PARANEOPLASTIC NEUROMU SCULARSYNDROMES
Paraneoplastic syndromes are
immune-mediateddiseases associated with an underlying cancer. Myasthenia gravis
is often considered a paraneo-plastic syndrome because it is an autoimmune
dis-order associated with thymic hyperplasia, including thymoma. Other
neurological or neuromuscular paraneoplastic syndromes include Lambert–Eaton
myasthenic syndrome, limbic encephalitis, neuro-myotonia, stiff person
syndrome, myotonic dystro-phy, and polymyositis.
The Lambert–Eaton myasthenic syndrome (LEMS)
is a paraneoplastic syndrome characterized by proximal muscle weakness that
typically begins in the lower extremities but may spread to involve upper limb,
bulbar, and respiratory muscles. Dry mouth, male impotence, and other
manifestations of autonomic dysfunction are also common. LEMS is usually
associated with small cell carcinoma of the lung but may also be seen with
other malignancies or as an idiopathic autoimmune disease. The disorder results
from a presynaptic defect of neuromuscular transmission in which antibodies to
voltage-gated calcium channels on the nerve terminal markedly reduce the
quantal release of acetylcholine at the motor end plate. Small cell lung
carcinoma cells express identical voltage-gated calcium channels, serving as a
trigger for the autoimmune response in patients with paraneoplastic LEMS.
In contrast to myasthenia gravis, muscle weak-ness associated with LEMS
improves with repeated effort and is improved less dramatically by
anti-cholinesterase drugs. Guanidine hydrochloride and 3,4-diaminopyridine
(DAP), which increase the presynaptic release of acetylcholine, often produce
significant improvement in LEMS. Corticosteroid or other immunosuppressive
medications, or plasma-pheresis, may also be of benefit.
Limbic encephalitis is a degenerative central ner-vous system disorder
characterized by personality changes, hallucinations, seizures, autonomic
dys-function, varying degrees of dementia, and asym-metric loss of sensation in
the extremities. It may involve the brain, brainstem, cerebellum, and spinal
cord. In approximately 60% of cases, limbic enceph-alitis is paraneoplastic.
There is a strong association with small cell lung carcinoma, and neurological
dysfunction often precedes the cancer diagnosis. Therapy includes treatment of
the underlying can-cer, if present, and administration of immunosup-pressive
medications.
Neuromyotonia is a condition of peripheral nerve hyperexcitability that
is frequently associated with an underlying cancer but may also be inher-ited
or associated with diabetic, drug- or toxin-induced, or other acquired
neuropathies. Its featuresinclude myokymia
(a continuous undulating move-ment of muscles described as being like a “bag of
worms”), stiffness, impaired muscle relaxation, painful muscle cramping,
hyperhidrosis, and muscle hypertrophy. Treatment includes immunoglobulin
therapy, plasma exchange, and administration of anticonvulsants.
Stiff person syndrome is a progressive
disorder characterized by axial stiffness and rigidity that may subsequently
involve the proximal limb muscles. In advanced cases, paraspinal rigidity may
cause marked spinal deformities, and the patient may have difficulty with
ambulation and a history of fre-quently falling. Although stiff person syndrome
is rare, when it occurs it is frequently associated with cancer. Therapy
includes treatment of the underly-ing cancer, if present, and administration of
immu-noglobulin and benzodiazepines.
Polymyositis is an inflammatory myopathy of
skel-etal musculature, especially proximal limb muscles, characterized by
weakness and easy fatigability. Patients are prone to aspiration and frequent
pneu-monias because of thoracic muscle weakness and dysphagia secondary to
oropharyngeal muscle involvement. They may also exhibit cardiac dys-rhythmias
due to conduction defects. Therapy includes treatment of the underlying
neoplasm, if present; plasma exchange; and administration of immunoglobulin,
corticosteroids, and immuno-modulators such as methotrexate, cyclosporine, and
tumor necrosis factor-α inhibitors.
Patients with LEMS and other neuromuscular
paraneoplastic syndromes are very sensitiveto both depolarizing and
nondepolarizing NMBs. Volatile agents alone are often sufficient to
providemuscle relaxation for both intubation and most surgical procedures. NMBs
should be given only in small increments and with careful neuromuscu-lar
monitoring. Because these patients frequently exhibit marked debility,
benzodiazepines, opioids, and other medications with sedative effects should be
administered with caution.
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