Chronic brain damage in HIV-infected individuals under antiretroviral therapy is associated with viral reservoirs, sulfatide release, and compromised cell-to-cell communication.

HIV infection has become a chronic and manageable disease due to the effective use of antiretroviral therapies (ART); however, several chronic aging-related comorbidities, including cognitive impairment, remain a major public health issue. However, these mechanisms are unknown. Here, we identified that glial and myeloid viral reservoirs are associated with local myelin damage and the release of several myelin components, including the lipid sulfatide. Soluble sulfatide compromised gap junctional communication and calcium wave coordination, essential for proper cognition. We propose that soluble sulfatide could be a potential biomarker and contributor to white matter compromise observed in HIV-infected individuals even in the current ART era.

Percutaneous Needle Tenotomy for the Treatment of Muscle and Tendon Contractures in Adults With Brain Damage: Results and Complications.

OBJECTIVE: To study the results and complications of percutaneous needle tenotomy for superficial retracted tendons in patients with brain damage. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients with severe brain damage (N=38; mean age, 60.7y; age range, 24-93y; 21 women) requiring surgical management of contractures and eligible for percutaneous needle tenotomy were enrolled between February 2015 and February 2016. INTERVENTIONS: The percutaneous needle tenotomy gesture was performed by a physical medicine and rehabilitation physician trained by an orthopedic surgeon, under local or locoregional anesthesia. Treated tendons varied among patients. MAIN OUTCOME MEASURES: All patients were evaluated at 1, 3, and 6 months to assess surgical outcomes (joint range of motion [ROM], pain, and functional improvement) while screening for complications. RESULTS: Improvements in ROM (37/38) and contractures-related pain (12/12) were satisfactory. Functional results were satisfactory (Goal Attainment Scale score ≥0) for most patients (37/38): nursing (n=12), putting shoes on (n=8), getting in bed or sitting on a chair (n=6), verticalization (n=7), transfers and gait (n=8), and grip (n=2). Five patients had complications related to the surgical gesture: cast-related complications (n=2), hand hematoma (n=2), and cutaneous necrosis of the Achilles tendon in a patient with previous obliterative arteriopathy of the lower limbs (n=1). CONCLUSIONS: Percutaneous needle tenotomy yields good results in the management of selected superficial muscle and tendon contractures. The complications rate is very low, and this treatment can be an alternative to conventional surgery in frail patients with neurologic diseases.

The Effects of Chronic Right Hemispheric Damage on the Allocation of Spatial Attention: Alterations of Accuracy and Reliability.

Right hemispheric damage (RHD) caused by strokes often induce attentional disorders such as hemispatial neglect. Most patients with neglect over time have a reduction in their ipsilesional spatial attentional bias. Despite this improvement in spatial bias, many patients remain disabled. The cause of this chronic disability is not fully known, but even in the absence of a directional spatial attentional bias, patients with RHD may have an impaired ability to accurately and precisely allocate their spatial attention. This inaccuracy and variable directional allocation of spatial attention may be revealed by repeated performance on a spatial attentional task, such as line bisection (LBT). Participants with strokes of their right versus left (LHD) hemisphere along with healthy controls (HC) performed 24 consecutive trials of 24 cm horizontal line bisections. A vector analysis of the magnitude and direction of deviations from midline, as well as their standard deviations (SD), were calculated. The results demonstrated no significant difference between the LHD, RHD and HC groups in overall spatial bias (mean bisection including magnitude and direction); however, the RHD group had a significantly larger variability of their spatial errors (SD), and made larger errors (from midline) than did the LHD and HC groups. There was a curvilinear relationship between the RHD participants' performance variability and their severity of their inaccuracy. Therefore, when compared to HC and LHD, the RHD subjects' performance on the LBT is more variable and inaccurate.

Facial self-mutilation: an analysis of published cases.

