Abstract
The authors describe two patients with acute sensory ataxic neuropathy. Both had a profound loss of proprioception and generalized areflexia. High titers of monospecific anti-GD1b IgG antibody were detected in their sera during the acute phase. Sensory ataxia resolved within 2 weeks after the onset. Taken together with the induction of experimental sensory ataxic neuropathy sensitized with GD1b ganglioside, GD1b may be a target molecule for autoantibody in some patients with acute sensory ataxic neuropathy.
Acute sensory ataxic neuropathy (ASAN) is characterized by acute onset of sensory ataxia, loss of deep tendon reflexes, and impaired vibratory and joint position sensations.1 Some patients with ASAN have antecedent infections, similar to patients with Guillain–Barré syndrome (GBS). Although GBS often is associated with antibodies against gangliosides, few cases of ASAN associated with antiganglioside antibodies have been reported.2,3⇓ We describe two patients with ASAN associated with anti-GD1b IgG antibody.
Case reports.
Patient 1.
A 59-year-old woman developed acute bilateral shooting pain in the lower extremities 3 days after a minor upper respiratory tract infection. Two days later she had severe unsteady gait due to a profound loss of kinesthetic sensation in all extremities. Numbness and tingling sensations rapidly ascended to the upper extremities. Her muscle strength was intact, and there was no double vision, swallowing difficulty, or autonomic dysfunction. Neurologic examinations revealed profoundly impaired vibratory sensation and joint positional sensation over all extremities, with a positive Romberg test. Sensations to pinprick and temperature were preserved. All tendon reflexes were absent. Despite the preservation of muscle strength, she could only lie in bed because of severe sensory ataxia and proprioceptive loss. Her CSF was clear and acellular, with an increased protein level of 141 mg/dL. Both serum and CSF protein immunoelectrophoresis revealed no monoclonal gammopathy. Nerve conduction studies were performed following standardized protocols before and after plasma exchange. The results of electrophysiology were summarized in tables 1 and 2⇓. The major findings on initial examinations were the absence of bilateral tibial H-reflexes. Subsequent studies showed either absence or markedly diminished amplitude of sensory action potential with normal motor nerve functions. On quantitative sensory testing, thresholds for vibratory sensation were markedly elevated in the lower extremities, with normal thresholds for warm and cold sensations. Plasma exchange was conducted for eight sessions. She experienced slight improvement in limb position sensation after the second exchange. After the fourth exchange, the paresthesia was markedly reduced and she could walk cautiously. At the completion of plasma exchanges she could walk for 60 to 70 meters without assistance. Fourth months later she could play tennis, and the electrophysiologic study showed restoration of sensory action potentials in all sampled nerves (see table 1).
Nerve conduction study (sensory nerves)
Patient 2.
A 34-year-old man developed numbness in the tongue tip 1 week before admission. Because of chronic bronchitis he could not recall whether there was preceding infection before the onset of symptoms. Subsequently numbness and paresthesia developed in the distal parts of the upper and lower extremities. The symptoms extended to both elbows and knees within 4 days after the onset, and he had a severe unsteady gait. Examinations revealed intact cranial nerve functions and there was no ophthalmoplegia. The muscle power was normal, but all tendon reflexes were absent. The vibratory sensation and proprioception of joints were profoundly impaired, with positive Romberg sign. The protein level in the CSF was 43 mg/dL, with one mononuclear cell. Both serum and CSF protein immunoelectrophoresis failed to detect monoclonal immunoglobulins. Nerve conduction studies showed absence of bilateral sural sensory action potentials, with normal motor nerve electrophysiology (see tables 1 and 2⇓). After two sessions of plasma exchange he showed substantial improvement in gait, and the paresthesia began to subside. At the end of the third exchange, he had a nearly normal gait and could walk for a long distance without assistance. Electrophysiologic studies after plasma exchange showed restoration of the sensory action potentials in sural nerves.
Examinations of antiganglioside antibodies.
Serum antiganglioside antibodies were examined by ELISA.4 In brief, individual 5-pmol samples of GM1, GM1b, GM2, GD1a, GalNAc-GD1a, GD1b, GD2, GT1a, GT1b, or GQ1b were placed in individual wells and serum samples diluted 1:500 were added. The immunoglobulin class of the antiganglioside antibodies was determined by the use of peroxidase-conjugated anti-human γ- or μ-chain-specific antibodies (1:1,000; Dako, Glostrup, Denmark). The serum was tested once in triplicate. Absorbance values at 492 nm were corrected by subtracting the optical densities obtained for each well without antigen. Antiganglioside antibody was considered positive when the absorbance value was 0.1 or more, and antiganglioside titer (1:×) was the highest serum dilution when the result was positive. Both patients had high titers of serum anti-GD1b IgG antibody at 1:2,000 during the acute phase of illness, and all the other tested antiganglioside antibodies were negative. Anti-GD1b IgG was not detected in the serum obtained from Patient 1 during the convalescent phase 2 months after onset of the symptoms.
Discussion.
Our patients had acute onset of sensory ataxia and generalized areflexia. ASAN was diagnosed based on the absence of ophthalmoplegia, cerebellar ataxia, and motor weakness. Only two cases of ASAN associated with antiganglioside antibodies have been reported.2,3⇓ A patient with a relapsing form of ASAN had extremely high titer of an IgM monoclonal antibody against b-series gangliosides GD2, GD1b, GT1b, and GQ1b, to which internal disialosyl structure is common.2 The patient’s IgM antibody caused cell death in an in vitro system of rat dorsal root ganglion culture.5 No cytotoxicity was found when the IgM had been absorbed with GD1b. Another patient with monophasic course had high titers of anti-GD3 and anti-GD1b IgG antibodies during the acute phase of the illness.3 Absorption studies showed thatthe antibodies were cross-reactive. Anti-GD1b IgG antibody was present in one patient with acute postinfectious sensory neuropathy who did not show sensory ataxia.4 In contrast, this is the first report of ASAN associated with monospecific anti-GD1b IgG antibody. Experimental sensory ataxic neuropathy can be induced in rabbits by sensitization with GD1b,6 and GD1b is expressed on human dorsal root ganglion neurons.7 These findings suggest that GD1b is a target molecule of autoantibodies in some patients with ASAN.
Nerve conduction study (motor nerves)
Whether ASAN is a variant of GBS remains a controversial issue. Interestingly, there has been a case report of GBS associated with monospecific anti-GD1b IgG antibody.8 The patient showed prominent sensory ataxia. This suggests that a common autoimmune mechanism operates in some cases of ASAN and of GBS with sensory ataxia. In a large series of 42 patients with ASAN,1 the therapeutic alternatives included corticosteroids (12 patients), plasma exchange (1 patient), and corticosteroids combined with plasma exchange (1 patient). Only two of the 42 patients had complete remission of neurologic deficits. In contrast, our patients had dramatic improvement shortly after plasma exchange. Their neurologic recovery was complete in less than 2 months. The electrophysiologic study demonstrated the reversibility of sensory nerve or neuronal damage. We treated these two patients with plasma exchange based on the autoimmune nature of ASAN. However, the possibility of spontaneous recovery should be taken into consideration. Alternatively, the timing of treatment for ASAN may also be important regarding the efficacy. Further studies are necessary to evaluate the therapeutic strategies for ASAN.
- Received April 30, 2001.
- Accepted June 15, 2001.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.