Dynamic oxygen-17 MRI with adaptive temporal resolution using golden-means-based 3D radial sampling.

PURPOSE: The aim of this study was to develop a high-resolution 3D oxygen-17 (17 O) MRI method to delineate the kinetics of 17 O-enriched water (H217 O) across the entire mouse brain after a bolus injection via the tail vein. METHODS: The dynamic 17 O signal was acquired with a golden-means-based 3D radial sampling scheme. To achieve adequate temporal resolution with preserved spatial resolution, a k-space-weighted view sharing strategy was used in image reconstruction with an adaptive window size tailored to the kinetics of the 17 O signal. Simulation studies were performed to determine the adequate image reconstruction parameters. The established method was applied to delineating the kinetics of intravenously injected H217 O in vivo in the post-stroke mouse brain. RESULTS: The proposed dynamic 17 O-MRI method achieved an isotropic resolution of 1.21 mm (0.77 mm nominal) in mouse brain at 9.4T, with the temporal resolution increased gradually from 3 s at the initial phase of rapid signal increase to 15 s at the steady-state. The high spatial resolution enabled the delineation of the heterogeneous H217 O uptake and washout kinetics in stroke-affected mouse brain. CONCLUSION: The current study demonstrated a 3D 17 O-MRI method for dynamic monitoring of 17 O signal changes with high spatial and temporal resolution. The method can be utilized to quantify physiological parameters such as cerebral blood flow and blood-brain barrier permeability by tracking injected H217 O. It can also be used to measure oxygen consumption rate in 17 O-oxygen inhalation studies.

National Institutes of Health StrokeNet Training Core.

Background and Purpose- The National Institutes of Health (NIH) StrokeNet provides a nationwide infrastructure to advance stroke research. Capitalizing on this unique opportunity, the NIH StrokeNet Training Core (NSTC) was established with the overarching goal of enhancing the professional development of a diverse spectrum of professionals who are embedded in the stroke clinical trials network of the NIH StrokeNet. Methods- This special report provides a descriptive account of the rationale, organization, and activities of the NSTC since its inception in 2013. Current processes and their evolution over time for facilitating training of NIH StrokeNet trainees have been highlighted. Data collected for monitoring training are summarized. Outcomes data (publications and grants) collected by NSTC was supplemented by publicly available resources. Results- The NSTC comprises of cross-network faculty, trainees, and education coordinators. It helps in the development and monitoring of training programs and organizes educational and career development activities. Trainees are provided directed guidance towards their mandated research projects, including opportunities to present at the International Stroke Conference. The committee has focused on developing sustainable models of peer-to-peer interaction and cross-institutional mentorships. A total of 124 professionals (43.7% female, 10.5% underrepresented minorities) have completed training between 2013 and 2018, of whom 55% were clinical vascular neurologists. Of the total, 85% transitioned to a formal academic position and 95% were involved in stroke research post-training. Altogether, 1659 indexed publications have been authored or co-authored by NIH StrokeNet Trainees, of which 58% were published during or after their training years. Based on data from 109 trainees, 33% had submitted 72 grant proposals as principal or co-principal investigators of which 22.2% proposals have been funded. Conclusions- NSTC has provided a foundation to foster nationwide training in stroke research. Our data demonstrate strong contribution of trainees towards academic scholarship. Continued innovation in educational methodologies is required to adapt to unique training opportunities such as the NIH StrokeNet.

High-resolution dynamic oxygen-17 MR imaging of mouse brain with golden-ratio-based radial sampling and k-space-weighted image reconstruction.