OBJECTIVES: Facial self-mutilation is rare. It is usually discussed from the psychiatric or psychoanalytic perspectives but has little prominence in general medical literature. Our objective was to describe facial self-mutilation in terms of its comorbidities, and to outline the different types of facial mutilation, as well as the basic approach to the patients with facial self-mutilation. METHODS: We undertook a review of all published cases of facial self-mutilation (1960-2011). RESULTS: We identified 200 published cases in 123 relevant papers. Four major groups of comorbidities emerged: psychiatric, neurological and hereditary disorders, and a group of patients without identified comorbidities. There were three general patterns of facial self-mutilation: (1) major and definitive mutilation, with the ocular globe as primary target--seen in patients with psychotic disorders; (2) stereotypical mutilation involving the oral cavity and of variable degree of severity, most often seen in patients with hereditary neuropathy or encephalopathy; (3) mild chronic self-mutilation, seen in patients with non-psychotic psychiatric disorders, acquired neurological disorders, and patients without comorbidities. About 20% of patients that mutilated their face also mutilated extra-facial structures. Patients with psychiatric conditions, especially those with psychotic disorders, had significantly higher (p<0.05) rates of permanent facial self-mutilation than others. Most treatment plans were very individually based, but some principles, such as prevention of irreversible loss of function and structure, or development of infection are applicable to all patients with facial self-mutilation. CONCLUSIONS: Facial self-mutilation is a potentially severe manifestation of diverse conditions. Several aspects of facial self-mutilation remain to be fully characterised from a clinical perspective.

Estimating the minimal clinically important difference of upper extremity outcome measures in chronic stroke patients with moderate to severe impairment: a cross-sectional study.

BACKGROUND: Approximately 70% of chronic stroke patients experience upper extremity (UE) functional impairments, and UE outcome measures are often used as quality-of-life indicators. OBJECTIVE: The purpose of this study was to estimate minimal clinically important difference (MCID) values for UE outcome measures in chronic stroke patients with moderate to severe UE hemiplegia. METHODS: This study was a cross-sectional study, conducted as a secondary analysis of data from the ReoGo-J study, a multicenter, prospective, randomized, parallel-group trial of robot-assisted self-training for UE hemiplegia in chronic stroke. The patients were randomized to 1 of 3 treatment groups. Treatment was provided 3 times a week for 10 weeks, and UE outcome measures were evaluated before and after treatment. The anchor-based method was used to estimate MCID values for UE outcome measures, with Stroke Impact Scale (SIS) subscales as anchors. MCID values were estimated by identifying cutoff values in a receiver operating characteristic (ROC) curve. RESULTS: Between-group comparisons of UE outcome measures, based on the clinically important difference (CID) values of SIS subscales, revealed significant differences in both the Amount of Use (AOU) and Quality of Movement (QOM) components of the Motor Activity Log (MAL)-14. The estimated MCID values were 0.89 for the AOU component and 0.77 for the QOM component. CONCLUSIONS: The estimated MCID values for the MAL-14 not only add information regarding the clinical characteristics of the MAL-14 but also facilitate interpretations of changing scores in chronic stroke patients with moderate to severe UE hemiplegia undergoing rehabilitation therapy. STUDY REGISTRATION: https://www.umin.ac.jp/ctr/index.htm (UMIN000022509; 1 July 2016).

Long-term outcomes after new onset seizure in children living with HIV: A cohort study.

