Neurology -- Correspondence for Takahashi et al., 60 (3) 503-505

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Correspondence published:

Reply to Second Letter to the Editor: Yuji Takahashi (24 April 2003)

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome: Gil I Wolfe, Dennis K Burns, Laura L Herbelin and Richard J Barohn (24 April 2003)

Reply to Letter to the Editor: Y Takahashi, M. Sakurai and I. Kanazawa (14 March 2003)

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome: Ted M Burns, Susanna Quijano-Roy and H. Royden Jones (14 March 2003)

Reply to Second Letter to the Editor 24 April 2003

Yuji Takahashi
University of Tokyo Japan
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Re: Reply to Second Letter to the Editor

takahashiy-int{at}h.u-tokyo.ac.jp Yuji Takahashi

We also thank Dr. Wolfe et al. for their interest in our paper and for their presentation of a similar patient with ours. It is encouraging that their patient also showed long-lasting improvement with IVIG. There are several similarities between their patient and ours. First, IVIG was effective in patients who did not respond to other immunotherapies. Second, even chronic patients with the disease improved in a relatively short time. Third, the effect of IVIG lasted for years after the completion of the treatment. In addition to above points, we confirmed the effect objectively using SEP in one patient, although we could not detect improvement using sensory NCS. In conclusion, their report and ours show that IVIG is a promising treatment for the disease. A large scale, placebo -controlled double blind study is needed to confirm the beneficial effect of IVIG.

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome 24 April 2003

Gil I Wolfe
UT Southwestern Medical Center Dallas TX,
Dennis K Burns, Laura L Herbelin and Richard J Barohn
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Re: Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome

Gil.Wolfe{at}UTSouthwestern.edu Gil I Wolfe, et al.

We read with interest the article by Takahashi et al. [1] on the use of IVIG in patients with long-standing ataxic sensory neuronopathy (ASN) from Sjögren's syndrome. ASN can be incapacitating and has responded poorly to a number of immunotherapies. Of their five patients, four had remarkable improvement from three courses of IVIG. We have encountered a patient with severe Sjögren's-related ASN who has had a dramatic long-term response to IVIG.
A 35 year-old woman presented with sensory loss in the left hand that spread to the right hand, leg and thigh, and left foot over 6 months. Over the next 12 months her balance progressively worsened so she could no longer ambulate independently. On examination she appeared diffusely weak, but strength improved markedly with visual attention. She was areflexic. Position sense was completely absent in the upper and lower limbs; she could appreciate movement only of the head and neck. Assisted gait was notable for severe ataxia. Motor nerve conduction studies (NCS) were normal, but sensory NCS were absent in upper and lower limbs. Cooling and vibration thresholds on quantitative sensory testing (CASE IV, WR Medical, Stillwater, MN) using the 4,2, and 1 stepping protocol were above the 99th percentile in all limbs. Pertinent positive laboratory studies included ANA 1:640, SSA 176 units (negative < 20 units), and normal SSB. Minor salivary gland biopsy demonstrated lymphocytic infiltration. A five-month trial of prednisone up to 60 mg daily was unsuccessful. Induction IVIG 2 gm/kg followed by 1 gm/kg monthly was begun. Within 2 months she again could ambulate independently and subsequently gave up her walker and cane. Monthly IVIG continued for 12 months. She has maintained independent ambulation for 5 years.
Molina et al. [2] have also reported a favorable response to IVIG in a 60 year-old man with Sjögren's-related ASN. Although reduction of a smoldering ganglionitis with rescue of remaining dorsal root ganglion cells is a proposed mechanism, neither Takahashi et al. nor we [1] could document improved sensory NCS. QST thresholds remained unchanged in our patient. Controlled trials are lacking, but these reports suggest that IVIG may produce a dramatic, persistent benefit for patients with this incapacitating syndrome. Although results from immunosuppressive agents and plasmapheresis have been disappointing or equivocal, [3] infliximab, a monoclonal antibody to tumor necrosis factor a, should be considered for IVIG non-responders. [4]
References
1.Takahashi Y, Takata T, Hoshino M, Sakurai M, Kanazawa I. Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. Neurology 2003;60:503-505.
2.Molina JA, Benito-Leon J, Bermejo F, Jimenez-Jimenez FJ, Olivan J. Intravenous immunoglobulin therapy in sensory neuropathy associated with Sjögren's syndrome. J Neurol Neurosurg Psychiatry 1996;60:699.
3.Griffin JW, Cornblath DR, Alexander E, et al. Ataxic sensory neuropathy and dorsal root ganglionitis associate with Sjögren's syndrome. Ann Neurol 2000;27:304-315.
4.Caroyer J-M, Manto MU, Steinfeld SD. Severe sensory neuronopathy responsive to infliximab in primary Sjögren's syndrome. Neurology 2002;59:1113-1114.

