Hole Peg Test Research Articles

Impact of comorbid primary headache on neurological function of patients with multiple sclerosis

Multiple Sclerosis (MS) is a progressive disease affecting the working population. Due to the demyelination process, patients have motor, sensory and cognitive impairments. Often patients with MS complain of headaches. Comorbid primary headache accompanies more than half of patients with MS. The aim of our study was to reveal the relationship between the presence of primary comorbid headache and the progression of MS. For this purpose, the Expanded Disability Status Scale (EDSS), motor testing for 25-Foot Walk Test (25FWT), 9-Hole Peg Test (9HPT) were used. International Classification of Headache - 3 (ICHD-3) scale was used for differential diagnosis of headache types. The obtained data were compared among patients with different types of MS: Relapsing-Remitting (RRMS); primary and secondary progressive, which was combined into Progressive forms of MS (PMS). 130 patients with MS were studied, among whom patients with RRMS prevailed (n=98), primary comorbid headache was found in 56.2% (n=73). Among patients with MS, migraine prevailed (p=0.015), in particular, the most cases were found in patients with RRMS. Among patients with PMS, tension headache prevailed (p<0.05). The 9HPT and 25FWT scores did not differ significantly between the groups with and without primary comorbid headache, however, according to the confidence intervals, the EDSS score exceeded the score in the group of patients with comorbid headache. It was found that patients with comorbid migraine performed the motor test faster than patients with tension type headache. Therefore, it can be concluded that comorbid primary headache may have an impact on motor function indicators among MS patients and requires further investigation to determine the role of comorbid headache in the patterns of initial MS symptoms. Keywords: central nervous system, demyelination, migraine, tension type headache, motor function, comorbidity.

Magnetic resonance fingerprinting in multiple sclerosis

BackgroundIn this cross sectional study, we used MRF to investigate tissue properties of normal-appearing white matter, gray matter, and lesions in relapsing remitting MS (n = 21), secondary progressive MS (n = 16) and healthy controls (n = 9). A FISP-based MRF sequence was used for acquisition, imaging time 5 min 15 s. MRF T1 and T2 relaxation times were measured from lesional tissue, normal-appearing frontal white matter, corpus callous, thalamus, and caudate. Differences between healthy controls and MS were examined using ANCOVA adjusted for age and sex. Spearman rank correlations were assessed between T1 and T2 relaxation times and clinical measures. ObjectivesTo examine brain T1 and T2 values using magnetic resonance fingerprinting (MRF) in healthy controls and MS. MethodsThe subjects included 21 relapsing-remitting (RR) MS, 16 secondary progressive (SP) MS, and 9 age- and sex-matched HC without manifest neurological disease participating in a longitudinal MRI study. A 3T/ FISP-based MRF sequence was acquired. Regions of interest were drawn for lesions and normal appearing white matter. ANCOVA adjusted for age and sex were used to compare the groups with significance set at 0.05. ResultsA step-wise increase in T1 and T2 relaxation times was found between healthy controls, relapsing remitting MS, and secondary progressive MS. Significant differences were found in T1 and T2 between MS and healthy controls in the frontal normal-appearing white matter, corpus callosum, and thalamus (p < 0.04 for all). Significant differences in T1 and T2 between RR and SPMS were found in the frontal normal-appearing white matter and T2 lesions (p < 0.02 for all). T1 relaxation from the frontal normal-appearing white matter correlated with the Expanded Disability Status Scale [ρ = 0.62, p < 0.001], timed 25 foot walk (ρ = 0.45, p = 0.01), 9 hole peg test (ρ = 0.62, p < 0.001), and paced auditory serial addition test (ρ = −0.4, p = 0.01). ConclusionThese results suggest that MRF may be a clinically feasible quantitative approach for characterizing tissue damage in MS.

Automated Quantifiable Assessments of Sensorimotor Function Using an Instrumented Fragile Object.

