Acute Ophthalmoparesis in a Child with Anti-GQ1 b IgG Antibody

Sir,

In childhood, the majority of cases of acquired isolated nervus abducens paresis are caused by neoplasm (39 %), trauma (20 %), and inflammation (17 %) [[6]]. In contrast, acquired isolated benign VIth cranial nerve palsy is a rare condition (3 to 5 %) in a pediatric setting [[6], [8]]. In several case series of unilateral benign paresis the symptomatology was believed to be due to neuritis after viral infection. Bilateral benign abducens nerve palsy has been reported only in single cases [[8]].

In adults, VIth nerve palsy can occur in Miller-Fisher syndrome (MFS), where it is characterized by acute onset of external ophthalmoplegia, cerebral ataxia, and very frequently a loss of tendon reflexes, which is regarded as a cranial nerve variant of Guillain-Barré syndrome (GBS). As in GBS and Bickerstaff brainstem encephalitis, MFS is believed to be of autoimmune pathogenesis. The fact that over 90 % of MFS show anti-ganglioside IgG-antibodies for the GQ1 b epitope [[5]], which is present predominantly in the extramedullary part of IIIrd, IVth, and VIth nerves [[2], [3]], speaks for this.

A previously healthy 9-year-old girl was admitted to our hospital with diplopia, which had become manifest one day earlier. Two weeks previously, she had suffered from fever up to 40 °C and upper airway infection.

Upon physical examination, she was found to have bilateral limitation of abduction in both eyes and slow pupillary reaction. The remaining status was without pathological findings; specifically, there was no history of headache, and visual acuity, tendon reflexes and coordinative functions were normal.

Gadolinium-enhanced magnetic resonance imaging showed no abnormalities in the orbits or the brain. In serum, no signs of acute infection were observed. The cerebrospinal fluid (CSF) showed normal cytosis (2 monocytes/mm³), glucose (3.7 mmol/l) and protein (0.17 g/l) content, and no oligoclonal bands were detectable. Antibodies for adenovirus, rhinovirus, influenza A and B, parainfluenza types 1, 2 and 3, RS virus, ECHO virus, tick-borne encephalitis, borrelia, Epstein-Barr virus, chlamydia, Mycoplasma pneumoniae and Campylobacter jejuni were absent in both serum and CSF. In contrast, the anti-GQ1 b IgG antibody titre in serum, as measured by enzyme-linked immunosorbent assay (Bühlmann Laboratories AG, Allschwil, Switzerland) was > 15,000 (normal < 800 units), whereas all other anti-ganglioside antibodies (asialo-GM1, GM1, GM2, GD1 A and GD1 B) tested by a screening test (Bühlmann Laboratories AG, Allschwil, Switzerland) had negative scores. The very high anti-GQ1 b IgG antibody titre persisted over 4 months, while the patient made a full recovery from the symptoms of VIth nerve palsy within this period without specific treatment.

Acute bilateral abducens nerve palsy is a very rare symptom in children. Acute ophthalmoparesis in Miller-Fisher and Guillain-Barré syndrome is known to be associated with serum anti-GQ1 b IgG antibody. The clinical spectrum in patients with positive anti-GQ1 b IgG antibody encompasses a wide array of symptoms such as diplopia, gait disturbances, limb weakness, dysarthria and dysphagia, consciousness disturbances like drowsiness, stupor or coma, external and internal ophthalmoplegia, nystagmus, facial weakness, decreased tendon reflexes, ataxia, sense impairment and, in isolated cases, acute ophthalmoparesis. Acute ophthalmoparesis was recorded in 8 % (15/194) of patients with this antibody. The vast majority (80 %) had a preceding upper airway infection [[5]], as was the case in the present patient. Anti-GQ1 b IgG antibody is an antibody against ganglioside with heterogeneous fine specificity and cross reactivity with other ganglioside antibodies [[7]], especially with anti-GT1a [[9]]. An analysis of the ganglioside composition of the human cranial nerves revealed a high proportion of GQ1 b epitopes in the paranodal region, such as Ranvier nodes of the extramedullary parts of the IIIrd, IVth, and VIth nerves involved in ocular movement [[2], [3]], supporting the role of serum anti-GQ1 b antibody in the pathogenetic mechanism of isolated AO or ophthalmoplegic MFS and GBS. Several lipopolysaccharides of Campylobacter jejuni bear epitopes common to gangliosides like GQ1 b, so that references exist that antibodies cross-react with host structures (molecular mimicry) and lead to an auto-immune neuropathy. Although our patient was negative for C. jejuni, this pathomechanism is also possible with other infectiological agents.

Functionally, GQ1 b antibodies were shown to exert pre- and postsynaptic blocking effects, leading to conduction block [[1]]. The higher susceptibility of the abducens and other external ocular nerves for paresis mediated by anti-GQ1 b antibody vis-à-vis other cranial nerves may be due to the differential distribution of the epitope in cranial nerves, although a low detection threshold for dysbalance in ocular motor function is also feasible.

With respect to our observation that the anti-GQ1 b antibodies persisted for several weeks despite the clinical symptoms subsiding, their pathophysiological relevance might be discussed. One possible explanation is that counter-regulatory mechanisms such as anti-idiotypic antibodies or suppression of antibody-mediated pro-inflammatory mechanisms such as complement activation may induce clinical recovery. No systematic data exist on the half-life of anti-GQ1 b IgG antibody.

As reported in two other cases [[4]], our patient recovered from the abducens paresis with no specific therapy such as intravenous immunoglobulins.

References

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