Funny "123, wooden man", not funny "stiff man syndrome"!

I believe that many people have seen a game link "123, wooden man" in a variety show In their spare time, watching such entertainment programs can really relax people However, in real life, if you suffer from this disease similar to "wooden man", it can't be easy.. Today we'll talk about this disease similar to "wooden man" ~ "stiff man syndrome"! What is stiff person syndrome??? Firstly, stiff person syndrome (SPS) is a rare autoimmune disease of central nervous system As early as 1956, moersch and Woltman followed up 14 patients with paroxysmal myotonic spasm and walking difficulty, found the disease and named it "stiff mansyndrome" After that, Gordon et al Described and summarized the clinical characteristics of the disease in 1966, and formulated the diagnostic criteria Later, because women patients are more common in clinic, Blum and others renamed it "stiff person syndrome" For SPS, the incidence rate is about 1/100 ~2/100, the age of onset is about 20~50 years old, and the incidence rate of female is about 2~3 times of that of male The main manifestations of SPS are progressive, fluctuating, stiff pain or painless spasm of the muscles in the middle axis of the body; it is easy to induce muscle spasm when stimulated by external lights, sounds or emotions, and most of them are accompanied by insomnia, depression, restlessness, hallucination, delusion, etc Its clinical characteristics are as follows: fluctuation, paroxysmal muscle spasm, plate rigidity, muscle ache, muscle rigidity as stone, antagonistic muscle contraction at the same time, active movement restriction, activity reduction, turning over difficulty, getting up difficulty, gait instability, dysuria, hyperhidrosis, etc., while intelligence is normal Sudden stimulation can cause painful spasm in SPS patients, but disappear during sleep In foreign countries, it is generally believed that the disease is more common in female population, most of which are recessive onset and chronic volatility progress However, in China, SPS is more common in young men, with more acute and subacute types and rapid progress in the course of disease What is the pathogenesis??? At present, the etiology of the disease is not clear enough, mainly including genetics, virus infection, autoimmunity and other theories In genetic research, the genetic susceptibility of HLA in SPS patients has been reported DQB1 * 0201 and DRB1 * 0301 alleles exist in 70% of SPS patients, while only 37% in the control group At the same time, virus infection may also be one of the causes of SPS Some studies have shown that GAD65 specific T cells will cross react with the main DNA binding protein human cytomegalovirus peptide In addition, dendritic cells can process the epitope derived from HCMV, and GAD65 reactive T cells can recognize the epitope, so it is speculated that T lymphocytes play an important role in SPS patients In recent years, the research mainly focuses on the autoimmune response The research shows that for glutamate decarboxylase (GAD), autoimmunity may participate in the occurrence of SPS GAD is the rate limiting enzyme for the transformation of glutamate into the inhibitory neurotransmitter γ - aminobutyric acid (GABA) There are two subtypes of GAD65 and GAD67 In 1988, solidena et al Found GAD antibody, GAD antibody mainly combined with GAD65, about 60% ~ 80% of typical SPS patients serum GAD65 antibody concentration significantly increased When the serum of SPS patients is input into the animal model, the animal will also show some motor and neuropsychological symptoms of SPS However, the clinical severity and therapeutic effect of SPS are not necessarily related to the concentration of GAD in CSF and serum, and the location of GAD in cells makes it relatively difficult to reach antigens, so the pathogenicity of this aspect is not clear enough What is the drug treatment of SPS??? Because the pathogenesis of SPS is not clear, the treatment of SPS is usually based on empirical drugs, and there is no unified international standard for SPS Through literature review, it is found that there are two kinds of drugs worth exploring, one is benzodiazepine drugs for symptomatic treatment, the other is monoclonal antibody drugs for immunity Diazepam, as a representative of benzodiazepines, can significantly improve the tonic clonus of skeletal muscle by acting on GABA-A receptor alone or in combination with baclofen, a bone relaxant A study of 99 SPS patients found that diazepam (average dose 40 mg / D) could improve the symptoms of patients continuously, with an effective rate of 100% However, although the effect of diazepam and other receptor agonists is accurate, but due to the poor drug tolerance, it is usually necessary to gradually increase the dose, prone to drowsiness, unclear language, ataxia and other adverse reactions In addition to diazepam, clonazepam in this kind of drugs has a stronger effect Its muscle relaxant effect is at least 5-10 times stronger than diazepam and nitrazepam, but the half-life of clonazepam is 28-49h, the metabolic time is relatively long, and the accumulation effect in the body will be enhanced, so that the patient's muscle tension will be significantly reduced, and adverse reactions such as muscle strength and muscle tension are prone to occur Compared with the "symptomatic" treatment of benzodiazepines, immunomodulatory therapy is the focus of SPS treatment in recent years, which is mainly for the treatment of patients with GAD antibody positive SPS In general, there are GAD antibodies in SPS patients, and GAD is located in the cytoplasm of GABAergic nerve endings, which is the rate limiting enzyme for GABA synthesis At present, it has been confirmed that rituxan, a monoclonal antibody of CD20, can eliminate GAD antibody by destroying B lymphocytes, and completely cure individual cases of SPS, especially the typical SPS with positive perm and GAD antibody, the tumor like SPS with positive amphiphysin antibody or the SPS with poor immunotherapy effect Of course, the role of GAD antibody in the pathogenesis of SPS needs to be further studied Whether anti GAD antibody only selectively affects some GABA energy pathways, and whether there are other antibodies of inhibitory neurotransmitters need to be further studied Some feelings!!! Maybe it's an occupational disease The "curiosity" about SPS can be inspired by an entertainment program! Yes, if people are not out of games and entertainment, but because of diseases, they will become real "wooden people" in life I believe that both parties and onlookers will have great helplessness Therefore, to sum up this article, I hope that more people can pay attention to this disease, and more research can go deep into it, so that "wooden man" will always be a game in the future, rather than helpless!