Accurate assessment of hand dexterity plays a critical role in informing rehabilitation and care of upper-limb hemiparetic stroke patients. Common upper-limb assessments, such as the Box and Blocks Test and Nine Hole Peg Test, primarily evaluate gross motor function in terms of speed. These assessments neglect an individual's ability to finely regulate grip force, which is critical in activities of daily living, such as manipulating fragile objects. Here we present the Electronic Grip Gauge (EGG), an instrumented fragile object that assesses both gross and fine motor function. Embedded with a load cell, accelerometer, and Hall-effect sensor, the EGG measures grip force, acceleration, and relative position (via magnetic fields) in real time. The EGG can emit an audible "break" sound when the applied grip force exceeds a threshold. The number of breaks, transfer duration, and applied forces are automatically logged in real-time. Using the EGG, we evaluated sensorimotor function in implicit grasping and gentle grasping for the non-paretic and paretic hands of 3 hemiparetic stroke patients. For all participants, the paretic hand took longer to transfer the EGG during implicit grasping. For 2 of 3 participants, grip forces were significantly greater for the paretic hand during gentle grasping. Differences in implicit grasping forces were unique to each participant. This work constitutes an important step towards more widespread and quantitative measures of sensorimotor function, which may ultimately lead to improved personalized rehabilitation and better patient outcomes.

Thalamic asymmetry in Multiple Sclerosis.

Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamicasymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p=0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p=0.037). In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

The rate of force relaxation scaling factor is highly sensitive to detect upper and lower extremity motor deficiencies in mildly affected people with multiple sclerosis.

The motor symptoms affecting upper and lower extremity functioning in people with multiple sclerosis (PwMS) are considered the cardinal symptoms of multiple sclerosis. There is still a need for outcome measures that can sensitively evaluate these symptoms. We aimed to investigate the sensitivity of the isometric outcomes (maximum force; Fmax, maximum rate of force development; RFDmax, rate of force development scaling factor; RFD-SF, and rate of force relaxation scaling factor; RFR-SF) and standard clinical tests (9-hole peg test; 9HPT and timed 25-feet walk test; T25FW) in detecting the upper and lower extremity motor deficiencies in PwMS and also in a subgroup of mildly affected PwMS whose performance in standard clinical tests were similar to controls. Twenty-nine PwMS (age: 47.9 (8.6) years, relapsing-remitting type, expanded disability status scale: 2.5 (1.5)) and their age- and gender-matched controls completed an identical testing protocol in the upper (grip force muscles) and lower (knee extensors) extremities. For each extremity, we assessed Fmax, RFDmax, RFD-SF, and RFR-SF. Additionally, participants completed standard clinical tests for the evaluation of upper- (9HPT) and lower-extremity (T25FW) function. Comparisons were made between controls and PwMS 1) using all study participants and 2) including only mildly affected PwMS whose performance in standard functional tests was comparable to controls. Independent sample t-tests were utilized to compare groups, with a p-value set at 0.01 to correct for multiple comparisons. P-values and effect sizes were used to evaluate the sensitivity of the outcome measures in detecting group differences. Our results indicate that most isometric outcomes and standard functional tests were sensitive in detecting motor deficiencies in both upper and lower extremities between groups (p<0.001). Among participants, 16 PwMS in 9HPT and 11 PwMS in T25FW demonstrated performance similar to that of the control group (9HPT: 18.85 (2.20) s vs 17.81 (2.19) s; p=0.19) and (T25FW: 3.60 (0.42) s vs 3.58 (0.29) s; p=0.92). The results of the comparisons between mildly affected PwMS and their controls indicate that RFR-SF is the only sensitive isometric outcome to detect differences between groups in the upper (-8.24 (0.76) 1/s vs -8.93 (0.6) 1/s; p=0.008) and lower extremity (-5.86 (1.13) 1/s vs -7.71 (1.11) 1/s; p<0.001). The rate of force relaxation scaling factor, which assesses the ability to rapidly relax muscle forces after quick contractions, demonstrates high sensitivity in detecting motor deficiencies in PwMS, even when the current standard clinical outcomes fail to detect these differences. Our findings emphasize the importance of future randomized controlled trials focusing on rehabilitative and therapeutic interventions that specifically target muscle force relaxation to enhance motor functioning in PwMS.

