Rituximab in AChR subtype of myasthenia gravis: systematic review.
Di Stefano V, Lupica A, Rispoli MG, Di Muzio A, Brighina F, Rodolico C.
JNNP 2020; 91:392-395.
Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype.
The authors undertook a literature search during the period of 1999-2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients’ evaluation, ranging from a minimum of two to a maximum of three cycles.
Rituximab led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with rituximab appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed.
Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment.
It is even true that at the extreme end of neurological practice, there are conditions that literally turn a deaf ear to all our entreaties, brush off everything we hurl at them, taunt us with reckless abandon, and run relentlessly mortal courses. Such is the dismal state of affairs with diseases such as rabies encephalitis, Creutzfeldt Jakob disease (CJD), and motor neurone disease (MND).
But beyond just treatment, what patients really want is total cure. And neurologists can lay claim to this as well. Some diseases of the nervous system can indeed be permanently remedied, their victims requiring no long-term medications to maintain the cure. To prove this, here are our 10 most eminently curable neurological disorders, linked to their treatment checklists.
It is important to note that curable neurological disorders are also potentially serious, and do carry the risk for serious complications, and even death, if not treated early and adequately. You may check out our previous blog posts to see the dark side of these disorders:
HLA and MuSK-positive myasthenia gravis: a systemic review and meta-analysis
Hong Y, Li HF, Romi F, Skeie GO, Gilhus NE.
Acta Neurol Scand 2018 (Epub ahead of print)
Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle-specific tyrosine kinase (MuSK) antibodies accounts for 1%-10% of all MG patients. We conducted a meta-analysis to evaluate the association between HLA genes and MuSK-MG susceptibility.
Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in MuSK-MG patients and healthy controls were extracted from each included study.
The meta-analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK-MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05). Haplotype analysis showed that these DQB1 and DRB1 alleles were closely linked, forming both risk (DQ5-DR14, DQ5-DR16, P < .0001) and protective (DQ3-DR4, DQ3-DR11, P < .05) haplotypes.
The distinct genetic patterns of MuSK-MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of MuSK-MG patients.
Muscle specific kinase (MuSK) myasthenia gravis (MG, MuSK-MG) is a rare subgroup of MG affecting mainly women during childbearing years. We investigated the influence of pregnancy in the course of MuSK-MG and pregnancy outcomes in females with MuSK-MG.
A multicentre cohort of 17 women with MuSK-MG was studied retrospectively; 13 of them with ≥1 pregnancy. MuSK-MG onset age was 35,4 years; 23,0% had other autoimmune disorder; 46,2% were treatment refractory. Thirteen women experienced 27 pregnancies, either after MG onset (group I) (n = 4; maternal age at conception = 29.8 years) or before MG onset (group II) (n = 23; maternal age at conception = 26.2 years).
In group I pregnancy occurred in average 9.8 years after the MG onset; it occurred in average 17.0 years before MG in group II. In group I, all were on steroids at time of conception, one on azathioprine and another receiving IVIG regularly. There were mild exacerbations that responded to treatment adjustments. There were no relapses in the 12 months following the delivery. There was no pre-eclampsia, birth defects or stillbirths in either group; 3 miscarriages in group II. One case of neonatal MG was recorded.
In this small series, pregnancy did not seem to precipitate MuSK-MG or to have a major influence in the MuSK-MG course, and there was no apparent negative impact in pregnancy outcomes in those where pregnancy followed the MG onset. The weight was lower in the newborn of the group I mothers, although none had low birth weight.
Clinical outcome and predictive factors of postoperative myasthenic crisis in 173 thymomatous myasthenia gravis patients
Li Y, Wang H, Chen P, Chen Z, Su C, Luo C, Feng H, Liu W.
Int J Neurosci 2018; 128:103-109.
Thymectomy is the first-line therapy for thymomatous myasthenia gravis patients. The aim of this study is to explore the clinical outcome and predictors of postoperative myasthenic crisis (POMC) in these patients.
Clinical data of 173 thymomatous myasthenia gravis patients undergoing thymectomy from January 2000 to March 2013 were, retrospectively reviewed. Variables potentially affecting the occurrence of POMC were evaluated using binary logistic regression analysis. The difference in survival was determined by the log-rank test.
Fifty-one patients experienced POMC. Univariate analysis revealed that events significantly associated with increased risk of POMC include symptom duration before operation >2.75months, preoperative bulbar symptoms, incomplete resection, operation time ≥122.5 min and advanced stages (stage III or IV). Multivariate logistic regression analysis showed that preoperative bulbar symptoms (OR = 3.207 [1.413-7.278]; P = 0.005) and incomplete resection (OR = 4.182 [1.332-13.135]; P = 0.014) were independent risk factors for POMC. Twenty-eight patients (16.9%) died during the follow-up. The log-rank test revealed survival for patients with POMC was significantly worse than that for patients without POMC (P = 0.042).