PURPOSE: The current study aimed to develop a three-dimensional (3D) dynamic oxygen-17 (17 O) MR imaging method with high temporal and spatial resolution to delineate the kinetics of 17 O water uptake and washout in the brains of mice with glioblastoma (GBM). METHODS: A 3D imaging method with a stack-of-stars golden-ratio-based radial sampling scheme was employed to acquire 17 O signal in vivo. A k-space-weighted image reconstruction method was used to improve the temporal resolution while preserving spatial resolution. Simulation studies were performed to validate the method. Using this method, the kinetics of 17 O water uptake and washout in the brains of mice with GBM were delineated after an intravenous bolus injection of 17 O water. RESULTS: The proposed 17 O imaging method achieved an effective temporal resolution of 7.56 s with a nominal voxel size of 5.625 µL in the mouse brain at 9.4 T. Reduced uptake and prolonged washout of 17 O water were observed in tumor tissue, suggesting compromised cerebral perfusion. CONCLUSION: This study demonstrated a promising dynamic 17 O imaging approach that can delineate 17 O water kinetics in vivo with high temporal and spatial resolution. It can also be used to image cerebral oxygen consumption rate in oxygen-17 inhalation studies. Magn Reson Med 79:256-263, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Fast magnetic resonance fingerprinting for dynamic contrast-enhanced studies in mice.

PURPOSE: The goal of this study was to develop a fast MR fingerprinting (MRF) method for simultaneous T1 and T2 mapping in DCE-MRI studies in mice. METHODS: The MRF sequences based on balanced SSFP and fast imaging with steady-state precession were implemented and evaluated on a 7T preclinical scanner. The readout used a zeroth-moment-compensated variable-density spiral trajectory that fully sampled the entire k-space and the inner 10 × 10 k-space with 48 and 4 interleaves, respectively. In vitro and in vivo studies of mouse brain were performed to evaluate the accuracy of MRF measurements with both fully sampled and undersampled data. The application of MRF to dynamic T1 and T2 mapping in DCE-MRI studies were demonstrated in a mouse model of heterotopic glioblastoma using gadolinium-based and dysprosium-based contrast agents. RESULTS: The T1 and T2 measurements in phantom showed strong agreement between the MRF and the conventional methods. The MRF with spiral encoding allowed up to 8-fold undersampling without loss of measurement accuracy. This enabled simultaneous T1 and T2 mapping with 2-minute temporal resolution in DCE-MRI studies. CONCLUSION: Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.

Understanding Edward Muybridge: historical review of behavioral alterations after a 19th-century head injury and their multifactorial influence on human life and culture.

Edward Muybridge was an Anglo-American photographer, well known for his pioneering contributions in photography and his invention of the "zoopraxiscope," a forerunner of motion pictures. However, this 19th-century genius, with two original patents in photographic technology, made outstanding contributions in art and neurology alike, the latter being seldom acknowledged. A head injury that he sustained changed his behavior and artistic expression. The shift of his interests from animal motion photography to human locomotion and gait remains a pivotal milestone in our understanding of patterns in biomechanics and clinical neurology, while his own behavioral patterns, owing to an injury to the orbitofrontal cortex, remain a mystery even for cognitive neurologists. The behavioral changes he exhibited and the legal conundrum that followed, including a murder of which he was acquitted, all depict the complexities of his personality and impact of frontal lobe injuries. This article highlights the life journey of Muybridge, drawing parallels with Phineas Gage, whose penetrating head injury has been studied widely. The wide sojourn of Muybridge also illustrates the strong connections that he maintained with Stanford and Pennsylvania universities, which were later considered pinnacles of higher education on the two coasts of the United States.

Impact of brain tissue filtering on neurostimulation fields: a modeling study.

Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson's disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods.

An unusual cause of stroke in a 55-year-old woman.

A 55-year-old woman presented with acute onset ataxia and right-sided dysmetria. Magnetic resonance imaging (MRI) confirmed clinical suspicion of stroke. She was found to have middiastolic murmur which led to urgent echocardiogram demonstrating left atrial myxoma. She underwent prompt surgical resection. Cardiac myxoma is a very rare cause of stroke. The presentation can be varied and diagnosis can be often missed. Early surgical intervention is a definitive treatment. Our case is unique and underlines importance of eliciting accurate physical signs at bedside.

Integrating Big Data, Artificial Intelligence, and motion analysis for emerging precision medicine applications in Parkinson's Disease.

