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Abbreviations AIWS: Alice in wonderland syndrome; BSD: Body Schema Disorders; CPAP: Continuous Positive Airway Pressure; CT: Computerized Tomography; DTI: Diffusion Tensor Imaging; DWI: Diffusion Weighted Imaging; ED: Emergency Department; LDL: Low Density Lipoproteins; M1: Primary motor cortex; MRI: Magnetic Resonance Imaging; MSG: Macrosomatognosia; MoCA: Montreal Cognitive Assessment; NIHSS: National Health Institute Stroke Scale; PCA: Posterior Cerebral Artery; S1: Primary somatosensory cortex; SLF: Superior Longitudinal Fasciculus; SPL: Superior Parietal Lobule; VPL: Ventral posterolateral nucleus
Source publication
Background
Macrosomatognosiais the illusory sensation of a substantially enlarged body part. This disorder of the body schema, also called “Alice in wonderland syndrome” is still poorly understood and requires careful documentation and analysis of cases. The patient presented here is unique owing to his unusual macrosomatognosia phenomenology, but...
Citations
... AIWS is a transient neurological disturbance causing sensory distortions, with a variable combination of micro-and macropsia (seeing objects smaller or larger), telo-and pelopsia (seeing objects further or closer), macro-and micro-somatognosia (perceiving parts of the own body as bigger or smaller), and slowing in perception of time (8)(9)(10)(11). Since it first description by the British neurologist J. Todd (9), AIWS has been linked to several underlying etiologies (8)(9)(10)(11), ranging from viral infections, such as Epstein-Barr (12), psychiatric comorbidities, adverse effects of common medications, stroke or brain tumors (13)(14)(15). Despite the numerous cases available in the literature (8,11), little is known about AIWS pathophysiological mechanisms. ...
Background
The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs.
Methods
We conducted a case–control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.
Results
We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC.
Conclusion
The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.
... Other authors put forth frontal lobe lesions associated with AIWS-type B symptoms (Morland, 2013), with type-A phenomenology being linked to right ventral posterolateral nucleus (VPL) lesions in the thalamus (ElTarhouni et al., 2020) or hypoperfusion in the frontoparietal operculum (Morland, 2013). Distortions in the sense of sense of self and somesthetic type-A symptoms also seem connected to alterations in visual and somatosensory integration regions or TPO-C junction-an intersection of temporo-occipital, parieto-occipital, and temporo-parietal junctions (Brumm, 2010;Mastria, 2016). ...
... Examples of investigations include: general check-ups (BP, bloodwork), neuro-imaging techniques (EEG, CT, PET, SPECT, MRI). Out of 107 treatment counts in scientific literature addressing underlying conditions, 3 were linked to treating infectious diseases (Kadia et al., 2017;Paniz-Mondolfi et al., 2018;Kubota et al., 2020), 92 were given antiepileptics/anti-migraine medication (Blom, 2016;Camacho Velasquez, 2016;Beh et al., 2018;Garcia-Cabo, 2019;Mastria et al., 2018;ElTarhouni, 2020;Matsudaira et al., 2020), 3 were given thermoregulators (Yokohama et al., 2017;Chirchiglia, 2019;Mudgal, 2021), 2 were given antipsychotic medication (Yokohama et al., 2017;Mudgal, 2021), 1 had a modification in psychostimulant dosage (Dugauquier et al., 2020), 2 had Electroconvulsive therapy (Blom, 2016), 1 transcranial magnetic stimulation (Blom, 2016), 1 patient had surgery and 2 treatments were non-pharmacological . ...
... According to Jerath et al. (2015), the thalamus is also involved in consciousness and body schema representation, and in a single case report, a lesion to the right thalamic ventral posterolateral nucleus gave rise to macrosomatognosia, that is the illusory sensation of enlarged body parts (El Tarhouni et al., 2020): a symptom that recalls the body image disturbances often observed in patients with AN (Gadsby, 2017). ...
Objective:
Recent neuroscientific findings have highlighted the role of the thalamus in several cognitive functions, ranging from perception to cognitive flexibility, memory, and body representation. Since some of these functions may be involved in the pathophysiology of Anorexia Nervosa (AN), this study aims at exploring thalamic structure in different phases of the disorder.
