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Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (Pâ ≤â 0.001), plasma cells (Pâ ≤â 0.001) and regulatory B cells (Pâ <â 0.05), and an elevation in switched memory B cells (Pâ ≤â 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (Pâ <â 0.05 and Pâ ≤â 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (râ =â -0.51, Pâ <â 0.05) and a moderate positive correlation with plasma cell ratios (râ =â 0.46, Pâ <â 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (râ =â 0.54, Pâ <â 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.
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Subpopulações de Linfócitos B , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/genética , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Leucócitos Mononucleares/metabolismo , Citocinas/genética , Subpopulações de Linfócitos B/metabolismo , Interleucina-10/genética , Interleucina-6/genéticaRESUMO
BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul. METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed. RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.
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Síndrome de Guillain-Barré , Humanos , Estudos Prospectivos , Condução Nervosa/fisiologia , Eletrodiagnóstico/métodos , Gangliosídeos , AnticorposRESUMO
The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).
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Esclerose Lateral Amiotrófica/genética , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Internet , Fenótipo , Turquia , Sequenciamento Completo do GenomaRESUMO
This study aims to investigate genetic susceptibility to early-onset and late-onset anti-acetylcholine receptor antibody positive myasthenia gravis (EOMG and LOMG) and anti-muscle specific kinase antibody positive MG (MuSK-MG) at genome-wide level in a single population. Using a custom-designed array and imputing additional variants and the classical HLA alleles in 398 patients, we detected distinct associations. In EOMG, rs113519545 in the HLA class I region (OR=5.71 [3.77-8.66], P=2.24×10(-16)), HLA-B*08:01 (OR=7.04 [3.95-12.52], P=3.34×10(-11)) and HLA-C*07:01 (OR=2.74 [1.97-3.81], P=2.07(-9)), in LOMG, rs111256513 in the HLA class II region (OR=2.22 [1.59-3.09], P=2.48×10(-6)) and in MuSK-MG, an intronic variant within HLA-DQB1 (rs68081734, OR=5.86, P=2.25×10(-14)) and HLA-DQB1*05:02 (OR=8.56, P=6.88×10(-13)) revealed the most significant associations for genome-wide significance. Differential genetic susceptibility within the HLA to EOMG, LOMG and MuSK-MG has been established in a population from Turkey.
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Heterogeneidade Genética , Antígenos HLA-B/imunologia , Antígenos HLA-C/imunologia , Cadeias beta de HLA-DQ/imunologia , Miastenia Gravis/imunologia , Idade de Início , Alelos , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Humanos , Desequilíbrio de Ligação , Masculino , Miastenia Gravis/epidemiologia , Miastenia Gravis/genética , Polimorfismo de Nucleotídeo Único , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Turquia/epidemiologiaRESUMO
AIM: In this study, cognitive functions of 9 patients developing parkinsonism due to chronic manganese intoxication by intravenous methcathinone solution were investigated using detailed neuropsychometric tests. METHOD: Attention deficit, verbal and nonverbal memory, visuospatial function, constructive ability, language, and executive (frontal) functions of 9 patients who were admitted to our clinic with manifestations of chronic manganese intoxication and 9 control subjects were assessed using neuropsychometric tests. Two years later, detailed repeat neuropsychometric tests were performed in the patient group. The results were evaluated using the χ(2) test, Fisher's exact probability test, Student's t test and the Mann-Whitney U test. RESULTS: While there was no statistically significant difference between the two groups in language functions, visuospatial functions and constructive ability, a statistically significant difference was noted between both groups regarding attention (p = 0.032), calculation (p = 0.004), recall and recognition domains of verbal memory, nonverbal memory (p = 0.021) and some domains of frontal functions (Stroop-5 and spontaneous recovery) (p = 0.022 and 0.012). Repeat neuropsychometric test results of the patients were not statistically significant 2 years later. CONCLUSION: It has been observed that cognitive dysfunction seen in parkinsonism secondary to chronic manganese intoxication may be long-lasting and may not recover as observed in motor dysfunction.