One of the key challenges in Big Data for clinical research and healthcare is how to integrate new sources of data, whose relation to disease processes are often not well understood, with multiple classical clinical measurements that have been used by clinicians for years to describe disease processes and interpret therapeutic outcomes. Without such integration, even the most promising data from emerging technologies may have limited, if any, clinical utility. This paper presents an approach to address this challenge, illustrated through an example in Parkinson's Disease (PD) management. We show how data from various sensing sources can be integrated with traditional clinical measurements used in PD; furthermore, we show how leveraging Big Data frameworks, augmented by Artificial Intelligence (AI) algorithms, can distinctively enrich the data resources available to clinicians. We showcase the potential of this approach in a cohort of 50 PD patients who underwent both evaluations with an Integrated Motion Analysis Suite (IMAS) composed of a battery of multimodal, portable, and wearable sensors and traditional Unified Parkinson's Disease Rating Scale (UPDRS)-III evaluations. Through techniques including Principal Component Analysis (PCA), elastic net regression, and clustering analysis we demonstrate how this combined approach can be used to improve clinical motor assessments and to develop personalized treatments. The scalability of our approach enables systematic data generation and analysis on increasingly larger datasets, confirming the integration potential of IMAS, whose use in PD assessments is validated herein, within Big Data paradigms. Compared to existing approaches, our solution offers a more comprehensive, multi-dimensional view of patient data, enabling deeper clinical insights and greater potential for personalized treatment strategies. Additionally, we show how IMAS can be integrated into established clinical practices, facilitating its adoption in routine care and complementing emerging methods, for instance, non-invasive brain stimulation. Future work will aim to augment our data repositories with additional clinical data, such as imaging and biospecimen data, to further broaden and enhance these foundational methodologies, leveraging the full potential of Big Data and AI.

The evolution of Big Data in neuroscience and neurology.

Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started to transform the fields of Neuroscience and Neurology. Scientists and clinicians are collaborating in global alliances, combining diverse datasets on a massive scale, and solving complex computational problems that demand the utilization of increasingly powerful computational resources. This Big Data revolution is opening new avenues for developing innovative treatments for neurological diseases. Our paper surveys Big Data's impact on neurological patient care, as exemplified through work done in a comprehensive selection of areas, including Connectomics, Alzheimer's Disease, Stroke, Depression, Parkinson's Disease, Pain, and Addiction (e.g., Opioid Use Disorder). We present an overview of research and the methodologies utilizing Big Data in each area, as well as their current limitations and technical challenges. Despite the potential benefits, the full potential of Big Data in these fields currently remains unrealized. We close with recommendations for future research aimed at optimizing the use of Big Data in Neuroscience and Neurology for improved patient outcomes. Supplementary Information: The online version contains supplementary material available at 10.1186/s40537-023-00751-2.

Cost-Effectiveness Analysis to Inform Randomized Controlled Trial Design in Chronic Pain Research: Methods for Guiding Decisions on the Addition of a Run-In Period.

Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT. Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period. Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs. Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.

Vascular cognitive impairment in small vessel disease: clinical and neuropsychological features of lacunar state and Binswanger's disease.

BACKGROUND: ischaemic cerebrovascular small vessel disease (SVD) is a prevalent and under-diagnosed condition that triggers vascular cognitive impairment (VCI). OBJECTIVE: to describe the neuropsychological and clinical profiles in SVD (Binswanger's disease, BD; lacunar state, LS) from the clinician's perspective at the VCI stage. METHODS: a total of 1257 patients admitted to a tertiary center with a diagnosis of stroke, neuroradiological vascular disease, cognitive impairment/dementia, during a 13-year period were investigated. We prospectively assessed cognition in a subset of 141 patients with VCI (LS n = 28, BD n = 69, large vessel disease-LVD-n = 44) with MMSE, CAMDEX-H, WAIS-R, EXIT-25 and Trail making test. RESULTS: executive dysfunction (ECD) (n = 89, 91.7% versus n = 10, 22.7%; P < 0.001) and gait disturbances (n = 74, 76.3% versus n = 15, 34.1%; P < 0.001) characterized SVD. Prior strokes (n = 9, 9.3% versus n = 23, 52.3%; P < 0.001) and embologenous cardiopathy (n = 39, 40.2% versus n = 28, 63.6%; P < 0.04) featured LVD cases. BD was defined by hypertension (n = 52, 75.4% versus n = 30, 44.1%; P < 0.001), ECD (n = 65, 94.2% versus n = 34, 47.2%; P < 0.001) and VCI onset with cognitive impairment but not strokes (n = 44, 63.8% versus n = 34, 50%; P < 0.01). CONCLUSIONS: ECD and a frontal gait are SVD's clinical landmarks in our sample. LS and BD cases share a similar cognitive profile.