Method:
The sample included 38 patients with acute AN, 20 patients who fully recovered from AN (recAN), and 38 healthy controls (HC), all female. All participants underwent high-resolution MRI. The volumes of the whole thalamus and 25 thalamic nuclei were extracted using an automated segmentation algorithm, and thalamic fractal dimension was estimated using the calcFD toolbox.
Results:
Patients with acute AN, compared to HC, displayed reduced thalamic volume and complexity both at the whole level and at the level of specific nuclei. In patients recAN, instead, alterations were observed only at the level of the right laterodorsal and central lateral nuclei.
Conclusions:
In the acute phase of the disorder patients with AN present a widespread reduction in thalamic volume and complexity. However, these alterations seem to normalise almost completely following weight restoration, thus suggesting the involvement of malnutrition-related mechanisms.
... Application of this non-invasive technique has allowed the identification of various resting-state networks (RSNs), or spatially distinct areas of the brain that demonstrate synchronous BOLD fluctuations at rest. Several RSNs showed atypical connectivity in MA patients (mainly visual) [17], some of which involved regions that were frequently associated with AIWS in individual brain-damaged patients and in task-evoked functional MRI (fMRI) and single-photon emission computerized tomography (SPECT) studies, including visual [9,12,15,18], salience and basal ganglia [19][20][21], and default and executive control networks [22,23]. ...
... Finally, a dimensionality of 30 was chosen since the explained data variance was sufficient to obtain good estimates of the signals and well-known RSNs were identified [32]. Several RSNs showed atypical connectivity in patients with migraine with aura [17]; of these, we selected those whose regions showed structural (single-case lesion studies) or functional (i.e., task fMRI, SPECT) alterations in patients with AIWS: visual (lateral and medial) [9,12,15,18], salience and basal ganglia [19][20][21], and default and executive control networks [22,23]. RSNs of interest were identified via spatial correlation coefficients (fslcc tool) using RSNs generated by Smith et al. [32] and Yeo et al. [35] as templates, and then verified by expert visual inspection (CP, NP, PP). ...
... Despite the recent evidence of thalamic white matter microstructural alterations [67], no study has investigated intrinsic FC alterations of basal ganglia network (or thalamic FC) in migraineurs with aura in the interictal state. It has previously been reported that thalamic lesions can cause AIWS [20,21]. In particular, FC alterations in this structure may explain the somesthetic distortions experienced by AIWS patients due to its role in controlling sensory information flow to the cerebral cortices. ...
Background and purposeAlice in Wonderland syndrome (AIWS) is a neurological disorder characterized by erroneous perception of the body schema or surrounding space. Migraine is the primary cause of AIWS in adults. The pathophysiology of AIWS is largely unknown, especially regarding functional abnormalities. In this study, we compared resting-state functional connectivity (FC) of migraine patients experiencing AIWS, migraine patients with typical aura (MA) and healthy controls (HCs).Methods
Twelve AIWS, 12 MA, and 24 HCs were enrolled and underwent 3 T MRI scanning. Independent component analysis was used to identify RSNs thought to be relevant for AIWS: visual, salience, basal ganglia, default mode, and executive control networks. Dual regression technique was used to detect between-group differences in RSNs. Finally, AIWS-specific FC alterations were correlated with clinical measures.ResultsWith respect to HCs, AIWS and MA patients both showed significantly lower (p < 0.05, FDR corrected) FC in lateral and medial visual networks and higher FC in salience and default mode networks. AIWS patients alone showed higher FC in basal ganglia and executive control networks than HCs. When directly compared, AIWS patients showed lower FC in visual networks and higher FC in all other investigated RSNs than MA patients. Lastly, AIWS-specific FC alterations in the executive control network positively correlated with migraine frequency.ConclusionsAIWS and MA patients showed similar FC alterations in several RSNs, although to a different extent, suggesting common pathophysiological underpinnings. However, AIWS patients showed additional FC alterations, likely due to the complexity of AIWS symptoms involving high-order associative cortical areas.
