Categories
Myasthenia gravis

How effective is rituximab in refractory myasthenia gravis?

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.

Abstract

Background:

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.

Methods:

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.

Results:

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.

Conclusions:

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.

This paper is cited in the neurochecklist:

Refractory myasthenia gravis (MG): treatment

By Ib intaspharmaOwn work, CC BY-SA 3.0, Link

Abstract link

Categories
Neurochecklists updates

8 practical neurology numbers to welcome the new year!

As 2020 kicks in…

And you make your resolutions….

Here are some practical numbers

To kickstart the new year.

Numbers. Andy Maguire on Flickr. https://www.flickr.com/photos/andymag/10947544804

 

 

“16”

The 16 MRI signs of IIH 

“21” 

The 21 predictors of conversion from CIS to MS

 

“25”

The 25 unusual types of headaches

 

“28”

The 28 unusual presentations of myasthenia gravis

 

“32”

The 32 migraine co-morbidities

 

“35”

The 35 unusual presentations of MS

 

“50”

The 50 adverse effects of pembrolizumab

 

“66”

The 66 causes of trigeminal neuralgia

The Numbers. Annie Pilon on Flickr. https://www.flickr.com/photos/anniehp/4326154694

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For more helpful neurology numbers in 2020

Keep up with www.neurochecklists.com

Numbers in a City. See-ming Lee on Flickr. https://www.flickr.com/photos/seeminglee/7994149144
Categories
General

What are the 10 most eminently curable neurological disorders?

Neurologists are often at the receiving end of the jokes of other medical specialists. They facetiously remark that neurologists know a lot, but do very little to cure their patients. Admittedly we do our fair share of dispensing weak platitudes, and we do break bad news with embarrassing regularity. There is no doubt that, for many diseases, all we have in stock are symptomatic or palliative. This is sadly the case with many familiar disorders such as Alzheimer’s disease (AD), Huntington’s disease, Charcot Marie Tooth disease (CMT), Freidreich’s ataxia (FA), essential tremor (ET), and myotonic dystrophy.

Three treatment capsules close-up. Marco Verch Professional Photographer and Speaker on Flickr. https://www.flickr.com/photos/30478819@N08/46513130444/in/photostream/

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).

 

Hypodermic needle-IMG7418. Steven Depolo on Flickr. https://www.flickr.com/photos/stevendepolo/3020361085

But neurologists don’t just tap their patients knees, and then raise their hands up in despair. We do more than just lend our patients a listening ear, or a leaning shoulder to cry on. We do have at our disposal a vast armamentarium that can control many neurological diseases, even if we need to use these chronically. Such is the state of play with diseases such as migraine, epilepsy, multiple sclerosis (MS), narcolepsy, myasthenia gravis (MG), restless legs syndrome (RLS)Wilson’s disease, and Parkinson’s disease (PD).

Mapping the brain. NIH History Office on Flickr. https://www.flickr.com/photos/historyatnih/14359347545

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.

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Bacterial meningitis

Viral encephalitis

Autoimmune encephalitis

Wernicke’s encephalopathy

Ischaemic stroke

Idiopathic intracranial hypertension (IIH)

Cervical compressive myelopathy

Guillain Barre syndrome (GBS)

Meningioma

Normal pressure hydrocephalus (NPH)

***

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:

on ‘Have we missed anyone out? Please drop us a hint!

By JustfixingawrongnumberOwn work, CC0, Link
Categories
Myasthenia gravis

What are the HLA biomarkers of anti-MUSK myasthenia gravis?

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)

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

This paper is cited in the neurochecklist:

Myasthenia gravis (MG): anti MUSK syndrome

Abstract link

Von Uwe Thormann aus der deutschsprachigen Wikipedia, CC BY-SA 3.0, Link
Categories
Myasthenia gravis

How does anti-MUSK myasthenia gravis affect pregnancy?

MuSK myasthenia gravis and pregnancy

Santos E, Braga A, Gabriel D, et al.

Neuromuscul Disord 2018; 28:150-153.

Abstract

Background:

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.

Methods:

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).

Results:

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.

Conclusions:

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.

This paper is cited in the neurochecklist:

Myasthenia gravis (MG): anti MUSK syndrome

Abstract link

https://pixabay.com/en/pregnant-woman-pregnancy-mother-735393/
Categories
Myasthenia gravis Uncategorized

What factors predict post-operative myasthenic crisis?

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.

Abstract

PURPOSE:

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.

METHOD:

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.

RESULT:

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).

CONCLUSION:

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.

This reference is cited in the neurochecklist:

Myasthenia gravis (MG): treatment of thymoma

Abstract link

By Gray’s Anatomy, Public Domain, Link
Categories
Neurological infections

The 7 most devastating viral neurological infections

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.

Bacteria. Cesar Herada on Flikr. https://www.flickr.com/photos/worldworldworld/4095866396/

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.

CC BY-SA 3.0, Link

1.  Viral encephalitis

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 causes of viral encephalitis and its management.

