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Myasthenia gravis (MG) is an autoimmune disease with acquired neuromuscular junction (NMJ) transmission disorder mediated by autoantibodies.
The "Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition)" is an updated revision of the Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2015).
Regarding the differential diagnosis of MG, what does the guide say? Differential diagnosis with ocular muscle type MG (OMG) (1) The onset of blepharospasm is older, manifested as excessive blinking, and may be accompanied by dryness and irritation of the eyes (Sjogren’s syndrome needs to be excluded), and may appear for a long time Eyes closed, mistaken for ptosis; strong light stimulation can aggravate blepharospasm, and patients need to wear sunglasses for a long time; blepharospasm can be unexpectedly improved when touching the corner of the eye, coughing and speaking.
Haloperidol, aripiprazole, or clonazepam are effective treatments.
(2) Miller-Fisher syndrome: it belongs to the variant of Guillain-Barré syndrome, which manifests as acute extraocular muscle palsy, ataxia, and loss of tendon reflexes.
It can also be manifested as simple extraocular muscle palsy, which is easy to be misdiagnosed as MG The electromyography examination showed that the nerve conduction speed was slowed down, the cerebrospinal fluid examination showed the phenomenon of protein-cell separation, and some patients' serum could detect anti-GQ1b antibody or GT1a antibody.
(3) Chronic progressive extraocular muscle palsy (CPEO) or Kearn-Sayre syndrome (KSS): belongs to mitochondrial encephalomyopathy, CPEO manifests as bilateral progressive non-fluctuation ptosis, extraocular muscle palsy, and may be accompanied by close Limbs are weak.
If combined with retinitis pigmentosa, cerebellar atrophy and heart block, it is KSS syndrome.
Electromyographic examination showed myogenic damage, and a small number of patients may be accompanied by a slowdown in peripheral nerve conduction velocity.
The blood lactic acid is slightly increased, and muscle biopsy and genetic examination can help confirm the diagnosis.
(4) Ocular pharyngeal muscular dystrophy (oculopharyngeal muscular dystrophy): autosomal dominant inheritance, with family history; manifested as senile-onset symmetrical eyelid drooping without fluctuations, strabismus is obvious, but without diplopia, it gradually appears Difficulty swallowing, dysarthria.
The electromyography showed myogenic damage.
Serum muscle enzymes are usually normal or slightly elevated.
Muscle biopsy and genetic testing are helpful for diagnosis.
(5) Brainstem diseases: including brainstem ischemic stroke, tumors, paraneoplastic syndromes, Wernicke encephalopathy, neuromyelitis optica spectrum diseases, Bickerstaff brainstem encephalitis and other infectious encephalitis, all of which can be led by acute ptosis Symptoms can be easily confused with MG.
Combining medical history, head MRI, and specific antibody testing can help confirm the diagnosis.
(6) Orbital space-occupying lesions: such as intraorbital tumors, abscesses or inflammatory pseudotumors, etc.
, which can be manifested as extraocular muscle paralysis with conjunctival hyperemia, exophthalmos, and eyelid edema.
Orbital MRI, CT or ultrasound can help diagnosis.
(7) Cerebral nerve palsy (Ⅲ, Ⅳ, Ⅵ): One cavernous sinus infection, tumor, non-specific inflammation, internal carotid cavernous fistula can be manifested as unilateral eyelid ptosis, extraocular muscle paralysis with pain, head MRI And cerebrospinal fluid examination can help differential diagnosis.
In addition, diabetes can also cause simple oculomotor nerve or abducens nerve palsy.
(8) Graves ophthalmopathy: It is an autoimmune thyroid disease, manifested as self-limiting extraocular muscle weakness, eyelid retraction, and no ptosis.
Orbital CT or MRI examination showed swelling of extraocular muscles, hyperthyroidism or hypothyroidism, and positive anti-thyroglobulin antibody, anti-thyroid microsomal antibody, or anti-thyroid stimulating hormone receptor antibody.