Assessment of Mobility in Working Age Stroke Patients during the Covid-19 pandemic

Abstract Aim. Early neurological rehabilitation is essential to regain functional efficiency and achieve an optimal level of independence, especially during the COVID-19 pandemic. The objective of the work was to assess the functional performance of patients of working age after hemorrhagic or ischemic brain stroke admitted to the neurological rehabilitation unit and to assess additional factors aff ecting the eff ectiveness of neurological rehabilitation. Material and methods. The study group included 89 patients admitted to the neurological rehabilitation unit. The eligibility criterion for the treatment group was the age of 25-55 years (professionally active people) and the suff ered hemorrhagic or ischemic brain stroke. The functional performance assessment was performed using the Barthel Index and the NHPT (Nine Hole Peg Test) test. Socio-demographic data were obtained from the analysis of medical records. The survey was conducted on the fi rst and last day of stay. Results. There was a signifi cant impact of age on the type of stroke, with people with an ischemic stroke being indeed statistically older than those with hemorrhagic stroke (50± 5 years), compared to those with hemorrhagic stroke (46± 8 years). It has been established that the time spent in a unit is dependent on the age of the patient, the older the patient the longer the hospitalization lasts. The tests assessing the functionality of the hands have showed statistically signifi cant improvements in the study group. It has been demonstrated that the improvement of functional performance depended on gender. People with diabetes performed statistically worse (Me=28 vs. Me=21). Conclusions. 1. Older people after stroke need more time to rehabilitate. 2. There is a need for more rehabilitation in people with diabetes. 3. Longer rehabilitation for men is advisable regardless of the type of stroke.

Evaluation of the functional status of the “unaffected” hand in hemiplegic patients

Objectives: To evaluate the functional status of the unaffected hand in hemiplegic patients and its relationships with activities of daily living. Methods: This cross-sectional study included 30 right, 30 left hemiplegic patients with ischemic cerebrovascular accident history in last year, and 30 healthy volunteers. All participants were right-hand dominant. Data on age, gender, height, weight, comorbidities, duration of stroke, Brunnstrom recovery stages were recorded. Handgrip strength (with Jamar-type dynamometer), pinch strengths (with pinch-meter), and hand dexterity [with Nine Hole Peg Test (NHPT)] were evaluated in unaffected hand in patient groups and in both hands in control group. Lawton Instrumental Activities of Daily Living Scale (Lawton-IADL) and Functional Independence Measure (FIM) were applied to patient groups. Results: Hand grip and pinch strengths were lower, NHPT duration was longer in right (p=0.004, p=0.03, p&lt;0.001) and left (p=0.03, p=0.02, p=0.002) hemiplegia groups compared to control group. Hand grip and pinch strengths were positively, NHPT duration was negatively correlated with FIM self-care performance (r:0.47 p&lt;0.00, r:0.38 p=0.003, r:-0.40 p=0.002), and Lawton-IADL scores (r:0.48 p&lt;0.001, r:0.42 p=0.001, r:-0.56 p&lt;0.001). Conclusion: Ipsilesional hand, which is considered unaffected, functions are impaired in hemiplegic patients. This functional impairment is associated with greater dependence on activities of daily living.

Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.

We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.

Upper limb dysfunction in people with early-stage Multiple Sclerosis: Perceived performance can be misleading

BackgroundAlthough the necessity of upper limb (UL) (dys)function assessment in people with Multiple Sclerosis (pwMS) has been demonstrated in recent years, this is still neglected at an early-stage. ObjectiveThe aim of our study was to comprehensively examine bilateral UL in early-stage pwMS who are thought to have no or minimal involvement in activities of daily living for the UL. MethodsUL muscle strength, sensation and dexterity of 44 pwMS (EDSS score<4, disease duration<5 years, who did not report problems in daily living activities specifically for the UL) were evaluated bilaterally and compared with 44 healthy controls (HC). The relationship between UL function and muscle strength, sensation, cognitive function, fatigue, mood status, participation, EDSS, and disease duration were examined. The results of the outcome measures evaluating the UL function objectively and subjectively were analyzed. ResultsMuscle strength, sensation and dexterity were similar in the dominant and nondominant extremities of pwMS and were affected compared to HC. A fair relationship was found between UL function and proximal muscle strength, fatigue, cognitive function, home participation and EDSS. According to the cut-off value (18 s) of Nine Hole Peg Test, only 9.09% of pwMS was unaffected, but 79.54% of affected pwMS had a full ABILHAND score. ConclusionEarly-stage pwMS are unaware of the dysfunction since their UL involvement does not affect their daily living activities yet. Patient-reported outcome measures such as ABILHAND can be misleading and have a ceiling effect in the early-stage of the disease. Objective functional evaluations reveal that UL capacity is affected from the early period. Even if pwMS do not report UL involvement, clinicians and researchers should evaluate UL function and include it in the treatment program from an early-stage to prevent further disease burden.

