patients in a geographically diverse, matched case-control, shotgun metagenomics study.ResultsHere, we show greater alpha-diversity in 445 PD patients versus 221 controls. The microbial signature of PD includes overabundance of 16 OTUs, including Streptococcus mutans and Bifidobacterium dentium, and depletion of 28 OTUs. Machine learning models indicate that subspecies level oral microbiome abundances best distinguish PD with reasonably high accuracy (area under the curve: 0.758). Microbial networks are disrupted in cases, with reduced connectivity between short-chain fatty acid-producing bacteria the the gut. Importantly, microbiome diversity metrics are associated with non-motor autonomic symptom severity.ConclusionsOur results provide evidence that predictive oral PD microbiome signatures could possibly be used as biomarkers for the early detection of PD, particularly when there is peripheral nervous system involvement.

Heterozygous loss-of-function variants in SPTAN1 cause a novel early childhood onset distal myopathy with chronic neurogenic features.

Neurogenetic disorders caused by pathogenic variants in four genes encoding non-erythrocytic spectrins ( SPTAN1, SPTBN1, SPTBN2, SPTBN4) range from peripheral and central nervous system involvement to complex syndromic presentations. Heterozygous pathogenic variants in SPTAN1 are exemplary for this diversity with phenotypes spanning almost the entire spectrum. Through international collaboration we identified 14 families with genetically unsolved distal weakness and unreported heterozygous SPTAN1 loss-of-function variants including frameshift, nonsense and splice-acceptor variants. Clinical data, electrophysiology, muscle CT or MRI and muscle biopsy findings were collected and standardized. SPTAN1 protein, mRNA expression analysis and cDNA sequencing was performed on muscle tissue from two patients. All 20 patients presented with early childhood onset distal weakness. The severity varied both within families and between different families. Foot abnormalities ranged from hammer toes and pes cavus to distal arthrogryposis. Electrophysiology showed mixed myogenic and neurogenic features. Muscle MRI or CT in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes with mild dystrophic and chronic neurogenic changes in 7 patients. Finally, we provide proof for nonsense mediated decay in tissues derived from two patients. We provide evidence for the association of SPTAN1 loss-of-function variants with childhood onset distal myopathy in 14 families. This finding extends the phenotypic spectrum of SPTAN1 loss-of-function variants ranging from intellectual disability to distal weakness with a predominant myogenic cause. SPTAN1 loss-of-function variants, including frameshift, nonsense and splice site variants cause a novel childhood onset distal weakness syndrome with primarily skeletal muscle involvement. Hereditary motor neuropathies and distal myopathic disorders present a well-known diagnostic challenge as they demonstrate substantial clinical and genetic overlap. The emergence of SPTAN1 loss-of-function variants serves as a noteworthy example, highlighting a growing convergence in the spectrum of genotypes linked to both hereditary motor neuropathies and distal myopathies.

Distinct Clinical Courses and Shortened Lifespans in Childhood-Onset DNA Polymerase Gamma Deficiency.

DNA polymerase subunit gamma (POLG) deficiency is likely the most frequent cause of nuclear-encoded mitochondrial disorders. POLG-related disorders reportedly constitute a spectrum of overlapping phenotypes from infancy to late adulthood. We retrospectively reviewed natural histories for 40 children carrying biallelic pathogenic POLG variants. The patients were identified by the French coordinating center for mitochondrial disorders (CARAMMEL), making this a large monocentric series on childhood-onset POLG deficiency. Three patterns of clinical course and survival were observed, distinguished by main category of symptoms: neurologic, hepatic, and gastrointestinal. A total of 24 patients needed urgent neurointensive care for tonic-clonic seizures, myoclonic epilepsy, and status epilepticus, occasionally precipitated by valproate administration. Other neurologic symptoms included dystonia, cerebellar ataxia, and peripheral neuropathy. We report 6 POLG-deficient patients with polyradiculoneuropathy mimicking subacute Guillain-Barré syndrome and provide postgadolinium MRI evidence of diffuse cranial nerve root and cauda equina enhancement, suggesting these disorders have an inflammatory component. Children presenting with enteral nervous system involvement had vomiting, gastroparesis, and chronic intestinal pseudo-obstruction. They had later ages of onset and lived much longer. Primarily, hepatic presentations had the earliest onset and shortest survivals. Secondary hepatic failure was frequently precipitated by valproate administration given before diagnosis to patients with focal impaired awareness seizures or absence of seizures. These POLG deficiencies were often fatal, with age at death ranging from 3 months to 10 years, with a significant difference in survival between the 3 clinical forms; 6 of the 40 children did survive. No genotype-phenotype correlations were found for the 3 clinical course types. The study demonstrates the prevalence of neurologic presentation and the extent of central, peripheral, and autonomous nervous system involvement in 60% of patients. Most of the patients with early onset and rapidly fatal hepatic failure did not live long enough to develop neurologic symptoms. The study revealed a new clinical form of POLG deficiency presenting with neurodigestive symptoms with longer lifespan. We also propose that POLG deficiency should be considered in children presenting with unexplained polyradiculoneuropathy, demyelinating neuropathy, and elevated CSF protein. Finally, valproate administration remains a notable cause of avoidable death in POLG-deficient patients.

