JCV seroconversion rate during the SARS COVID-19 pandemic.

The transmission route of the John Cunningham virus (JCV) is not clearly understood. The high prevalence of JCV in urine and sewage and the stability of the viral particles observed suggest that contaminated water, food, and fomites could be the vehicles of JCV transmission through the oral route. Multiple Sclerosis (MS) patients treated with Natalizumab are at risk of developing progressive multifocal leukoencephalopathy (PML), and hence, JCV serology is monitored for risk stratification. Social restrictions introduced in 2020 which intended to limit the transmission of SARS-CoV-2 are associated with decreased rates of other communicable diseases, as has been shown in recent observational studies. We evaluated the prevalence of seroconversion prior to and during the coronavirus disease (COVID -19) pandemic based on clinical records of JCV serology status in a single-center cohort of Natalizumab-treated Multiple Sclerosis patients. We hypothesized that seroconversion rates would decrease due to behavioral changes. However, seroconversion rates were stable during the COVID-19 pandemic compared to the pre-pandemic. These findings support the notion that JCV is transmitted via the GI tract rather than the respiratory system.

Legal concerns in health-related artificial intelligence: a scoping review protocol.

BACKGROUND: Medical innovations offer tremendous hope. Yet, similar innovations in governance (law, policy, ethics) are likely necessary if society is to realize medical innovations' fruits and avoid their pitfalls. As innovations in artificial intelligence (AI) advance at a rapid pace, scholars across multiple disciplines are articulating concerns in health-related AI that likely require legal responses to ensure the requisite balance. These scholarly perspectives may provide critical insights into the most pressing challenges that will help shape and advance future regulatory reforms. Yet, to the best of our knowledge, there is no comprehensive summary of the literature examining legal concerns in relation to health-related AI. We thus aim to summarize and map the literature examining legal concerns in health-related AI using a scoping review approach. METHODS: The scoping review framework developed by (J Soc Res Methodol 8:19-32, 2005) and extended by (Implement Sci 5:69, 2010) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guided our protocol development. In close consultation with trained librarians, we will develop a highly sensitive search for MEDLINE® (OVID) and adapt it for multiple databases designed to comprehensively capture texts in law, medicine, nursing, pharmacy, other healthcare professions (e.g., dentistry, nutrition), public health, computer science, and engineering. English- and French-language records will be included if they examine health-related AI, describe or prioritize a legal concern in health-related AI or propose a solution thereto, and were published in 2012 or later. Eligibility assessment will be conducted independently and in duplicate at all review stages. Coded data will be analyzed along themes and stratified across discipline-specific literatures. DISCUSSION: This first-of-its-kind scoping review will summarize available literature examining, documenting, or prioritizing legal concerns in health-related AI to advance law and policy reform(s). The review may also reveal discipline-specific concerns, priorities, and proposed solutions to the concerns. It will thereby identify priority areas that should be the focus of future reforms and regulatory options available to stakeholders in reform processes. TRIAL REGISTRATION: This protocol was submitted to the Open Science Foundation registration database. See https://osf.io/zav7w .

Reinforcing the evidence of oligoclonal bands as a prognostic factor in patients with Multiple sclerosis.

The prognostic value of oligoclonal bands in the cerebrospinal fluid of Multiple Sclerosis (MS) patients is controversial. While several studies have demonstrated a worse disease course in OCB positive patients, others did not reproduce these findings. We evaluated the prognostic significance of OCB retrospectively based on clinical records of OCB status upon diagnosis and severity outcomes including the MS Severity Score, Progression Index and regional involvement in Magnetic Resonance Imaging. OCB positive patients had a higher median MSSS and PI, and a greater proportion of spinal cord involvement. These findings provide further evidence of the prognostic importance of OCB in MS patients.

Increased incidence of Susac syndrome: a case series study.

BACKGROUND: Susac syndrome (SuS) is a rare condition characterized by a clinical triad of sensorineural hearing loss, branch artery occlusion and encephalopathy. This study reports an increased incidence of SuS in Israel. We describe the clinical characteristics of these patients, diagnostic procedures and the use and subsequent outcomes of newly published treatment guidelines. METHODS: This is a single center retrospective study. Patients who were diagnosed with SuS between July 2017 and August 2018 were enrolled in this study. RESULTS: Seven patients were diagnosed with SuS according to the diagnostic criteria in a time period of 13 months. The annual incidence was recently evaluated in Austria to be 0.024/100000, therefore, our case series represent at least a 5.4- fold increase in the annual incidence of SuS expected in Israel and a 7-fold increase in the annual incidence expected in our medical center. Mean time from the onset of the symptoms to diagnosis was three weeks and follow-up time was twenty four months. Recent exposure to cytomegalovirus was serologically evident in three patients and one patient had high titer of anti-streptolysin antibody. All patients underwent brain MRI, fluorescein angiography and audiometry. All patients were treated according to the newly recommended guidelines. All patients achieved clinical and radiological stability. CONCLUSIONS: We report of an increased incidence of SuS in Israel. Infectious serological findings may imply a post infectious mechanism. The use of the recommended diagnostic procedures reduced the time to diagnosis. Newly published treatment guidelines led to favorable clinical outcomes.

