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  1. Article: The Effect of Anti-seizure Medications on the Propagation of Epileptic Activity: A Review.

    Khateb, Mohamed / Bosak, Noam / Herskovitz, Moshe

    Frontiers in neurology

    2021  Volume 12, Page(s) 674182

    Abstract: The propagation of epileptiform events is a highly interesting phenomenon from the pathophysiological point of view, as it involves several mechanisms of recruitment of neural networks. ... ...

    Abstract The propagation of epileptiform events is a highly interesting phenomenon from the pathophysiological point of view, as it involves several mechanisms of recruitment of neural networks. Extensive
    Language English
    Publishing date 2021-05-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2021.674182
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Coronaviruses and Central Nervous System Manifestations.

    Khateb, Mohamed / Bosak, Noam / Muqary, Maryam

    Frontiers in neurology

    2020  Volume 11, Page(s) 715

    Abstract: SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, ... ...

    Abstract SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has resulted in significant morbidity and mortality. The most prominent symptoms of SARS-CoV-2 infection are respiratory. However, accumulating evidence highlights involvement of the central nervous system (CNS). This includes headache, anosmia, meningoencephalitis, acute ischemic stroke, and several presumably post/para-infectious syndromes and altered mental status not explained by respiratory etiologies. Interestingly, previous studies in animal models emphasized the neurotropism of coronaviruses; thus, these CNS manifestations of COVID-19 are not surprising. This minireview scans the literature regarding the involvement of the CNS in coronavirus infections in general, and in regard to the recent SARS-CoV-2, specifically.
    Keywords covid19
    Language English
    Publishing date 2020-06-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2020.00715
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Coronaviruses and Central Nervous System Manifestations

    Khateb, Mohamed / Bosak, Noam / Muqary, Maryam

    Front. Neurol.

    Abstract: SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, ... ...

    Abstract SARS-CoV-2 is a highly pathogenic coronavirus that has caused an ongoing worldwide pandemic. Emerging in Wuhan, China in December 2019, the virus has spread rapidly around the world. Corona virus disease 2019 (COVID-19), which is caused by SARS-CoV-2, has resulted in significant morbidity and mortality. The most prominent symptoms of SARS-CoV-2 infection are respiratory. However, accumulating evidence highlights involvement of the central nervous system (CNS). This includes headache, anosmia, meningoencephalitis, acute ischemic stroke, and several presumably post/para-infectious syndromes and altered mental status not explained by respiratory etiologies. Interestingly, previous studies in animal models emphasized the neurotropism of coronaviruses; thus, these CNS manifestations of COVID-19 are not surprising. This minireview scans the literature regarding the involvement of the CNS in coronavirus infections in general, and in regard to the recent SARS-CoV-2, specifically.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #642061
    Database COVID19

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  4. Article ; Online: Structural brain connectivity predicts early acute pain after mild traumatic brain injury.

    Branco, Paulo / Bosak, Noam / Bielefeld, Jannis / Cong, Olivia / Granovsky, Yelena / Kahn, Itamar / Yarnitsky, David / Apkarian, A Vania

    Pain

    2022  Volume 164, Issue 6, Page(s) 1312–1320

    Abstract: Abstract: Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long- ... ...

    Abstract Abstract: Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision. We extracted white matter structural connectivity networks and used a machine learning approach to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamiccortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in 2 independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6 months after the collision still predicted mTBI pain at that timepoint (n = 36). These white matter connections were associated with 2 nociceptive psychophysical outcomes tested at a remote body site-namely, conditioned pain modulation and magnitude of suprathreshold pain-and with pain sensitivity questionnaire scores. Our findings demonstrate a stable white matter network, the properties of which determine an important amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.
    MeSH term(s) Humans ; Brain Concussion ; Acute Pain/diagnostic imaging ; Acute Pain/etiology ; Brain/diagnostic imaging ; White Matter/diagnostic imaging ; Pain Perception
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002818
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  5. Article ; Online: Brain Connectivity Predicts Chronic Pain in Acute Mild Traumatic Brain Injury.

    Bosak, Noam / Branco, Paulo / Kuperman, Pora / Buxbaum, Chen / Cohen, Ruth Manor / Fadel, Shiri / Zubeidat, Rabab / Hadad, Rafi / Lawen, Amir / Saadon-Grosman, Noam / Sterling, Michele / Granovsky, Yelena / Apkarian, Apkar Vania / Yarnitsky, David / Kahn, Itamar

    Annals of neurology

    2022  Volume 92, Issue 5, Page(s) 819–833

    Abstract: Objectives: Previous studies have established the role of the cortico-mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated ...

