The patient we describe presented with signs suggesting MFS but rapidly developed impaired consciousness and tetraplegia indicating an overlap with BBE and GBS. IgG anti-GQ1b were detected and serology documented a recent Mycoplasma Pneumoniae infection. MFS overlapping with GBS or BBE has been reported respectively in 15 and 12% of cases but the triple overlap has rarely been described [6, 7]. Prior Mycoplasma Pneumoniae infection has been reported in GBS, MFS and also in BBE . A common denominator to MFS, BBE and GBS is the presence of anti-GQ1b antibody .GQ1b gangliosides are highly expressed in the nodal and paranodal regions of the oculomotor nerves, muscle spindle afferents, peripheral nerves and possibly in the brainstem reticular formation [10, 11]. The presence of anti-GQ1b antibodies may explain the complex symptomatology of the patient we report. The overlap among MFS, BBE, and GBS reemphasizes that these disorders are all part of a wide clinical spectrum . The patient presented electrophysiologically with severely reduced or non-recordable CMAPs and SNAPs without demyelinating features indicating, at first test, the electrodiagnosis of acute motor and sensory axonal neuropathy with axonal degeneration and suggesting, in presence of tetraplegia, a poor prognosis. However, distal CMAPs greatly improved in 10 weeks suggesting the resolution of distal CBs whereas CBs in intermediate and proximal nerve segments emerged and unusually persisted for four to 7 months without the development of excessive temporal dispersion of CMAPs, which is considered one of the electrophysiological correlates of de-remyelination [13, 14]. These electrophysiological features and the fact that the resolution of CBs mirrored the clinical improvement suggest that weakness was due to a sustained, antibody-mediated attack at the nodal region inducing a non-demyelinating conduction failure [15,16,17]. CBs in axonal GBS predominate where the blood-nerve barrier is anatomically deficient, as in the nerve endings, nerve roots, and the common entrapment sites [15, 18]. We hypothesize that, in the patient we report, the improving of distal conduction blocks revealed already existing proximal conduction blocks that persisted for months . Alternatively, the persistence of the autoimmune attack, supported by the high rate of IgG anti GQ1b 5 months after the onset of symptoms, might have caused the appearance of new CBs in more proximal sites.In this last case, other humoral factors present in our patient’s serum probably intervened favoring the disruption of the blood-nerve barrier .
Currently, axonal GBS subtypes and MFS are thought to represent acute autoimmune nodopathies with a common pathogenic mechanism characterized by anti-gangliosides mediated dysfunction/disruption of the NAv channel clusters at the Ranvier node and by an electrophysiological continuum from conduction failure, reversible in few weeks, to axonal degeneration [20, 21]. Acute onset and long lasting CBs as in the patient we report, have been described in few patients with IgM antibodies against GM1, GD1a or GD1Q and variably categorized as acute variant of multifocal motor neuropathies or chronic forms of acute motor conduction block neuropathies [22,23,24]. In neuropathies with anti-ganglioside antibodies it is not explained why most patients have an acute onset with conduction failure that may be promptly reversible or progress to axonal degeneration whereas few others are characterized by persistent CBs. In addition to the duration of the immune attack, intrinsic properties of anti-ganglioside antibodies, such as isotype, affinity and capability to activate complement may be implicated.
Notably, except in the first electrophysiological study, the patient showed slowing of nerve conduction that is commonly assumed to be a characteristic of a de-remyelinating process. However, inactivation of Nav channels by intravenous infusion of lidocaine or tetrodotoxin intoxication reduces conduction velocity, even reaching the “demyelinating” range, possibly by increasing the rise time of the action potential and the internodal conduction time [25, 26]. These findings may well explain the occurrence of slow conduction velocity in an autoimmune neuropathy targeting the excitable axolemma of the node of Ranvier as in the patient we describe .
In conclusion, in this patient with an unusual and severe clinical overlap of MFS, BBE, and GBS, serial electrophysiological studies allowed to understand the underlying pathophysiology as attributable to an acute onset, long lasting, nodopathy. Moreover, serial electrophysiology allowed by the second study to formulate a more correct prognosis and guided the treatment as the persistence of CBs encouraged us to carry out a third cycle of IVIg which possibly accelerated the clinical recovery and prevented further axonal degeneration.