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Transtornos Cognitivos/induzido quimicamente , Intoxicação por Manganês/complicações , Transtornos Parkinsonianos/induzido quimicamente , Propiofenonas/intoxicação , Psicotrópicos/intoxicação , Adulto , Humanos , Masculino , Testes Neuropsicológicos , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto JovemRESUMO
Epstein-Barr virus (EBV) has been associated with a plethora of neurological manifestations including polyneuropathy and polyradiculopathy. A 27-year-old man with a recent upper respiratory system infection presented with difficulty in walking. His neurological examination revealed reduced muscle strength in both proximal and distal lower limb muscles without sensory and autonomic signs. Needle electromyography showed abnormal spontaneous activity and reduced recruitment of motor units in muscles innervated by multiple lumbo-sacral roots. Cerebrospinal examination showed increased protein levels with normal cell counts. While spinal MRI was normal, whole-body CT and PET examination showed disseminated lymph node enlargement. Anti-EBV viral capsid antigen and anti-nuclear antigen IgG but not IgM was positive, whereas EBV PCR was negative in blood. Analysis of inguinal lymph node biopsy showed reactive lymphoid hyperplasia and EBV DNA. Leucine-rich glioma-inactivated protein 1 (LGI1) antibody was found in serum but not in CSF. All clinical, imaging, and electrophysiological findings improved following steroid and intravenous immunoglobulin treatment. These findings suggested the acute involvement of lumbo-sacral spinal roots and/or motor neurons. Purely motor polyradiculopathy has been reported in both EBV-positive and LGI1 antibody-positive patients, and EBV infection is known to precede different autoimmune manifestations. Whether EBV infection may trigger LGI1 autoimmunity and cause involvement of spinal motor roots and/or motor neurons needs to be further studied.
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Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4+ T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4+ T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4+ T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4+ T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-γ production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4+ T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5+ and CXCR5- CD4+ T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5+PD-1+ in CD4+ T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4+T cells are identified mainly as PD-1+ or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucina-17/biossíntese , Interleucina-4/biossíntese , Interleucinas/biossíntese , Miastenia Gravis/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Feminino , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/terapia , Receptores Colinérgicos/imunologia , Transdução de Sinais/efeitos dos fármacos , Adulto JovemAssuntos
Adenocarcinoma/complicações , Autoanticorpos/efeitos adversos , Síndrome de Guillain-Barré/etiologia , Neoplasias Pulmonares/complicações , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Adenocarcinoma/imunologia , Adenocarcinoma de Pulmão , Adulto , Autoanticorpos/biossíntese , Síndrome de Guillain-Barré/imunologia , Células HEK293 , Humanos , Neoplasias Pulmonares/imunologia , MasculinoRESUMO
INTRODUCTION: Activation of the trigeminovascular system and sensitization of brainstem trigeminal nuclei play a significant role in the physiopathology of migraine. Our aim was to investigate blink reflex (BR) and its recovery in episodic and chronic migraine patients. METHODS: Twenty-eight chronic migraine patients, thirty-two episodic migraine without aura patients and thirty healthy controls were included in the study. The study was performed using a portable electromyography device with a software specifically prepared for BR. Blink reflex assessments were performed in patients during the pain-free period and in healthy controls using the 'standard method - double stimulation' technique in 200 ms, 500 ms, 1000 ms, 2000 ms, and 5000 ms intervals. RESULTS: Blink reflex recovery was significantly increased in both patient groups as compared to the control group in 200 ms interstimulus interval (ISI) on both sides (p<0.005). Moreover, when it was compared to the control group, recovery was also significantly increased in the chronic migraine group in 2000 ms ISI on the right side and in 5000 ms ISI on the left side as well as in 500 and 1000 ms ISIs on the left side in the migraine without aura group (p<0.002, p<0.003). R2 recovery curve was noted to be higher in both patient groups as compared to the control group, although could not be demonstrated statistically in all intervals. A statistically significant increase was observed in the migraine group without auras compared with the controls (p <0,037, p <0,011) in the left side at 500 and 1000 ms ISIs. For all intervals in our study, although the increase in recovery was not statistically significant, it was noted that the R2 recovery curve was higher in the patient groups, with respect to the normals. The increase in R2 recovery noted in both patient groups suggested increased sensitization of the trigeminal structures. Significantly increased recovery in low ISI (200 ms) in the two patient groups as compared to the control group raised the thought that the migraine brain goes through two different excitability periods (ictal and interictal). CONCLUSION: In conclusion, similar to the previous studies, the findings of this study suggested that there was a reduction in central inhibitory mechanisms during interictal period in migraine patients.
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The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.