Effects of Peripheral Cooling on Upper Limb Tremor Severity and Functional Capacity in Persons with MS.

Upper limb intention tremor in persons with multiple sclerosis (pwMS) affects the ability to perform activities of daily life and is difficult to treat. The study investigated the effect of peripheral upper limb cooling on tremor severity and functional performance in MS patients with intention tremor. In experiment 1, 17 patients underwent two 15 min cooling conditions for the forearm (cold pack and cryomanchet) and one control condition. In experiment 2, 22 patients underwent whole arm cooling for 15 min using multiple cold packs. In both experiments, patients were tested at four time points (pre- and post-0, -25 and -50 min cooling) on unilateral tasks of the Test Evaluant les Membres supérieurs des Personnes Agées (TEMPA), Fahn's tremor rating scale (FTRS), Nine Hole Peg Test (NHPT). In experiment 1, the mean FTRS ranged from 13.2 to 14.1 across conditions. A two-way ANOVA showed mainly time effects, showing that cooling the forearm significantly reduced the FTRS, the performance on the NHPT, and three out of four items of the TEMPA, mostly independent of the cooling modality. In experiment 2, the mean FTRS was 13.1. A repeated measures ANOVA showed that cooling the whole arm reduced the FTRS and time needed to execute two out of four items of the TEMPA. These effects occurred immediately after cooling lasting at least 25 min. Cooling the whole upper limb led to a clinically noticeable effect on tremor severity and improved functional performance, which was pronounced during the first half-hour after cooling.

Glial fibrillary acidic protein and multiple sclerosis progression independent of acute inflammation.

The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified. To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS). We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study (n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses. We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed. Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.

Immediate Effect of Mirror Therapy Using Pegboard Training on Hand Function and Muscle Activities in Individuals With Asymmetrical Hand Function

Objectives: A proper function of hands is critical for doing daily activities and work, especially when using electronic devices. This study determined the effect of mirror therapy on individuals with asymmetrical hand function. Methods: Forty-two men with asymmetrical hand function were recruited. All participants were randomly divided into sham control (n=21) and mirror therapy (n=21) groups. Both groups were tested before and after training using the 9-hole peg test (9HPT). The sham control group received pegboard training, and the mirror therapy group received mirror therapy using the pegboard. During training, hand muscle activities were recorded using surface electromyography. The obtained data were analyzed using the t-test and Mann-Whitney U test. Results: Non-dominant hand function on the 9HPT showed significant improvement in the mirror therapy group compared with the sham control group (P=0.021). The asymmetric hand function was also improved in the mirror therapy group. Muscle activities of the non-dominant hand were not significantly different between groups. Discussion: Mirror therapy using the pegboard had an immediate effect on improving non-dominant hand function. This finding has implications for possible preventive strategies against common hand problems and improving the efficient use of both hands.