The spectrum of anti-GQ1B antibody syndrome: beyond Miller Fisher syndrome and Bickerstaff brainstem encephalitis.

Since the initial identification of Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE),significant milestones have been achieved in understanding these diseases.Discoveries of common serum antibodies (IgG anti-GQ1b), antecedent infections, neurophysiological data, andneuroimaging suggested a shared autoimmune pathogenetic mechanism rather than distinct pathogenesis, leadingto the hypothesis that both diseases are part of a unified syndrome, termed "Fisher-Bickerstaff syndrome". The subsequent identification of atypical anti-GQ1b-positive forms expanded the classification to a broader condition known as "Anti-GQ1b-Antibody syndrome". An exhaustive literature review was conducted, analyzing a substantial body of research spanning from the initialdescriptions of the syndrome's components to recent developments in diagnostic classification and researchperspectives. Anti-GQ1b syndrome encompasses a continuous spectrum of conditions defined by a common serological profilewith varying degrees of peripheral (PNS) and central nervous system (CNS) involvement. MFS and BBE represent theopposite ends of this spectrum, with MFS primarily affecting the PNS and BBE predominantly involving the CNS.Recently identified atypical forms, such as acute ophthalmoparesis, acute ataxic neuropathy withoutophthalmoparesis, Guillain-Barré syndrome (GBS) with ophthalmoparesis, MFS-GBS and BBE-GBS overlap syndromes,have broadened this spectrum. This work aims to provide an extensive, detailed, and updated overview of all aspects of the anti-GQ1b syndromewith the intention of serving as a stepping stone for further shaping thereof. Special attention was given to therecently identified atypical forms, underscoring their significance in redefining the boundaries of the syndrome.

Dynamics of Trypanosoma cruzi infection in hamsters and novel association with progressive motor dysfunction.

Chagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Clinical outcomes range from long-term asymptomatic carriage to cardiac, digestive, neurological and composite presentations that can be fatal in both acute and chronic stages of the disease. Studies of T. cruzi in animal models, principally mice, have informed our understanding of the biological basis of this variability and its relationship to infection and host response dynamics. Hamsters have higher translational value for many human infectious diseases, but they have not been well developed as models of Chagas disease. We transposed a real-time bioluminescence imaging system for T. cruzi infection from mice into female Syrian hamsters (Mesocricetus auratus). This enabled us to study chronic tissue pathology in the context of spatiotemporal infection dynamics. Acute infections were widely disseminated, whereas chronic infections were almost entirely restricted to the skin and subcutaneous adipose tissue. Neither cardiac nor digestive tract disease were reproducible features of the model. Skeletal muscle had only sporadic parasitism in the chronic phase, but nevertheless displayed significant inflammation and fibrosis, features also seen in mouse models. Whereas mice had normal locomotion, all chronically infected hamsters developed hindlimb muscle hypertonia and a gait dysfunction resembling spastic diplegia. With further development, this model may therefore prove valuable in studies of peripheral nervous system involvement in Chagas disease.

ETMR-31. A UNIQUE CASE OF CNS DIFFUSE, NON-SYSTEMIC ALK+ HISTIOCYTOSIS IN A PEDIATRIC PATIENT

Abstract BACKGROUND Histiocytic disorders are a group of rare diseases with accumulation of of macrophages, monocytes, or dendritic cells in various parts of the body. ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 that is very rarely described in pediatrics. METHODS A 20 month old male presented to an adult hospital after a prolonged period of headaches, vomiting, and loss of developmental milestones. Imaging demonstrated severe hydrocephalus and extensive thickened leptomeningeal enhacement with mass effect. He underwent VP shunt placement and revision, a T7-T10 laminectomy, and tumor debulking. Extensive molecular testing, including DNA and RNA analysis by NGS was performed and a CLTC::ALK fusion was identified, along with Tier III DNA variants, yielding a diagnosis consistent with ALK-Positive Histiocytosis, with diffusivity in the CNS system. Full evaluation demonstrated no involvement of the peripheral nervous system or other systemic involvement. He initially demonstrated signs of neuro-irritation, altered tone, and lower extremity clonus. RESULTS After review of very little literature published on similar patients, although none with a clinical picture matching his, he was started on a treatment course of high dose dexamethasone, vinblastine, and lorlatinib targeting the ALK+, likely driver, mutation of his disease. On evaluation scans two months into treatment, he showed no change in his disease burden. He was transitioned to clofarabine cycles with daily lorlatinib for continued targetted therapy. After six total cycles, he demonstrated a high partial to complete remission (allowing for evidence of scarred tissue) and tremendous neurologic and developmental milestone gains. CONCLUSIONS This case demonstrates a unique presentation in which there is little described in the literature in way of clinical features or treatment standards, and further none exactly similar to this patient. After undergoing extensive evaluation and therapy modication, he responded remarkably well and continues to have optimal quality of life.