    Abstract Objectives: Previous studies have established the role of the cortico-mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated for prediction. In this study, we set out to study whether functional connectivity (FC) of the nucleus accumbens (NAc) and the periaqueductal gray matter (PAG) is predictive of pain chronification in early-acute mTBI.
    Methods: To estimate FC, resting-state functional magnetic resonance imaging (fMRI) of 105 participants with mTBI following a motor vehicle collision was acquired within 72 hours post-accident. Participants were classified according to pain ratings provided at 12-months post-collision into chronic pain (head/neck pain ≥30/100, n = 44) and recovery (n = 61) groups, and their FC maps were compared.
    Results: The chronic pain group exhibited reduced negative FC between NAc and a region within the primary motor cortex corresponding with the expected representation of the area of injury. A complementary pattern was also demonstrated between PAG and the primary somatosensory cortex. PAG and NAc also shared increased FC to the rostral anterior cingulate cortex (rACC) within the recovery group. Brain connectivity further shows high classification accuracy (area under the curve [AUC] = .86) for future chronic pain, when combined with an acute pain intensity report.
    Interpretation: FC features obtained shortly after mTBI predict its transition to long-term chronic pain, and may reflect an underlying interaction of injury-related primary sensorimotor cortical areas with the mesolimbic and pain modulation systems. Our findings indicate a potential predictive biomarker and highlight targets for future early preventive interventions. ANN NEUROL 2022;92:819-833.
    MeSH term(s) Humans ; Brain Concussion/complications ; Brain Concussion/diagnostic imaging ; Chronic Pain/diagnostic imaging ; Chronic Pain/etiology ; Brain/diagnostic imaging ; Periaqueductal Gray ; Brain Mapping/methods
    Language English
    Publishing date 2022-09-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.26463
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  6. Article ; Online: Conditioned pain modulation is more efficient in patients with painful diabetic polyneuropathy than those with nonpainful diabetic polyneuropathy.

    Granovsky, Yelena / Shafran Topaz, Leah / Laycock, Helen / Zubiedat, Rabab / Crystal, Shoshana / Buxbaum, Chen / Bosak, Noam / Hadad, Rafi / Domany, Erel / Khamaisi, Mogher / Sprecher, Elliot / Bennett, David L / Rice, Andrew / Yarnitsky, David

    Pain

    2021  Volume 163, Issue 5, Page(s) 827–833

    Abstract: Abstract: Endogenous pain modulation, as tested by the conditioned pain modulation (CPM) protocol, is typically less efficient in patients with chronic pain compared with healthy controls. We aimed to assess whether CPM is less efficient in patients ... ...

    Abstract Abstract: Endogenous pain modulation, as tested by the conditioned pain modulation (CPM) protocol, is typically less efficient in patients with chronic pain compared with healthy controls. We aimed to assess whether CPM is less efficient in patients with painful diabetic polyneuropathy (DPN) compared with those with nonpainful DPN. Characterization of the differences in central pain processing between these 2 groups might provide a central nervous system explanation to the presence or absence of pain in diabetic neuropathy in addition to the peripheral one. Two hundred seventy-one patients with DPN underwent CPM testing and clinical assessment, including quantitative sensory testing. Two modalities of the test stimuli (heat and pressure) conditioned to cold noxious water were assessed and compared between patients with painful and nonpainful DPN. No significant difference was found between the groups for pressure pain CPM; however, patients with painful DPN demonstrated unexpectedly more efficient CPMHEAT (-7.4 ± 1.0 vs -2.3 ± 1.6; P = 0.008). Efficient CPMHEAT was associated with higher clinical pain experienced in the 24 hours before testing (r = -0.15; P = 0.029) and greater loss of mechanical sensation (r = -0.135; P = 0.042). Moreover, patients who had mechanical hypoesthesia demonstrated more efficient CPMHEAT (P = 0.005). More efficient CPM among patients with painful DPN might result from not only central changes in pain modulation but also from altered sensory messages coming from tested affected body sites. This calls for the use of intact sites for proper assessment of pain modulation in patients with neuropathy.
    MeSH term(s) Humans ; Chronic Pain/complications ; Diabetes Mellitus ; Diabetic Neuropathies/complications ; Neuralgia/complications ; Pain Threshold/physiology ; Sensation
    Language English
    Publishing date 2021-08-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002434
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  7. Article ; Online: Alemtuzumab mediates the CD39

    Remez, Lital / Ganelin-Cohen, Esther / Safina, Dina / Hellmann, Mark A / Lotan, Itay / Bosak, Noam / Buxbaum, Chen / Vaknin, Adi / Shifrin, Alla / Rozenberg, Ayal

    Immunology and cell biology

    2021  Volume 99, Issue 5, Page(s) 521–531

    Abstract: Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T-regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may ...