Comparison of manual dexterity of people with Alzheimer’s disease and cognitively healthy older adults: The impact of cognition

AbstractBackgroundAlzheimer’s disease (AD) not only effects the cognitive level, but also leads to significant decline in motor skill. Manual dexterity emerges with the interaction of cognitive and motor processes and is seen as an important predictor of functional independence. The aim of this study was to compare manual dexterity in people with AD with healthy older adults and to investigate the effect of cognitive level on manual dexterity.MethodThe Nine Hole Peg Test (NHPT) was used for manual dexterity assessment. Cognitive function were assessed with Montreal Cognitive Assessment (MoCA). Statistical analysis was performed by Mann Whitney U Test and regression analysis in SPSS 22.0 package program.ResultTwenty nine people with AD (78.04±6.49, 48.27% female) and ten cognitively healthy older adult (74.8±7.22, 30% female) included study. NHPT results of the dominant hand were 31.87±7.33 sec. and 21.66±2.85 sec.; MoCA scores were 13.79±5.76 and 24.5±2.32, respectively, in the people with AD and cognitively healthy older adults. There was significant difference in NHPT results between groups (p&lt;.001). Significant correlation was found between NHPT and MoCA (p&lt;.001, r = .648). It was found that cognitive level significantly predicted manual dexterity (β = .648, R2 = .42, F [1,27] = 19.58, p&lt;.001).ConclusionManual dexterity in AD shows a significant decrease compared to the cognitively healthy older adults. In our study, it was shown that the decrease in manual dexterity occurs with the effect of cognition at a rate of 42%. Deteriorating manual dexterity with decreased cognition is likely to accelerate patients' withdrawal from activities of daily living. Also, rehabilitation programs that include activities for manual dexterity may slow down the process of participation restriction in AD.

Impact of extended interval dosing of ocrelizumab on immunoglobulin levels in multiple sclerosis

Long-term B cell depletion with ocrelizumab in multiple sclerosis (MS) is associated with severe side effects such as hypogammaglobulinemia and infections. Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing (EID) scheme. Immunoglobulin levels of 51 patients with ≥24months of treatment with ocrelizumab were analyzed. After ≥4 treatment cycles, patients chose to either continue on the standard interval dosing (SID) regimen (n= 14) or, in the case of clinically and radiologically stable disease, switch to B cell-adapted EID (n= 12, next dose at CD19+ Bcells >1% of peripheral blood lymphocytes). Levels of immunoglobulin M (IgM) declined rapidly under ocrelizumab treatment. Risk factors for IgM and IgA hypogammaglobulinemia were lower levels at baseline and more previous disease-modifying therapies. B cell-adapted EID of ocrelizumab increased the mean time until next infusion from 27.3 to 46.1weeks. Ig levels declined significantly in the SID group over 12months but not in the EID group. Previously stable patients remained stable under EID as measured by expanded disability status scale (EDSS), neurofilament light chain, timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT), symbol digit modalities test (SDMT), and multiple sclerosis impact scale (MSIS-29). In our pilot study, B cell-adapted EID of ocrelizumab prevented the decline of Ig levels without affecting disease activity in previously stable patients with MS. Based on these findings, we propose a new algorithm for long-term ocrelizumab treatment. This study was supported by the Deutsche Forschungsgemeinschaft (SFB CRC-TR-128, SFB 1080, and SFB CRC-1292) and the Hertie Foundation.

Acute Intermittent Hypoxia and UE Strength and Function changes in Multiple Sclerosis: A Case Report