Imaging Guidance for Therapeutic Delivery: The Dawn of Neuroenergetics.

Modern neurocritical care relies on ancillary diagnostic testing in the form of multimodal monitoring to address acute changes in the neurological homeostasis. Much of our armamentarium rests upon physiological and biochemical surrogates of organ or regional level metabolic activity, of which a great deal is invested at the metabolic-hemodynamic-hydrodynamic interface to rectify the traditional intermediaries of glucose consumption. Despite best efforts to detect cellular neuroenergetics, current modalities cannot appreciate the intricate coupling between astrocytes and neurons. Invasive monitoring is not without surgical complication, and noninvasive strategies do not provide an adequate spatial or temporal resolution. Without knowledge of the brain's versatile behavior in specific metabolic states (glycolytic vs oxidative), clinical practice would lag behind laboratory empiricism. Noninvasive metabolic imaging represents a new hope in delineating cellular, nigh molecular level energy exchange to guide targeted management in a diverse array of neuropathology.

Increased cerebral vascularization and decreased water exchange across the blood-brain barrier in aquaporin-4 knockout mice.

Aquaporin-4 (AQP4) plays an important role in regulating water exchange across the blood-brain barrier (BBB) and brain-cerebrospinal fluid interface. Studies on AQP-4 knockout mice (AQP4-KO) have reported considerable protection from brain edema induced by acute water intoxication and ischemic stroke, identifying AQP4 as a potential target for therapeutic interventions. However, the long-term effects of chronic AQP4 suppression are yet to be elucidated. In the current study, we evaluated the physiological and structural changes in adult AQP4-KO mice using magnetic resonance imaging (MRI) and immunohistochemical analysis. Water exchange across BBB was assessed by tracking an intravenous bolus injection of oxygen-17 (17O) water (H217O) using 17O-MRI. Cerebral blood flow (CBF) was quantified using arterial spin-labeling (ASL) MRI. Capillary density was determined by immunohistochemical staining for glucose transporter-1 (GLUT1). Compared to wildtype control mice, AQP4-KO mice showed a significant reduction in peak and steady-state H217O uptake despite unaltered CBF. Interestingly, a 22% increase in cortical capillary density was observed in AQP4-KO mice. These results suggest that increased cerebral vascularization may be an adaptive response to chronic reduction in water exchange across BBB in AQP4-KO mice.

Visual phosphene perception modulated by subthreshold crossmodal sensory stimulation.

Crossmodal sensory interactions serve to integrate behaviorally relevant sensory stimuli. In this study, we investigated the effect of modulating crossmodal interactions between visual and somatosensory stimuli that in isolation do not reach perceptual awareness. When a subthreshold somatosensory stimulus was delivered within close spatiotemporal congruency to the expected site of perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse delivered to the occipital cortex evoked a visual percept. The results suggest that under subthreshold conditions of visual and somatosensory stimulation, crossmodal interactions presented in a spatially and temporally specific manner can sum up to become behaviorally significant. These interactions may reflect an underlying anatomical connectivity and become further enhanced by attention modulation mechanisms.

Vascular cognitive impairment: prodromal stages of ischemic vascular dementia.

