Lesions Causing Alice in Wonderland Syndrome Map to a Common Brain Network Linking Body and Size Perception.

OBJECTIVE: Alice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map to a distributed brain network. METHODS: A retrospective case-control study analyzing 37 cases of lesion-induced AIWS identified through systematic literature review was conducted. Using resting-state functional connectome data from 1,000 healthy individuals, the whole-brain connections of each lesion were estimated and contrasted with those from a control dataset comprising 1,073 lesions associated with 25 other neuropsychiatric syndromes. Additionally, connectivity findings from lesion-induced AIWS cases were compared with functional neuroimaging results from 5 non-lesional AIWS cases. RESULTS: AIWS-associated lesions were located in various brain regions with minimal overlap (≤33%). However, the majority of lesions (≥85%) demonstrated shared connectivity to the right extrastriate body area, known to be selectively activated by viewing body part images, and the inferior parietal cortex, involved in size and scale judgements. This pattern was uniquely characteristic of AIWS when compared with other neuropsychiatric disorders (family-wise error-corrected p < 0.05) and consistent with functional neuroimaging observations in AIWS due to nonlesional causes (median correlation r = 0.56, interquartile range 0.24). INTERPRETATION: AIWS-related perceptual distortions map to one common brain network, encompassing regions critical for body representation and size-scale processing. These findings lend insight into the neuroanatomical localization of higher-order perceptual functions, and may inform future therapeutic strategies for perceptual disorders. ANN NEUROL 2024.

Biomechanical changes following corneal crosslinking in keratoconus patients.

PURPOSE: To evaluate the biomechanical and tomographic outcomes of keratoconus patients up to four years after corneal crosslinking (CXL). METHODS: In this longitudinal retrospective-prospective single-center case series, the preoperative tomographic and biomechanical results from 200 keratoconus eyes of 161 patients undergoing CXL were compared to follow-up examinations at three-months, six-months, one-year, two-years, three-years, and four-years after CXL. Primary outcomes included the Corvis Biomechanical Factor (CBiF) and five biomechanical response parameters obtained from the Corvis ST. Tomographically, the Belin-Ambrósio deviation index (BAD-D) and the maximal keratometry (Kmax) measured by the Pentacam were analyzed. Additionally, Corvis E-staging, the thinnest corneal thickness (TCT), and the best-corrected visual acuity (BCVA) were obtained. Primary outcomes were compared using a paired t-test. RESULTS: The CBiF decreased significantly at the six-month (p < 0.001) and one-year (p < 0.001) follow-ups when compared to preoperative values. E-staging behaved accordingly to the CBiF. Within the two- to four-year follow-ups, the biomechanical outcomes showed no significant differences when compared to preoperative. Tomographically, the BAD-D increased significantly during the first year after CXL with a maximum at six-months (p < 0.001), while Kmax decreased significantly (p < 0.001) and continuously up to four years after CXL. The TCT was lower at all postoperative follow-up visits compared to preoperative, and the BCVA improved. CONCLUSION: In the first year after CXL, there was a temporary progression in both the biomechanical CBiF and E-staging, as well as in the tomographic analysis. CXL contributes to the stabilization of both the tomographic and biomechanical properties of the cornea up to four years postoperatively.

Peripheral nerve injury elicits microstructural and neurochemical changes in the striatum and substantia nigra of a DYT-TOR1A mouse model with dystonia-like movements.