Background/Purpose Recovery of upper extremity (UE) function is a priority for individuals with multiple sclerosis (MS) whose disease sequalae often results in loss of UE strength and motor control. Acute Intermittent Hypoxia (AIH) is a novel intervention where an individual breathes bouts of air with low oxygen (∼9% O2) to set off a cascade of cellular events that may induce neuroplasticity and improve motor function. This intervention has shown promising effects in individuals with motor incomplete spinal cord injury (iSCI), even after a single bout. The purpose of this case report was to assess the ability of a single-bout AIH protocol to improve UE strength and function in an individual with chronic, relapsing-remitting MS. Methods A 30-year-old, right-handed female with a 10-year history of MS (Expanded Disability Status Scale score 3.0), who presented with LUE weakness and increased LUE tone participated in two treatment sessions. In the first session, she received a sham intervention where she was delivered normal room air, through the hypoxia generator for the entire treatment. The following week she received AIH. The 9-Hole Peg Test (9HPT) and Hand-held dynamometry (HHD) were performed immediately before and after the intervention Results Following the single bout of AIH, compared to baseline, left shoulder abduction strength increased 8% immediately after treatment and 21% at the 30-minute assessment. Left wrist extension strength increased 26% and 30%, respectively. Left shoulder flexion and elbow extension did not change. Comparatively, right shoulder abduction strength increased 27% and 7%. Right wrist extension strength increased 12% and 1%. Functionally, the participant's 9HPT time decreased from 44.88 to 41.41 seconds on her left but increased from 15.69 to 16.06 seconds on her right. Discussion AIH treatment was well tolerated by our participant and a single bout of AIH resulted in positive changes in UE strength and function on her more involved side. These results are promising, and further research is required to further assess safety, feasibility, and potential efficacy of AIH in people with MS. Recovery of upper extremity (UE) function is a priority for individuals with multiple sclerosis (MS) whose disease sequalae often results in loss of UE strength and motor control. Acute Intermittent Hypoxia (AIH) is a novel intervention where an individual breathes bouts of air with low oxygen (∼9% O2) to set off a cascade of cellular events that may induce neuroplasticity and improve motor function. This intervention has shown promising effects in individuals with motor incomplete spinal cord injury (iSCI), even after a single bout. The purpose of this case report was to assess the ability of a single-bout AIH protocol to improve UE strength and function in an individual with chronic, relapsing-remitting MS. A 30-year-old, right-handed female with a 10-year history of MS (Expanded Disability Status Scale score 3.0), who presented with LUE weakness and increased LUE tone participated in two treatment sessions. In the first session, she received a sham intervention where she was delivered normal room air, through the hypoxia generator for the entire treatment. The following week she received AIH. The 9-Hole Peg Test (9HPT) and Hand-held dynamometry (HHD) were performed immediately before and after the intervention Following the single bout of AIH, compared to baseline, left shoulder abduction strength increased 8% immediately after treatment and 21% at the 30-minute assessment. Left wrist extension strength increased 26% and 30%, respectively. Left shoulder flexion and elbow extension did not change. Comparatively, right shoulder abduction strength increased 27% and 7%. Right wrist extension strength increased 12% and 1%. Functionally, the participant's 9HPT time decreased from 44.88 to 41.41 seconds on her left but increased from 15.69 to 16.06 seconds on her right. AIH treatment was well tolerated by our participant and a single bout of AIH resulted in positive changes in UE strength and function on her more involved side. These results are promising, and further research is required to further assess safety, feasibility, and potential efficacy of AIH in people with MS.

Cerebrospinal Fluid Biomarkers Associated with Intrathecal Cell Therapy in Patients with Progressive Multiple Sclerosis (P1-3.001)

<h3>Objective:</h3> To identify cerebrospinal fluid (CSF) biomarkers of clinical response to intrathecal (IT) mesenchymal stem cell-neural progenitor (MSC-NP) treatment in patients with progressive multiple sclerosis (MS). <h3>Background:</h3> MSC-NPs are a bone marrow-derived population of cells with trophic and immunomodulatory properties with therapeutic potential in MS. A phase II randomized, double-blind, placebo-controlled clinical trial was performed to investigate whether multiple intrathecal (IT) injections of autologous MSC-NPs was associated with clinical efficacy. Study subjects received either 6 IT injections of autologous MSC-NPs or 6 placebo injections spaced 2 months apart. In the crossover study design, subjects treated with placebo in the first year were treated with MSC-NPs in the second year, and vice versa. Safety and clinical efficacy will be reported elsewhere. <h3>Design/Methods:</h3> For biomarker discovery, CSF was collected from 36 study subjects at the time of their first and sixth IT-MSC-NP treatment reflecting pre-treatment and post-treatment timepoints, respectively. CSF supernatants were analyzed using SOMAScan multiplex proteomic assay. Differentially expressed proteins were identified using a multivariate linear mixed effect model. Biomarkers were validated using ELISA/Luminex assays. Treatment responders were defined by improvement in any of the following outcomes: EDSS, timed 25-foot walk, 9-hole peg test, 6-minute walk test, or muscle strength. <h3>Results:</h3> Proteomic analysis of CSF identified matrix metalloproteinase-9 (MMP-9), complement C3a and the chemokine CCL2 as potential biomarkers of IT-MSC-NP treatment. MMP-9 was significantly increased post-treatment and was observed independent of clinical response. Relative concentration of C3a, C3 and C3b were decreased post-treatment and subgroup analysis demonstrated significance only in the responder group. CCL2 was significantly decreased post-treatment with higher significance associated with clinical response. Decreased CCL2 was validated in an independent cohort of patients treated with IT-MSC-NPs. <h3>Conclusions:</h3> These results identify multiple CSF biomarkers of IT-MSC-NP treatment that may correlate with therapeutic response to this novel cell therapy in MS. <b>Disclosure:</b> Miss Kizilbash has nothing to disclose. Ms. Carlson has nothing to disclose. Violaine K. Harris, PhD has nothing to disclose. Dr. Sadiq has nothing to disclose.