(9) Congenital myasthenia syndrome (CMS): It is a group of rare genetic diseases that cause NMJ transmission disorder caused by mutations in genes encoding NMJ structural and functional proteins.
According to the distribution of mutant gene encoding proteins in NMJ, CMS can Divided into pre-synaptic, synaptic and postsynaptic mutations.
The clinical manifestations of CMS are very heterogeneous and can easily be misdiagnosed as antibody-negative MG, mitochondrial myopathy, etc.
Symptoms such as drooping eyelids, difficulty in opening eyes, difficulty in feeding, and retardation of motor development often occur at birth and in infancy.
Eyeball fixation gradually appears in adolescence, which is similar to the clinical and electrophysiological manifestations of MG.
The identification mainly depends on serological antibody detection and whole exome sequencing.
Differential diagnosis from AChR-systemic MG (GMG) (1) Lambert-Eaton myasthenia syndrome (LEMS): It is an immune-mediated disease involving the NMJ presynaptic membrane voltage-gated calcium channel (VGCC), which belongs to the nerve Systemic paraneoplastic syndromes are mostly secondary to small cell lung cancer, but can also be secondary to other neuroendocrine tumors.
Clinical manifestations: Symmetrical weakness of the proximal extremities, decreased tendon reflexes, autonomic symptoms with dry mouth as prominent manifestations, very rare involvement of extraocular muscles, tendon reflexes can be recovered briefly after exercise, other autonomic symptoms such as constipation, sex Dysfunction and abnormal sweating are rare.
RNS is a low-frequency stimulation (2~3Hz) with a CMAP amplitude decrease greater than 10%; a high-frequency stimulation (20-50Hz) or a 10s CMAP amplitude increase greater than 60% or 100% after a vigorous contraction.
Serum VGCC antibodies are mostly positive, and LEMS with small cell lung cancer can also be positive for SOX-1 antibodies.
(2) Motor neuron disease (progressive bulbar palsy): especially need to be differentiated from MuSK-MG, patients with bulbar symptoms are prominent manifestations, progressive bulbar palsy may have evidence of upper motor neuron damage; if the patient has a longer course of disease , Drooping eyelids and diplopia occur during the course of the disease, and there is no evidence of upper motor neuron damage.
Beware of the possibility of MuSK-MG.
MuSK antibody testing is recommended.
(3) CMS: The clinical manifestations of CMS are very heterogeneous, and CMS caused by mutations of DOK7, RAPSN, CHAT and GFPT1 hardly have extraocular muscle paralysis.
CMS caused by GFPT1 mutation can be manifested as limb muscle fatigue, muscle biopsy can show tube aggregation or vacuole-like changes, GMPPB mutation caused CMS serum muscle enzymes to increase significantly, muscle biopsy suggests muscular dystrophy-like changes; CMS electromyography can Manifested as myogenic damage.
Therefore, muscle biopsy and high-throughput whole-exome sequencing can help confirm the diagnosis.
(4) Botulism: It is caused by the involvement of botulinum toxin on the presynaptic membrane of NMJ, which manifests as paralysis of the extraocular muscles and weakness in swallowing, phonation, and chewing, symmetrical flaccid paralysis of the limbs, and respiratory muscles may be involved.
In the case of food botulinum toxin poisoning, severe nausea and vomiting may occur before muscle weakness.
Dilated pupils, slow light reflex, loss of tendon reflexes in the limbs, and prominent autonomic symptoms can help distinguish botulism from MG.
The result of electrophysiological examination is similar to that of LEMS: the visible wave amplitude of low-frequency RNS decreases, and the wave amplitude of high-frequency RNS increases or does not respond, depending on the degree of poisoning.
Botulinum isolation and toxin identification of serum, feces and food can confirm the diagnosis.
(5) Guillain-Barré syndrome: It is an immune-mediated acute inflammatory demyelinating peripheral neuropathy characterized by flaccid limb weakness, loss of sensation, and decreased or disappearance of tendon reflexes.
