A 34-year-old female with stiff-person syndrome(SPS)is reported in this paper.She experienced short-term memory impairment and was diagnosed with anti-glutamic add decarboxylase(GAD)autoimmune encephalitis(AE)at the l...A 34-year-old female with stiff-person syndrome(SPS)is reported in this paper.She experienced short-term memory impairment and was diagnosed with anti-glutamic add decarboxylase(GAD)autoimmune encephalitis(AE)at the local hospital.However,after the treatment with intravenous immunoglobulin and highdose glucocorticoids,her symptoms unchanged.Two months later,she was admitted to our hospital due to an unstable gait and persistent leg stiffness,at which point she was diagnosed as anti-GAD AE concomitant with SPS.Her clinical symptoms improved with an increased dose of y-aminobutyric acid(GABA)-enhancing drug and plasma exchange.Anti-GAD antibody-associated AE combined with SPS is extremely rare.Treatment with GABA-enhancing drugs and appropriate immunotherapy can improve the neurological function of patients suffering from the combination of SPS and limbic encephalitis.展开更多
Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with ...Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.展开更多
Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known f...Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.展开更多
Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess ...Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess the levels of FCP, GADA and ICA in subjects below the age of 25 years with DM and compare their levels to differentiate between Autoimmune and Non-Autoimmune Type 1 DM. Methodology: Blood samples of 93 subjects diagnosed with DM, reporting to the tertiary care hospital, were analysed for ICA, GADA and FCP. Receiver operating characteristics (ROC) curves were analysed to check the ability of autoimmune markers, BMI and C-peptide to differentiate between Autoimmune (Ai) and Non-Autoimmune (NonAi) diabetes. Results: 30/93 (32.2%) were positive for anti-GAD ab and/or ICA and categorised as Autoimmune (Ai), the most common antibody being, anti-GAD ab (80%) in them. The level of FCP among Ai compared to NonAi, was significantly low (p 20.75 nmol/l) as a very dependable test for diagnosing Ai, Type 1 DM, in children and young adults. Its sensitivity and specificity are in the range of 86.2% and 96.8% respectively. Low level of C-peptide (Conclusion: This study revealed predominant positivity for anti-GAD ab (80%) among Ai+ patients. ROC analysis shows GADA above 20.75 nmol/l and Fasting C-peptide < 0.36 nmol/l as a good indicator for diagnosing Ai in children and young adults.展开更多
Objective To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD 65 Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD Ab in Chinese patients initially di...Objective To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD 65 Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD Ab in Chinese patients initially diagnosed as non insulin dependent diabetes mellitus (NIDDM) Methods Forty five control subjects and 195 consecutive inpatients initially classified as NIDDM with ≥35 years of age at onset and nonketotic history for >6 months after diagnosis, were recruited In vitro transcripted and translated recombinant human 35 S GAD 65 was used in radioligand assay of GAD Ab Results The overall prevalence of GAD 65 Ab was 14 8% (29/195) in NIDDM patients and 2 2% (1/45) in control subjects, respectively Of the 29 GAD 65 Ab positive patients, 17 (58 6%) were insulin deficient while 12 (41 4%) were non insulin deficient The prevalence of GAD 65 Ab in NIDDM group with age of <40 years at diabetes onset, ketotic history, body mass index (BMI) <21 kg/m 2, were significantly higher than that of corresponding control diabetic subgroups (2 5, 4 1 and 3 2 times, respectively) The sex, duration, symptoms of polyphagia, polydipsia, polyuria and weight loss at onset of the disease were not related to the prevalence of GAD 65 Ab positivity Conclusions In China, patients initially diagnosed as NIDDM may in many cases suffer from LADA Testing by GAD 65 Ab may be of assistance to identifying LADA at the earliest stage of disease展开更多
Central nervous system autoimmunity in the pediatric age group represents an evolving constellation of various syndromes distinct from the adult age group.One of the rarely described pathogenic auto-antibodies(ab)is t...Central nervous system autoimmunity in the pediatric age group represents an evolving constellation of various syndromes distinct from the adult age group.One of the rarely described pathogenic auto-antibodies(ab)is the one directed against glutamic acid decarboxylase(GAD).While its pathogenic role is controversial,literature concerning adult patients abounds with heterogeneous presentations with epilepsy often as part of limbic encephalitis or chronic temporal lobe epilepsy and cerebellar ataxia accompanying endocrinopathies or paraneoplastic disorders.Diagnosis is often delayed until late adulthood.The authors report hitherto under-reported syndromes in the pediatric age group.The first case was a 3-year-old boy with sub-acute myoclonus-ataxia following a flu-like illness akin to para-infectious cerebellitis.The second case was a 7-year-old girl with long-standing chronic extratemporal partial epilepsy and electrical status epilepticus in sleep(ESES)with right hemiparesis and developmental delay.Investigations revealed two-four fold elevations in titres of GAD-65-ab.The absence of systemic diseases like diabetes and the dramatic clinical response to steroids as well as intravenous immunoglobulin in both the cases argued for GAD-ab mediated neuronal injury rather than a chance association.The concern exists regarding other potentially co-existent auto-ab to gamma-amino butyric acid and glycine receptors,and demonstration of intrathecal synthesis of GAD-ab would be ideal.This entity should be contemplated in children presenting with acute/sub-acute onset episodic or progressive ataxia or refractory cryptogenic focal epilepsy syndromes,epileptic encephalopathy such as ESES and worsening neurological deficits.These children ought to be maintained on regular follow-up for monitoring evolution of other autoimmune disorders in adult life.展开更多
Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D)...Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.展开更多
文摘A 34-year-old female with stiff-person syndrome(SPS)is reported in this paper.She experienced short-term memory impairment and was diagnosed with anti-glutamic add decarboxylase(GAD)autoimmune encephalitis(AE)at the local hospital.However,after the treatment with intravenous immunoglobulin and highdose glucocorticoids,her symptoms unchanged.Two months later,she was admitted to our hospital due to an unstable gait and persistent leg stiffness,at which point she was diagnosed as anti-GAD AE concomitant with SPS.Her clinical symptoms improved with an increased dose of y-aminobutyric acid(GABA)-enhancing drug and plasma exchange.Anti-GAD antibody-associated AE combined with SPS is extremely rare.Treatment with GABA-enhancing drugs and appropriate immunotherapy can improve the neurological function of patients suffering from the combination of SPS and limbic encephalitis.