The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still insufficiently understood. DYT-TOR1A dystonia has a remarkably reduced penetrance of 20-30%, which has led to the second-hit hypothesis emphasizing an important role of extragenetic factors in the symptomatogenesis of TOR1A mutation carriers. To analyze whether recovery from a peripheral nerve injury can trigger a dystonic phenotype in asymptomatic hΔGAG3 mice, which overexpress human mutated torsinA, a sciatic nerve crush was applied. An observer-based scoring system as well as an unbiased deep-learning based characterization of the phenotype showed that recovery from a sciatic nerve crush leads to significantly more dystonia-like movements in hΔGAG3 animals compared to wildtype control animals, which persisted over the entire monitored period of 12 weeks. In the basal ganglia, the analysis of medium spiny neurons revealed a significantly reduced number of dendrites, dendrite length and number of spines in the naïve and nerve-crushed hΔGAG3 mice compared to both wildtype control groups indicative of an endophenotypical trait. The volume of striatal calretinin+ interneurons showed alterations in hΔGAG3 mice compared to the wt groups. Nerve-injury related changes were found for striatal ChAT+, parvalbumin+ and nNOS+ interneurons in both genotypes. The dopaminergic neurons of the substantia nigra remained unchanged in number across all groups, however, the cell volume was significantly increased in nerve-crushed hΔGAG3 mice compared to naïve hΔGAG3 mice and wildtype littermates. Moreover, in vivo microdialysis showed an increase of dopamine and its metabolites in the striatum comparing nerve-crushed hΔGAG3 mice to all other groups. The induction of a dystonia-like phenotype in genetically predisposed DYT-TOR1A mice highlights the importance of extragenetic factors in the symptomatogenesis of DYT-TOR1A dystonia. Our experimental approach allowed us to dissect microstructural and neurochemical abnormalities in the basal ganglia, which either reflected a genetic predisposition or endophenotype in DYT-TOR1A mice or a correlate of the induced dystonic phenotype. In particular, neurochemical and morphological changes of the nigrostriatal dopaminergic system were correlated with symptomatogenesis.

Current-dependent ocular tilt reaction in deep brain stimulation of the subthalamic nucleus: Evidence for an incerto-interstitial pathway?

BACKGROUND AND PURPOSE: The aim was to characterize a combined vestibular, ocular motor and postural syndrome induced by deep brain stimulation (DBS) of the subthalamic nucleus in a patient with Parkinson's disease. METHODS: In a systematic DBS programming session, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fibre tracts were segmented on magnetic resonance imaging using both individual and normative structural connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. RESULTS: Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and body retropulsion were observed. Symptoms were consistent with an irritative effect on the INC. Symptom-associated VTA was found to overlap with the dorsal ZI and the ipsilateral vestibulothalamic tract, while lying rather distant to the INC proper. A ZI-to-INC 'incerto-interstitial' tract with contact to the medial-uppermost portion of the VTA could be traced. CONCLUSION: Unilateral stimulation of INC-related circuitry induces an ipsilateral vestibular, ocular motor and postural roll-plane syndrome, which converts into a pitch-plane syndrome when functional activation expands bilaterally. In this case, tractography points to an incerto-interstitial pathway, a tract previously only characterized in non-human primates. Directional current steering proved useful in managing this rare side effect.

The evolution of dystonia-like movements in TOR1A rats after transient nerve injury is accompanied by dopaminergic dysregulation and abnormal oscillatory activity of a central motor network.

TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30-40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify central mechanism of dystonia development. Dystonia-like movements (DLM) were assessed using the tail suspension test and implementing a pipeline of deep learning applications. Neuron numbers of striatal parvalbumin+, nNOS+, calretinin+, ChAT+ interneurons and Nissl+ cells were estimated by unbiased stereology. Striatal dopaminergic metabolism was analyzed via in vivo microdialysis, qPCR and western blot. Local field potentials (LFP) were recorded from the central motor network. Deep brain stimulation (DBS) of the entopeduncular nucleus (EP) was performed. Nerve-injured ∆ETorA rats developed long-lasting DLM over 12 weeks. No changes in striatal structure were observed. Dystonic-like ∆ETorA rats presented a higher striatal dopaminergic turnover and stimulus-induced elevation of dopamine efflux compared to the control groups. Higher LFP theta power in the EP of dystonic-like ∆ETorA compared to wt rats was recorded. Chronic EP-DBS over 3 weeks led to improvement of DLM. Our data emphasizes the role of environmental factors in TOR1A symptomatogenesis. LFP analyses indicate that the pathologically enhanced theta power is a physiomarker of DLM. This TOR1A model replicates key features of the human TOR1A pathology on multiple biological levels and is therefore suited for further analysis of dystonia pathomechanism.

Perampanel and decanoic acid show synergistic action against AMPA receptors and seizures.

