Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) involving Ocular Cranial Nerves
This patient presented with the gradual onset of progressive weakness that eventually involved all four extremities. The pattern of weakness suggested localization to the muscle, neuromuscular junction, peripheral nerve, nerve root, or anterior horn cell. Diplopia can result from disorders of the extraocular muscles, neuromuscular junction, or the cranial nerves involved in eye movements (III, IV, VI). The later development of bilateral leg numbness is most consistent with peripheral nerve involvement, but can also be seen in polyradiculopathy or spinal cord disease.
The neurologic exam confirmed symmetric weakness of all extremities, perhaps proximally more than distally. This pattern of weakness is usually more consistent with either a myopathy or a disorder of neuromuscular transmission. However, other neuropathies may begin proximally (Guillain-Barré syndrome, chronic inflammatory demyelinating neuropathy, diabetes). The exam also confirmed the presence of ocular motility dysfunction involving bilateral lateral recti and bilateral third nerves. Glove-stocking sensory loss suggested a peripheral neuropathy. The presence of hyporeflexia/areflexia increased the possibility of a polyneuropathy/polyradiculopathy, but could also be seen in myopathies and neuromuscular junction disorders.
The EMG/NCV and CSF analysis provided valuable information. The EMG/NCV confirmed the presence of a mainly motor demyelinating polyneuropathy. The absence of CSF pleocytosis also lowered the likelihood of an infectious or neoplastic etiology. However, the elevated CSF protein suggested an inflammatory condition, which was supported by an elevated CSF IgG synthesis and IgG index. The elevated CSF Q-albumin implied an impairment in the blood-brain barrier. The normal MRI of the brain made intrinsic brainstem pathology (such as ischemia or demyelination) less likely.
The key issue was whether or not the patient's diplopia was related in etiology to her progressive weakness. Conditions which can cause both extremity weakness and ophthalmoparesis include:
She was treated with three cycles of plasmapheresis, followed by IV Cytoxan for three days. Cytoxan had to be discontinued secondary to the development of neutropenia. As alternative immunosuppressive therapy, she was given six monthly doses of intravenous IgG.
On follow-up (two months following discharge), she no longer had diplopia and felt her strength and eye movements had improved. Objectively, she demonstrated improvement in extremity strength as well as eye motility and was not diplopic during the examination.
CIDP is an important clinical diagnosis because: (1) it represents about one third of all initially undiagnosed acquired neuropathies; and (2) most patients with CIDP will respond to immunosuppressive therapy, although relapses are common.
Patients with CIDP usually present with progressive, step-wise or relapsing muscle weakness that is present for at least two months. The degree of weakness is variable. Sensory complaints usually consists of numbness and tingling; painful paresthesias are uncommon. The peak incidence is 40-60 years of age.
Neurologic exam usually reveals proximal muscle weakness, sometimes even more affected than distal musculature. Both upper and lower extremities are involved, although the legs are usually affected more severely. Neck flexor weakness distinguishes CIDP from most other neuropathies. Cranial nerves are usually spared, although facial muscles may be affected. Ophthalmoplegia in CIDP is rare and the prevalence ranges from 3 to 8 percent in several case series. Of note, the ophthalmoplegia may precede the systemic weakness by days to months. Deep tendon reflexes are absent or depressed. Sensory findings are typically mild and often include impaired touch and vibratory sensation, with less involvement of small-fiber sensation (pain and temperature).
The major laboratory tests for CIDP are electrophysiologic studies, CSF examination, and nerve biopsy.
The immunopathogenesis of CIDP is not understood. Support for a cell-mediated component comes from the finding of mononuclear cell infiltration, both diffuse and perivascular, in spinal roots, spinal ganglia, and proximal nerve trunks of postmortem cases. Evidence for a humoral component comes from the observation of clinical response of patients with CIDP to plasma exchange.
James Austin first documented the steroid responsiveness of CIDP in 1958. More recent randomized controlled studies have documented that prednisone and plasma exchange are both beneficial. Some advocate initiation of single, daily-dose prednisone until patients show significant improvement. The mean time for initial response is two months. After attaining maximum benefit (usually 6-12 months), prednisone is slowly tapered. Unfortunately, the tapering of prednisone may result in a relapse of CIDP. The addition of azathioprine offers no advantage over prednisone alone. The possible adverse effects of long-term steroid use must also be considered. The use of high-dose intravenous steroids has only recently been investigated.
Plasma exchange performed twice weekly for three weeks generally result in transient improvement in both progressive and recurrent cases. The optimal schedule for plasma exchanges has not been established.
Intravenous immune globulin (IVIG) has also been found to be beneficial. IVIG is usually given in divided doses over 4 or 5 consecutive days. Maintenance doses are often needed at variable intervals to maintain clinical response. Serious side effects of IVIG treatment are rare (fatal anaphylaxis in IgA-deficient patients; potential nephrotoxicity, especially in patients with pre-existing renal disease). The main recognized role for IVIG treatment in CIDP is for patients refractory to corticosteroids or for patients with steroid side effects or contraindications (e.g., diabetes).
For patients refractory to steroids, plasma exchange, and IVIG, alternative forms of immunosuppressive treatment can be considered. These agents include azathioprine, cyclophosphamide, and cyclosporine. However, there are no clear guidelines for their use in the treatment of CIDP.
A recent report suggests the possible benefit of interferon-alpha 2A in CIDP patients. The authors of that report postulate that interferon-alpha may modulate proinflammatory cytokines that have a role in immune-mediated demyelination.
Unlike the overall good prognosis in Guillain-Barré syndrome, CIDP is less likely to have spontaneous remissions and is often associated with prolonged neurological disability. Although 95% of patients will show initial improvement following immunosuppressive therapy, the relapse rate is high. In the series of Dyck et al, only 64% of 53 patients were improved or in remission and able to return to work, 8% were ambulatory but unable to work, 11% were bedridden or wheelchair bound, and 11% died of the disease. Six percent died from other diseases.
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