Tracking Motor Impairment in People with Neurosarcoidosis (P9-5.009)

<h3>Objective:</h3> Evaluate NIH Toolbox motor battery (NIHTB-M), a multidimensional set of measures used to track motor impairment, for use in people with neurosarcoidosis (PwNS). <h3>Background:</h3> Despite its profound impact on quality of life, there are no validated measures of neurologic impairment in NS to track disability progression or treatment response. <h3>Design/Methods:</h3> Cross-sectional study of adults with NS recruited from a tertiary referral center for sarcoidosis. All participants were adults meeting NS Consortium diagnostic criteria for NS. NIHTB-M measures were compared to age-, education-, sex-, and race/ethnicity-matched peers using neurologically healthy individuals from the NIHTB norming project. NIHTB-M measures were compared to patient-reported assessments of mobility and fine motor control using Quality of Life in Neurological Disorders (Neuro-QoL) and clinician-assessed functional impairment using Barthel Index (BI). <h3>Results:</h3> 41 PwNS were enrolled, 62% female, 29% African American, 71% Caucasian, 86% with biopsy-proven sarcoidosis. 7% had severe, 27% moderate, 7% slight, and 56% no functional dependence by BI. Compared to propensity-matched healthy controls, impairment (≥ 1 standard deviation worse than normative mean) was more common in PwNS on 9-Hole Peg Test (9-HPT) (81% vs. 14%, OR: 19.53, 95%CI [6.51, 67.56]) and 4-Meter Walk Test (4-MWT) (77% vs. 15%, OR: 18.89, 95% CI [6.41, 64.41]). There were moderate correlations between 9-HPT and Neuro-QoL fine motor scores (r = 0.39, 95% CI [0.03, 0.66]) and strong correlations between 4-MWT and 2-Minute Walk Test (2-MWT) and Neuro-QoL mobility scores (r = −0.69, 95% CI [−0.84, −0.44]; 0.66, 95% CI [0.44, 0.78], respectively). Scores on 9-HPT (<i>P</i>=0.008), 4-MWT (<i>P</i>=0.007), 2-MWT (<i>P</i>=0.032), and select measures of Standing Balance Test (SBT) (<i>P</i> &lt; 0.001) were significantly different between subjects who were functionally dependent versus independent by BI. <h3>Conclusions:</h3> We provide preliminary evidence for validity of 9-HPT as a measure of fine motor control and 4-MWT, 2-MWT, and SBT as measures of mobility in PwNS. <b>Disclosure:</b> Dr. Moss has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. An immediate family member of Dr. Moss has stock in Pfizer. The institution of Dr. Moss has received research support from Novartis. The institution of Dr. Moss has received research support from Genentech. Nicholas Thompson has nothing to disclose. Daniel Culver has nothing to disclose.

Remote Monitoring of Neurological Patients (P14-3.018)