Perampanel is an adjunctive treatment for epilepsy that works through the direct inhibition of AMPA receptors. The same molecular mechanism has recently been shown for a fatty acid, decanoic acid, prescribed in the medium chain triglyceride ketogenic diet for the treatment of patients with drug-resistant epilepsy. Because each compound has been proposed to act through a distinct AMPA receptor binding site, we predicted that perampanel and decanoic acid would act synergistically against AMPA receptors and, consequently, seizures. Here, we show a synergistic interaction between perampanel and decanoic acid in direct AMPA receptor inhibition, in an ex vivo model of seizure activity, and against seizure-induced activity in human brain slices. These data support a potential role for combination treatment using perampanel and dietary decanoic acid to provide enhanced seizure control.

Vestibulo-Ocular Reflex Suppression: Clinical Relevance and Assessment in the Digital Age.

Background: Visual acuity and image stability are crucial for daily activities, particularly during head motion. The vestibulo-ocular reflex (VOR) and its suppression (VORS) support stable fixation of objects of interest. The VOR drives a reflexive eye movement to counter retinal slip of a stable target during head motion. In contrast, VORS inhibits this countermovement when the target stimulus is in motion. The VORS allows for object fixation when it aligns with the direction of the head's movement, or when an object within or outside the peripheral vision needs to be focused upon. Summary: Deficits of the VORS have been linked to age-related diseases such as balance deficits associated with an increased fall risk. Therefore, the accurate assessment of the VORS is of particular clinical relevance. However, current clinical assessment methods for VORS are mainly qualitative and not sufficiently standardised. Recent advances in digital health technology, such as smartphone-based videooculography, offer a promising alternative for assessing VORS in a more accessible, efficient, and quantitative manner. Moreover, integrating mobile eye-tracking technology with virtual reality environments allows for the implementation of controlled VORS assessments with different visual inputs. These assessment approaches allow the extraction of novel parameters with potential pathomechanistic and clinical relevance. Key Messages: We argue that researchers and clinicians can obtain a more nuanced understanding of this ocular stabilisation reflex and its associated pathologies by harnessing digital health technology for VORS assessment. Further research is warranted to explore the technologies' full potential and utility in clinical practice.

Midbrain lesion-induced disconjugate gaze: a unifying circuit mechanism of ocular alignment?

BACKGROUND: Disconjugate eye movements are essential for depth perception in frontal-eyed species, but their underlying neural substrates are largely unknown. Lesions in the midbrain can cause disconjugate eye movements. While vertically disconjugate eye movements have been linked to defective visuo-vestibular integration, the pathophysiology and neuroanatomy of horizontally disconjugate eye movements remains elusive. METHODS: A patient with a solitary focal midbrain lesion was examined using detailed clinical ocular motor assessments, binocular videooculography and diffusion-weighted MRI, which was co-registered to a high-resolution cytoarchitectonic MR-atlas. RESULTS: The patient exhibited both vertically and horizontally disconjugate eye alignment and nystagmus. Binocular videooculography showed a strong correlation of vertical and horizontal oscillations during fixation but not in darkness. Oscillation intensities and waveforms were modulated by fixation, illumination, and gaze position, suggesting shared visual- and vestibular-related mechanisms. The lesion was mapped to a functionally ill-defined area of the dorsal midbrain, adjacent to the posterior commissure and sparing nuclei with known roles in vertical gaze control. CONCLUSION: A circumscribed region in the dorsal midbrain appears to be a key node for disconjugate eye movements in both vertical and horizontal planes. Lesioning this area produces a unique ocular motor syndrome mirroring hallmarks of developmental strabismus and nystagmus. Further circuit-level studies could offer pivotal insights into shared pathomechanisms of acquired and developmental disorders affecting eye alignment.

Pearls & Oy-sters: INO Plus From Downward Herniation-A Cautionary Tale Regarding Neuro-Ophthalmologic Signatures of Brainstem Compression.

Pupillary assessment is a quintessential part of the clinical examination in neuro-intensive care patients because it provides insight into the integrity of midbrain reflex arcs. Abnormal pupils, particularly anisocoria and later bilateral fixed mydriasis, are classically used to assess expansive intracranial processes because they are frequently considered early indicators of transtentorial midbrain compression due to elevated intracranial pressure. Complex ocular motor deficits mapping to the midbrain are rarely described in the setting of high transtentorial pressure. This is likely because ocular motor deficits typically occur in conjunction with decreased consciousness and corticospinal tract dysfunction reflecting advanced midbrain compromise. We present a case of left midbrain compression due to downward herniation in a patient with acute-on-chronic bilateral subdural hematoma. Ocular motor assessment demonstrated left internuclear ophthalmoplegia (INO) and an ocular tilt reaction, termed INO plus. However, pupillary, mental status, and sensorimotor examinations were unremarkable. Head magnetic resonance imaging revealed acute perforator ischemia in the left pontomesencephalic tegmentum, localizing to the ipsilateral medial longitudinal fasciculus and graviceptive oculocephalic circuits. Microvascular compromise secondary to mechanical pressure is discussed as a causative mechanism. We caution against overreliance on "telltale pupils" in suspected brainstem compression and recommend checking for other oculomotor signs.

