This document provides information on myasthenia gravis (MG), including:
- MG is an autoimmune neuromuscular junction disorder causing muscle weakness.
- Treatment involves immunomodulation with pyridostigmine, corticosteroids, immunosuppressants like azathioprine and mycophenolate, IVIG, or plasma exchange.
- Diagnosis is based on symptoms, serologic testing for acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibodies, and electrodiagnostic testing showing decremental response on repetitive nerve stimulation.
Here is very good and amazing presentation on Multiple sclerosis ..its about brain
read this carefully and work on this because the work on brain is very good for future research...
Here is very good and amazing presentation on Multiple sclerosis ..its about brain
read this carefully and work on this because the work on brain is very good for future research...
A wonderful and interesting presentation on Multiple Sclerosis! It includes videos, pictures and great insight into the possible cure for MS. I truly hope whoever downloads it enjoys it as much as I do. Blessings!
brief description and summary of Acute disseminated Encephalomyelitis-most common Paediatric demyelinating disorder-clinical features, epidemiology. Approach between MS and ADEM
A wonderful and interesting presentation on Multiple Sclerosis! It includes videos, pictures and great insight into the possible cure for MS. I truly hope whoever downloads it enjoys it as much as I do. Blessings!
brief description and summary of Acute disseminated Encephalomyelitis-most common Paediatric demyelinating disorder-clinical features, epidemiology. Approach between MS and ADEM
Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles.
The underlying defect is a decrease in the number of available acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack
Atrial fibrillation is the most common type of cardiac arrhythmia. It is the leading cardiac cause of stroke
https://www.youtube.com/watch?v=4pSobW-a6gQ&list=PL2XcrMWxPBLQyEdWnJuO4qSI2m-WTrglH&pp=gAQBiAQB
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic inflammatory neuropathy. CIDP is diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria
https://www.youtube.com/watch?v=AYEhL1LdONY
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
4. MG is an autoimmune disease affecting the NMJ
causing fatigable ocular, limb,and bulbar muscle
weakness.
The prevalence is 1 in 5000.
MG affects patients of all ages with a peak in younger
women and older men.
Antibodies against the AChR or the MuSK are found
in the majority of patients, but seronegative cases
occur in 50% of purely ocular cases and 20% of
generalized cases.
Severity varies from mild weakness limited to the
ocular muscles (purely ocular MG) to generalized limb
and bulbar weakness (generalized MG).
In 15%; severe weakness of respiratory muscles
causes respiratory failure (ie, myasthenic crisis).
5. MG is treatable with immunomodulation with
corticosteroid, long-term immunosuppressive
drugs as azathioprine and mycophenolate
mofetil, IV immunoglobulin (IVIg), and plasma
exchange. Thymectomy improve clinical
outcome.
Pharmacologic remission is common, and the
prognosis is good with a mortality of less than
5%.
Treatment should be tailored to the individual
patient, and special consideration should be
given to women of childbearing age, pregnant
women, children, and the elderly when
choosing the most suitable
immunosuppressant medication.
6. Congenital myasthenic syndromes are very
rare genetic diseases and causing ocular,
bulbar, and limb muscle weakness of varying
severity and usually with an onset early in life.
The diagnosis is based on clinical signs and
symptoms, a lack of serum antibodies, an
abnormal repetitive nerve stimulation test
with compound muscle action potential
(CMAP) decrement, and no response to
immunosuppressive therapy.
Multiple genes encoding proteins expressed
at the neuromuscular junction are associated
with different subtypes of congenital
myasthenic syndromes.
7. EPIDEMIOLOGY
the prevalence of MG has been steadily increasing for
the past 50 years because of better diagnosis.
MG is uncommon disease with approximately 60,000
estimated cases in the US.
Prevalence is 20 in 100,000 and varies in different
countries. In patients younger than 40, women are
more commonly affected with aratio of 7:3, whereas
men are more commonly affected among patients
older than 50,with aratio of 3:2.
More men are now affected than are women, and the
majority of MG patients in the US are over age 50.
Pediatric MG is very rare.
8. ETIOLOGY
MG is immune disease affecting epitopes in the postsynaptic
membrane of the neuromuscular junction. The antibody-
mediated, T cell dependent immunologic attack on the
postsynaptic membrane results in damage of the post
synaptic muscle membran causing simplification of the highly
folded surface and a reduced number and density of AChRs.
Antibodies against the AChR bind alpha subunit of the
AChR.
