2,4-Dinitrophenol does not exert neuro-regenerative potential in experimental autoimmune neuritis.

OBJECTIVE: We evaluated the potential neuro-regenerative effects of the mitochondrial uncoupler 2,4-Dinitrophenol in experimental autoimmune neuritis, an animal model for an acute autoimmune neuropathy. METHODS: Experimental autoimmune neuritis was induced in Lewis rats. Different concentrations of 2,4-Dinitrophenol (1 mg/kg, 0.1 mg/kg and 0.01 mg/kg) were applied during the recovery phase of the neuritis (at days 18, 22 and 26) and compared to the vehicle. Any effects were assessed through functional, electrophysiological, and morphological analysis via electron microscopy of all groups at day 30. Additional immune-histochemical analysis of inflammation markers and remyelination of the sciatic nerves were performed for the dosage of 1 mg/kg and control. RESULTS: No enhancement of functional or electrophysiological recovery was observed in all 2,4-Dinitrophenol-treated groups. Cellular inflammation markers of T cells (CD3+) were comparable to control, and an increase of macrophages (IbA1+) invasion in the sciatic nerves was observed. Treatment with 2,4-Dinitrophenol reduced axonal swelling in myelinated and unmyelinated fibers with an increased production of brain-derived neurotrophic factor. CONCLUSION: Our findings do not support the hypothesis that repurposing of the mitochondrial uncoupler 2,4-Dinitrophenol exerts functionally relevant neuro-regenerative effects in autoimmune neuritis.

TS-HDS autoantibody: clinical characterization and utility from real-world tertiary care center experience.

OBJECTIVES: To evaluate clinical utility of trisulfated-heparin disaccharide (TS-HDS) IgM testing from real-world tertiary care center experience. METHODS: Medical records of patients with positive TS-HDS antibodies who were evaluated at Mayo Clinic from 2009 to 2022 were reviewed. RESULTS: Seventy-seven patients (50 females) had positive TS-HDS antibody. Median age was 48 (9-77) years. Median titer was 25,000 (range 11,000-350,000). Twenty-six patients (34%) did not have objective evidence of peripheral neuropathy. Nine patients (12%) had other known causes of neuropathy. Among the remaining 42 patients, half presented with subacute progressive course; the other half had chronic indolent course. Most common phenotypes were length-dependent peripheral neuropathy (n = 20, 48%), length-dependent small-fiber neuropathy (n = 11, 26%), and non-length-dependent small-fiber neuropathy (n = 7, 17%). Nerve biopsies showed epineurial inflammatory cell collections in 2 but no interstitial abnormalities in the remaining 7. The majority of intraepidermal nerve fiber densities (7/10), thermoregulatory sweat tests (12/21) and autonomic reflex screens (27/49) were normal. Post-immunotherapy improvement in mRS/INCAT disability score/pain was only seen in 13/42 (31%) TS-HDS IgM positive patients. Patients presenting with sensory ganglionopathy, non-length dependent small-fiber neuropathy, or subacute progressive neuropathy with and without TS-HDS antibody responded similarly to immunotherapy (40% vs 80%, p = 0.30). DISCUSSION: TS-HDS IgM has limited phenotypic or disease specificity; it was found to be positive among patients with various neuropathy phenotypes as well as patients without objective evidence of neuropathy. Clinical improvement with immunotherapy, although was observed in a small proportion of TS-HDS IgM seropositive patients, was not more frequent when compared to seronegative patients with similar presentations.

Kinesin-5 inhibition improves neural regeneration in experimental autoimmune neuritis.

BACKGROUND: Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequate first-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies. Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in a rodent model of acute autoimmune neuropathies, experimental autoimmune neuritis. METHODS: Experimental autoimmune neuritis was induced in Lewis rats with the neurogenic P2-peptide. At the beginning of the recovery phase at day 18, the animals were treated with 1 mg/kg monastrol or sham and observed until day 30 post-immunisation. Electrophysiological and histological analysis for markers of inflammation and remyelination of the sciatic nerve were performed. Neuromuscular junctions of the tibialis anterior muscles were analysed for reinnervation. We further treated human induced pluripotent stem cells-derived secondary motor neurons with monastrol in different concentrations and performed a neurite outgrowth assay. RESULTS: Treatment with monastrol enhanced functional and histological recovery in experimental autoimmune neuritis. Motor nerve conduction velocity at day 30 in the treated animals was comparable to pre-neuritis values. Monastrol-treated animals showed partially reinnervated or intact neuromuscular junctions. A significant and dose-dependent accelerated neurite outgrowth was observed after kinesin-5 inhibition as a possible mode of action. CONCLUSION: Pharmacological kinesin-5 inhibition improves the functional outcome in experimental autoimmune neuritis through accelerated motor neurite outgrowth and histological recovery. This approach could be of interest to improve the outcome of autoimmune neuropathy patients.