BACKGROUND/AIMS: To describe the natural history of the prodromal stages of ischemic vascular dementia (pVaD). METHODS: A sample of 314 inpatients with pVaD or a clini- cal diagnosis of vascular dementia (VaD; lacunar state, Binswanger's disease, pure cortical VaD, corticosubcortical and strategic infarctions) admitted to a teaching tertiary center during a 13-year period was assessed (retrospectively n = 88, prospectively n = 226). Prospective neuropsychological assessment consisted of Mini Mental State Examination, Revised Wechsler Adult Intelligence Scale, Exit-25, Trail Making tests, Blessed Dementia Scale and Camdex H, Global Depression Scale and Hamilton Depression Rating Scale tests. Univariate analysis and logistic regressions are displayed. RESULTS: An unrecognized pVaD was related with a clinical onset with cognitive impairment no dementia (CIND) versus symptomatic cerebrovascular events (p < 0.0001), and with being under therapy with anticoagulant or antiplatelet agents (p < 0.01). Age <85 years at diagnosis of VaD (p < 0.01) correlated with a delayed pVaD diagnosis. CIND onset was associated with a longer prodromal stage (p < 0.01), no clinical strokes during pVaD (p < 0.001), silent ischemia (p < 0.01) and Binswanger's disease (p < 0.01). CONCLUSIONS: Vascular cognitive impairment remains an underdiagnosed, yet treatable entity. A brief neuropsychological examination and informant interviews should become standard practice in elderly populations with vascular risk factors. Small-vessel disease is a prevalent condition with a distinct natural history.

Transcranial magnetic stimulation and brain atrophy: a computer-based human brain model study.

This paper is aimed at exploring the effect of cortical brain atrophy on the currents induced by transcranial magnetic stimulation (TMS). We compared the currents induced by various TMS conditions on several different MRI derived finite element head models of brain atrophy, incorporating both decreasing cortical volume and widened sulci. The current densities induced in the cortex were dependent upon the degree and type of cortical atrophy and were altered in magnitude, location, and orientation when compared to healthy head models. Predictive models of the degree of current density attenuation as a function of the scalp-to-cortex distance were analyzed, concluding that those which ignore the electromagnetic field-tissue interactions lead to inaccurate conclusions. Ultimately, the precise site and population of neural elements stimulated by TMS in an atrophic brain cannot be predicted based on healthy head models which ignore the effects of the altered cortex on the stimulating currents. Clinical applications of TMS should be carefully considered in light of these findings.

Prolonged Intracisternal Papaverine Toxicity: Index Case Description and Proposed Mechanism of Action.

BACKGROUND: Intracisternal papaverine (iPPV) is a vasodilator used for prophylaxis of intraoperative vasospasm during aneurysmal clipping. Postoperative side effects of iPPV include transient cranial nerve palsies, most commonly mydriasis owing to oculomotor nerve involvement, with rapid resolution. METHODS: We critically reviewed current literature on the adverse effects of iPPV in aneurysmal surgery with a focus on oculomotor nerve involvement. We also present the index case of prolonged bilateral mydriasis secondary to iPPV irrigation toxicity and its putative underlying mechanism. RESULTS: Papaverine toxicity occurs in the setting of its antimuscarinic action and blood-cerebrospinal fluid and blood-brain barrier compromise owing to acute subarachnoid hemorrhage and direct effect of papaverine. Our patient also experienced severe vasospasm and a minor stroke, both contributing to further blood-brain barrier disruption, and relatively acidic pH of the subarachnoid hemorrhage milieu. CONCLUSIONS: We propose that these factors perpetuate phase dynamics of papaverine crystals and facilitate a sustained slow release of papaverine within the cisternal system. Were it indicated, 0.3% iPPV would reasonably diminish the risk for neurotoxicity.

Bedside optical coherence tomography for Terson's syndrome screening in acute subarachnoid hemorrhage: a pilot study.

