There is no consensus about the specific treatment of neurological involvement in pSS. Generally, corticosteroid therapy is initiated in patients with either CNS or PNS [15
]. CNS involvement is usually treated with high corticosteroid dose. In some cases, response to treatment is exceptional. For example, Caselli et al. [87
] showed one patient with dementia who markedly improved after corticosteroid treatment. Concerning the treatment of acute and chronic myelopathies, de Seze et al. [88
] showed the tolerance and clinical response of a combination regimen of steroids and monthly cyclophosphamide. Fourteen patients (6 with acute and 8 with chronic myelopathies) were evaluated. Tolerance was good, and nine patients improved clinically (including the total 6 patients with acute myelopathy), three patients remained stable, and the other two patients presented moderate progression. Although randomized studies are necessary, this treatment needs to be considered in patients with progressive disease.
Classically, peripheral neuropathy in patients with pSS responds poorly to treatment [11
]. Some groups recommend only treating the symptoms according to the severity. In other patients, immunosuppressive therapy based on corticosteroids, cyclophosphamide, azathioprine, and even plasmapheresis has shown only mild success [89
In the series reported by Terrier et al. [79
], patients with necrotizing vasculitis have a better response to immunosuppressive treatment, mainly with cyclophosphamide (71% of patients with necrotizing vasculitis showed good response compared to 25% of patients with lymphocytic vasculitis). Griffin et al. reported a treatment based on corticosteroids and associated in some cases with azathioprine, intravenous cyclophosphamide or plasma exchanges [54
]. Only one patient with a relapsing course responded to corticosteroid treatment. Mori et al. suggested that corticosteroids are suitable for multiple neuropathy and multiple cranial neuropathy [11
IVIg has been also reported as a good therapeutic option in some painful sensory neuropathy cases [92
] and in radiculoneuropathy. In a recently series of 19
pSS patients with peripheral neuropathy, intravenous immunoglobulin treatment was evaluated [93
]. In this study, 8 patients (42%) showed a decrease of the disability Modified Rankin Scale, corresponding to a clinical improvement. Patients with sensorimotor or nonataxic sensory neuropathy were markedly improved compared to patients with ataxic neuropathy (2/9). The authors concluded that clinical benefits of IVIg treatment depend on the specific clinical subtype.
Caroyer et al. [94
] showed improvement in sensory ganglioneuronopathy treated with infliximab. However, no controlled trials have shown efficacy of infliximab or others anti-TNFα
in pSS-related neuropathy.
Rituximab, an anti-CD20 antibody, may be useful in systemic complications in pSS patients [95
] and in some cases of refractory neuropathy. Recently, Mekinian et al. [97
] reported 17 patients with pSS and PNS involvement treated with rituximab. Neurological improvement was observed in 11/17 patients (65%) at three months. Best results were observed in patients with cryoglobulinemia or vasculitis-related PNS involvement (9/10 patients improved).
The benefits from treatment with oromucosal IFN-α
in pSS have been reported by several groups [98
]. Due to possible effects on sicca symptoms, Yamada et al. [102
] reported three cases of pSS-associated neuropathy treated with oral IFN-α
(two patients with sensory ataxic neuronopathy and one patient with axonal sensorimotor neuropathy with demyelinating features). All three patients responded well to IFN-α
, improving the neurological symptoms. Sicca symptoms, antibodies titres, and focus score of salivary gland biopsy were also improved. However, the mechanisms whereby IFN-α
induces neurological improvement in pSS are uncertain.
In conclusion, neurological manifestations are common in pSS and often precede the diagnosis. The accurate prevalence of these manifestations is difficult to assess, because the heterogeneity of the series. The pathogenic mechanisms responsible for most forms of neurological involvement in pSS remain unknown, but vascular, ischemic, and immunological mechanisms have been described. Controlled and population-based trials are necessary to better characterize the neurological manifestations in pSS and their therapeutic response.