Caspr1 antibodies autoimmune paranodopathy with severe tetraparesis: Potential relevance of antibody titers in monitoring treatment response.

AIM: Nodopathies and paranodopathies are autoimmune neuropathies associated with antibodies to nodal-paranodal antigens (neurofascin 140/186 and 155, contactin-1, contactin-associated protein 1 [Caspr1]) characterized by peculiar clinical features, poor response to standard immunotherapies (e.g., intravenous immunoglobulins, IVIg). Improvement after anti-CD20 monoclonal antibody therapy has been reported. Data on Caspr1 antibodies pathogenicity are still preliminary, and longitudinal titers have been poorly described. METHODS: We report on a young woman who developed a disabling neuropathy with antibodies to the Caspr1/contactin-1 complex showing a dramatic improvement after rituximab therapy, mirrored by the decrease of antibody titers. RESULTS: A 26-year-old woman presented with ataxic-stepping gait, severe motor weakness at four limbs, and low frequency postural tremor. For neurophysiological evidence of demyelinating neuropathy, she was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg without benefit. MRI showed symmetrical hypertrophy and marked signal hyperintensity of brachial and lumbosacral plexi. Cerebrospinal fluid showed 710 mg/dL protein. Despite intravenous methylprednisolone, the patient progressively worsened, and became wheelchair-bound. Antibodies to nodal-paranodal antigens were searched for by ELISA and cell-based assay. Anticontactin/Caspr1 IgG4 antibodies resulted positive. The patient underwent rituximab therapy with slow progressive improvement that mirrored the antibodies titer, measured throughout the disease course. CONCLUSIONS: Our patient had a severe progressive course with early disability and axonal damage, and slow recovery starting only a few months after antibody-depleting therapy. The close correlation between titer, disability, and treatment, supports the pathogenicity of Caspr1 antibodies, and suggest that their longitudinal evaluation might provide a potential biomarker to evaluate treatment response.

Guillain-Barré Syndrome following intravesical Bacillus Calmette-Guérin therapy for bladder cancer: a rare and intriguing case report.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is a standard treatment for non-muscle invasive bladder cancer, but some patients experience side effects that lead to treatment discontinuation. Local side effects are typically mild, while systemic side effects can be severe and life-threatening. BCG therapy has immunotherapy effects on bladder cancer, but the mechanism is not fully understood. Due to its effect on the immune system, patients may also develop rare autoimmune complications, such as neuropathy. This case report suggests a potential association between BCG therapy and Guillain-Barré Syndrome (GBS), as a patient developed GBS after receiving intravesical BCG therapy for invasive bladder cancer.

Conformation-stabilizing ELISA and cell-based assays reveal patient subgroups targeting three different epitopes of AGO1 antibodies.