OBJECTIVE: To determine the long-term outcomes, including mortality and recurrent seizures, among children living with HIV (CLWH) who present with new onset seizure. METHODS: Zambian CLWH and new onset seizure were enrolled prospectively to determine the risk of and risk factors for recurrent seizures. Demographic data, clinical profiles, index seizure etiology, and 30-day mortality outcomes were previously reported. After discharge, children were followed quarterly to identify recurrent seizures and death. Given the high risk of early death, risk factors for recurrent seizure were evaluated using a model that adjusted for mortality. RESULTS: Among 73 children enrolled, 28 died (38%), 22 within 30-days of the index seizure. Median follow-up was 533 days (IQR 18-957) with 5% (4/73) lost to follow-up. Seizure recurrence was 19% among the entire cohort. Among children surviving at least 30-days after the index seizure, 27% had a recurrent seizure. Median time from index seizure to recurrent seizure was 161 days (IQR 86-269). Central nervous system opportunistic infection (CNS OI), as the cause for the index seizure was protective against recurrent seizures and higher functional status was a risk factor for seizure recurrence. SIGNIFICANCE: Among CLWH presenting with new onset seizure, mortality risks remain elevated beyond the acute illness period. Recurrent seizures are common and are more likely in children with higher level of functioning even after adjusting for the outcome of death. Newer antiseizure medications appropriate for co-usage with antiretroviral therapies are needed for the care of these children. CNS OI may represent a potentially reversible provocation for the index seizure, while seizures in high functioning CLWH without a CNS OI may be the result of a prior brain injury or susceptibility to seizures unrelated to HIV and thus represent an ongoing predisposition to seizures. PLAIN LANGUAGE SUMMARY: This study followed CLWH who experienced a new onset seizure to find out how many go on to have more seizures and identify any patient characteristics associated with having more seizures. The study found that mortality rates continue to be high beyond the acute clinical presentation with new onset seizure. Children with a CNS OI causing the new onset seizure had a lower risk of later seizures, possibly because the trigger for the seizure can be treated. In contrast, high functioning children without a CNS OI were at higher risk of future seizures.

Acetylcholine facilitates recovery of episodic memory after brain damage.

Episodic memory depends on a network of interconnected brain structures including the inferior temporal cortex, hippocampus, fornix, and mammillary bodies. We have previously shown that a moderate episodic memory impairment in monkeys with transection of the fornix is exacerbated by prior depletion of acetylcholine from inferotemporal cortex, despite the fact that depletion of acetylcholine from inferotemporal cortex on its own has no effect on episodic memory. Here we show that this effect occurs because inferotemporal acetylcholine facilitates recovery of function following structural damage within the neural circuit for episodic memory. Episodic memory impairment caused by lesions of the mammillary bodies, like fornix transection, was exacerbated by prior removal of temporal cortical acetylcholine. However, removing temporal cortical acetylcholine after the lesion of the fornix or mammillary bodies did not increase the severity of the impairment. This lesion order effect suggests that acetylcholine within the inferior temporal cortex ordinarily facilitates functional recovery after structural lesions that impair episodic memory. In the absence of acetylcholine innervation to inferotemporal cortex, this recovery is impaired and the amnesia caused by the structural lesion is more severe. These results suggest that humans with loss of cortical acetylcholine function, for example in Alzheimer's disease, may be less able to adapt to memory impairments caused by structural neuronal damage to areas in the network important for episodic memory.

Elevated concentrations of inflammation-related proteins in postnatal blood predict severe developmental delay at 2 years of age in extremely preterm infants.

OBJECTIVE: To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants. STUDY DESIGN: We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean). RESULTS: For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P<.01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood. CONCLUSION: In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years.

Emergence of complex partial epilepsy-like experiences following closed head injuries: personality variables and neuropsychological profiles.

To pursue Richard Roberts' epileptic spectrum disorder (ESD) and the emergence of complex partial epilepsy-like experiences, items and total scores for the ESD Inventory were examined for 185 patients who had sustained mechanical impacts (and were diagnosed with or without neuropsychological impairment) and a reference group (n=68) of university students. Results from neuropsychological, personality, neurological screening, and interview data supported the role of temporal lobe origins for these experiences. The incidences of these experiences were sufficient to adversely affect adaptation and to produce psychiatric profiles. Although only 70% of the patients who were impaired versus not impaired could be differentiated by items from the ESD Inventory, >95% of the patients with scores >100 on the ESD Inventory displayed abnormal scores on more than four Minnesota Multiphasic Personality Inventory scales. These results support Roberts' ESD concept and strongly suggest that persistent, subclinical occurrence of these experiences could be the cause or major correlate of neuropsychological impairment for these patients.