Validation and application of computer vision algorithms for video-based tremor analysis.

Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for granular phenotyping. Instrumented neurophysiological analyses have proven useful, but are highly resource-intensive and lack broad accessibility. In contrast, bedside scores are simple to administer, but lack the granularity to capture subtle but relevant tremor features. We utilise the open-source computer vision pose tracking algorithm Mediapipe to track hands in clinical video recordings and use the resulting time series to compute canonical tremor features. This approach is compared to marker-based 3D motion capture, wrist-worn accelerometry, clinical scoring and a second, specifically trained tremor-specific algorithm in two independent clinical cohorts. These cohorts consisted of 66 patients diagnosed with essential tremor, assessed in different task conditions and states of deep brain stimulation therapy. We find that Mediapipe-derived tremor metrics exhibit high convergent clinical validity to scores (Spearman's ρ = 0.55-0.86, p≤ .01) as well as an accuracy of up to 2.60 mm (95% CI [-3.13, 8.23]) and ≤0.21 Hz (95% CI [-0.05, 0.46]) for tremor amplitude and frequency measurements, matching gold-standard equipment. Mediapipe, but not the disease-specific algorithm, was capable of analysing videos involving complex configurational changes of the hands. Moreover, it enabled the extraction of tremor features with diagnostic and prognostic relevance, a dimension which conventional tremor scores were unable to provide. Collectively, this demonstrates that current computer vision algorithms can be transformed into an accurate and highly accessible tool for video-based tremor analysis, yielding comparable results to gold standard tremor recordings.

Head movement dynamics in dystonia: a multi-centre retrospective study using visual perceptive deep learning.

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.

Experimental analysis of recommended corneal incision sizes in cataract surgery using 13 intraocular lens injector systems.

Smaller corneal incisions in cataract surgery are linked with a better visual outcome and less frequent postoperative endophthalmitis. The insertion of intraocular lens (IOL) injector systems into the anterior chamber of the eye to implant an IOL is associated with incision enlargement (IE) impeding these positive effects. The aim of this study was to compare manufacturers' recommended incision sizes (IS) of 13 different intraocular lens injector systems in regard of intraoperative IE and postoperative IS. In total, 499 corneal incisions in ex vivo porcine eyes were analyzed. The preoperative ISs depended on the recommended IS of the examined injector system. The IS was measured right before and after IOL injector insertion with an incision gauge set. There was intraoperative IE in 87% of the incisions with a mean IE of 0.26 ± 0.18 mm. IE was often significantly larger in small IS compared to larger IS concerning an injector system (P < 0.05). Five injector systems needed to have a significantly larger IS than the manufacturers' recommended IS with an average difference of 0.3 mm when applying study criteria (P < 0.05). Thus, the present study shows that IS recommendations require to be critically analyzed by ophthalmic surgeons to enable evidence-based practice.

Late central graft detachment due to double endothelial layer after repeat Descemet membrane endothelial keratoplasty.

Purpose: To report late central graft detachment after repeat Descemet membrane endothelial keratoplasty (DMEK) without visual reduction. Observations: A 71-year-old patient with Fuchs' endothelial corneal dystrophy received a DMEK in his left eye. At 11 month post-operatively, a subtotal graft detachment was noted. Due to increasing corneal edema with vision loss, the first DMEK was removed and a repeat-DMEK was performed. At four months post repeat-DMEK, the graft was fully adherent to the posterior stroma. There was no significant corneal edema, and the best corrected visual acuity was 20/25. At 16-months after repeat-DMEK, a central graft detachment was noted, but there was no concurrent corneal edema or any loss of visual acuity. The mean density of the central endothelial cells was measured at 842 cells/mm2. Given the lack of corneal edema, visual reduction or subjective visual complaint, the graft detachment was followed-up for up to 20-months post repeat-DMEK with no further intervention, where the central cornea remained clear. Conclusions and Importance: To our knowledge, this is the first report of a central repeat-DMEK graft detachment that occurred 16 months after surgery despite initial attachment. Interestingly, there was no concurrent corneal edema or vision reduction. We describe a potential mechanism for clear central cornea in the presence of a central graft detachment after repeat-DMEK.

