Acute ET in a 42 yo male with recent diarrhoea

OMCFumtiaka Nonaka

17/10/2011 ED (2wk from onset)• 42yo Male• c/o binocular diplopia (mainly horizontal, with

vertical and torsional component) • difficulty in focusing, pain behind the eyes for 2/52• 3-4/52 ago had acute gastroenteritis, pins and

needles, unbalanced• denies: ataxia, inco-ordination, other motor/sensory

symptoms • POH: red-green color blindness• PMH: nil, no head trauma

On Examination in ED• VA: R 6/5-3, L 6/9+3 • Ishihara 2/15, R+L• no RAPD• CT: Alternating ET (PCT: not performed)• EOM: LLR-, RIO+, LSR-, end point nystagmus, normal

saccades, pain on looking up, no INO• Bloods: FBE, U+E normal, CRP<1, RF –ve, TSH WNL,

ANA detected (titre 1:80, <1:80 = negative)• MRI brain (25/10/11): normal, no evidence for

intracranial demyelination

What’s next?

What’s next?

Anti-ganglioside antibodies

04/11/11 OMC (5wk from onset)• VA: R 6/5 L 6/6• HVF: W.N.L. • EOM: RLR-, LLR- (see Hess)• PCT: Near 35ΔET’ LH’6Δ Distance 50ΔET LH6Δ• Bloods:

– GQ1b IgG Ab +ve– MAG IgM IFA –ve– GM1 IgG Ab –ve, GM1 IgM Ab –ve– AChR Ab –ve

• S: still diplopia to sides, after midday• PCT: Near 6ΔET’ LH’3Δ Distance 6ΔET LH2Δ (see Hess)

18/11/11 OMC (7wk)• Much better, SV in am, gradually develops diplopia

as day progresses• EOM RLR-, LLR- (see Hess)• PCT: Near 14ΔET’ LH’3Δ Distance 25ΔET LH3Δ• Saccades fast and accurate, no fatigue

02/12/11 OMC (9wk)

04/11/11 (5wk) 18/11/11 (7wk)

02/12/11 (9wk)

Distance 50ΔET LH6Δ Distance 25ΔET LH3Δ

Distance 6ΔET LH2Δ

Miller-Fisher syndrome

a variant of Guillain-Barre syndrome a triad of ophthalmoplegia, ataxia, and areflexia full triad of MFS is not always present anti-GQ1b ganglioside antibodies +ve in 90% of MFS Campylobacter jejuni, cytomegalovirus, Epstein-

Barr virus, and Streptococcus pyogenes have been reported as antecedent infectious agents in MFS. (J Neurol Sci 1998;160:64–6)

good recovery with or without treatment

´

Charles Miller Fisher MD1913 - 2011

Acute conditions Miller-Fisher Syndrome Acute ophthalmoparesis (ophthalmoplegia without ataxia)

Chronic conditionsOtherwise unexplained ophthalmoplegia

Anti-GQ1b antibody

Anti-Gq1bAnti-Gq1b

Immunolocalization of GQ1b and Related Gangliosides in Human Extraocular Neuromuscular Junctions and Muscle Spindles. F. Pedrosa-Domellof et al, IOVS 2009;50:3226 –3232

Abundant staining anti-GQ1b Abs: NMJs of human EOMs > limb muscles

Absence of a blood-nerve barrier High capillary supply

NMJs of EOMs may be easily targeted by anti-GQ1b Abs

*NMJ = Neuromuscular junction

*

Anti-ganglioside antibodies& diplopia

“ANTI GM1 ANTIBODIES – THE CAUSE OF OTHERWISE UNEXPLAINED OPHTHALMOLPLEGIAS?” L Kowal et al, 2003

– Four patients with otherwise unexplained ophthalmoplegia – No other neurological problems– Elevated levels of IgM GM1 Ab– Normal anti-GQ1b Ab

Anti-GQ1b IgG antibody syndrome: clinical and immunological range. K Hirata, et al, J Neurol Neurosurg Psychiatry 2001;70:50–55

– 194 patients with anti-GQ1b IgG– 94% had antecedent illnesses

84% upper respiratory tract infection10% diarrhoea

– As initial symptoms67% diplopia29% gait disturbance

• The case described might be labelled “ophthalmoparesis due to presumed microvascular causes” or “presumed breakdown of latent squint” as no other explainable causes have been found.

• Measurement of anti-ganglioside antibodies should be considered in cases of otherwise unexplained ophthalmoplegia.