EMG showed that the latency of the conduction terminal of the motor and sensory nerves was prolonged, the conduction speed was slowed, and the conduction wave amplitude was reduced; the cerebrospinal fluid examination showed the phenomenon of protein-cell separation.
Pharyngocervical brachial plexus Guillain-Barré syndrome (PCB) is mainly manifested by bulbar palsy, neck lift, and proximal weakness of the upper limbs, which is easily misdiagnosed as MG, especially MuSK-MG.
PCBs usually have a history of pro-infection.
Physical examination shows that the tendon reflexes of both upper limbs are reduced or disappeared.
There may be protein-cell separation in the cerebrospinal fluid.
The serum anti-GT1a antibody may be positive.
When comorbid with Fisher syndrome, the GQ1b antibody may also be positive.
(6) Chronic inflammatory demyelinating polyneuropathy: Immune-mediated chronic motor sensory peripheral neuropathy, manifested as flaccid weakness of the limbs, hypoesthesia in the sleeve, and decreased or disappeared tendon reflexes.
The electromyography showed slowing of motor and sensory nerve conduction speed, decreased amplitude and conduction block.
Protein-cell separation can be seen in the cerebrospinal fluid, and peripheral nerve biopsy is helpful for diagnosis.
(7) Inflammatory myopathy: Interstitial inflammatory lesions of skeletal muscle caused by various reasons, manifested as progressive exacerbation of flaccid limb weakness and pain.
EMG shows myogenic damage.
Blood muscle enzymes are significantly elevated, and muscle biopsy is helpful for diagnosis.
Glucocorticoid therapy is effective.
(8) Metabolic myopathy: For example, muscle diseases caused by muscle metabolic enzymes, lipid metabolism or mitochondrial damage are manifested as flaccid limb weakness, inability to tolerate fatigue, reduction or disappearance of tendon reflexes, and other organ damage.
EMG shows myogenic damage.
Blood muscle enzymes are normal or slightly elevated.
Muscle biopsy and genetic testing help diagnosis.
The above content is taken from: Neuroimmune Branch of Chinese Society of Immunology.
Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition).
Chinese Journal of Neuroimmunology and Neurology.
2021.
28(1):1-12.
The "Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition)" is an updated revision of the Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2015).
Regarding the differential diagnosis of MG, what does the guide say? Differential diagnosis with ocular muscle type MG (OMG) (1) The onset of blepharospasm is older, manifested as excessive blinking, and may be accompanied by dryness and irritation of the eyes (Sjogren’s syndrome needs to be excluded), and may appear for a long time Eyes closed, mistaken for ptosis; strong light stimulation can aggravate blepharospasm, and patients need to wear sunglasses for a long time; blepharospasm can be unexpectedly improved when touching the corner of the eye, coughing and speaking.
Haloperidol, aripiprazole, or clonazepam are effective treatments.
(2) Miller-Fisher syndrome: it belongs to the variant of Guillain-Barré syndrome, which manifests as acute extraocular muscle palsy, ataxia, and loss of tendon reflexes.
It can also be manifested as simple extraocular muscle palsy, which is easy to be misdiagnosed as MG The electromyography examination showed that the nerve conduction speed was slowed down, the cerebrospinal fluid examination showed the phenomenon of protein-cell separation, and some patients' serum could detect anti-GQ1b antibody or GT1a antibody.
(3) Chronic progressive extraocular muscle palsy (CPEO) or Kearn-Sayre syndrome (KSS): belongs to mitochondrial encephalomyopathy, CPEO manifests as bilateral progressive non-fluctuation ptosis, extraocular muscle palsy, and may be accompanied by close Limbs are weak.
If combined with retinitis pigmentosa, cerebellar atrophy and heart block, it is KSS syndrome.
Electromyographic examination showed myogenic damage, and a small number of patients may be accompanied by a slowdown in peripheral nerve conduction velocity.
The blood lactic acid is slightly increased, and muscle biopsy and genetic examination can help confirm the diagnosis.