Autoantibodies (Abs) are biomarkers for many disease conditions and are increasingly used to facilitate diagnosis and treatment decisions. To guarantee high sensitivity and specificity, the choice of their detection method is crucial. Via cell-based assays, we recently found 21 patients with neurological diseases positive for antibodies against argonaute (AGO), 10 of which having a neuropathy (NP). Here, we established a simple and conformation-sensitive ELISA with the aim to distinguish between AGO1 Abs against conformational epitopes and non-conformational epitopes and to reveal further characteristics of AGO1 antibodies in NP and autoimmune disease (AID). In a retrospective multicenter case/control and observational study, we tested 434 patients with NP, 274 disease controls with AID, and 116 healthy controls (HC) for AGO1 Abs via conformation-stabilizing ELISA. Seropositive patients were also tested for conformation-specificity via comparative denaturing/stabilizing ELISA (CODES-ELISA), CBA positivity, AGO1 titers and IgG subclasses, and AGO2 reactivity. These parameters were statistically compared among different epitope-specific patient groups. We found Abs in 44 patients, including 28/434 (6.5%) NP, 16/274 (5.8%) AID, and 0/116 (0%) HC. Serum reactivity was consistently higher for AGO1 than AGO2. Globally among the 44 AGO1 Abs-positive patients, 42 were also tested in CBA for AGO1 Abs positivity and 15 (35.7%) were positive. Furthermore, 43 were tested for conformation-specificity and 32 (74.4%) bound a conformational epitope. Among the subgroups of highly positive patients (ELISA z-score >14) with sera binding conformational epitopes (n=23), 14 patient sera were also CBA positive and 9 bound a second conformational but CBA-inaccessible epitope. A third, non-conformational epitope was bound by 11/43 (15.6%). Among the epitope-specific patient subgroups, we found significant differences regarding the Abs titers, IgG subclass, and AGO2 reactivity. When comparing AGO1 Abs-positive NP versus AID patients, we found the conformation-specific and CBA inaccessible epitope significantly more frequently in AID patients. We conclude that 1) conformational ELISA was more sensitive than CBA in detecting AGO1 Abs, 2) serum reactivity is higher for AGO1 than for AGO2 at least for NP patients, 3) AGO1 Abs might be a marker-of-interest in 6.5% of NP patients, 4) distinguishing epitopes might help finding different patient subgroups.

Adherence and Reactogenicity to Vaccines against SARS-COV-2 in 285 Patients with Neuropathy: A Multicentric Study.

Background: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. Methods: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. Results: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96.3%) were fully vaccinated. Adherence to vaccination was higher in patients with hereditary neuropathies compared to others, while it was lower in patients with anti-MAG neuropathy (all p < 0.05). The overall prevalence of adverse events (AEs) was 61.2% and its occurrence was not associated with neuropathy type. Being female and of younger age were factors associated with higher risk of AEs, while having an inflammatory neuropathy and steroids assumption were associated with a lower risk (all p < 0.05). Younger age, having had an AE, and COVID-19 before vaccination were factors associated with symptoms worsening after vaccination (all p < 0.05). (4) Conclusions: Patients with neuropathy showed a high level of adherence to COVID-19 vaccination. Safety of vaccines in patients with neuropathies was comparable to the general population and it was more favorable in those with inflammatory neuropathy.

Campylobacter jejuni and Postinfectious Autoimmune Diseases: A Proof of Concept in Glycobiology.

Glycans, one of the most diverse groups of macromolecules, are ubiquitous constituents of all cells and have many critical functions, including the interaction between microbes and their hosts. One of the best model organisms to study the host-pathogen interaction, the gastrointestinal pathogen Campylobacter jejuni dedicates extensive resources to glycosylation and exhibits a diverse array of surface sugar-coated displays. The first bacterium where N-linked glycosylation was described, C. jejuni can additionally modify proteins by O-linked glycosylation, has extracellular capsular polysaccharides that are important for virulence and represent the major determinant of the Penner serotyping scheme, and has outer membrane lipooligosaccharides that participate in processes such as colonization, survival, inflammation, and immune evasion. In addition to causing gastrointestinal disease and extraintestinal infections, C. jejuni was also linked to postinfectious autoimmune neuropathies, of which Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) are the most extensively characterized ones. These postinfectious autoimmune neuropathies occur when specific bacterial surface lipooligosaccharides mimic gangliosides in the host nervous system. C. jejuni provided the first proof of concept for the involvement of molecular mimicry in the pathogenesis of an autoimmune disease and, also, for the ability of a bacterial polymorphism to shape the clinical presentation of the postinfectious autoimmune neuropathy. The scientific journey that culminated with elucidating the mechanistic details of the C. jejuni-GBS link was the result of contributions from several fields, including microbiology, structural biology, glycobiology, genetics, and immunology and provides an inspiring and important example to interrogate other instances of molecular mimicry and their involvement in autoimmune disease.

Therapeutic plasma exchange for peripheral neuropathy associated with trisulfated heparan disaccharide IgM antibodies: A case series of 17 patients.