    Abstract Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T-regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may be indirectly affected by monocyte-derived cells, which are resistant to ALM cytotoxicity. We aimed to examine whether ALM modulates monocytes and whether the crosstalk between monocytes and lymphocytes previously exposed to ALM would result in anti-inflammatory effects. The CD14
    MeSH term(s) Alemtuzumab ; Humans ; Leukocytes, Mononuclear ; Macrophages ; Monocytes ; T-Lymphocytes, Regulatory
    Chemical Substances Alemtuzumab (3A189DH42V)
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12431
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  8. Article ; Online: Head- and neck-related symptoms post-motor vehicle collision (MVC): Separate entities or two-sides of the same coin?

    Kuperman, Pora / Granovsky, Yelena / Fadel, Shiri / Bosak, Noam / Buxbaum, Chen / Hadad, Rafi / Sprecher, Elliot / Bahouth, Hany / Ben Lulu, Hen / Yarnitsky, David / Granot, Michal

    Injury

    2021  Volume 52, Issue 5, Page(s) 1227–1233

    Abstract: Background and aim: Although post-motor vehicle collision (MVC) pain and symptoms are largely convergent among those with mild traumatic brain injury (mTBI) and whiplash associated disorder (WAD), and patients oftentimes report initial neck and head ... ...

    Abstract Background and aim: Although post-motor vehicle collision (MVC) pain and symptoms are largely convergent among those with mild traumatic brain injury (mTBI) and whiplash associated disorder (WAD), and patients oftentimes report initial neck and head complaints, the clinical picture of mTBI and WAD has been primarily studied as separate conditions which may result in an incomplete clinical picture. As such, this study was conducted to explore the role of pain and post-traumatic psychological features in explaining both head and neck-related symptom variability in a cohort of post-collision patients. This is with the goal of disentangling if contributory factors are uniquely related to each diagnosis, or are shared between the two.
    Methods: Patients recruited in the very early acute phase (<72 h) returned for clinical and psychological assessment at 6 months post-accident. In order to determine which factors were unique and which ones were overlapping the same potential contributors: mean head pain, mean neck pain, female gender, number of post-collision painful body areas, PTSD, and depression were included in the regression models for both neck disability index (NDI) and Rivermead post-concussion symptoms questionnaire (RPQ).
    Results: Of 223 recruited participants, 70 returned for a follow-up visit (age range 18-64, mean(SD) 37.6 (11.9), 29F). This cohort primarily met the criteria for mTBI, but also fulfilled the criteria for whiplash, reinforcing the duality of injury presentation. Correlations existed between the NDI and RPQ scores (Spearman's ρ=0.66, p<0.001), however overlap was only partial. Regression analysis showed that after the removal of area-of-injury pain neck related disability (r = 0.80, p <0.001) was explained solely by number of painful body areas (ß=0.52, p <0.001). In contrast, post-concussion syndrome symptoms (r = 0.86, p<0.001) are influenced by clinical pain, painful body areas (ß=0.31, p = 0.0026), female gender (ß=0.19, p = 0.0053), and psychological factors of depression (ß=0.31, p = 0.0028) and PTSD symptoms (ß=0.36, p = 0.0013).
    Conclusions: It seems that while mechanisms of neck- and head-related symptoms in post-collision patients do share a common explanatory feature, of residual body pain, they are not entirely overlapping. In that psychological factors influence post-concussion syndrome symptoms, but not post-whiplash neck disability.
    MeSH term(s) Accidents, Traffic ; Adolescent ; Adult ; Cohort Studies ; Female ; Humans ; Middle Aged ; Motor Vehicles ; Neck Pain/etiology ; Whiplash Injuries/complications ; Young Adult
    Language English
    Publishing date 2021-03-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 218778-4
    ISSN 1879-0267 ; 0020-1383
    ISSN (online) 1879-0267
    ISSN 0020-1383
    DOI 10.1016/j.injury.2021.03.003
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  9. Article ; Online: Electroencephalography functional connectivity-A biomarker for painful polyneuropathy.

    Topaz, Leah Shafran / Frid, Alex / Granovsky, Yelena / Zubidat, Rabab / Crystal, Shoshana / Buxbaum, Chen / Bosak, Noam / Hadad, Rafi / Domany, Erel / Alon, Tayir / Meir Yalon, Lian / Shor, Merav / Khamaisi, Mogher / Hochberg, Irit / Yarovinsky, Nataliya / Volkovich, Zeev / Bennett, David L / Yarnitsky, David

    European journal of neurology

    2022  Volume 30, Issue 1, Page(s) 204–214

    Abstract: Background and purpose: Advanced analysis of electroencephalography (EEG) data has become an essential tool in brain research. Based solely on resting state EEG signals, a data-driven, predictive and explanatory approach is presented to discriminate ... ...