A multi-modal virtual reality treadmill intervention for enhancing mobility and cognitive function in people with multiple sclerosis: Protocol for a randomized controlled trial.

BACKGROUND: Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training. METHODS: This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. Primary outcome measures include dual-task gait speed and information processing speed, which will be measured prior to training, one-week post-training, and three months following training. DISCUSSION: This study will provide insight into the ability of a multi-modal cognitive-motor intervention to reduce dual-task cost and to enhance information processing speed in those with MS. This is one of the first studies that is powered to understand whether targeted dual-task training can improve MS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.

Deterioration of specific aspects of gait during the instrumented 6-min walk test among people with multiple sclerosis.

Prolonged walking is typically impaired among people with multiple sclerosis (pwMS), however, it is unclear what the contributing factors are or how to evaluate this deterioration. We aimed to determine which gait features become worse during sustained walking and to examine the clinical correlates of gait fatigability in pwMS. Fifty-eight pwMS performed the 6-min walk test while wearing body-fixed sensors. Multiple gait domains (e.g., pace, rhythm, variability, asymmetry and complexity) were compared across each minute of the test and between mild- and moderate-disability patient groups. Associations between the decline in gait performance (i.e., gait fatigability) and patient-reported gait disability, fatigue and falls were also determined. Cadence, stride time variability, stride regularity, step regularity and gait complexity significantly deteriorated during the test. In contrast, somewhat surprisingly, gait speed and swing time asymmetry did not change. As expected, subjects with moderate disability (n = 24) walked more poorly in most gait domains compared to the mild-disability group (n = 34). Interestingly, a group × fatigue interaction effect was observed for cadence and gait complexity; these measures decreased over time in the moderate-disability group, but not in the mild group. Gait fatigability rate was significantly correlated with physical fatigue, gait disability, and fall history. These findings suggest that sustained walking affects specific aspects of gait, which can be used as markers for fatigability in MS. This effect on gait depends on the degree of disability, and may increase fall risk in pwMS. To more fully understand and monitor correlates that reflect everyday walking in pwMS, multiple domains of gait should be quantified.

Long-Term Training-Induced Gains of an Auditory Skill in School-Age Children As Compared With Adults.

The few studies that compared auditory skill learning between children and adults found variable results, with only some children reaching adult-like thresholds following training. The present study aimed to assess auditory skill learning in children as compared with adults during single- and multisession training. It was of interest to ascertain whether children who do not reach adult-like performance following a single training session simply require additional training, or whether different mechanisms underlying skill learning need to reach maturity in order to become adult-like performers. Forty children (7-9 years) and 45 young adults (18-35 years) trained in a single session. Of them, 20 children and 24 adults continued training for eight additional sessions. Each session included six frequency discrimination thresholds at 1000 Hz using adaptive forced-choice procedure. Retention of the learning-gains was tested 6 to 8 months posttraining. Results showed that (a) over half of the children presented similar performance and time course of learning as the adults. These children had better nonverbal reasoning and working memory abilities than their non-adult-like peers. (b) The best predicting factor for the outcomes of multisession training was a child's performance following one training session. (c) Performance gains were retained for all children with the non-adult-like children further improving, 6 to 8 months posttraining. Results suggest that mature auditory skill learning can emerge before puberty, provided that task-related cognitive mechanisms and task-specific sensory processing are already mature. Short-term training is sufficient, however, to reflect the maturity of these mechanisms, allowing the prediction of the efficiency of a prolonged training for a given child.

Nap it or leave it in the elderly: A nap after practice relaxes age-related limitations in procedural memory consolidation.

Using a training protocol that effectively induces procedural memory consolidation (PMC) in young adults, we show that older adults are good learners, robustly improving their motor performance during training. However, performance declined over the day, and overnight 'offline' consolidation phase performance gains were under-expressed. A post-training nap countered these deficits. PMC processes are preserved but under-engaged in the elderly; sleep can relax some of the age-related constraints on long-term plasticity.

Brain activation associated with practiced left hand mirror writing.

