FUEL for an ‘Alice in Wonderland’ syndrome

Sir,

Alice in Wonderland syndrome (AIWS) is a perceptual disorder with distortions of visual perception (metamorphopsias), body schema or the experience of time [1]. AIWS is associated mostly with migraine or encephalitis. Non-ketotic hyperglycemia (NKH) is not known to be associated with AIWS. We describe a case of AIWS occurring in the setting of hyperglycemia and with MRI findings mimicking Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

A 54-year-old man presented us with complaints of distortion of visual images of 3 days duration and right sided headache. The headache had a gradual onset and gradually increased and was associated with nausea and vomiting. His wife noticed that he had intermittent episodes of disorientation and slurring of speech during these 3 days. He was a long-standing diabetic on oral hypoglycemic agents. An MRI brain with MRA was normal, and he was started on dual antiplatelets for presumed transient ischemic attacks. As his events did not subside, he was admitted and blood glucose levels were noticed to be 440 mg/dl. He was started on insulin three times a day, and an EEG was performed which showed multiple right posterior head region electro-clinical events. The possibilities considered were hyperglycemic seizures or a focal encephalitis. He was started on three anticonvulsants (levetiracetam, sodium valproate and Clobazam). CSF examination was normal. Considering the possibility of a viral/autoimmune encephalitis, Acyclovir and methyl Prednisolone injections were also started. However, as his visual complaints increased, he was referred to us.

On admission, he complained of persistent metamorphopsias [micropsia (seeing things and people smaller than they are), macropsia (seeing things and people larger than they are), proso-metamorphopsia (distortion of faces) and polyopia (seeing multiple images of each person)] for 3 days,  and persisted throughout the day.

On examination, there were no focal deficits. Repeat continuous EEG showed only right hemispheric slowing. Repeat blood sugars were in the range of 350–440 mg/dl. HbA1c was 12.3%, and SARS CoV-2 RT PCR was negative. A repeat CSF examination was also normal. Serum and CSF NMO & MOG antibodies were negative. A repeat MRI brain on the 7th day showed asymmetric gyral DWI and FLAIR hyperintensity along the cortex and the intervening sulci, in the right posterior temporal and parietal cortex, with corresponding thin leptomeningeal enhancement suggestive of FLAIR-variable Unilateral Enhancement of the Leptomeninges (FUEL) as well as FLAIR-hyperintense lesions, which are characteristically associated with MOGAD (FLAIR hyperintense lesions in anti-MOG associated encephalitis with seizures [(FLAMES)][2]. Serum anti-neuronal and paraneoplastic antibodies were also negative. He was continued on IV anticonvulsants and intensive glucose control with insulin infusions. On day 9, after controlling his blood glucose, ¹⁸FDG PET-CT showed hypermetabolic areas in the right posterior temporal and adjoining parietal cortex corresponding to the MRI detected areas of leptomeningeal enhancement. There were no other FDG avid foci anywhere else. Due to the MRI changes suggestive of FUEL and FLAMES, 1 g of Rituximab was administered for possible MOGAD on day 10. Serum NMO and MOG antibodies were negative on repeated testing on day 11. Over the next 3 days, his symptoms completely resolved and he was transitioned to thrice a day insulin therapy. His anticonvulsants were tapered over 3 months.

The combination of side-locked headache, seizures and focal cortical deficits localizing to the MRI area showing FUEL or FLAMES pattern is a distinct clinico-radiographic syndrome associated with Myelin oligodendrocyte glycoprotein antibody disease [2]. Our patient had features of AIWS, FUEL, FLAMES and NKH without detectable MOG antibodies.

Alice in Wonderland Syndrome (AIWS) is a perceptual disorder that perturbs the sensory associative cortices integrative pathways involved in modulating our internal–external relationship. The relationship between self and ‘not self’ (the external world) is impaired, such that patients erroneously misinterpret the external world with respect to their own body size or vice versa.

External visual distortions [Metamorphopsias] (rather than fleeting visual illusions or hallucinations) along with internal ‘somesthetic symptoms’ are the core features of AIWS. Other complex psychic symptoms (derealization, depersonalisation, chronotaraxis, somatopsychic duality) may also occur [3]. The predominant area involved in AIWS is the carrefour of three major areas, the temporooccipital, parietooccipital, and temporoparietal junctions [TPO-C] [4]. Visual and somatosensory information is integrated in the TPO-C to generate an internal as well as an external representation of self. Thus, misintegration of somatosensory input with the external visual input leads to AIWS [1]. A large number of metamorphopsias (visual disturbances) have been described in AIWS.

The neurological complications of NKH include focal seizures, epilepsia partialis continua, chorea-hemiballismus, hemiparesis, hemianopia, ocular flutter, encephalopathy and coma [5]. Occipital seizures are associated with reversible subcortical T2/fluid attenuation inversion recovery (FLAIR) hypointensities. Infrequently cortical or leptomeningeal T1 or FLAIR enhancement accompanies these transient findings. FLAIR imaging may show overlying gyral hyperintensities, and diffusion-weighted imaging shows mildly restricted diffusion in these regions.

Although NKH is an unusual cause of FUEL, FLAMES or an Alice in Wonderland syndrome, it should be considered in the differential diagnosis [2] (Fig. 1).

Fig. 1.

A and B T2 weighted axial sequences showing subcortical hyperintensity (arrows). C and D FLAIR sequences showing gyral hyperintensity with subcortical hyperintensity (arrows). E and F Axial T1 post-contrast images showing leptomeningeal and sulcal hyperintensity (arrows). G Axial FDG PET CT image showing right temporo-occipital hypermetabolism (arrow)

Declarations

Conflict of interest

No conflict of interest.

Data availability

Any further data is available on request.