    Abstract Background and purpose: Advanced analysis of electroencephalography (EEG) data has become an essential tool in brain research. Based solely on resting state EEG signals, a data-driven, predictive and explanatory approach is presented to discriminate painful from non-painful diabetic polyneuropathy (DPN) patients.
    Methods: Three minutes long, 64 electrode resting-state recordings were obtained from 180 DPN patients. The analysis consisted of a mixture of traditional, explanatory and machine learning analyses. First, the 10 functional bivariate connections best differentiating between painful and non-painful patients in each EEG band were identified and the relevant receiver operating characteristic was calculated. Later, those connections were correlated with selected clinical parameters.
    Results: Predictive analysis indicated that theta and beta bands contain most of the information required for discrimination between painful and non-painful polyneuropathy patients, with area under the receiver operating characteristic curve values of 0.93 for theta and 0.89 for beta bands. Assessing statistical differences between the average magnitude of functional connectivity values and clinical pain parameters revealed that painful DPN patients had significantly higher cortical functional connectivity than non-painful ones (p = 0.008 for theta and p = 0.001 for alpha bands). Moreover, intra-band analysis of individual significant functional connections revealed a positive correlation with average reported pain in the previous 3 months in all frequency bands.
    Conclusions: Resting state EEG functional connectivity can serve as a highly accurate biomarker for the presence or absence of pain in DPN patients. This highlights the importance of the brain, in addition to the peripheral lesions, in generating the clinical pain picture. This tool can probably be extended to other pain syndromes.
    MeSH term(s) Humans ; Biomarkers ; Brain ; Electroencephalography ; Pain ; Polyneuropathies/diagnosis
    Chemical Substances Biomarkers
    Language English
    Publishing date 2022-10-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1280785-0
    ISSN 1468-1331 ; 1351-5101 ; 1471-0552
    ISSN (online) 1468-1331
    ISSN 1351-5101 ; 1471-0552
    DOI 10.1111/ene.15575
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  10. Article ; Online: MRI in predicting conversion to multiple sclerosis within 1 year.

    Eran, Ayelet / García, Melissa / Malouf, Robair / Bosak, Noam / Wagner, Raz / Ganelin-Cohen, Ester / Artsy, Elinor / Shifrin, Alla / Rozenberg, Ayal

    Brain and behavior

    2018  Volume 8, Issue 9, Page(s) e01042

    Abstract: Objectives: Most patients diagnosed with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS). We aimed to verify previously reported imaging and clinical findings, and to identify new MRI findings that might serve as prognostic ... ...

    Abstract Objectives: Most patients diagnosed with multiple sclerosis (MS) present with a clinically isolated syndrome (CIS). We aimed to verify previously reported imaging and clinical findings, and to identify new MRI findings that might serve as prognostic factors for a second clinical episode or a change in the MRI scan during the first year following a CIS.
    Materials and methods: We identified from our medical records, 46 individuals who presented with an episode of CIS, which was followed clinically and with imaging studies. A neuroradiologist blinded to the clinical data reviewed the images and recorded the number of lesions, lesion location, and the largest longitudinal diameter of the lesion.
    Results: One year after the first MRI, 25 (54%) patients had progressed to MS. The clinical presentation of those who were and were not diagnosed with MS was predominantly motor or sensory deficit. Patients with lesions that were temporal, occipital, or perpendicular to the corpus callosum at the first episode were more likely to have recurrence. Individuals with a combination of more than 13 lesions, with maximal lesion length greater than 0.75 cm, and a lesion perpendicular to the corpus callosum, had a 19 times higher chance of conversion MS during the following year.
    Conclusions: Assessment of the number of lesions, lesion location, and maximal lesion size can predict the risk to develop another clinical episode or a new lesion/new enhancement in MRI during the year after CIS. For patients with a higher risk of recurrence, we recommend closer follow-up.
    MeSH term(s) Adult ; Brain/diagnostic imaging ; Brain/pathology ; Disease Progression ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/pathology ; Retrospective Studies ; Young Adult
    Language English
    Publishing date 2018-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2623587-0
    ISSN 2162-3279 ; 2162-3279
    ISSN (online) 2162-3279
    ISSN 2162-3279
    DOI 10.1002/brb3.1042
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