Treatment of Primary Autoimmune Cerebellar Ataxia with Mycophenolate

Abstract

Immune-mediated ataxias account for a substantial number of sporadic otherwise idiopathic ataxias. Despite some wellcharacterised entities such as paraneoplastic cerebellar degeneration where diagnostic markers exist, the majority of immune ataxias remained undiagnosed and untreated. We present here our experience in the treatment of suspected primary autoimmune cerebellar ataxia (PACA) using mycophenolate. All patients reported attend the Sheffield Ataxia Centre on a regular basis and had undergone extensive investigations, including genetic testing using next-generation sequencing, with other causes of ataxia excluded. The diagnosis of PACA was strongly suspected based on investigations, pattern of disease progression, and cerebellar involvement. Patients were treated with mycophenolate and monitored using MR spectroscopy of the cerebellar vermis. Thirty patients with PACA are reported here. Of these, 22 received mycophenolate (group 1). The remaining 8 were not on treatment (group 2-control group). Out of the 22 treated patients, 4 underwent serial MR spectroscopy prior to starting treatment and thus were used as controls making the total number of patients in the control group 12. The mean change of the MRS within the vermis (NAA/Cr area ratio) in the treatment group was + 0.144 ± 0.09 (improved) and in the untreated group − 0.155 ± 0.06 (deteriorated). The difference was significant. We also demonstrated a strong correlation between the spectroscopy and the SARA score. We have demonstrated the effectiveness of mycophenolate in the treatment of PACA. The results suggest that immune-mediated ataxias are potentially treatable, and that there is a need for early diagnosis to prevent permanent neurological deficit. The recently published diagnostic criteria for PACA would hopefully aid the diagnosis and treatment of this entity.

Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia—Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias

“…paraneoplastic cerebellar degeneration (PCD) [ 1 ], gluten ataxia (GA) [ 2 ], post-infectious cerebellitis (PIC) [ 3 ] as well as ataxias where neuronal antibodies have been convincingly shown to be directly involved in the pathogenesis of the ataxia. The term primary autoimmune cerebellar ataxia (PACA) was introduced to describe a group of patients with suspected IMCA in which neither a trigger nor any pathogenic neuronal antibodies have been discovered as yet [ 4 ].…”

Recognition and management of rapid-onset gluten ataxias: case series

“…Regardless of modality, clinically meaningful outcomes appear to be dependent on instigating treatment early, to stop cerebellar cell loss beyond an irreversible threshold (sometimes referred to as cerebellar reserve) [ 9 ]. In rapidly progressive cases the use of steroids and intravenous immunoglobulins to provide a rapid induction prior to mycophenolate and then gluten free diet reaching full efficacy is advisable [ 8 ]. In our described cases, clinical stability or improvement was achieved only with aggressive immunotherapy.…”

Indirect immunofluorescent assay as an aid in the diagnosis of suspected immune mediated ataxias

“…None of the patients in this IMCA group were found to have an alternative explanation for their ataxia. Detail clinical characterisation of these 3 different types of immune ataxias have already been published [4][5][6]. (2).…”

“…Unlike GA, PCD and post-infectious cerebellitis, in which an antigenic trigger is known, in some suspected autoimmune ataxias the antigenic trigger is not known and any associated neuronal antibodies are not well characterized or of proven pathogenicity. The term Primary Autoimmune Cerebellar Ataxia (PACA) was introduced to describe this latter group of patients [ 2 ].…”

“…The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. These criteria are important because PACA is potentially treatable with immunosuppression [ 4 ].…”