Thymic pathology includ:
thymoma in 15% of MG
thymichyperplasia with lymphofollicularhyperplasia in 65%.
antibodies to MuSK are in 1/3 of patients with MG who are
AChR seronegativ. MuSK plays a role in the clustering of
AChR and in endplate formation and maintenance
11. The core clinical feature of MG is fluctuating and
fatigable weakness of muscle groups that worsens
with exercise and improves with rest.
1. Ptosis, frequently asymmetric and varies during
sustained activity. Chronic contraction of the
frontalis muscle produces a worried or surprised
look. Patients may tilt their head back. Eyelid
closure is usually weak
2. Diplopia are the most common presenting
symptoms and appear in most cases early in the
disease course. the medial rectus is frequently
and more severely involved. Ptosis and/or
diplopia are the initial symptoms of MG in 85%.
12.
13. OMG is 10%–15% of MG. The diagnosis of
OMG may be a challenge as RNS studies and
anti-AChR antibodies are often negative, and
SFEMG testing may be required.
3. Bulbar weakness resulting in flaccid
dysarthria, dysphagia, jaw closure
weakness, and facial weakness (weak
smile or a “myasthenic snarl”). Patients
report nasal speech, liquids escaping
through the nose; an inability to drink
through a straw or to whistle; food getting
stuck in the throat.
14. 4. Neck flexion is usually more affected than
neck extension, but dropped head syndrome
can occur
5. Weakness of limb muscles is usually
proximal more than distal and symmetric,
but fingers and wrist extension and foot
dorsiflexion are also commonly affected.
There is difficulty in::
Performing tasks that require the arms to be
above the head
Getting up from low seats or toilets, walking
for prolonged distances, and climbing stairs
Selective or predominant weakness of triceps
muscles has been described especially in
African American patients
15. 6. Patients with anti-MuSK antibody can
have atypical clinical presentations,
including either:
Neck extensor, shoulder, and respiratory
muscle weakness
Severe oculobulbar weakness, fixed facial
muscle weakness, and weakness of the
tongue and pharyngeal muscles that
respond poorly to treatment.
Many MuSK MG patients do not improve
with cholinesterase inhibitors, some
become worse, and many have profuse
fasciculations with these medications
16. 7. MG with anti-ryanodine receptor
antibodies positive is associated with
more severe, generalized, or
predominantly oropharyngeal weakness,
and frequent myasthenic crises
8. Focal distal predominant weakness
affecting finger flexors or extensors,
sometimes asymmetric, and foot drop
have also been described
17. 9. Myasthenic crisis occurs in about 15%
and is caused by severe weakness of the
diaphragm and accessory breathing
muscles, causing respiratory failure. It
needs to be managed in ICU with
ventilatory support and treatment with
corticosteroids with IVIg or plasma
exchange.
10.Refractory MG is defined by unchanged
or worsened symptoms after corticosteroid
treatment and at least 2 other
immunosuppressants used at adequate
doses for an adequate duration or until
intolerable side effects occurred.
18. Factors That Worsen MG
1) Surgery
2) Pregnancy and Postpartum
Period
3) Heat
4) Stress
5) Viral Infections
6) Bone Marrow Transplantation
7) Medications
Antibiotics
A. Aminoglycosides
B. Fluoroquinolones
C. Tetracyclines
D. Sulfonamides
E. Penicillins
F. Nitrofurantoin
G. Telithromycin
Magnesium and magnesium-
containing medications (eg,
laxatives, antacids)
Botulinum toxin
Interferon alfa
D-Penicillamine
Cardiovascular medications
a) Quinidine, quinine
b) Beta-blockers
c) Calcium channel blockers
Anesthetics (eg, methoxyflurane)
Neuromuscular blockers (eg,
succinylcholine)
Checkpoint inhibitors (eg,
pembrolizumab)
20. A. Serologic testing:
Positive AChR-binding antibodies are very
specific for autoimmune MG and are found
in 80% generalized MG, 50% of ocular
MG, and in 50% of children with MG.
False-positive results are extremely rare
and have been found in some patients
such as GBS and in patients with
thymoma without signs of MG.
21. Istriational antibodies are in 30% of MG and in
80% of patients with thymoma without MG.
they are more commonly found in older
patients.
MuSK antibodies are tested if AChR
antibodies are negative; MuSK antibodies are
found in 13 of seronegative patients with
generalized MG, usually female patients
(85%).
In 20% of patients who are double
seronegative (negative AChR and MuSK
antibodies), autoantibodies against the low-
density lipoprotein receptor related protein
4 (LRP4) is identified.