Mirror writing occurs in healthy children, in various pathologies and occasionally in healthy adults. There are only scant experimental data on the underlying brain processes. Eight, right-handed, healthy young adults were scanned (BOLD-fMRI) before and after practicing left-hand mirror-writing (lh-MW) over seven sessions. They wrote dictated words, using either the right hand with regularly oriented writing or lh-MW. An MRI compatible stylus-point recording system was used and online visual feedback was provided. Practice resulted in increased speed and readability of lh-MW but the number of movement segments was unchanged. Post-training signal increases occurred in visual, right lateral and medial premotor areas, and in right anterior and posterior peri-sylvian areas corresponding to language areas. These results suggest that lh-MW may constitute a latent ability that can be reinstated by a relatively brief practice experience. Concurrently, right hemisphere language processing areas may emerge, reflecting perhaps a reduction in trans-hemispheric suppression.

Extra-cranial venous flow in patients with multiple sclerosis.

INTRODUCTION: Recently, a chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI) was claimed to be a pathologic condition exclusively seen in patients with multiple sclerosis (MS), suggesting that cerebral venous congestion plays a significant role in the pathogenesis of MS. This hypothesis has gained enormous attention among patients and physicians but has been questioned since. METHODS: Twenty seven patients with MS and 32 healthy controls underwent color extra cranial Doppler exam aimed to detect four parameters of abnormal venous flow: no Doppler-detected flow in the IJV or vertebral veins (VV), reflux in the internal jugular veins (IJVs), venous flow stenosis in the IJVz (cross sectional area <0.3 cm) or reverted postural control in the IJV. RESULTS: Except for one healthy patient, blood flow direction in the IJVs was normal in all subjects. When aiming to detect at least one parameter of abnormal venous flow per subject, two parameters or three parameters no significant difference was found between subjects and controls (p = 0.707, 0.62, 0.849 respectively). CONCLUSION: We found no evidence to suggest that MS patients have excess of CCSVI. In addition we failed to observe a typical venous flow pattern in MS patients. Until carefully designed controlled studies to investigate CCVSI have been completed, invasive and potentially dangerous endovascular procedures as therapy for MS should be discouraged.

Characteristics of first ever ischemic stroke in the very elderly: profile of vascular risk factors and clinical outcome.

PURPOSE: Age is the most significant non-modifiable risk factor for ischemic stroke (IS). With increasing expectancy of life, the majority of IS patients will be elderly subjects. We studied the epidemiological, clinical and rehabilitation features of patients aged ≥85 years with first-ever IS. METHODS: Demographic data, prevalence of risk factors, etiology of stroke, severity of neurological deficit, major complications and mortality rates were collected from a hospital-based stroke registry and compared between patients at the age of 65-84 and ≥85. Clinical assessment was performed by means of the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS). RESULTS: Among 216 patients aged ≥85 years there was significantly higher proportion of a history of atrial fibrillation than in 128 patients at the age of 65-84 years and lower prevalence of hypertension, diabetes mellitus, hyperlipidemia and smoking. Large artery atherosclerosis was more frequently identified in the older patients (49% vs. 32%, p=0.002). Although NIHSS scores on admission were lower in the older patients they were more disabled at discharge. CONCLUSIONS: With respect to the patients aged <85 years very old IS patients showed different vascular risk factors profile, clinical and rehabilitation course. These findings suggest specializing stroke care in the very elderly.

Fast and slow spindle involvement in the consolidation of a new motor sequence.

This study aimed to determine the distinct contribution of slow (11-13 Hz) and fast (13-15 Hz) spindles in the consolidation process of a motor sequence learning task (MSL). Young subjects (n = 12) were trained on both a finger MSL task and a control (CTRL) condition, which were administered one week apart in a counterbalanced order. Subjects were asked to practice the MSL or CTRL task in the evening (approximately 9:00 p.m.) and their performance was retested on the same task 12h later (approximately 9:00 a.m.). Polysomnographic (PSG) recordings were performed during the night following training on either task, and an automatic algorithm was used to detect fast and slow spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Statistical analyses revealed higher fast (but not slow) spindle density after training on the MSL than after practice of the CTRL task. The increase in fast spindle density on the MSL task correlated positively with overnight performance gains on the MSL task and with difference in performance gain between the MSL and CTRL tasks. Together, these results suggest that fast sleep spindles help activate the cerebral network involved in overnight MSL consolidation, while slow spindles do not appear to play a role in this mnemonic process.

Procedural and declarative knowledge of word recognition and letter decoding in reading an artificial script.