... Todd (9), AIWS has been linked to several underlying etiologies (8)(9)(10)(11), ranging from viral infections, such as Epstein-Barr (12), psychiatric comorbidities, adverse effects of common medications, stroke or brain tumors (13)(14)(15). Despite the numerous cases available in the literature (8,11), little is known about AIWS pathophysiological mechanisms. ...
Background
the Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by visual and somatosensory misperceptions most frequently associated with migraine. The heterogeneity of the etiologies and techniques applied to investigate the reported cases have so far prevented to draw strong conclusions about the origin of AIWS symptoms. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in a population of migraineurs.
Methods
we acquired resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups.
Results
we found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or trigger a diaschisis phenomenon causing the AIWS symptoms during the ictal phase.
Conclusions
taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas. The altered connectivity between early visual and multisensory associative areas provides a model for the pathophysiology of AIWS associated with other transient neurological conditions or with a structural etiology.
... Two patients showed thalamic lesions [20,22]. In both studies, anatomic disconnection between the posterior part of the thalamus and the ipsilateral cortex (insula as well as primary somatosensory cortex, precuneus, and superior parietal lobule) was found by means of tractography. ...
Background and purposeAlice in Wonderland syndrome (AIWS) is a rare neurological disorder, characterized by an erroneous perception of the body schema or surrounding space. It may be caused by a variety of neurological disorders, but to date, there is no agreement on which brain areas are affected. The aim of this study was to identify brain areas involved in AIWS.Methods
We conducted a literature search for AIWS cases following brain lesions. Patients were classified according to their symptoms as type A (somesthetic), type B (visual), or type C (somesthetic and visual). Using a lesion mapping approach, lesions were mapped onto a standard brain template and sites of overlap were identified.ResultsOf 30 lesions, maximum spatial overlap was present in six cases. Local maxima were identified in the right occipital lobe, specifically in the extrastriate visual cortices and white matter tracts, including the ventral occipital fasciculus, optic tract, and inferior fronto-occipital fasciculus. Overlap was primarily due to type B patients (the most prevalent type, n = 22), who shared an occipital site of brain damage. Type A (n = 5) and C patients (n = 3) were rarer, with lesions disparately located in the right hemisphere (thalamus, insula, frontal lobe, hippocampal/parahippocampal cortex).Conclusions
Lesion-associated AIWS in type B patients could be related to brain damage in visual pathways located preferentially, but not exclusively, in the right hemisphere. Conversely, the lesion location disparity in cases with somesthetic symptoms suggests underlying structural/functional disconnections requiring further evaluation.
... Two patients showed thalamic lesions [20,22]. In both studies, anatomic disconnection between the posterior part of the thalamus and the ipsilateral cortex (insula as well as primary somatosensory cortex, precuneus, and superior parietal lobule) was found by means of tractography. ...
Alzheimer’s disease (AD) patients show abnormal cortical sources of resting state EEG rhythms, especially at delta (1–4 Hz) and alpha (8–13 Hz) bands. Here we hypothesized that this abnormality is correlated to impaired structural brain connectivity. Eyes closed resting state EEG and structural MRI-DTI (diffusion tensor imaging) data were acquired in 21 AD and in 9 mild cognitive impairment (MCI) patients. LORETA and FSL were used for data analysis. Compared to MCI subjects, AD patients showed a reduction of DTI fractional anisotropy (FA) in several white matter brain bundles (p < 0.05 corrected). Among these bundles, there was a negative correlation in AD patients between delta sources and FA in Forceps minor, left Superior longitudinal fasciculus, and bilateral Inferior longitudinal fasciculus (p < 0.05 corrected). Analogously, there was a positive correlation in AD patients between alpha sources and FA in Forceps minor, right Superior longitudinal, and left Inferior longitudinal fasciculus (p < 0.05 corrected). In AD patients, abnormal cortical sources of delta and alpha rhythms are correlated to the atrophy of structural long-tract brain connectivity. Cortical sources of resting state EEG rhythms in AD patients reflect a neurodegenerative brain disconnection.