22.
23. B. Electrodiagnostic testing
2-Hz to 5-Hz repetitive nerve stimulation
studies are more sensitive in generalized
than ocular MG. A CMAP decrement
greater than 10% is indicative of a
neuromuscular transmission defect.
Submaximal stimulation, and limb
temperature less than 35°C (95°F) during
repetitive nerve stimulation testing can
affect the validity of the results.
24. Single-fiber EMG, when performed in a
weak muscle, is the most sensitive
diagnostic test to confirm a neuromuscular
transmission disorder (positive in 97% of
affected patients). Usually, the extensor
digitorum communis muscle is studied
first, and if it is normal, a facial muscle
(frontalis or orbicularis oculi) should be
tested next. If single-fiber EMG is
normal in clinically affected muscles,
the diagnosis of MG is excluded.
25.
26. Edrophonium test; IV edrophonium chloride is
a acetylcholinesterase inhibitor with a 30sec
onset and 5minute duration. Incremental
doses starting at 2mg and up to a total 10mg
are administered with intervals of 1-2 minutes
to observe for improvement or muscarinic SE
(sweating, lacrimation, salivation, nausea,
vomiting, diarrhea, bradycardia and
bronchospasm) atropine should be available.
27. The ice pack test has a high specificity
and sensitivity for distinguishing
myasthenic ptosis from other causes of
ptosis. An ice pack is applied to the eyelid
for 5minutes, an improvement of palpebral
fissure of 2 mm is considered a positive
test.
Chest CT to rule out thymoma or thymoma
recurrence.
Thyroid function testing
30. MG needs to be differentiated from other neuromuscular
junction disorders, such as:
1) Lambert-Eaton myasthenic syndrome
2) Congenitalmyasthenic syndromes
3) Botulism
4) Lyme disease
5) Bulbar ALS
6) Brainstem ischemia
7) Acute inflammatory demyelinating
polyradiculoneuropathy (AIDP), such as Miller Fisher
syndrome and pharyngeal-cervical-brachial variants.
31. Purely ocular MG needs to be differentiated
from mitochondrial disorders, such as
chronic progressive external ophthalmoplegia
and oculopharyngeal muscular dystrophy.
The ptosis in these disorders is usually
symmetric, chronically progressive, and non-
fatigable or fluctuating.
32. Ophthalmoplegia in chronic progressive
external ophthalmoplegia and
oculopharyngeal muscular dystrophy,
rarely causes significant diplopia because
of the slow progression and uniform
involvement of intrinsic ocular muscles.
Muscle biopsy and DNA testing confirm
the diagnosis of chronic progressive
external ophthalmoplegia or
oculopharyngeal muscular dystrophy.
33. In cases with predominantly bulbar
weakness and minimal ocular symptoms,
bulbar ALS is the alternative diagnosis:
UMN signs and atrophy and fasciculations
in the tongue and other muscles
distinguish ALS from MG. The dysarthria
in MG is flaccid and nasal, while in bulbar
ALS is frequently a spastic. One
confusing feature is the presence of
fasciculations and atrophy of the tongue in
some MuSK-positive MG patients.
34. Patients with a primary symptom of
generalized fatigue without weakness in
specific muscle groups, especially if pain
is also present, are usually not affected by
MG. Electrodiagnostic evaluation that
includes EMG, repetitive nerve stimulation,
and single-fiber EMG of affected muscles
is very helpful in differentiating the above
disorders.
36. The goal in the management of MG is to
achieve remission (no signs or symptoms of
myasthenic weakness) or minimal
manifestations (no subjective symptoms and
only mild weakness found on objective
neurologic examination that does not interfere
with normal function).
Plasma exchange and IVIg are used in
generalized MG as rapid-onset short-term
immunotherapy,
37. Plasma exchange and IVIg are used in generalized MG,
for severe acute exacerbations, and preoperatively to
optimize the patient’s strength prior to surgery.
In refractory patients and in patients who do not respond
to or cannot tolerate oral immunosuppressants, IVIg and
plasma exchange are used more chronically.
1) Plasma exchange
5 to 6 exchanges of 2 to 3 liters on alternating days, is
effective in improving strength in majority of patients with
MG and is the treatment of choice in true myasthenic
crisis because of its fast onset (usually after the 2nd or 3rd
exchange).
.
38. 2) IVIg
Dose of 1 g/kg to 2 g/kg divided over 2 to 5 days is
used to treat moderate to severe exacerbations and
for patients who do not respond to or cannot tolerate
any immunosuppressant.