Smartphone video nystagmography using convolutional neural networks: ConVNG.

BACKGROUND: Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances. METHODS: A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the "two one-sample t-test" (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation. RESULTS: ConVNG tracking accuracy reached 9-15% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms' precision was inferior to VOG. CONCLUSIONS: ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.

Influence of Subclinical Corneal Edema on Contrast Sensitivity in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The aim of this study was to compare visual function, with a focus on contrast sensitivity, between patients with Fuchs endothelial corneal dystrophy (FECD) with and without subclinical corneal edema. METHODS: In this cross-sectional, observational, single-center study, 46 pseudophakic eyes of 31 patients with FECD were divided into 2 groups depending on the presence of subclinical corneal edema. All eyes presented with a Krachmer grade of 5 and no clinical corneal edema. The criteria for subclinical corneal edema were loss of regular isopachs, displacement of the thinnest point, and focal posterior surface depression in Scheimpflug tomography. If more than 1 criterion was present, subclinical corneal edema was diagnosed. The corrected distance visual acuity, contrast sensitivity (Pelli-Robson chart and CSV-1000 test with optional glare), and straylight were measured. The differences between both groups were analyzed using clustered Wilcoxon rank-sum tests. RESULTS: The corrected distance visual acuity and the contrast sensitivity, measured with a Pelli-Robson chart, were significantly inferior in eyes with subclinical corneal edema compared with eyes without subclinical edema ( P < 0.05). At all spatial frequencies, eyes with subclinical edema demonstrated lower contrast sensitivity with a statistically significantly reduction in total contrast sensitivity when tested with ( P = 0.005) and without ( P = 0.002) glare. The straylight did not significantly differ between both groups ( P > 0.05). CONCLUSIONS: The corrected distance visual acuity and contrast sensitivity were significantly reduced in FECD eyes with subclinical corneal edema compared with those with no subclinical edema. This decrease in visual quality may be considered when evaluating the need for surgical intervention at earlier stages of FECD.

Adverse drug reactions in geriatric psychiatry-retrospective cohort study of a 6-year period.

OBJECTIVE: To investigate the frequency and characteristics of adverse drug reactions (ADRs) that occurred on the gerontopsychiatric ward of Hannover Medical School over a 6-year period. DESIGN: Retrospective monocentric cohort study. RESULTS: Six hundred thirty-four patient cases (mean age 76.6 ± 7.1 years; 67.2% female) were analysed. In total, 92 ADRs in 56 patient cases were registered in the study population. The overall ADR prevalence, the ADR prevalence upon hospital admission, and the ADR prevalence during hospitalisation were 8.8%, 6.3%, and 4.9%, respectively. The most frequent ADRs were extrapyramidal symptoms, alterations in blood pressure or heart rate, and electrolyte disturbances. Of note, two cases of asystole and one case of obstructive airway symptoms related to general anaesthesia in the context of electroconvulsive therapy (ECT) were detected. The presence of coronary heart disease was associated with an increased risk of ADR occurrence (odds ratio (OR) 2.92, 95% confidence interval (CI) 1.37-6.22), while the presence of dementia was associated with a decreased risk of ADR development (OR 0.45, 95% CI 0.23-0.89). CONCLUSIONS: Type and prevalence of ADRs in the present study were largely in accordance with previous reports. By contrast, we did not observe a relationship between advanced age or female sex and ADR occurrence. We detected a risk signal for cardiopulmonary ADRs related to general anaesthesia in the context of ECT that warrants further investigation. Elderly psychiatric patients should be carefully screened for cardiopulmonary comorbidities before initiation of ECT.

A vertigo network derived from human brain lesions and brain stimulation.

