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    • br Discussion The clinical course of our patient

    2023-01-16


    Discussion The clinical course of our patient until May 2012 was rather typical of early onset AChR-MG. Later on, the pattern of the disease was more typical of MuSK-MG, as evidenced by the distribution of myasthenic weakness and the unprovoked exacerbations. The AS-252424 of MuSK-MG appears to be clinically distinct with individuals generally exhibiting prominent oculobulbar, neck and respiratory muscle involvement. Furthermore, exacerbations are common and can occur in the absence of triggering factors and despite high dose immunosuppression (Guptill et al., 2011). The finger extensor weakness of our patient emerged during the last year, it greatly interferes with daily activities and is refractory to immunotherapy, even PE. Although weakness of distal extremity muscles is unusual in MG, the propensity for finger extensor weakness has been described in the limited references of distal weakness in MG (Nations et al., 1999). Whereas repetitive nerve stimulation of distal muscles is normal in many MG patients, single-fiber electromyography (SF-EMG) of the extensor digitorum communis (EDC) muscle reveals excessive jitter in the majority of generalized MG patients (Oh et al., 1992). This finding emphasizes that neuromuscular transmission is impaired in the finger extensors of many MG patients, even if there is no clinical weakness. Distal weakness is highly unusual finding in MuSK-MG. However, in some of these patients an abnormal jitter in the EDC muscle can be found on SF-EMG (Stickler et al., 2005). In light of the biphasic clinical course of our patient, serological re-assessment was undertaken which revealed the presence of both AChR Abs and MuSK Abs. Interestingly, the titer of AChR Abs remained high during the whole course, despite the immunotherapy, the thymectomy and the radiological absence of residual thymic tissue. MuSK Abs were not detected by the classical radioimmunoprecipitation assay but only by the novel CBA assay, which is known to detect MuSK Abs in several previously MuSK Ab negative patients (Vincent et al., 2012). This may suggest that MuSK CBA should be applied in both AChR Ab positive and negative patients with MuSK phenotype. The occurrence of both AChR Abs and MuSK Abs in the same individual is rare. We have recently reported a double seropositive case at the onset of MG and prior to any therapeutic intervention. The patient was a 36-year old woman with oculobulbar distribution of myasthenic weakness, responder to pyridostigmine and prednisolone and with low titer of AChRAbs (Zouvelou et al., 2013). A double-seropositive MG patient has also been identified 8 years after the onset of the disease and 6 years after thymectomy. The antibody status at the onset or prior to thymectomy was not known (Suhail et al., 2010). Another case of double-seropositive MG patient was identified after administration of d-penicillamine, where both antibodies disappeared after d-penicillamine discontinuation (Poulas et al., 2012). Furthermore, there are three reports of childhood onset AChR-MG who “seroconverted” to MuSK-MG after thymectomy, possibly as a result of “epitope spread”. None had MuSK Ab titers checked at the onset and all had relatively low AChR Abs (Saulat et al., 2007, Sanders and Juel, 2008, Kostera-Pruszczyk and Kwiecinski, 2009). Recently, a case of clinically biphasic MG with both AChR and MuSK Abs has been reported (Rajakulendran et al., 2012). The onset was at age 13 with bulbar predilection of the myasthenic weakness. The patient underwent thymectomy and responded favorably for over 15 years, when exacerbations started to occur. In contrast to our case, AChR or MuSK Abs had never been tested before clinical “switch” i.e. at the onset, before thymectomy or during the clinical stable state. We have documented that our patient was AChR-positive at the onset, prior to thymectomy and after thymectomy till the “switch” of the phenotypic pattern. Indeed, the double seropositivity was detected upon clinical “switch” from a predominantly AChR-MG to a MuSK-MG. We excluded the possibility of its previous existence as sera derived during 2008 were found negative for MuSK antibodies tested both by radioimmunoprecipitation assay and CBA. The development of MuSK Abs many years after the disease onset and thymectomy as well the persistence of high titers of AChR Abs is intriguing. A plausible explanation for the emergence of MuSK Abs would be the immunological changes following thymectomy in AChR-MG. In particular, these immunological changes consist in an expansion in the T cell repertoire and a greater prevalence of autoantibodies and autoimmune diseases than in non-thymectomy cases (Gerli et al., 1999).