Improvement occurs between a few days and 2weeks
and usually lasts weeks to months.
SE include idiosyncratic reactions (chills, fever,
headaches) and aseptic meningitis.
Premedication with acetaminophen, diphenhydramine,
and hydrocortisone help in preventing or mitigating the
side effects.
Caution is taken in patients with cardiomyopathy or
valve disease and renal impairment due to the risk of
volume overload.
39. 3) Pyridostigmine
It is acetylcholinesterase inhibitor used for the
symptomatic treatment of MG, alone in pure
ocular and mild generalized cases or in
combination with immunosuppressants in
severe cases.
The symptomatic effect starts in 30 to 60
minutes and lasts for 3 to 4 hours. The dose
should be administered 30 minutes before
meals.if dysphagia is the main symptom or
every 4 hours while the patient is awake if
diplopia is the main symptom.
Common side effects include abdominal
cramps, diarrhea, and excessive lacrimation
40. 4) Corticosteroids
They are the first choice for ocular and generalized
MG if require more than pyridostigmine.
The dose is 60 mg/d-80 mg/d until improvement
occur, but because of the possible risk of short-term
exacerbation especially in bulbar weakness, this
option is reserved for the inpatient setting whereas
in the outpatient setting taper up.
In the outpatient, prednisone is started at 10 mg/d-
20 mg/d and increased by 5 mg/d every week till
improvement. Once improvement is reached, a slow
taper should starte on an alternating day schedule
and a long term steroid-sparing immunosuppressant
added if symptoms recur.
41. 5) Mycophenolate mofetil and azathioprine
They are the commonest used
immunosuppressants in management of MG.
They are the first choice if corticosteroids are
contraindicated.
that
suppresses cell-mediated immune response
and antibody formation. The doses in adults
are 2 g/d-3 g/d divided in 2 doses. Side
effects include abdominal pain, diarrhea, and
nausea. Because of potential leukopenia and
anemia, periodic monitoring of complete blood
cell counts is performed. The therapeutic
effect takes few weeks to 2 months.
42. . The dose is 2
mg/kg/d-3 mg/kg/d, and side effects
include myelosuppression, toxic hepatitis,
idiosyncratic allergic flu-like reaction, and
pancreatitis. Monitoring of complete blood
cell count and liver enzymes is required.
The therapeutic effect takes 4 to 8 months.
43. 6) Rituximab
it is a synthetic CD20 antibody given IV. It induce
significant improvement and even remission in some
patients with severe and refractory generalized MG,
especially in MuSK-positive patients. Side effects include
hepatitis B virus reactivation, infusion reactions, skin and
mouth ulcers, and progressive multifocal
leukoencephalopathy.
Indications of rituximab
A. CD20 positive B-cell Non Hodgkin lymphoma
B. Chronic lymphocytic leukemia
C. Rheumatoid arthritis
D. Wagener granulomatosis and microscopic polyangitis
E. Pemphigus vulgaris
F. Rasmussen encephalitis
44. 7) Eculizumab
It is a complement inhibitor recently approved by the FDA
for the treatment of adult patients with AChR-antibody
positive generalized MG. Its use is indicated for patients
with severe or refractory disease who either have not
responded to or are unable to tolerate other
immunosuppressants. Because of the risk of
meningococcal and other serious bacterial infections,
vaccination recommendations should be followed prior to
use.
Indications of eculizumab
A. paroxysmal noctornal hemoglobinuria
B. hemolytic uremic syndrome
C. MG
D. NMOSD
45. 8) Efgartigimod
it is a first in class neonatal Fc receptor antagonist being
developed for treatment of autoimmune diseases including
MG.
The neonatal Fc receptor plays a key role in prolonging the
life-span of IgG as it protects them from lysosomal
degradation by recycling them back into the circulation
In December 2021, IV efgartigimod received the FDA
approval for the treatment of generalized MG in adults who
are anti AChR antibody positive.
The dose is 10 mg/kg ( MAX 1200mg), is administered as a
1h IV infusion once weekly for 4 weeks as one treatment
cycle; It is diluted with 0.9% NaCL injection to a total of 125
mL. Patient is monitored for signs and symptoms of
hypersensitivity reactions. Subsequent cycles are
administered based on clinical evaluation; not less than 50
days after previous cycle. It causes transient decrease in IgG
levels so immunization with live or live-attenuated vaccines is
not recommended during treatment