(4) Ocular pharyngeal muscular dystrophy (oculopharyngeal muscular dystrophy): autosomal dominant inheritance, with family history; manifested as senile-onset symmetrical eyelid drooping without fluctuations, strabismus is obvious, but without diplopia, it gradually appears Difficulty swallowing, dysarthria.
The electromyography showed myogenic damage.
Serum muscle enzymes are usually normal or slightly elevated.
Muscle biopsy and genetic testing are helpful for diagnosis.
(5) Brainstem diseases: including brainstem ischemic stroke, tumors, paraneoplastic syndromes, Wernicke encephalopathy, neuromyelitis optica spectrum diseases, Bickerstaff brainstem encephalitis and other infectious encephalitis, all of which can be led by acute ptosis Symptoms can be easily confused with MG.
Combining medical history, head MRI, and specific antibody testing can help confirm the diagnosis.
(6) Orbital space-occupying lesions: such as intraorbital tumors, abscesses or inflammatory pseudotumors, etc.
, which can be manifested as extraocular muscle paralysis with conjunctival hyperemia, exophthalmos, and eyelid edema.
Orbital MRI, CT or ultrasound can help diagnosis.
(7) Cerebral nerve palsy (Ⅲ, Ⅳ, Ⅵ): One cavernous sinus infection, tumor, non-specific inflammation, internal carotid cavernous fistula can be manifested as unilateral eyelid ptosis, extraocular muscle paralysis with pain, head MRI And cerebrospinal fluid examination can help differential diagnosis.
In addition, diabetes can also cause simple oculomotor nerve or abducens nerve palsy.
(8) Graves ophthalmopathy: It is an autoimmune thyroid disease, manifested as self-limiting extraocular muscle weakness, eyelid retraction, and no ptosis.
Orbital CT or MRI examination showed swelling of extraocular muscles, hyperthyroidism or hypothyroidism, and positive anti-thyroglobulin antibody, anti-thyroid microsomal antibody, or anti-thyroid stimulating hormone receptor antibody.
(9) Congenital myasthenia syndrome (CMS): It is a group of rare genetic diseases that cause NMJ transmission disorder caused by mutations in genes encoding NMJ structural and functional proteins.
According to the distribution of mutant gene encoding proteins in NMJ, CMS can Divided into pre-synaptic, synaptic and postsynaptic mutations.
The clinical manifestations of CMS are very heterogeneous and can easily be misdiagnosed as antibody-negative MG, mitochondrial myopathy, etc.
Symptoms such as drooping eyelids, difficulty in opening eyes, difficulty in feeding, and retardation of motor development often occur at birth and in infancy.
Eyeball fixation gradually appears in adolescence, which is similar to the clinical and electrophysiological manifestations of MG.
The identification mainly depends on serological antibody detection and whole exome sequencing.
Differential diagnosis from AChR-systemic MG (GMG) (1) Lambert-Eaton myasthenia syndrome (LEMS): It is an immune-mediated disease involving the NMJ presynaptic membrane voltage-gated calcium channel (VGCC), which belongs to the nerve Systemic paraneoplastic syndromes are mostly secondary to small cell lung cancer, but can also be secondary to other neuroendocrine tumors.
Clinical manifestations: Symmetrical weakness of the proximal extremities, decreased tendon reflexes, autonomic symptoms with dry mouth as prominent manifestations, very rare involvement of extraocular muscles, tendon reflexes can be recovered briefly after exercise, other autonomic symptoms such as constipation, sex Dysfunction and abnormal sweating are rare.
RNS is a low-frequency stimulation (2~3Hz) with a CMAP amplitude decrease greater than 10%; a high-frequency stimulation (20-50Hz) or a 10s CMAP amplitude increase greater than 60% or 100% after a vigorous contraction.
Serum VGCC antibodies are mostly positive, and LEMS with small cell lung cancer can also be positive for SOX-1 antibodies.
(2) Motor neuron disease (progressive bulbar palsy): especially need to be differentiated from MuSK-MG, patients with bulbar symptoms are prominent manifestations, progressive bulbar palsy may have evidence of upper motor neuron damage; if the patient has a longer course of disease , Drooping eyelids and diplopia occur during the course of the disease, and there is no evidence of upper motor neuron damage.