Vertigo is a common neurological complaint, which can result in significant morbidity and decreased quality of life. While pathology to peripheral and subtentorial brain structures is a well-established cause of vertigo, cortical lesions have also been linked to vertigo and may lend insight into relevant neuroanatomy. Here, we investigate the supratentorial lesion locations associated with vertigo and test whether they map to a common brain network. We performed a systematic literature search and identified 23 cases of supratentorial brain lesions associated with vertigo. We mapped the lesion locations to a standard brain template and computed the network of brain regions functionally connected to each lesion location, using a 'wiring diagram' of the human brain termed the human connectome (n = 1000). Sensitivity was assessed by identifying the most common connection to lesion locations associated with vertigo, and specificity was assessed through comparison with control lesions associated with symptoms other than vertigo (n = 68). We found that functional connectivity between lesion locations and the bilateral ventral posterior insula was both sensitive (22/23 lesions) and specific (voxel-wise family-wise error-corrected P < 0.05) for lesion-induced vertigo. We computed connectivity with this hub region to define a lesion-based vertigo network, which included regions in the bilateral insula, somatosensory cortex, higher-level visual areas, cingulate sulcus, thalamus and multiple cerebellar regions in the territory of the posterior inferior cerebellar artery. Next, we used stereo-electroencephalography (80 stimulation sites across 17 patients) to test whether stimulation sites associated with vertigo mapped to this same network. We found that 36/42 (86%) of stimulation sites eliciting vertigo fell within the lesion-based vertigo network in contrast to 16/39 (41%) of stimulation sites that did not elicit vertigo. Connectivity between stimulation sites and our lesion-based hub in the ventral posterior insula was also significantly associated with vertigo (P < 0.0001). We conclude that cortical lesions and direct electrical stimulation sites associated with vertigo map to a common brain network, offering insights into the causal neuroanatomical substrate of vertigo.

Rapidly progressive dementia: Extending the spectrum of GFAP-astrocytopathies?

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a steroid-responsive meningoencephalomyelitis, sometimes presenting with atypical clinical signs such as movement disorders or psychiatric and autonomic features. Beyond clinical presentation and imaging, diagnosis relies on detection of GFAP-antibodies (AB) in CSF. Using quantitative behavioral, serologic, and immunohistochemical analyses, we characterize two patients longitudinally over 18-24 months who presented with rapidly progressive neurocognitive deterioration in the context of GFAP-AB in CSF and unremarkable cranial MRI studies. Intensified immunotherapy was associated with clinical stabilization. The value of GFAP-AB screening in selected cases of rapidly progressive dementias is discussed.

Disruption evaluation in end-to-end semiconductor supply chains via interpretable machine learning.

COVID-19 has posed unprecedented challenges to global health and the world economy. Two years into the pandemic, the widespread impact of COVID-19 continues to deepen, impacting different industries such as the automotive industry and its supply chain. This study presents a hybrid approach combining simulation modeling and tree-based supervised machine learning techniques to explore the implications of end-market demand disruptions. Specifically, we apply the concept of born-again tree ensembles, which are powerful and, at the same time, easily interpretable classifiers, to the case of the semiconductor industry. First, we show how to use born-again tree ensembles to explore data generated by a supply chain simulation model. To this end, we demonstrate the influence of varying behavioral and structural parameters and show the impact of their variation on specific key performance indicators, e.g., the inventory level. Finally, we leverage a counterfactual analysis to identify detailed managerial insights for semiconductor companies to mitigate adverse impacts on one echelon or the entire supply chain. Our hybrid approach provides a simulation model enhanced by a tree-based supervised machine learning model that companies can use to determine optimal measures for mitigating the adverse effects of end-market demand disruptions. We close the loop of our analysis by integrating the findings of the counterfactual analysis backward into the simulation model to understand the overall dynamics within the multi-echelon supply chain.

Comparing rural ground and air emergency medical services: a level I trauma center's experience.

We sought to compare differences in patients transported by ground and air emergency medical services directly from the scenes of their injuries to a rural level I trauma facility. Variables examined included age, gender, vital signs, Glasgow Coma Scale score, discharge location, length of stay, and survival metrics. Student t tests and odds ratios were used for analysis. Demographics and vital signs differed between trauma patients transported by air versus those transported by ground. Generally, length of stay was longer in air-transported patients, who also had poorer survival metrics with negligible risk of death. Significant differences exist in the markers of physiology such as vital signs, expected survival, and degree of injury.