BACKGROUND: Small fiber neuropathy (SFN) can be associated with autoantibodies, including those of IgM class with specificity for the trisulfated heparan disaccharide (TS-HDS) antigen. We hypothesized that, as an IgM autoantibody-mediated disorder, TS-HDS-associated SFN symptoms may be reduced with therapeutic plasma exchange (TPE). STUDY METHODS: This was an observational analysis of all patients referred for TPE from 2018 to 2020 following laboratory confirmation of SFN with TS-HDS autoantibodies; a loading course of 3 to 5 procedures over 2 weeks was completed, with some patients returning for monthly procedures. The following data were collected: demographics, symptoms and duration, TS-HDS levels, skin biopsy results, reported responses to TPE, and TPE-associated adverse events. RESULTS: Of the 17 subjects, 12 (71%) were female and the mean age was 57.5 years (range 27-94). The most common reported symptom was lower extremity paresthesia (88% of subjects). The mean number of TPE procedures completed per subject was 9 (range 3-18), with 71% (12/17) reporting symptomatic improvement or slowed disease progression. About 15% of procedures were associated with an adverse event, with vasovagal reactions being the most common; 53% of patients had at least one adverse event. CONCLUSIONS: Given a reported symptomatic response rate of more than 70%, TPE may be a treatment option for individuals with autoimmune-mediated SFN associated with increased titers of TS-HDS IgM autoantibodies. Since TPE-associated adverse events appear common in this population, close monitoring during procedures is warranted.

Síndrome de Miller Fisher, un desafío diagnóstico de oftalmoplejía: reporte de un caso / Miller Fisher syndrome, a diagnostic challenge of ophthalmoplegia: a case report

El síndrome de Guillain-Barré (SGB), y sus derivados, entre ellos el síndrome de Miller Fisher (SMF); junto a otras patologías de origen neurológico como la Polineuropatía desmielinizante inflamatoria crónica (CIDP), las polineuropatías de causa metabólica, miastenia gravis, esclerosis lateral amiotrófica (ELA), síndrome de Lambert-Eaton, encefalopatía de Wernicke entre otras; presentan signos y síntomas neurológicos de presentación común. De este modo, la importancia del examen neurológico acabado; y los exámenes de apoyo diagnóstico como: laboratorio -destacando el líquido cefalorraquídeo (LCR)-, electromiografía, y toma de imágenes, son cruciales para esclarecer el diagnóstico. Así, es posible ofrecer un tratamiento de forma precoz, basado en la evidencia, y con el objetivo de disminuir la letalidad de la enfermedad. En el presente texto se plasma un subgrupo de patología de SGB, el SMF, el cual posee una incidencia significativamente baja, una clínica característica, y un pronóstico bastante ominoso sin un tratamiento adecuado. En el presente texto se plasma el reporte de un caso abordado en el Hospital San Pablo de Coquimbo, Chile.

Guillain-Barré syndrome (GBS) and its derivatives, including Miller Fisher syndrome (MFS), along others pathologies of neurological origin such as chronic inflammatory demyelinating polyneuropathy (CIDP), metabolic polyneuropathies, myasthenia gravis, amyotrophic lateral sclerosis (ALS), Lambert-Eaton syndrome, Wernicke's encephalopathy and well as others, have common neurological signs and symptoms. In this way, the importance of a thorough neurological examination, and supporting diagnostic tests such as: laboratory, -cerebrospinal fluid (CSF)-electromyography, and imaging, are crucial to clarify the diagnosis. Thus, it is possible to offer early, evidence-based treatment with an aim of reducing the disease's lethality. In the text below we present a subgroup of GBS pathology, MFS, which has a significantly low incidence, a characteristic clinical picture, and a rather ominous prognosis without adequate treatment. In the following text/paper is shown the report of a case approached in San Pablo Hospital, from Coquimbo, Chile.

Immune mechanisms, the role of complement, and related therapies in autoimmune neuropathies.

INTRODUCTION: Autoimmune neuropathies have diverse presentations and underlying immune mechanisms. Demonstration of efficacy of therapeutic agents that inhibit the complement cascade would confirm the role of complement activation. AREAS COVERED: A review of the pathophysiology of the autoimmune neuropathies, to identify those that are likely to be complement mediated. EXPERT OPINION: Complement mediated mechanisms are implicated in the acute and chronic neuropathies associated with IgG or IgM antibodies that target the Myelin Associated Glycoprotein (MAG) or gangliosides in the peripheral nerves. Antibody and complement mechanisms are also suspected in the Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy, given the therapeutic response to plasmapheresis or intravenous immunoglobulins, even in the absence of an identifiable target antigen. Complement is unlikely to play a role in paraneoplastic sensory neuropathy associated with antibodies to HU/ANNA-1 given its intracellular localization. In chronic demyelinating neuropathy with anti-nodal/paranodal CNTN1, NFS-155, and CASPR1 antibodies, myotonia with anti-VGKC LGI1 or CASPR2 antibodies, or autoimmune autonomic neuropathy with anti-gAChR antibodies, the response to complement inhibitory agents would depend on the extent to which the antibodies exert their effects through complement dependent or independent mechanisms. Complement is also likely to play a role in Sjogren's, vasculitic, and cryoglobulinemic neuropathies.