基金Supported by The European Union-NextGenerationEU,Through The National Recov-ery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.
文摘Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.
文摘Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess the levels of FCP, GADA and ICA in subjects below the age of 25 years with DM and compare their levels to differentiate between Autoimmune and Non-Autoimmune Type 1 DM. Methodology: Blood samples of 93 subjects diagnosed with DM, reporting to the tertiary care hospital, were analysed for ICA, GADA and FCP. Receiver operating characteristics (ROC) curves were analysed to check the ability of autoimmune markers, BMI and C-peptide to differentiate between Autoimmune (Ai) and Non-Autoimmune (NonAi) diabetes. Results: 30/93 (32.2%) were positive for anti-GAD ab and/or ICA and categorised as Autoimmune (Ai), the most common antibody being, anti-GAD ab (80%) in them. The level of FCP among Ai compared to NonAi, was significantly low (p 20.75 nmol/l) as a very dependable test for diagnosing Ai, Type 1 DM, in children and young adults. Its sensitivity and specificity are in the range of 86.2% and 96.8% respectively. Low level of C-peptide (Conclusion: This study revealed predominant positivity for anti-GAD ab (80%) among Ai+ patients. ROC analysis shows GADA above 20.75 nmol/l and Fasting C-peptide < 0.36 nmol/l as a good indicator for diagnosing Ai in children and young adults.
文摘Objective To investigate the diagnostic role of antibodies to glutamic acid decarboxylase (GAD 65 Ab) in latent autoimmune diabetes of adults (LADA) and the frequency of GAD Ab in Chinese patients initially diagnosed as non insulin dependent diabetes mellitus (NIDDM) Methods Forty five control subjects and 195 consecutive inpatients initially classified as NIDDM with ≥35 years of age at onset and nonketotic history for >6 months after diagnosis, were recruited In vitro transcripted and translated recombinant human 35 S GAD 65 was used in radioligand assay of GAD Ab Results The overall prevalence of GAD 65 Ab was 14 8% (29/195) in NIDDM patients and 2 2% (1/45) in control subjects, respectively Of the 29 GAD 65 Ab positive patients, 17 (58 6%) were insulin deficient while 12 (41 4%) were non insulin deficient The prevalence of GAD 65 Ab in NIDDM group with age of <40 years at diabetes onset, ketotic history, body mass index (BMI) <21 kg/m 2, were significantly higher than that of corresponding control diabetic subgroups (2 5, 4 1 and 3 2 times, respectively) The sex, duration, symptoms of polyphagia, polydipsia, polyuria and weight loss at onset of the disease were not related to the prevalence of GAD 65 Ab positivity Conclusions In China, patients initially diagnosed as NIDDM may in many cases suffer from LADA Testing by GAD 65 Ab may be of assistance to identifying LADA at the earliest stage of disease
文摘Central nervous system autoimmunity in the pediatric age group represents an evolving constellation of various syndromes distinct from the adult age group.One of the rarely described pathogenic auto-antibodies(ab)is the one directed against glutamic acid decarboxylase(GAD).While its pathogenic role is controversial,literature concerning adult patients abounds with heterogeneous presentations with epilepsy often as part of limbic encephalitis or chronic temporal lobe epilepsy and cerebellar ataxia accompanying endocrinopathies or paraneoplastic disorders.Diagnosis is often delayed until late adulthood.The authors report hitherto under-reported syndromes in the pediatric age group.The first case was a 3-year-old boy with sub-acute myoclonus-ataxia following a flu-like illness akin to para-infectious cerebellitis.The second case was a 7-year-old girl with long-standing chronic extratemporal partial epilepsy and electrical status epilepticus in sleep(ESES)with right hemiparesis and developmental delay.Investigations revealed two-four fold elevations in titres of GAD-65-ab.The absence of systemic diseases like diabetes and the dramatic clinical response to steroids as well as intravenous immunoglobulin in both the cases argued for GAD-ab mediated neuronal injury rather than a chance association.The concern exists regarding other potentially co-existent auto-ab to gamma-amino butyric acid and glycine receptors,and demonstration of intrathecal synthesis of GAD-ab would be ideal.This entity should be contemplated in children presenting with acute/sub-acute onset episodic or progressive ataxia or refractory cryptogenic focal epilepsy syndromes,epileptic encephalopathy such as ESES and worsening neurological deficits.These children ought to be maintained on regular follow-up for monitoring evolution of other autoimmune disorders in adult life.
文摘Background Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.