Reply to Letter to the Editor 14 March 2003

Y Takahashi
University of Tokyo Japan,
M. Sakurai and I. Kanazawa
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Re: Reply to Letter to the Editor

TAKAHASHIY-INT{at}h.u-tokyo.ac.jp Y Takahashi, et al.

We thank Burns et al. for their comments. It is encouraging that a similar beneficial effect of IVIG has been observed in cases with chronic, long-standing SSASN, particularly those of a different race from a different facility. Their experience supports ours, although there are several differences. Our study included patients with pure sensory ataxia without any motor involvement, and none of our patients had a familial history. The treatment regimen was also slightly different. Clinical improvement in their cases might be more prominent than ours, considering the disappearance of Romberg sign, probably because their cases might be less severe. Further studies should be carried out in order to predict what types of patients are responsive to IVIG therapy, and to determine the optimal IVIG regimen for SSASN. However, their results may provide us with a clue for elucidating the pathogenesis of SSASN and the mechanisms of the IVIG effect. As they mentioned, a randomized, placebo-controlled double-blind trial should be warranted to confirm the benefit of IVIG for SSASN.

Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome 14 March 2003

Ted M Burns
Charlottesville VA,
Susanna Quijano-Roy and H. Royden Jones
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Re: Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren’s syndrome

TMB8R{at}hscmail.mcc.virginia.edu Ted M Burns, et al.

Takahashi et al. has reported on the benefit of IV immunoglobulin (IVIg) in five patients with long-standing ataxic sensory neuronopathy with Sjögren's syndrome (SSASN). [1] We would like to report a similar experience in two siblings with SSASN:
A 62-year-old woman presented with a 1-year history of progressive sensory symptoms with prominent ataxia causing marked gait difficulty, associated with dryness of eyes and mouth (sicca complex) and 40-pound weight loss. Her examination was remarkable for a moderate-to-severe sensory>motor polyneuropathy, with positive Romberg and wide-based, ataxic gait.
Her 69-year-old brother reported a 5-year history of progressive stocking-glove distribution sensory symptoms. His examination similarly revealed findings of sensory>motor polyneuropathy, with marked ataxia and positive Romberg.
Prominent lymphocytic infiltration was seen on salivary gland biopsy of both patients. Electrodiagnostic testing demonstrated a predominantly axonal sensorimotor polyneuropathy. The sister had elevated SS-A and SS-B antibodies, but the brother did not. The sister's sural nerve biopsy demonstrated prominent perivascular inflammation of small epineurial vessels and multifocal myelinated nerve fiber loss.
They were treated with IVIg 2 g/kg total dose over 5 days followed by 0.4gm/kg every 3 weeks (sister) or every week (brother). After 3 months of treatment, there was unequivocal improvement in sensory symptoms and dramatic improvement in gait and functional status. The sister also reported improvement in sicca complex symptoms. In both cases, follow-up examination revealed improvement in gait, absence of Romberg sign, and less severe sensory deficits. Clinical improvement has persisted for up to 14 months and then to 20 months.
The beneficial experience of IVIg seen in our two patients with SSASN is further anecdotal evidence of efficacy [1,2,3] even with individuals having this disease for as long as 5 years. Because IVIg is expensive and has potential side effects, candidates for IVIg must be carefully selected. Criteria should include a sensory ataxic phenotype and diagnosis of probable or definite SS.[4]Our experience and the experience of Takahashi et al. demonstrated that even the long-standing SSASN patient needs to be considered for treatment. A randomized, placebo-controlled trial is necessary to confirm the efficacy of IVIg in this condition.
References:
1. Takahashi Y, Takata T, Hoshino M, Sakurai M, Kanazawa I. Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. Neurology 2003;60:503-505.
2. Molina JA, Benito-Leon J, Bermejo F, Jimenez-Jimenez FJ, Olivan J. Intravenous immunoglobulin therapy in sensory neuropathy associated with Sjögren's syndrome. J Neurol Neurosurg Psychiatry 1996;60:699. Letter.
3.Pascual J, Cid C, Berciano J. High-dose IV immunoglobulin for peripheral neuropathy associated with Sjögren's syndrome. Neurology 1998;51:650-651.
4. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum 1993;36:340-347.