The important risk factors for developing POMC in thymomatous myasthenia gravis patients include the preoperative bulbar symptoms and incomplete resection of thymoma. Moreover, the patients with POMC had a worse prognosis compared with patients without POMC. Our study highlights the need of appropriate preoperative management of thymomatous myasthenia gravis patients to prevent the occurrence of POMC.
One may be forgiven for thinking that neurology is all about neuroinflammatory and neurodegenerative diseases. This is because these disorders seem to get a lot of attention. But nothing could be further from the truth-globally, infections impose a heavier burden on neurological practice than say Multiple Sclerosis (MS) or Parkinson’s disease (PD). And medical advances have done very little to deter all sorts of creatures from invading the nervous system.
The major types of organisms that infect the nervous system are viruses and bacteria, but fungi and parasites also take their toll. In this blog we will focus on the 7 most devastating viral neurological infections.
Encephalitis is infection of the brain substance, as opposed to meningitis which is infection of the covering of the brain. Viral encephalitis, for some reason, tends to favour the temporal lobes of the brain causing seizures and memory problems, amongst other symptoms. The main villain responsible for viral encephalitis is herpes simplex type 1 (HSV1), but almost every other virus can carry out the job with deadly precision. The list is long and includes geographically specific viruses as West Nile and Japanese B. Check out the full list of causesof viral encephalitis and its management.
Hepatitis E virus is just emerging as a scourge of neurology. It is particularly villainous because of its protean manifestations, from Guillain Barre syndrome (GBS) to neuralgic amyotrophy (brachial neuritis), from transverse myelitis to idiopathic intracranial hypertension (IIH). Check out thefull neurological manifestations of HEV.
Influenza is bad, and H1N1 is a particularly nasty variant. This subtype of Influenza A is epidemic in pigs and birds, and unleashes havoc when it crosses over to humans. Its nervous system manifestations include encephalopathy, Guillain Barre syndrome (GBS), acute demyelinating encephalomyelopathy (ADEM), and stroke. Not one to be treated lightly at all. Check out everythingabout Influenza H1N1 and the different ways influenzaaffects the nervous system.
This new kid on the infection block is fast establishing itself as a menace. Apart from causing myelitis, meningoencephalitis, encephalitis, encephalomyelitis, Guillain-Barre syndrome (GBS), and myasthenia gravis (MG), it is responsible for a variety of congenital defects, particularly microcephaly. Zika virus pathology and management are extensively covered in neurochecklists. Or check out 20things we now know for certain about the Zika virusonour sister blog, The Neurology Lounge.
This ancient virus gained recent notoriety when it ravaged a large section of West Africa, sending chilling waves across the world. It is an RNA filovirus whose main reservoir is bats. It causes, among other things, an encephalitis and meningoencephalitis. It appears to be on vacation in the meantme, but it will surely rear its ugly head sometime soon. Check out the comprehensive clinical features and management of Ebola virus disease on neurochecklists.
The varicella virus must take the prize for the most diverse ways a virus affects the nervous system. Neurochecklists has listed >20 neurological manifestations of VZV, ranging from herpes zoster to post herpetic neuralgia (PHN), from meningitis to encephalitis. VZV also causes all forms of cranial and peripheral neropathy, and may result in stroke, aneurysms, and giant cell arteritis (GCA). Not to mention the curiously named progressive outer retinal necrosis (just don’t mention its acronym!). Check out thefull VZV on neurochecklists.
Check out the other deadly viral neurological infections on neurochecklists:
Zika virus infection and myasthenia gravis: report of 2 cases
Molko N, Simon O, Guyon D, Biron A, Dupont-Rouzeyrol M, Gourinat AC.
Neurology 2017; 88:1097-1098.
Zika virus (ZIKV) infection is known as a benign infection usually presenting as an influenza-like illness. However, clusters of microcephaly cases and other neurologic disorders following ZIKV outbreaks in Brazil, as well as a cluster of Guillain-Barré syndrome following an outbreak in French Polynesia in 2014, constitute a Public Health Emergency of International Concern according to WHO. An outbreak of ZIKV infection in New Caledonia occurred in 2014 with 1,380 confirmed cases within a population of 263,000. We report 2 cases of myasthenia gravis (MG) with prior ZIKV infection.