Bulbar symptoms were infrequent among our patients, while ocular symptoms were relatively common. observational studies. We only included case reports, case series, and observational studies written in English with patients formally diagnosed with CANOMAD and treated with rituximab. We excluded systematic reviews, literature reviews, and meta-analyses. We investigated the clinical and biological responses of the patients to rituximab. The clinical response was classified as complete recovery (CR), partial response (PR), stable disease (SD), and non-response (NR). We gathered 34 patients. The literature uses a modified Rankin score to define complete improvement (CR), partial response (PR), stable disease (SD), and progression. Clinically, there were three patients with CR, five with PR, 15 with SD, and 11 with progression. The biological response was assessed by measuring the decrease in antibody titers in 27 patients. Among those, six patients had CR, 12 had PR, eight had SD, and one had progression. Among 15 patients with ADOS neurological evaluation, 10 had ocular symptoms, and two presented with bulbar symptoms. Seven of the ten patients with ocular symptoms had SD, two had Rabbit polyclonal to AGBL1 PR, and one had progression. Only 14 patients had a report of demyelinating features. Three had an axonal pattern, six had a demyelinating pattern, and five had a mixed pattern. Among patients with an axonal pattern, three had an SD. Among patients with a demyelinating pattern, three had a PR, two had an SD, and one had progression. Among patients with a mixed pattern, four had SD, and one ADOS had progression. We concluded that patients with CR have a shorter disease duration than patients with PR, SD, or progression. In addition, patients with CR had longer follow-ups than the other groups, suggesting that being treated early with rituximab improves the clinical outcome and has a sustained effect. There were no differences in the frequency of ocular and bulbar symptoms among patients with CANOMAD. The axonal pattern is more common in patients with SD, suggesting that axonal and mixed patterns could be markers of a bad prognosis. Keywords: opthalmoplegia, bulbar symptoms, igm, rituximab, gammapathy, canomad Introduction and background CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M (IgM) paraprotein, cold agglutinins, and the presence of disialosyl antibodies) is a rare type of gammopathy that includes a series of clinical, radiological, and laboratory features [1]. CANOMAD is a rare condition, ADOS with less than 100 cases reported in the literature [2]. The disease usually presents with peripheral neuropathy and chronic sensory ataxia. Pulmonary and ocular symptoms develop in the later stages of the disease as relapsing symptoms [2]. The features and progression of CANOMAD are usually variable [1]. The most common clinical features include sensory symptoms (78%), ataxia (47%), ophthalmoplegia (13%), bulbar symptoms (7%), facial nerve palsy (4%), motor weakness/myoclonus (7%), and dyspnea (2%) [1]. Importantly, the disease is usually associated with malignancy in 38% of the cases, with Waldenstr?m macroglobulinemia being the most commonly associated malignancy [1]. The course of the disease can have a relapsing-remitting pattern (31%), be chronically progressive (67%), or present with symptomatic flare-ups (2%) [1]. Canoma is caused by IgM antibodies against disialosyl antibodies (GQ1b, GT1B, or GD1b) [3]. On a microscopic level, initially, there is an IgM antibody/antigen reaction against disialosyl epitopes at nodal and para-nodal regions [3]. Eventually, this response progresses from antigen-dependent B-cell proliferation to antigen-independent B-cell proliferation, activating the complement, which leads to membrane attack complex (MAC) activation, causing a disruption of sodium.