OBJECTIVE: Approximately 10% of patients with subarachnoid hemorrhage (SAH) become permanently, legally blind. The average cost of lifetime support and unpaid taxes for each blind person amounts to approximately $900,000. This study evaluates the feasibility and potential role of bedside optical coherence tomography (OCT) in Terson's syndrome (TS) in patients with acute SAH (aSAH) and its potential role in blindness prevention. METHODS: The authors conducted an open-label pilot study, in which 31 patients with an angiographic diagnosis of aSAH were first screened for TS with dilated funduscopy and then with OCT in the acute phase and at 6-week followup visits. Outpatient mood assessments (Patient Health Questionnaire­depression module, Hamilton Depression Scale), and quality of life general (NIH Patient-Reported Outcomes Measurement Information System) and visual scales (25-item National Eye Institute Visual Functioning Questionnaire) were measured at 1 and 6 weeks after discharge. Exclusion criteria included current or previous history of severe cataracts, severe diabetic retinopathy, severe macular degeneration, or glaucoma. RESULTS: OCT identified 7 patients with TS, i.e., a 22.6% incidence in our aSAH sample: 7 in the acute phase, including a large retinal detachment that was initially missed by funduscopy and diagnosed by OCT in follow-up clinic. Dilated retinal funduscopy significantly failed to detect TS in 4 (57.1%) of these 7 cases. Intraventricular hemorrhage was significantly more common in TS cases (85.7% vs 25%). None of the participants experienced any complications from OCT examinations. Neither decreased quality of life visual scale scores nor a depressed mood correlated with objective OCT pathological findings at the 6-week follow-up after discharge. There were no significant mood differences between TS cases and controls. CONCLUSIONS: OCT is the gold standard in retinal disease diagnosis. This pilot study shows that bedside OCT examination is feasible in aSAH. In this series, OCT was a safe procedure that enhanced TS detection by decreasing false-negative/inconclusive funduscopic examinations. It allows early diagnosis of macular holes and severe retinal detachments, which require acute surgical therapy to prevent legal blindness. In addition, OCT aids in ruling out potential false-positive visual deficits in individuals with a depressed mood at follow-up.

The Emerging Role of Inhaled Heroin in the Opioid Epidemic: A Review.

Importance: Opioid addiction affects approximately 2.4 million Americans. Nearly 1 million individuals, including a growing subset of 21 000 minors, abuse heroin. Its annual cost within the United States amounts to $51 billion. Inhaled heroin use represents a global phenomenon and is approaching epidemic levels east of the Mississippi River as well as among urban youth. Chasing the dragon (CTD) by heating heroin and inhaling its fumes is particularly concerning, because this method of heroin usage has greater availability, greater ease of administration, and impressive intensity of subjective experience (high) compared with sniffing or snorting, although it also has a safer infectious profile compared with heroin injection. This is relevant owing to peculiar and often catastrophic brain complications. Following the American Medical Association Opioid Task Force mandate, we contribute a description of the pharmacology, pathophysiology, clinical spectrum, neuroimaging, and neuropathology of CTD leukoencephalopathy, as distinct from other heroin abuse modalities. Observations: The unique spectrum of CTD-associated health outcomes includes an aggressive toxic leukoencephalopathy with pathognomonic neuropathologic features, along with sporadic instances of movement disorders and hydrocephalus. Clinical CTD severity is predominantly moderate at admission, frequently unmodified at discharge, and largely improved in the long term. Mild cases survive with minor sequelae, while moderate to severe presentations might deteriorate and progress to death. Other methods of heroin use may complicate with stroke, seizure, obstructive hydrocephalus, and (uncharacteristically) leukoencephalopathy. Conclusions and Relevance: The distinct pharmacology of CTD correlates with its specific clinical and radiological features and prompts grave concern for potential morbidity and long-term disability costs. Proposed diagnostic criteria and standardized reporting would ameliorate the limitations of CTD literature and facilitate patient selection for a coenzyme Q10 therapeutic trial.

Time-dependent changes in cortical excitability after prolonged visual deprivation.

Transcranial magnetic stimulation applied to the occipital cortex can elicit phosphenes. Changes in the phosphene threshold provide a measure of visual cortex excitability. Phosphene threshold was measured in participants blindfolded for five consecutive days to assess the effects of prolonged visual deprivation on visual cortical excitability. After 48 h of blindfolding, an acute decrease in phosphene threshold was observed, followed by a significant increase by day 5. Phosphene threshold returned to preblindfold levels within 2 h of light re-exposure. Thus, light deprivation is characterized by a transient increase in visual cortical excitability, followed by a sustained decrease in visual cortex excitability that quickly returns to baseline levels after re-exposure to light.