Spatial probability cuing and right hemisphere damage.

In this experiment we studied statistical learning, inter-trial priming, and visual attention. We assessed healthy controls and right brain damaged (RBD) patients with and without neglect, on a simple visual discrimination task designed to measure priming effects and probability learning. All participants showed a preserved priming effect for item color. Contrary to healthy controls and RBD participants without neglect, RBD participants with neglect did not show positional priming and both RBD groups learned the underlying spatial probability distribution of target locations to a lesser degree. To see if the latter deficiency could be improved, we tested a patient with long standing chronic spatial neglect on three separate days and observed improved identification times for left sided, high probability, targets. In summary, we found preservation of priming per se in people with spatial neglect. However, this was only clearly demonstrable for color priming and not for positional priming. Associated with this impairment was a difficulty in learning the overall statistical structure of target locations. In a patient with severe persistent neglect we were able to demonstrate that the deficit in statistical learning was not absolute, as this subject improved his identification times for targets appearing in high probability regions of the test display.

Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex.

Reduced synaptic inhibition is an important factor contributing to posttraumatic epileptogenesis. Axonal sprouting and enhanced excitatory synaptic connectivity onto rodent layer V pyramidal (Pyr) neurons occur in epileptogenic partially isolated (undercut) neocortex. To determine if enhanced excitation also affects inhibitory circuits, we used laser scanning photostimulation of caged glutamate and whole-cell recordings from GAD67-GFP-expressing mouse fast spiking (FS) interneurons and Pyr cells in control and undercut in vitro slices to map excitatory and inhibitory synaptic inputs. Results are 1) the region-normalized excitatory postsynaptic current (EPSC) amplitudes and proportion of uncaging sites from which EPSCs could be evoked (hotspot ratio) "increased" significantly in FS cells of undercut slices; 2) in contrast, these parameters were significantly "decreased" for inhibitory postsynaptic currents (IPSCs) in undercut FS cells; and 3) in rat layer V Pyr neurons, we found significant decreases in IPSCs in undercut versus control Pyr neurons. The decreases were mainly located in layers II and IV, suggesting a reduction in the efficacy of interlaminar synaptic inhibition. Results suggest that there is significant synaptic reorganization in this model of posttraumatic epilepsy, resulting in increased excitatory drive and reduced inhibitory input to FS interneurons that should enhance their inhibitory output and, in part, offset similar alterations in innervation of Pyr cells.

Effects of social cognitive demand on Theory of Mind in conversations of adults with traumatic brain injury.

BACKGROUND: A requisite skill for successful conversation is the ability to adjust one's language according to contextual factors. AIMS: This study examined one aspect of language use in context-the use of mental-state terms, i.e. words that communicate thoughts, beliefs or feelings-in conversations between adult males with and without traumatic brain injury (TBI) and familiar partners. METHODS & PROCEDURES: Participants were five males in the chronic stage of recovery following severe TBI and five male peers matched for age, conversing with friends. Conversational context was manipulated using conversation starters that were designed to induce differing levels of self-disclosure or intimacy, with the expectation that mental-state term use would increase when participants talked about more intimate topics. OUTCOMES & RESULTS: Participants in both groups used more mental-state terms in more intimate conversations; however, adults with TBI did not increase their mental-state term use to the same extent as matched peers. Adults with TBI also used a significantly different pattern of mental-state term types across intimacy levels as compared with peers. CONCLUSIONS & IMPLICATIONS: These quantitative and qualitative differences may contribute to social conversation problems of adults with TBI.

The Coping with Attention and Memory Complaints Questionnaire (CAMQ): psychometric evaluation of an instrument in suspected chronic solvent-induced encephalopathy (CSE).