Herpes Simplex Virus Type 1: Procapsid and Mature Capsid. NIH Image gallery on Flikr. https://www.flickr.com/photos/nihgov/28295539863

2. HIV associated neurological infections

No part of the nervous system is immune to the ravages of the dreaded HIV. The list includes HIV  associated neurocognitive disorders (HAND)myelopathiesneuropathies, drug-induced syndromes, and tumours. The worst aspect of HIV, of course, is that it opens the flood gates for opportunistic infections to invade the nervous system.

By BruceBlausOwn work, CC BY-SA 4.0, Link

3. Hepatitis E virus (HEV)

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 the full neurological manifestations of HEV.

By Transferred from en.wikipedia to Commons.This media comes from the Centers for Disease Control and Prevention‘s Public Health Image Library (PHIL), with identification number #5605.Note: Not all PHIL images are public domain; be sure to check copyright status and credit authors and content providers.English | Slovenščina | +/−, Public Domain, Link

4. Influenza H1N1

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 encephalopathyGuillain Barre syndrome (GBS), acute demyelinating encephalomyelopathy (ADEM), and stroke. Not one to be treated lightly at all. Check out everything about Influenza H1N1 and the different ways influenza affects the nervous system.

H1N1 influenza viral particles. NIAID on Flikr. https://www.flickr.com/photos/niaid/8414750984

5. Zika virus infection (ZIKV)

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 20 things we now know for certain about the Zika virus on our sister blog, The Neurology Lounge.

By Manuel Almagro RivasOwn work, CC BY-SA 4.0, Link

6. Ebola virus disease (EVD)

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.

By Scientific Animations – http://www.scientificanimations.com/wiki-images/, CC BY-SA 4.0, Link

7. Varicella zoster virus (VZV)

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 the full VZV on neurochecklists.

 

Check out the other deadly viral neurological infections on neurochecklists:

Dengue virus infection (DENV)

West Nile virus (WNV) infection

Japanese encephalitis virus (JEV)

Rabies encephalitis

Categories
Myasthenia gravis Neurological infections

Is Zika virus infection a risk factor for myasthenia gravis?

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.

Abstract

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.

This reference is included in the neurochecklist:

Zika virus infection (ZIKV): clinical features

Abstract link

By Manuel Almagro RivasOwn work, CC BY-SA 4.0, Link
Categories
Neurochecklists updates

40 very handy and practical neurochecklists

Neurochecklists now contains >2000 checklists on all aspects of neurology.
https://pixabay.com/en/brain-anatomy-neurology-medical-1132229/
https://pixabay.com/en/brain-anatomy-neurology-medical-1132229/
Many checklists come to the rescue only to fill a knowledge gap.
By Samurai Gandhi - Own work, CC BY-SA 4.0, Link
By Samurai GandhiOwn work, CC BY-SA 4.0, Link
Most neurochecklists however address important practical questions or outline pragmatic steps in managing neurological disorders.
House of Knowledge. Ian Parkes on Flikr. https://www.flickr.com/photos/parksy/2934000145
House of Knowledge. Ian Parkes on Flikr. https://www.flickr.com/photos/parksy/2934000145
To illustrate, below is a selection of 40 handy neurochecklists

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Anticoagulants: bridging therapy for surgery
Antiepileptic drugs (AEDs): choice with medical conditions
Apomorphine test
Cluster headache (CH): chronic prophylaxis
Cerebral vein thrombosis (CVT): investigations

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Dementia: safety and driving risks
Diaphragmatic paralysis: neurological causes
Drug induced Parkinsonism: risk factors and causes
Epilepsy: patient information
Essential tremor (ET): drug treatment

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Falls: management
Genetic counselling
HyperCKaemia: neurological causes
Lumbar puncture (LP): indications and precautions
Lyme Neuroborreliosis: management

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Migraine prophylaxis: drugs
Mitochondrial diseases: investigations
Motor neurone disease (MND): supportive care
Multiple sclerosis (MS): general investigations
Pregnancy and myasthenia gravis (MG): management

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Myelopathy with normal MRI
Myotonic dystrophy type 1: assessments and monitoring
Neurological complications of liver transplantation
Neurosarcoidosis: treatment
Neurosyphilis: clinical features

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Peripheral neuropathy (PN): red flags for ominous causes
Pineal cysts: monitoring
Psychogenic seizures: management
Subarachnoid haemorrhage (SAH): complications
Sudden unexpected death in epilepsy (SUDEP): management

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Syncope: red flags for admission
Thrombolysis: bleeding risk prediction tools
Trigeminal neuralgia (TN): management
Tic disorders: differential diagnosis and management
Passive tilt table test: indications and contraindications

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Transient loss of consciousness (TLOC): assessment
Vitamin B12 deficiency: tests of B12 metabolites 
Warfarin: switching to new oral anticoagulants
Wernicke’s encephalopathy: risks and clinical features
Young onset dementia

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Explore these and many other practical checklists on Neurochecklists

By Ansonlobo - Own work, CC BY-SA 4.0, Link
By AnsonloboOwn work, CC BY-SA 4.0, Link