Beware of the possibility of MuSK-MG.
MuSK antibody testing is recommended.
(3) CMS: The clinical manifestations of CMS are very heterogeneous, and CMS caused by mutations of DOK7, RAPSN, CHAT and GFPT1 hardly have extraocular muscle paralysis.
CMS caused by GFPT1 mutation can be manifested as limb muscle fatigue, muscle biopsy can show tube aggregation or vacuole-like changes, GMPPB mutation caused CMS serum muscle enzymes to increase significantly, muscle biopsy suggests muscular dystrophy-like changes; CMS electromyography can Manifested as myogenic damage.
Therefore, muscle biopsy and high-throughput whole-exome sequencing can help confirm the diagnosis.
(4) Botulism: It is caused by the involvement of botulinum toxin on the presynaptic membrane of NMJ, which manifests as paralysis of the extraocular muscles and weakness in swallowing, phonation, and chewing, symmetrical flaccid paralysis of the limbs, and respiratory muscles may be involved.
In the case of food botulinum toxin poisoning, severe nausea and vomiting may occur before muscle weakness.
Dilated pupils, slow light reflex, loss of tendon reflexes in the limbs, and prominent autonomic symptoms can help distinguish botulism from MG.
The result of electrophysiological examination is similar to that of LEMS: the visible wave amplitude of low-frequency RNS decreases, and the wave amplitude of high-frequency RNS increases or does not respond, depending on the degree of poisoning.
Botulinum isolation and toxin identification of serum, feces and food can confirm the diagnosis.
(5) Guillain-Barré syndrome: It is an immune-mediated acute inflammatory demyelinating peripheral neuropathy characterized by flaccid limb weakness, loss of sensation, and decreased or disappearance of tendon reflexes.
EMG showed that the latency of the conduction terminal of the motor and sensory nerves was prolonged, the conduction speed was slowed, and the conduction wave amplitude was reduced; the cerebrospinal fluid examination showed the phenomenon of protein-cell separation.
Pharyngocervical brachial plexus Guillain-Barré syndrome (PCB) is mainly manifested by bulbar palsy, neck lift, and proximal weakness of the upper limbs, which is easily misdiagnosed as MG, especially MuSK-MG.
PCBs usually have a history of pro-infection.
Physical examination shows that the tendon reflexes of both upper limbs are reduced or disappeared.
There may be protein-cell separation in the cerebrospinal fluid.
The serum anti-GT1a antibody may be positive.
When comorbid with Fisher syndrome, the GQ1b antibody may also be positive.
(6) Chronic inflammatory demyelinating polyneuropathy: Immune-mediated chronic motor sensory peripheral neuropathy, manifested as flaccid weakness of the limbs, hypoesthesia in the sleeve, and decreased or disappeared tendon reflexes.
The electromyography showed slowing of motor and sensory nerve conduction speed, decreased amplitude and conduction block.
Protein-cell separation can be seen in the cerebrospinal fluid, and peripheral nerve biopsy is helpful for diagnosis.
(7) Inflammatory myopathy: Interstitial inflammatory lesions of skeletal muscle caused by various reasons, manifested as progressive exacerbation of flaccid limb weakness and pain.
EMG shows myogenic damage.
Blood muscle enzymes are significantly elevated, and muscle biopsy is helpful for diagnosis.
Glucocorticoid therapy is effective.
(8) Metabolic myopathy: For example, muscle diseases caused by muscle metabolic enzymes, lipid metabolism or mitochondrial damage are manifested as flaccid limb weakness, inability to tolerate fatigue, reduction or disappearance of tendon reflexes, and other organ damage.
EMG shows myogenic damage.
Blood muscle enzymes are normal or slightly elevated.
Muscle biopsy and genetic testing help diagnosis.
The above content is taken from: Neuroimmune Branch of Chinese Society of Immunology.
Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition).
Chinese Journal of Neuroimmunology and Neurology.
2021.
28(1):1-12.