Long-term occupational exposure to organic solvents may induce chronic solvent-induced encephalopathy (CSE), leading to neuropsychological impairments. We developed the Coping with Attention and Memory Complaints Questionnaire (CAMQ), an instrument for the assessment of coping strategies in patients suspected of CSE with neuropsychological complaints. Items for the CAMQ were based on existing coping dimensions and constructed by experts. The psychometric properties of the CAMQ were evaluated in a sample of 307 workers suspected of CSE. Factor analysis revealed four coping subscales: active coping, avoidance, acceptance, and seeking social support, all with good internal consistency (alphas .71-.78) and good test-retest reliability (ICCs .67-.82). The subscales demonstrated moderate correlations with related external constructs such as anxiety and depression, locus of control, meta-memory, mastery and generic coping styles. In conclusion, this study: (1) shows that the newly developed CAMQ is a reliable instrument, and (2) provides evidence for its validity in assessing coping with complaints of memory and attention in CSE-suspected patients. These results may serve for further study on coping with complaints of memory and attention, psychological adjustment and well-being in CSE patients.

[The neutral and affective verbal fluency in people with right, left or both hemisphere brain pathology]. / Fluencja slowna neutralna i afektywna u chorych z uszkodzeniem prawej, lewej lub obu pólkul mózgu.

AIM: The comparison of neutral and affective fluency realisation in patients with right, left or both hemisphere brain damage and the control group, was the aim of our study. 31 healthy persona and 31 persons with vascular brain damage participated. (the left hemisphere (N = 11), right (N = 14) or both hemispheres (N = 6)). METHOD: 4 fluency tasks were used: animals, "k" letter (the neutral tasks), pleasant and unpleasant (the affective tasks). The aim of our research was the assessment of the number of correct answers, number of mistakes, clusters as well as the switches between compliant and discordant with the type of the task. The level of depression as well as the level of linguistic abilities were considered in analyses. RESULTS: The group of people with the CNS pathology generated less words and less clusters of both types (compliant and discordant with type of the task) in comparison to healthy people. The character of CNS pathology did not differ the results, however we noted the tendencies to diverse realisation of affective fluency. In the neutral tasks persons generated more words than affective tasks independently of their clinical state, and they applied strategies compliant with the type of the task. CONCLUSIONS: The applying of the affective fluency can enrich the workshop of the clinical diagnosis. Tasks of this type engage other psychological and neuronal mechanisms than the traditional neutral fluency.

A Comprehensive and Advanced Mouse Model of Post-Traumatic Epilepsy with Robust Spontaneous Recurrent Seizures.

Traumatic brain injury (TBI) is a leading cause of epilepsy in military persons and civilians. Spontaneous recurrent seizures (SRSs) occur in the months or years following the injury, which is commonly referred to as post-traumatic epilepsy (PTE). Currently, there is no effective treatment or cure for PTE; therefore, there is a critical need to develop animal models to help further understand and assess mechanisms and interventions related to TBI-induced epilepsy. Despite many attempts to induce PTE in animals, success has been limited due to a lack of consistent SRSs after TBI. We present a comprehensive protocol to induce PTE after contusion brain injury in mice, which exhibit robust SRSs along with neurodegeneration and neuroinflammation. This article provides a complete set of protocols for injury, outcomes, troubleshooting, and data analysis. Our broad profiling of a TBI mouse reveals features of progressive, long-lasting epileptic activity, hippocampal sclerosis, and comorbid mood and memory deficits. Overall, the PTE mouse shows striking consistency in recapitulating major hallmark features of human PTE. This mouse model will be helpful in assessing mechanisms of and interventions for TBI-induced epileptogenesis, epilepsy, and neuropsychiatric dysfunction. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Inducing controlled cortical impact injuries Support Protocol: Creating the custom domed camp Basic Protocol 2: Recording long-term video-EEG signals Basic Protocol 3: Analyzing video-EEG recordings.

