Miller Fisher syndrome (MFS), a subtype of Guillain-Barre syndrome (GBS), is an acute immune-mediated polyneuropathy characterized by a clinical triad of ophthalmoplegia, ataxia, and areflexia [1]. However, in clinical practice, a considerable number of unusual clinical manifestations of MFS or similar syndromes have been documented, which has led to the emergence of the concept of anti-GQ1b antibody syndrome [2]. There have been rare reports of anti-GQ1b antibody syndrome without ophthalmoplegia, the main clinical feature. In addition, unlike the typical symptoms of ascending paralysis, atypical symptoms in the form of weakness progressing from the upper extremities to the lower extremities have been reported in MFS [3]. We present a patient diagnosed with anti-GQ1b antibody syndrome, based on clinical findings and neurophysiological examinations indicative of acute motor axonal neuropathy (AMAN) type of GBS with descending paralysis.

A 66-year-old female presented to the emergency room with bilateral upper limb weakness that had started two weeks prior and subsequently progressed to lower limb weakness. The patient had no limitation of extraocular movements, and the muscle strength of the bilateral upper limbs was rated as Medical Research Council grade II on the right and grade III on the left, while the bilateral lower limbs strength was grade II. There were no sensory changes, and deep tendon reflexes were absent. There was no recent history of infection. Laboratory findings, including complete blood count, electrolyte levels, and thyroid-stimulating hormone, were within the normal range. Autoimmune antibodies, including ANA, ANCA, anti-ds-DNA immunoglobulin (Ig) M & IgG, anti-CCP, and anti-phospholipase A2 receptor IgG, were negative. Additionally, paraneoplastic antibody tests, including anti-Hu, anti-Ri, anti-Yo, anti-amphiphysin, anti-CV2, anti-PNMA2 (Ma2/Ta), anti-Recoverin, anti-SOX1, and anti-titin (MGT-30), were also negative. Brain and spinal cord magnetic resonance imaging results had no abnormal findings. Cerebrospinal fluid analysis revealed that the pressure was 11 cmH₂O, white blood cells at 2/µL, and a protein increased to 99.3 mg/dL, confirming albumino-cytologic dissociation. Nerve conduction studies showed in abnormal F-wave latency in right median, ulnar nerves and bilateral peroneal, posterior tibial nerves, absent H-reflex, and decreased compound muscle action potential and motor conduction velocity (CV) (Table 1). However, no conduction block or temporal dispersion was observed, so AMAN was considered according to Hadden’s criteria. In the serum test, only the anti-GQ1b IgM antibody was positive, while the anti-GD1b and anti-GM1 antibodies were negative. The patient started intravenous immunoglobulin treatment with a total of five doses, and the muscle strength gradually improved to grade III in both lower limbs. The patient was transferred to the Department of Rehabilitation Medicine to improve motor symptoms.

The patient exhibited clinical features of weakness in the upper limbs progressing downwards and areflexia, without sensory impairment. Electrophysiological studies indicated a pattern consistent with AMAN type of GBS. However, the patient was diagnosed with anti-GQ1b antibody syndrome considering the clinical features and albmino-cytologic disassociation findings as anti-GQ1b antibody was detected in the serum. Descending paralysis in patients has also been reported rarely in MFS [3].

A case of anti-GQ1b antibody syndrome, similar to our case, fulfilled the diagnostic criteria for classical GBS, presenting limb weakness and areflexia [4]. The NCS results differed from our results in that there was only a decrease in motor nerve CV. AMAN is known to be associated with GM1 antibodies, but the pathogenesis of axonal damage caused by these antibodies is not yet fully understood. However, both the GM1 antibody and the GQ1b antibody were found to be abundantly present in the neuronal cell membrane and were shown to have extensive effects in signal transduction [5]. While GQ1b antibody is known to be mainly located in the extraocular muscles, experimental studies have demonstrated its neurotoxicity, leading to conduction blockage at the motor nerve terminals [6]. Therefore, we propose that the anti-GQ1b antibody syndrome can manifest symptoms similar to AMAN since it can directly cause synaptic membrane damage and contribute to muscle weakness. This case suggests that the possibility of anti-GQ1b antibody syndrome should be considered, even if electrophysiological findings similar to those of GBS are observed without ophthalmoplegia, which is the main clinical symptom.