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.

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.

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.

Dependence on REM sleep of overnight improvement of a perceptual skill.

Several paradigms of perceptual learning suggest that practice can trigger long-term, experience-dependent changes in the adult visual system of humans. As shown here, performance of a basic visual discrimination task improved after a normal night's sleep. Selective disruption of rapid eye movement (REM) sleep resulted in no performance gain during a comparable sleep interval, although non-REM slow-wave sleep disruption did not affect improvement. On the other hand, deprivation of REM sleep had no detrimental effects on the performance of a similar, but previously learned, task. These results indicate that a process of human memory consolidation, active during sleep, is strongly dependent on REM sleep.

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.

Learning perceptual skills: behavioral probes into adult cortical plasticity.

Recent studies of the improvement of perceptual performance as a function of training - perceptual learning - have provided new insights into the neuronal substrates of this type of skill learning in the adult brain. Issues such as where in the brain, when and under what conditions practice-related changes occur are under investigation. The results of these studies suggest that a behaviorally relevant degree of plasticity is retained in the adult cortex, even within early, low-level representations in sensory and motor processing streams. The acquisition and retention of skills may share many characteristics with the functional plasticity subserving early-life learning and development. While the specificity of learning provides localization constraints, an important clue to the nature of the underlying neuronal changes is the time course of learning.

Applications of magnetic resonance imaging to the study of human brain function.

Important questions relating to the coupling of local neuronal activity to the hemodynamic response measured using functional magnetic resonance imaging (fMRI), as well as issues concerning imaging sequence, paradigm design and data analysis processing, have been addressed during the past year. Initial fMRI studies identified visual, somatosensory, auditory and motor activation areas in the primary cortices. Current 'second generation' studies aim to identify changes in the fMRI signal associated with specific tasks and stimulus parameters. Dynamic aspects of brain processing for performing higher order cognitive functions, such as language, attention, mental imagery, and learning and memory, have also been explored.

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.

Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis.

OBJECTIVE: To evaluate the presence and specificity of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. SETTING: Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES: Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P = .005 and P = .03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti-MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs (P = .003 for both comparisons) and with controls (P = .03 and P = .04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82, respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.

HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews.

OBJECTIVE: To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel. DESIGN: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years. SETTING: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. PATIENTS: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls. MAIN OUTCOME MEASURES: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease. RESULTS: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P =.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*030 with MS was detected (P = .03). The MS susceptibility alleles, DRB 1* 1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1* 1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). CONCLUSIONS: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.

Association of MS with thyroid disorders.

A controlled prospective study was conducted to determine whether thyroid disorders are present with increased frequency in patients with MS. We found that thyroid disorders were at least three times more common in women with MS than in female controls. This was accounted for mainly by the prevalence of hypothyroidism among the female MS patients. Because hypothyroidism is usually due to Hashimoto's thyroiditis, its association with MS may support the hypothesis of autoimmune pathogenesis for MS. Our findings might have therapeutic implications because interferon treatment can induce antithyroid antibodies and thyroiditis.

Reactivity of T cells from seronegative patients with myasthenia gravis to T cell epitopes of the human acetylcholine receptor.

Seronegative (SN) patients with myasthenia gravis (MG) have clinical and electrophysiologic features similar to those of seropositive (SP) patients, and they respond to the same therapeutic measures. However, because SN patients lack detectable (by standard radioimmunoassays) serum antibodies to acetylcholine receptor (AChR), which are considered to have a crucial role in MG, the pathophysiologic basis for the disease is not clear. We therefore compared the ability of peripheral blood lymphocytes (PBL) of SN patients (11) and SP patients (39) to respond to myasthenogenic T cell epitopes of human AChR. We tested two aspects that relate to T-cell immunity: 1) T cell responses to myasthenogenic peptides by proliferation and IL-2 production, and 2) the ability of antigen-presenting cells to bind these T-cell epitopes. T cells of SN patients did not differ from those of SP patients in their ability to respond and to bind the two human AChR-derived myasthenogenic peptides. This supports the belief that most SN patients indeed suffer from an autoimmune disease directed against the AChR. The presence of T-cell immunity in the absence of antibodies may emphasize the importance of AChR-specific T cells in MG.

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.

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.

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.

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.

Hemispheric specialization for English and ASL: left invariance-right variability.

Functional magnetic resonance imaging (fMRI) was used to compare the cerebral organization during sentence processing in English and in American sign language (ASL). Classical language areas within the left hemisphere were recruited by both English in native speakers and ASL in native signers. This suggests a bias of the left hemisphere to process natural languages independently of the modality through which language is perceived. Furthermore, in contrast to English, ASL strongly recruited right hemisphere structures. This was true irrespective of whether the native signers were deaf or hearing. Thus, the specific processing requirements of the language also in part determine the organization of the language systems of the brain.