Role of the corpus callosum in speech comprehension: interfacing syntax and prosody.

The role of the corpus callosum (CC) in the interhemispheric interaction of prosodic and syntactic information during speech comprehension was investigated in patients with lesions in the CC, and in healthy controls. The event-related brain potential experiment examined the effect of prosodic phrase structure on the processing of a verb whose argument structure matched or did not match the prior prosody-induced syntactic structure. While controls showed an N400-like effect for prosodically mismatching verb argument structures, thus indicating a stable interplay between prosody and syntax, patients with lesions in the posterior third of the CC did not show this effect. Because these patients displayed a prosody-independent semantic N400 effect, the present data indicate that the posterior third of the CC is the crucial neuroanatomical structure for the interhemispheric interplay of suprasegmental prosodic information and syntactic information.

Left dorsomedial frontal brain damage is associated with insomnia.

Insomnia is a common sleep disorder, yet its pathophysiological basis remains poorly understood. Studying a group of 192 patients with focal brain lesions, we show a significant association between insomnia and left dorsomedial prefrontal damage. Our findings are the first to demonstrate a link between insomnia and a discrete locus of brain damage, providing novel insight into the neurobiological mechanisms of sleep maintenance.

A common processing system for the concepts of artifacts and actions? Evidence from a case of a disproportionate conceptual impairment for living things.

We report the results of a single-case study carried out with a brain-damaged patient, G.C., whose conceptual knowledge of living things (animals and plants) was significantly more impaired than his knowledge of artifacts and his knowledge of actions, which were similarly impaired. We examined whether this pattern of conceptual impairment could be accounted for by the "sensory/functional" or the "manipulability" account for category-specific conceptual impairments advocated within the feature-based organization theory. To this end, we assessed, first, the patient's knowledge of sensory compared to functional and motor features and, second, his knowledge of nonmanipulable compared to manipulable items. The findings showed that the patient's disproportionate impairment for living things compared to both artifacts and actions was not associated with a disproportionate impairment of sensory compared to functional or motor knowledge or with a relative sparing of manipulable compared to nonmanipulable items. We then discuss how alternative theories of conceptual knowledge organization could account for G.C.'s pattern of category-specific deficit.

Dissociation between memory accuracy and memory confidence following bilateral parietal lesions.

Numerous functional neuroimaging studies have observed lateral parietal lobe activation during memory tasks: a surprise to clinicians who have traditionally associated the parietal lobe with spatial attention rather than memory. Recent neuropsychological studies examining episodic recollection after parietal lobe lesions have reported differing results. Performance was preserved in unilateral lesion patients on source memory tasks involving recollecting the context in which stimuli were encountered, and impaired in patients with bilateral parietal lesions on tasks assessing free recall of autobiographical memories. Here, we investigated a number of possible accounts for these differing results. In 3 experiments, patients with bilateral parietal lesions performed as well as controls at source recollection, confirming the previous unilateral lesion results and arguing against an explanation for those results in terms of contralesional compensation. Reducing the behavioral relevance of mnemonic information critical to the source recollection task did not affect performance of the bilateral lesion patients, indicating that the previously observed reduced autobiographical free recall might not be due to impaired bottom-up attention. The bilateral patients did, however, exhibit reduced confidence in their source recollection abilities across the 3 experiments, consistent with a suggestion that parietal lobe lesions might lead to impaired subjective experience of rich episodic recollection.

Is recurrent perseveration a product of deafferented functional systems with otherwise normal post-activation decay rates?

Recent work in neuropsychology, clinical aphasiology and neuropharmacology have presented evidence that the causative substrates of recurrent perseveration in adults with aphasia are more recondite and subject to distinct interpretations than originally thought. This article will discuss and evaluate how various proposals from theory, from the clinic and from drug therapy interact and compete in the search for a cause or causes of recurrent perseveration.