Neurology Flashcards
What is a unique aspect of muscle strength testing or deep tendon reflex testing in patients with Lambert-Eaton myasthenic syndrome?
Post-exercise (or post-activation) facilitation - vigorous, brief muscle activation (e.g. maximal isometric contraction of the relevant muscle for 10 to 15 seconds) can sometimes lead to temporary reappearance of previously depressed or absent deep tendon reflexes, and to temporary improvement of muscle weakness
What cancer is paraneoplastic Lambert-Eaton myasthenic syndrome most commonly associated with?
Small cell lung cancer (mostly), occasionally lymphoproliferative diseases including Hodgkin’s Lymphoma - rarely atypical carcinoid, Merkel cell etc
What are the causes of Lambert-Eaton myasthenic syndrome?
- Paraneoplastic phenomena secondary to small cell lung cancer or lymphoproliferative malignancies
- Autoimmunity secondary to thyroid disease or T1DM
- Toxic secondary to immunotherapy/immune checkpoint inhibitor therapy
What is the pathophysiology of Lambert-Eaton myasthenic syndrome?
LEMS is the result of reduced ACh release from the presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration, and normal postsynaptic ACh receptors. It results from autoimmunity with antibodies directed at the P/Q subtype of Voltage Gated Calcium Channels which interferes with the normal calcium influx required for ACh release
Is the age of onset of paraneoplastic Lambert-Eaton myasthenic syndrome younger or older than non-paraneoplastic LEMS?
Older
What percentage of Lambert-Eaton myasthenic syndrome is paraneoplastic?
50%
What are the key clinical features of Lambert-Eaton myasthenic syndrome
Consider in patients presenting with proximal muscle weakness, dry mouth, hyporeflexia, and any combination of oropharyngeal muscle weakness or ptosis
Key features:
1. Slowly progressive proximalmuscle weakness (lower extremity > upper extremity) - typically describe an alteration in gait or difficulty arising from a chair or managing stairs
- usually symmetrical
- may describe muscle pain/stiffness/cramping or fatigability
- degree of weakness on exam usually less than would expect based on disability
- usually limited muscle atrophy
- Distinctive autonomic findings
- dry mouth
- sluggish pupillary response
- erectile dysfunction - Smattering of oculobulbar findings
- typically less severe or striking than in myasthenia gravis
- ptosis or diplopia are most common
- excessive or paradoxical eyelid elevation with sustained upward gaze - Depressed or absent deep tendon reflexes
- classical feature is “post-activation facilitation” which refers to recovery of lost deep tendon reflexes or improvement in muscle strength with vigorous, brief muscle activation - Respiratory failure
- often late in illness
- need to consider in differential diagnosis of patients presenting with neuromuscular respiratory failure
How do you diagnose Lambert-Eaton myasthenic syndrome?
Electrodiagnostic studies, including repetitive nerve stimulation (RNS), and anti-P/Q-type voltage-gated calcium channel (VGCC) antibody testing
The diagnosis of LEMS is confirmed on high-frequency RNS by a reproducible postexercise increase in compound muscle action potential (CMAP) amplitude of at least 100 percent compared with pre-exercise baseline value
A high titer P/Q-type VGCC antibody result is strongly suggestive of LEMS in the appropriate clinical setting -However, P/Q-type VGCC antibodies are present in a variety of clinical situations where LEMS is not present.
Is a high titre of P/Q-type VGCC antibodies diagnostic of Lambert-Eaton myasthenic syndrome?
No - whilst present in approximately 85 to 95 percent of patients with LEMS and considered confirmatory if clinical and electrophysiology features of LEMS are also present they are also found in a variety of other conditions/clinical situations where LEMS is not present including: healthy control patients, in patients with myasthenia gravis, motor neurone disease, other malignancies
What percentage of patients with Small Cell Lung Cancer also have Lambert-Eaton myasthenic syndrome as a paraneoplastic syndrome?
3%
What test should you order in patients diagnosed with Lambert-Eaton myasthenic syndrome?
CT chest, abdomen, and pelvis
Also consider:
1. Magnetic resonance imaging (MRI) of the brain and/or spinal cord should also be obtained if there are focal neurologic symptoms or signs suggesting involvement of the central nervous system (CNS).
- 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) if high risk for malignancy but CT scan non-diagnostic
What factors are associated with a higher risk of SCLC in Lambert-Eaton myasthenic syndrome?
A high Dutch-English LEMS Tumour Association Prediction (DELTA-P) score
And
Presence of SOX antibodies
How do you treat Lambert-Eaton myasthenic syndrome?
Symptomatic management:
- Mild weakness - monitor only
- Moderate to Severe weakness - Amifampridine or pyridostigmine
Refractory disease:
- IVIG
- Prednisolone
- Azathioprine
- Mycophenolate
- Rituximab
How does Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome work?
Amifamipridine blocks potassium channels which significantly prolongs the presynaptic nerve terminal membrane depolarization, enhancing calcium entry and thereby improving the release of acetylcholine.
What are the main side effects of Amifampridine?
Perioral and extremity paraesthesiaes
Headache
Nausea
Abdominal pain
Diarrhoea
Elevated liver enzymes
Seizures