In a previous study [Cogn. Brain Res. 16 (2003) 325], we found that letter knowledge did not evolve from implicit training on whole-word recognition in an artificial Morse-like script, although the participants were adults, experienced in alphabetical reading. Here we show minimal conditions in which letter knowledge may evolve in some individuals from training on whole-word recognition. Participants received multi-session training in reading nonsense words, written in an artificial script, in which each phoneme was represented by two discrete symbols. Three training conditions were compared: alphabetical whole words with letter decoding instruction (Explicit), alphabetical whole words (Implicit), and non-alphabetical whole words (Arbitrary). Subjects were assigned to training either on the explicit and arbitrary or on the implicit and arbitrary conditions. Our results show that: (a) Letter-decoding knowledge evolved implicitly from training on alphabetical whole-word recognition, in some individuals. However, (b) a clear double dissociation was found between effectively applied implicit letter knowledge and declarative letter knowledge. (c) There was no advantage of the implicitly derived over the explicitly instructed letter knowledge. (d) Long-term retention was more effective in the explicit compared to the arbitrary condition. (e) Word-specific recognition contributed significantly to performance in all three training conditions, i.e. even under conditions that presumably afford advantage for word segmentation. Altogether, our results suggest that both declarative and procedural knowledge contributed to letter decoding as well as to word-specific recognition performance. Moreover, a greater dependency on declarative knowledge may not be an inherent characteristic of word-specific recognition, but rather that both letter decoding and word-recognition routines can become proceduralized given sufficient practice.

Skill learning in mirror reading: how repetition determines acquisition.

Practice makes perfect, but the role of repetitions in skill learning is not yet fully understood. For example, given a similar number of trials on a given task, it is debated whether repeating and non-repeating items are learned by the same neural process. When one is given training with both types of items--does one learn two separate skills, or only one? Here we show, using a mirror reading task, that practice trials with trial-unique words, and practice trials with repeated words, count towards learning to a different degree. There was no interaction between the time-course of learning repeated and unique words even within the same individuals given mixed training. While repeated words were learned faster than unique words, the repetitions-dependent gains diminished with training beyond a small number of repetitions. Moreover, the gains in performance could not be accounted for solely by the number of repetitions, as assumed by power-law models of learning; rather, the passage of time was a critical factor. Finally, our results suggest that although both repeated and new words were learned by both declarative and procedural memory mechanisms, even a single repetition of specific words could lead to the establishment of a selective differential representation in memory. The results are compatible with the notion of a repetition-sensitive process, triggered by specific repeating events. This 'repetition counter' may be a critical trigger for the effective formation of procedural as well as some type of declarative memory.

Alphabetical knowledge from whole words training: effects of explicit instruction and implicit experience on learning script segmentation.

We investigated the possibility that pattern segmentation skills, specifically, phonological decoding, evolve implicitly in adult readers given training in an artificial script. In this Morse-like script each phoneme was represented by 2-3 discrete symbols. Subjects were trained in five consecutive sessions, on reading six nonsense words using a forced choice task that required translating symbol strings to sound patterns written in Latin letters. Three training conditions were compared within subject in terms of the time-course of learning and the ability to generalize the acquired knowledge (transfer): alphabetical whole words with letter decoding instruction (Explicit); alphabetical whole words (Implicit), and non-alphabetical whole words (Arbitrary). In separate blocks in each training session, a visual-matching task was administered using the same stimuli. Our results show: (a). that while all three training conditions were equally effective in terms of magnitude and time-course of learning accurate translation, each training condition resulted in a different type of knowledge (i.e. differential transfer). (b). Declarative knowledge of letters evolved from training on whole words only in subjects with previous experience in Explicit training. However, even with declarative knowledge of the specific letters subjects did not develop general letter segmentation skills. (c). Contrary to the robust transfer of learning gains to different stimuli within a given task, there was no significant transfer across tasks indicating that the locus of learning was task dependent. Altogether our results suggest that even given explicit letter instruction, training on word decoding may result in letter recognition rather than in alphabetic segmentation skills.

fMRI of triggerable aurae in musicogenic epilepsy.

The authors studied a patient with musicogenic epilepsy triggered by one specific musical piece using 3D PRESTO fMRI. During epileptic aurae initiated by the stimulus, signal increases were found in the left anterior temporal lobe, correlating with ictal EEG and SPECT showing a left anterior temporal focus, and the right gyrus rectus. Because fMRI indicated a cascade of recruitment of the ventral frontal lobes by epileptogenic music, left anterior temporal lobe activity could be secondary to a right gyrus rectus focus, possibly triggered by emotional processing of music.