Assessment of Skin Biopsy as a Diagnostic Biomarker in CSF1R-Related Disorder.

To validate a recently published study in which skin biopsy was reported as a valuable alternative to brain biopsy in diagnosing CSF1R-related disorder (CSF1R-RD). Blinded evaluation of skin samples was performed by independent reviewers using light and electron microscopy collected from a group of CSF1R variant carriers (n = 10) with various genotypes (mono and biallelic), different stages of the disease (asymptomatic and symptomatic), and exposed to different therapies (glucocorticoids, hematopoietic stem cell transplantation, and TREM2 agonist), and from a group of healthy controls (n = 5). Biopsies from patients with CSF1R-RD at various disease stages were indistinguishable from controls determined using light microscopy and electron microscopy. We found no distinctive axonal pathology in skin biopsies collected from CSF1R variant carriers at all stages of the disease. Our results are consistent with clinical and neurophysiologic features of the CSF1R-RD, in that peripheral nervous system involvement has not been reported. Studies aiming to discover new biomarkers are important, but the results must be validated with larger numbers of patients and healthy controls. Based on blinded light and electron microscopic studies of skin biopsies, there is no evidence that CSF1R-RD is associated with distinctive changes in cutaneous peripheral nerves. This suggests that skin biopsy is not useful in diagnosis of CSF1R-RD. This study provides Class III evidence that skin biopsy does not distinguish those with CSF1R-RD, or carriers, from normal controls.

Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges.

Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.

Acyclovir treatment of varicella-zoster virus meningeal infections and acute kidney injury: a multicentre case series study

Background Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. Methods Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). Results 154 patients were included (median age 66 (interquartile range 43–77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. Conclusions Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.

Unique clinical and electrophysiological features in the peripheral nerve system in patients with sialidosis – a case series study

BackgroundTo investigate the peripheral nervous system involvement in S sialidosis with typical features of myoclonus, seizure, and giant waves in somatosensory evoked potentials suggesting hyperexcitability in the central nervous system.MethodsThe clinical presentation of patients with genetically confirmed sialidosis was recorded. Neurophysiological studies, including nerve conduction studies (NCSs), F-wave studies, and needle electromyography (EMG), were performed on these patients.ResultsSix patients (M/F: 2:4) were recruited. In addition to the classical presentation, intermittent painful paresthesia was noted in four patients, and three of whom reported it as the earliest symptom. In the NCSs, one patient had reduced compound muscle action potential amplitudes in the right ulnar nerve, while another patient had prolonged distal motor latency in the bilateral tibial and peroneal nerves. Prolonged F-wave latency (83.3%), repeater F-waves (50%), and neurogenic polyphasic waves in EMG (in 2 out of 3 examined patients) were also noted. Interestingly, a very late response was noted in the F-wave study of all patients, probably indicating lesions involving the proximal peripheral nerve or spinal cord.ConclusionIn addition to the central nervous system, the peripheral nervous system is also involved in sialidosis, with corresponding clinical symptoms. Further study on these phenomena is indicated.

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.

Chapter 16 - HSCT for systemic autoimmune diseases with neurologic involvement

Over the past 25 years, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory systemic autoimmune diseases, where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. In addition to autoimmune neurologic diseases, such as multiple sclerosis (MS) or neuromyelitis optica (NMO), rheumatic diseases with central or peripheral nervous system involvement and insufficient response to conventional immunosuppressive or biologic therapies represent a growing indication for autologous HSCT. They most commonly include connective tissue diseases, such as systemic lupus erythematosus (SLE), vasculitides, or rarer diseases from the autoinflammatory spectrum, such as Behçet's disease, where neurologic manifestations may represent the greatest disease burden. Neurologic manifestations may resemble those of MS, including myelitis optic neuropathy, stroke, or seizures. Outcomes of such manifestations are variable after autologous HSCT but most frequently improve or even resolve with the underlying disease, especially in SLE. This article will provide the current evidence and summarize the outcomes of HSCT for rheumatic autoimmune diseases with neurologic manifestations.

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.