Guillain-Barré syndrome following ChAdOx1 nCoV-19 COVID-19 vaccination: A case series.

ChAdOx1 nCoV-19 is an effective and well-tolerated coronavirus disease 2019 (COVID-19) vaccine. Rare cases of serious adverse events have been reported with this vaccine. We report three patients who developed Guillain-Barré syndrome following ChAdOx1 nCoV-19 vaccination, who did not have active or prior COVID-19 infection. The neurological illness in all patients had an onset of 11-13 days after the first dose of vaccine. All were characterized by sensorimotor weakness of the upper and lower limbs, with facial diplegia in one and dysautonomia in the other. Nerve conduction studies were consistent with demyelination in two and axonopathy in one. Cerebrospinal fluid analysis showed albuminocytological dissociation in two patients. All patients had moderate-to-severe disability. They were treated with intravenous immunoglobulin, with stabilization of the disease. Proper monitoring and prompt reporting of such cases is required to ensure safety of the vaccine.

Small fiber neuropathy: Swiss cohort characterization.

INTRODUCTION/AIM: There is currently insufficient clinical and epidemiological data concerning small fiber neuropathy (SFN). This research analyzes data from medical records to determine epidemiology, demographics, clinical characteristics and etiology of SFN. METHODS: This is a retrospective, observational study of sequential patients diagnosed with definite SFN (typical clinical features, normal nerve conduction studies, abnormal epidermal nerve fiber density) from the end of November 2016 to the middle of July 2019 at the Cantonal Hospital Lucerne, central Switzerland. RESULTS: A total of 84 patients (64.3% female) with a mean age of 54.7 y were analyzed. Symptoms had been present in patients for an average of 4.8 y when entering the study. A length dependent clinical pattern was seen in 79.8%. All patients had sensory discomfort. Etiology could not be determined in 35.7% of patients, who were diagnosed with idiopathic SFN; 34.5% of patients had an apparently autoimmune SFN, followed by14.3% of patients with metabolic causes. The estimated incidence was at least 4.4 cases/100.000 inhabitants/y. The minimum prevalence was 131.5 cases/100.000 inhabitants. DISCUSSION: This study indicates significant incidence and prevalence rates of SFN in Switzerland. SFN can vary greatly in its symptoms and severity. Extensive work-up resulted in two thirds of the patients being assigned an etiological association. The largest group of patients could not be etiologically defined, underlining the importance of further research on etiologic identification. We expect increased awareness of the developing field of SFN.

Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature.

Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves. Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR-, ALK-, and PDL1 90%). According to the molecular profile, pembrolizumab was started. After three administrations, the patient developed facial paresis, ptosis, ophthalmoplegia, and dysphonia. As brain metastases and paraneoplastic markers were excluded, a drug-related disorder was suspected and pembrolizumab was discontinued. A nerve conduction study and electromyography excluded signs of neuropathy and myopathy at four limbs, and repetitive nerve stimulation was negative. However, altered blink reflex and nerve facial conduction were consistent with an acute neuropathy of the cranial district. Thus, the patient was treated with two cycles of intravenous immunoglobulins (IVIg), which rapidly allowed improvement of both symptoms and neurophysiological parameters. However, the patient died in October 2018 for a progression of lung tumor. Discussion: Only 16 cases of pembrolizumab-related neuropathies have been described so far. Our case is of particular interest for the isolated involvement of cranial nerves and the prompt response to IVIg. Conclusion: N-irAEs are insidious conditions that require solid knowledge of onco-immunotherapy complications: it is mandatory not to delay any treatment that would potentially modify the course of a neurological complication.

