Alice in Wonderland Syndrome as a Presenting Manifestation of Creutzfeldt-Jakob Disease

Abstract

Background: Alice in Wonderland syndrome (AIWS) is a rare neurological disorder characterized by distortions of visual perception (metamorphopsias), the body image, and the experience of time, along with derealization and depersonalization. Some 85% of patients present with perceptual distortions in a single sensory modality, e.g., only visual or only somesthetic in nature. Moreover, the majority experience only a single type of distortion, e.g., only micropsia or only macropsia. AIWS has many different etiologies, and hence an extensive differential diagnosis. Its amenability to treatment depends on the underlying pathological process, which in children is mostly encephalitis, and in adults, migraine. In the literature, no more than 180 “clinical” cases of AIWS have been described (i.e., cases in need of medical attention). Of them, some 50% showed a favorable prognosis. However, non-clinical cases (i.e., fleeting, transient cases of AIWS for which no professional help is needed) have been described in up to 30% of the general population. This indicates that AIWS is perhaps not as rare as traditionally assumed, and has led some authors to conclude that, prognostically, AIWS is usually harmless. Methods: From our own clinical practice, we describe the first known case of Creutzfeldt-Jakob Disease (CJD, Heidenhain variant) that presented with symptoms of AIWS. Results: In our patient, disease onset was sudden and rapidly progressive, starting with isolated visual symptoms. Symptoms of AIWS comprised akinetopsia, chloropsia, micropsia, macropsia, zoom vision, and time distortions (quick-motion phenomenon and protracted duration). Soon, these were complicated by paraesthesias, gait instability, aphasia, expressive amusia, cognitive decline, and behavioral changes in the form of agitation and emotional lability. The diagnosis of probable sporadic CJD was confirmed with the aid of a head MRI and cerebrospinal fluid (14-3-3 protein). In the absence of any treatment options, our patient was discharged home and died within 2 months after his visual symptoms had begun. Autopsy consent was not obtained. Conclusion: We conclude that AIWS is not always as harmless as sometimes suggested, and that CJD, although extremely rare, must be part of its extensive differential diagnosis, notably in the presence of rapid cognitive decline.

Visual Neuropsychology in Development: Anatomo-Functional Brain Mechanisms of Action/Perception Binding in Health and Disease

“…Even if chronic cases have been reported (Cooper et al, 2012), akinetopsia seems a rather transient condition (Shipp et al, 1994), suggesting the existence of functionally neuroplastic changes able to establish alternative neural interactions to restore sensitivity to visual motion. Such a relative ease to naturally react to akinetopsia makes it difficult to detect, especially in populations characterized by high neural plasticity like children, where in fact akinetopsia is relatively rare and usually present in combination with the Alice in Wonderland syndrome as a results of encephalitis (Naarden et al, 2019).…”

Alice in Wonderland syndrome (AIWS): a research overview

“…Such clinical presentations may lead to differential diagnoses including AIWS. Similar care studies highlight complex clinical presentations including migrainous hallucinations [29] , Creutzfeldt-Jakob Disease [30] , paroxysmal nonepileptic events [31] , and other medical conditions. Similar scarcity of studies was found for therapeutic measures.…”

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease: First Reported Case from East Africa

“… 2 , 4 , 11 Other visual presentations reported in literature include blurred vision, visual field restriction, disturbed color perception, cortical blindness, 11 and even “Alice in Wonderland” syndrome consisting of visual metamorphopsias. 12 There are reports of non-specifically altered vision associated with depressive symptoms but being mistaken for a primary psychiatric disease instead of sCJD. 13 …”

“…2,4,11 Other visual presentations reported in literature include blurred vision, visual field restriction, disturbed color perception, cortical blindness, 11 and even "Alice in Wonderland" syndrome consisting of visual metamorphopsias. 12 There are reports of non-specifically altered vision associated with depressive symptoms but being mistaken for a primary psychiatric disease instead of sCJD. 13 The pathognomonic MRI findings in the Heidenhain variant of sCJD are the DWI cortical ribboning appearances involving the occipital lobes; 14 temporal and parietal lobe involvement without basal ganglia signal change, as seen in our patient's neuro-imaging, have also been described.…”