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Doença de Depósito de Glicogênio Tipo II/epidemiologia , Idade de Início , Creatina Quinase/sangue , Bases de Dados Factuais , Doença de Depósito de Glicogênio Tipo II/sangue , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Humanos , Programas de Rastreamento , Prevalência , Sistema de Registros , Turquia/epidemiologiaRESUMO
INTRODUCTION: Cramp-fasciculation syndrome (CFS) is a rare peripheral nerve hyperexcitability syndrome. There are only a few reports on clinical and serological profile of a CFS cohort that was followed up by a single outpatient clinic. METHODS: Clinical, electrophysiological, and serological features of 6 CFS patients (5 men, 1 woman; 27-65 years old) were investigated. RESULTS: All patients presented with cramps, fasciculations, muscle pain, and autonomic symptoms, and 2 also reported numbness and burning sensation in limbs, suggestive of neuropathic pain. Antibodies to uncharacterized voltage-gated potassium channel (VGKC)-complex proteins were found in 2 patients and to contactin-associated protein-like 2 (CASPR2) in 1 patient. None of the patients had a tumor. Most of the patients revealed prolonged after-discharges following tibial nerve stimulation. Nerve conduction studies and R-R interval variability tests were normal, whereas sympathetic skin responses were increased in amplitude in 3 seronegative patients. Five patients showed favorable response to carbamazepine or pregabalin treatment, whereas 1 VGKC-antibody-positive patient was resistant to carbamazepine and immunosuppressant treatment. CONCLUSION: Neuropathic pain and VGKC-complex antibodies may be encountered in CFS patients. Although autonomic symptoms are commonly found in CFS, routine autonomic system tests which are done in electrophysiology laboratories might yield normal results.
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INTRODUCTION: Various causes influence the etiology of tarsal tunnel syndrome including systemic diseases with progressive neuropathy, such as diabetes. PRESENTATION OF CASE: We describe a 52-year-old male patient with complaints of numbness, burning sensation and pain in both feet. The laboratory results showed that the patient had uncontrolled diabetes, and the EMG showed distal symmetrical sensory-motor neuropathy and nerve entrapment at the right. Ultrasonography and MRI showed the cyst in relation to medial plantar nerve, and edema- moderate atrophy were observed at the distal muscles of the foot. DISCUSSION: Foot neuropathy in diabetic patients is a complex process. So, in planning the initial treatment, medical or surgical therapy is selected based on the location and type of the pathology. Foot deformities can be corrected with resting, anti-inflammatory treatment, appropriate shoes, orthesis and socks, and if required, ankle stabilization can be attempted. If the patient is still unresponsive, surgical treatment may be applied. CONCLUSION: It is essential to investigate more localized reasons like tarsal tunnel syndrome that may mimic diabetic neuropathy, should be treated primarily.
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B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.
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Linfócitos B/imunologia , Linfócitos B/metabolismo , Interleucina-10/biossíntese , Interleucina-6/biossíntese , Miastenia Gravis/imunologia , Miastenia Gravis/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Criança , Citocinas/biossíntese , Citocinas/genética , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Imunossupressores/uso terapêutico , Interleucina-10/genética , Interleucina-6/genética , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/diagnóstico , Miastenia Gravis/genética , Miastenia Gravis/terapia , Fenótipo , Receptores Colinérgicos/imunologia , Fator de Necrose Tumoral alfa/genética , Adulto JovemRESUMO
Regulatory T cells were investigated in early-onset (EO) and late-onset (LO) myasthenia gravis patients with anti-acetylcholine receptor antibody (AChR-MG). Alterations in PD-1 and PD-L1 on CD4(+)CD25(++) (Treg) and responder T cells (Tresp, CD4(+)CD25(-)) were observed in LOMG patients. GITR was decreased on CD4(+)CD25(++) of all patients. Decrease of FOXP3 was associated with lower phosphorylation of STAT5.1,25-dihydroxyvitamin D3 (VitD3) increased suppression in co-culture with a stronger effect in patients by acting possibly both on cell groups. Changes in surface molecules and intracellular pathways contribute to the defects of Treg in non-thymomatous AChR-MG and VitD3 can have modulatory effects.
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Linfócitos T CD4-Positivos/fisiologia , Calcitriol/farmacologia , Subunidade alfa de Receptor de Interleucina-2/fisiologia , Miastenia Gravis/metabolismo , Fenótipo , Fator de Transcrição STAT5/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients differentially.
