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.