In a case published in the Canadian Journal of Ophthalmology, William A. Sanfelippo from the University of Virginia Department of Ophthalmology and colleagues describe what is believed to be only the second documented instance of AIWS occurring in association with glioblastoma. AIWS is a rare neurological condition first described in 1955 and is characterized by alterations in visual perception, body schema, and the subjective experience of time. The syndrome derives its name from Lewis Carroll’s Alice’s Adventures in Wonderland, which famously depicts changes in body size and perception.
The patient, a 63-year-old man with a complex medical history including coronary artery disease, hypertension, type 2 diabetes, and prior buccal squamous cell carcinoma, presented with a two-week history of dizziness, positional headaches, and a striking visual disturbance known as micropsia. He described people and faces appearing unusually small, a hallmark feature of AIWS. Importantly, he had no prior history of migraine, the most common cause of this syndrome.
Initial evaluation in the emergency department included a CT scan of the head, which revealed a necrotic and cystic mass involving the parietal, occipital, and posterior temporal regions. Subsequent brain MRI demonstrated a large, peripherally enhancing lesion centered at the junction of the right temporal, parietal, and occipital lobes, measuring over 6 cm in its largest dimension. Neurological examination showed micropsia, left-sided dysmetria, and chronic right facial palsy, without an obvious visual field defect.
Given concern for a primary brain malignancy, neuro-oncology and neurosurgery teams were consulted. The patient underwent gross total resection via right craniotomy using neuronavigation and intraoperative neuromonitoring. Histopathology confirmed glioblastoma, World Health Organization grade 4. Following surgery, the patient developed an incomplete left superior quadrantanopia, while micropsia persisted. He was discharged in stable condition and continued multidisciplinary follow-up with neuro-oncology, neurosurgery, radiation oncology, and neuro-ophthalmology services.
Over the next 18 months, the patient required two additional surgical resections along with radiation and chemotherapy. Despite aggressive treatment, his disease progressed, leading to cognitive and functional decline, and he died 20 months after the initial diagnosis.
The authors emphasize the neuroanatomical relevance of this case. The temporo-parieto-occipital junction is a critical hub for integrating visual and somatosensory information, and lesions in this region have been strongly linked to AIWS symptoms, particularly micropsia. While the precise mechanism remains unclear, proposed explanations include direct tumor involvement of the TPO junction, seizure activity, or cortical spreading depolarization resembling migraine aura.
The case highlights the importance of considering structural brain lesions in older patients presenting with new-onset perceptual distortions, especially in the absence of migraine history. The report also reinforces the relevance of AIWS beyond pediatrics and migraine, highlighting its significance for neurologists, neuro-ophthalmologists, and ophthalmologists alike.
Reference:
Sanfelippo WA, Harrelson H, Oley M, Vilar N. Glioblastoma at the temporo-parieto-occipital junction associated with Alice in Wonderland Syndrome. Can J Ophthalmol. 2025 Dec 23:S0008-4182(25)00505-8. doi: 10.1016/j.jcjo.2025.12.001. Epub ahead of print. PMID: 41453403.
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