Sindrome de Guillain-Barre variante axonal en pediatria: reporte de caso / Guillain-Barre Syndrome axonal variant in pediatrics: case report

RESUMEN El síndrome de Guillain-Barré es una polirradiculoneuropatía inflamatoria aguda, caracterizada por debilidad simétrica de carácter progresivo, de inicio distal asociado con arreflexia y síntomas sensitivos leves. La variante NMAA es una entidad poco frecuente en América Latina. Se reporta el caso de un paciente de sexo masculino, de seis años, previamente sano, con diagnóstico de síndrome de Guillain-Barré variante axonal, secundario a cuadro de vías aéreas superiores. La importancia del reporte radica en informar al pediatra y a otros profesionales de la salud acerca de la existencia de esta entidad y así aumentar la sospecha diagnóstica, considerando su baja incidencia. Se destaca también la posibilidad de encontrar variabilidad en las formas clínicas típicas de presentación, como lo fue el caso presentado, ya que es un subtipo de la enfermedad que está clásicamente caracterizada como grave, de evolución tórpida y con frecuentes secuelas.

SUMMARY Guillain-Barre syndrome is an acute inflammatory polyradiculoneuropathy characterized by progressive symmetric weakness of distal onset associated with areflexia and mild sensory symptoms. The AMAN variant is a rare entity in Latin America. The case of a 6-year-old male patient, previously healthy, with a diagnosis of Guillain-Barre Syndrome, axonal variant, secondary to upper airway symptoms, is reported. The importance of the report lies in informing the pediatrician and other health professionals about the existence of this entity and thus increasing the diagnostic suspicion considering its low incidence. We also highlight the possibility of finding variability in the typical clinical forms of presentation, as was the case presented, since it is a subtype of the disease that is classically characterized as severe and with torpid evolution. It is also associated with frequent sequelae.

Guillain-Barré Syndrome in a Patient with Sickle Cell Anemia.

Description A 24-year-old African American male with a history of sickle cell anemia (Hb S/S) presented to an outside hospital with acute colitis, acute renal failure and sickle cell crisis and was treated with supportive measures. On day 3 of hospitalization, he developed bilateral ascending paralysis with sacral numbness. Magnetic resonance imaging (MRI) demonstrated epidural lipomatosis, which was attributed as the cause of his paralysis. He was transferred to our facility for neurosurgery evaluation. Based on the physical examination, Guillain-Barré Syndrome (GBS) was suspected. This conclusion lead to a lumbar puncture with cerebrospinal fluid (CSF) analysis that confirmed the diagnosis. He was then treated with intravenous immunoglobulin (IVIg), which resolved his symptoms. We present this case to highlight the importance of a physical exam rather than relying heavily on imaging studies. Physical exam findings lead to a diagnosis, which was then confirmed with appropriate testing.

Immune-Mediated Neuropathies.

The immune-mediated neuropathies are a broad category of diseases differentiated by time course, affected nerve fibers, and disease associations. This article spans the common, well-defined inflammatory demyelinating polyradiculoneuropathies (Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy) to the rarer, acquired demyelinating neuropathy variants (Miller-Fisher syndrome and multifocal motor neuropathy), vasculitic neuropathies, and sensory neuronopathies (dorsal root ganglionopathies). These case studies illustrate the characteristic clinical patterns of the immune-mediated neuropathies encountered in neurologic practice. Recommendations for diagnostic evaluation and treatment approach accompany each case. Prompt recognition of these disorders is imperative; delays in treatment may result in prolonged morbidity and permanent disability.

Neuro-Sjögren: Uncommon or underestimated problem?

OBJECTIVES: Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune background with possible complications from peripheral (PNS) and central nervous system (CNS). The aim of this study was to assess the prevalence and to describe the phenotype of peripheral neuropathies in patients with SS. MATERIALS & METHODS: We studied fifty patients with primary Sjögren's syndrome for peripheral nervous system involvement. All patients underwent neurological and rheumatological examination followed by nerve conduction studies (NCS) of nine peripheral nerves. RESULTS: Thirty-six patients (72%) fulfilled the criteria for the diagnosis of neuropathy. Carpal tunnel syndrome (54%) and axonal sensorimotor neuropathy (22%) were the most common. Neurological symptoms preceded the diagnosis of SS in eight patients. CONCLUSIONS: Peripheral neuropathies are frequent in SS patients. Neurologists should be aware of possible autoimmune causes of neuropathies because clinical manifestations of neuropathy may precede the development of other symptoms of the autoimmune disease.