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Autoanticorpos/imunologia , Citocinas/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Adulto , Complexo CD3/metabolismo , Linfócitos T CD4-Positivos/imunologia , Ligante de CD40/genética , Ligante de CD40/metabolismo , Separação Celular , Demografia , Feminino , Humanos , Terapia de Imunossupressão , Subunidade p40 da Interleucina-12/sangue , Leucócitos Mononucleares/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The frequency of amyotrophic lateral sclerosis (ALS) mutations has been extensively investigated in several populations; however, a systematic analysis in Turkish cases has not been reported so far. In this study, we screened 477 ALS patients for mutations, including 116 familial ALS patients from 82 families and 361 sporadic ALS (sALS) cases. Patients were genotyped for C9orf72 (18.3%), SOD1 (12.2%), FUS (5%), TARDBP (3.7%), and UBQLN2 (2.4%) gene mutations, which together account for approximately 40% of familial ALS in Turkey. No SOD1 mutations were detected in sALS patients; however, C9orf72 (3.1%) and UBQLN2 (0.6%) explained 3.7% of sALS in the population. Exome sequencing revealed mutations in OPTN, SPG11, DJ1, PLEKHG5, SYNE1, TRPM7, and SQSTM1 genes, many of them novel. The spectrum of mutations reflect both the distinct genetic background and the heterogeneous nature of the Turkish ALS population.
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Esclerose Lateral Amiotrófica/genética , Estudos de Associação Genética , Mutação/genética , Proteínas/genética , Proteína FUS de Ligação a RNA/genética , Superóxido Dismutase/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Proteínas Relacionadas à Autofagia , Proteína C9orf72 , Proteínas de Ciclo Celular/genética , Proteínas do Citoesqueleto , Proteínas de Ligação a DNA/genética , Exoma/genética , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Proteína Desglicase DJ-1 , Proteínas Serina-Treonina Quinases/genética , Proteína Sequestossoma-1 , Superóxido Dismutase-1 , Canais de Cátion TRPM/genética , Fator de Transcrição TFIIIA/genética , Turquia , Ubiquitinas/genética , Adulto JovemRESUMO
OBJECTIVE: Somatosensory evoked potential (SSEP) abnormalities were reported in patients with ankylosing spondylitis (AS). This study aimed to investigate SSEP abnormalities and its relation with clinical findings in AS patients. MATERIALS AND METHODS: The study included 26 patients with AS and 17 age-matched health volunteers (Control for SSEP). Median nerve SSEP findings were normal in all AS cases. RESULTS: However, delayed latency and/or very low amplitude of tibial nerve SSEP was found in 20 (76.9%) AS patients. There were significant correlations between tibial SSEP latency and disease duration (R=0.433 to 0.635). There was also an inverse correlation between tibial SSEP amplitude and disease duration (R=-0.429, p=0.047). Serum estradiol level, hip total bone mineral density, The Bath Ankylosing Spondylitis Functional Index (BASFI) score and Beck depression score were significantly lower in AS patients with SSEP abnormalities (37.3±10.8 pg/mL, 0.916±0.123 g/cm(2), 35.0±27.9, 12.8±8.4, respectively) than in AS patients without SSEP abnormalities (53.7±12.3 pg/mL, 1.103±0.197 g/cm(2), 64.8±15.5, 24.8±10.1, respectively). CONCLUSION: Significant inverse correlations between SSEP latencies and dehydroepiandrosterone sulphate (DHEAS) levels were found (R=-0.400 to -0.713). There were also significant inverse correlation between SSEP latencies and DHEAS/oestrogen index (R=-0.596 to -0.868), and between SSEP latencies and DHEAS/Progesterone index (R=-0.467 to -0.685). As a conclusion, this study indicates that tibial nerve SSEP abnormalities are common in patients with AS and there are significant correlations between clinical findings of AS and SSEP abnormalities.
Assuntos
Atrofias Musculares Espinais da Infância/complicações , Adolescente , Medula Cervical/anormalidades , Medula Cervical/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Compressão da Medula Espinal/complicações , Compressão da Medula Espinal/diagnóstico por imagem , Atrofias Musculares Espinais da Infância/diagnóstico por imagemRESUMO
OBJECTIVE: Electrophysiological diagnosis of ulnar nerve entrapment at the wrist is sometimes difficult. The aim was to evaluate the diagnostic role of ulnar nerve stimulation above and below the Guyon channel in ulnar nerve entrapment at the wrist. METHODS: Supramaximal ulnar nerve stimulation at the wrist and palm, in addition to the standard nerve conduction studies, in 10 patients with ulnar nerve entrapment at the wrist and 40 controls. RESULTS: Motor latencies to the first dorsal interosseous muscle with wrist stimulation were prolonged unilaterally in six and bilaterally in four patients. Palmar stimulation showed partial conduction blocks on the more symptomatic side in all. In two bilateral cases, there were 28.8% and 44.3% amplitude loss on the less symptomatic side. Motor responses elicited with palm stimulation were also found to have prolonged latencies and decreased amplitudes. CONCLUSIONS: Stimulation of the deep branch of the ulnar nerve can expand the information about ulnar nerve entrapment at the wrist by providing evidence about its nature, prognosis, precise localization, and distal extent.