From primed to learn: the saturation of repetition priming and the induction of long-term memory.

Although practice can make perfect, it is not clear how much practice is needed to trigger long-lasting performance gains on a given task. Here, using a letter enumeration task, we show that the transition of experience dependent performance gains to a relatively stable form, as well as the triggering of delayed, long-lasting, between session gains (both effects are considered manifestations of consolidation processes) is amount-of-practice dependent. We then show (a) that consolidation processes, once triggered, can proceed without further practice as a function of time and (b) that the triggering of consolidation processes is related to repetition priming effects--performance gains in processing a previously experienced item. However, we show that repetition priming effects saturate after a limited number of consecutive repetitions and reflect an initial, but potentially reversible, response to the repeated experience. Moreover, we show that one critical parameter determining the occurrence of repetition priming (but not skill learning) is the presence of interference (by a somewhat different set of items) prior to the primer presentation. Thus, our results suggest that the saturation of repetition priming effects, rather than priming per se, may be critical to the induction of slow learning processes and consolidation.

Traumatic head injury in the anticoagulated elderly patient: a lethal combination.

Warfarin is the most common oral anticoagulant used for chronic anticoagulation therapy. Even without any antecedent trauma overanticoagulation can result in intracranial hemorrhage. The triad of anticoagulation with warfarin, age greater than 65 years, and traumatic head injury frequently produces a lethal brain hemorrhage. A retrospective review of more than 2000 patients admitted to the Trauma Service between September 1998 and May 2000 produced 278 patients with head injury and CT-documented intracranial hemorrhage. Of these patients 21 were admitted with an elevated prothrombin time (PT) due to anticoagulation with warfarin. Eighteen patients (86%) were above the age of 70. The most common indications for anticoagulation were atrial fibrillation (71%), deep venous thrombosis (19%), aortic valve replacement (9%), and ischemic cerebral infarcts (9%). Fourteen injuries were the result of a fall, one resulted from a gunshot wound, and one resulted from an assault. The remaining five patients were excluded as their history, workup, and evaluation by neurosurgery suggested a spontaneous bleed leading to fall rather than a fall causing a traumatic bleed. The average Glasgow Coma Score on admission was 11. The average PT and International Normalized Ratio (INR) on admission were 19.2 and 2.99 respectively. Eight of the 16 patients analyzed died. The risk of intracranial hemorrhage with relatively minor head injury is increased dramatically in the anticoagulated patient. A mortality rate of 50 per cent far exceeds the mortality rate in patients with similar head injuries who are not anticoagulated. In addition the risk/benefit equation of anticoagulation for the elderly is more complex and differs from that for younger patients. Perhaps more frequent and judicious monitoring of prothrombin time levels with lower therapeutic ranges (INR 1.5-2) is necessary.

A transition between eye and object rivalry determined by stimulus coherence.

Two orthogonal patterns presented to the two eyes, respectively, are perceived as alternating in time, a phenomenon often assumed to reflect competition between neuronal activities corresponding to the two eyes, presumably in the primary visual cortex. Recent evidence supports a competition between neuronal activities corresponding to the two patterns (objects) at some higher cortical processing stage after inputs from the two eyes have converged. Here, using textures made of Gabor signals, we present psychophysical data showing that the level of visual processing at which competition takes place and is resolved, is determined by the degree of stimulus coherence. Moreover, depending on stimulus parameters, competition may occur at several levels of processing at the same time.

Effects of sex hormones on experimental autoimmune myasthenia gravis.

To examine whether exacerbation of myasthenia gravis (MG) can be induced by changes in sex hormone levels we immunized 20 female Lewis rats with torpedo antigen to induce experimental autoimmune MG (EAMG). Ten of the animals underwent surgical ovariectomy prior to the induction of EAMG and 10 served as controls. Anti-acetylcholine receptor antibody (AChR-ab) titres and the degree of decrement on repetitive stimulation electromyography (REMG) at 3 Hz were obtained at base line and compared between rats with and without ovariectomy and a second control group of naïve rats. Three rats in each group were then injected with excess oestrogen and progesterone for one week, and three of the remaining rats in each group were given sham injections, and the degree of decrement on REMG and AchR-ab titres were re-evaluated. Immune reactivity of peripheral lymphocytes and splenic lymphocytes from all groups and controls was also determined. A comparable number of animals with and without ovariectomy developed clinical and electromyographic EAMG. The extent of decrement on REMG and AChR-ab titres did not change following hormonal replacement. Lymphocyte reactivity was similar for rats with and without ovariectomy. In conclusion, sex hormones do not appear to have an influence on the susceptibility to and the severity of MG.