<h3>Objective:</h3> Our long-term goal is to employ smartphone-embedded sensors to measure various neurological functions in a patient-autonomous manner. The interim goal is to develop simple smartphone tests and evaluate the clinical utility of these tests by selecting optimal outcomes that correlate well with clinician-measured disability in different neurological domains. <h3>Background:</h3> There is a world-wide shortage of neurologists, which is predicted to only worsen as the world population ages. This shortage along with the recent Covid-related restrictions, has resulted in fewer neurological exams and this can result in a delayed diagnosis and cause suboptimal care for the patient. DTM Health worked with NIH to address this “gap in care” with a self-administered mobile app that can remotely monitor a patient’s condition. <h3>Design/Methods:</h3> We hypothesized that aggregating data from two simple smartphone tests of fine finger movements with differing contributions of specific neurological domains ( strength, cerebellar functions, vision, and reaction time) will allow establishment of secondary outcomes that reflect domain-specific deficit. This hypothesis was tested by assessing correlations of smartphone-derived outcomes with relevant parts of neurological examination in multiple sclerosis patients. We developed a mobile app consisting of two simple tests: Finger Tapping and Balloon Popping. The study consisted of 76 multiple sclerosis (MS) patients and 19 healthy volunteers (HV). The balloon popping and finger tapping tests were self-administered by the participants while the 9-hole peg test (9HPT) was administered by an investigator. <h3>Results:</h3> The primary outcomes of smartphone tests, the average number of taps and the average number of pops differentiated MS from HV with similar power to traditional, investigator-administered test of fine finger movements of 9HPT. <h3>Conclusions:</h3> In the time necessary for performing 9HPT, smartphone tests provide much richer and reliable measurements of several distinct neurological functions. This data suggests that combining more creatively-construed smartphone apps may one day recreate the entire neurological examination. <b>Disclosure:</b> Marc Fischer has nothing to disclose.

Disability progression and worse cognitive status are associated with higher concurrent brain atrophy rates (P13-3.007)

<h3>Objective:</h3> To determine associations between brain atrophy rate and clinical outcome measures in multiple sclerosis (MS). <h3>Background:</h3> The determination and treatment of neurodegenerative aspects of MS remains a challenge. One indirect form of assessment is the whole brain atrophy rate as determined by longitudinal MRI. Integration of brain atrophy rate assessments into clinical practice is hampered by multiple technical and translational factors, including incomplete clinical validation. It remains unclear to what extent clinical assessments are reflected and associated with this measure. <h3>Design/Methods:</h3> In a large retrospective observational cohort, we used FSL-SIENA to determine annualized percent brain volume change (aPBVC) from longitudinal clinical 3T MRI obtained using a uniform hardware and software acquisition protocol. Clinical outcomes, including confirmed disability progression, the 9-hole peg test (9HPT), the symbol digit modalities test (SDMT), and the timed-25-foot walk (T25w) were determined from retrospective chart review. SDMT, 9HPT, and T25w were averaged between the first and second MRI sessions to produce a single number. Using forward regression models, we assessed clinical predictors of aPBVC, including CDP and secondary clinical outcome measures, as independent variables along with age of onset and type of MS. <h3>Results:</h3> 123 patients met inclusion criteria (102 RMS, 21 PMS; mean age = 36 ±SD 11) with available clinical and MRI data. In univariable analyses, confirmed disability progression showed the strongest association with concurrent aPBVC (β=0.31, p &lt;0.001), followed by the SDMT (β=0.27, p=0.006) whereas 9HPT and T25 were not significant (p&gt;0.05). Change in EDSS and cross-sectional SDMT both remained significantly associated in multivariable models (p=0.008 and p=0.04, respectively). <h3>Conclusions:</h3> Both disability progression as well as the SDMT are independently associated with the observed brain atrophy rate. <b>Disclosure:</b> Dr. Garcia-Dominguez has nothing to disclose. Dr. Hemond has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for VIVIO Health. Dr. Hemond has stock in VIVIO Health. The institution of Dr. Hemond has received research support from Consorium of Multiple Sclerosis Centers. The institution of Dr. Hemond has received research support from National Multiple Sclerosis Society. The institution of Dr. Hemond has received research support from National Center for Advancing Translational Sciences, National Institutes of Health. The institution of Dr. Hemond has received research support from University of Massachusetts Memorial Medical Center. The institution of Dr. Hemond has received research support from National Institute Of Neurological Disorders And Stroke of the National Institutes of Health. Dr. Hemond has received personal compensation in the range of $0-$499 for serving as a Member of Data Safety and Monitoring Board with National Institute Of Neurological Disorders And Stroke of the National Institutes of Health.

Long-COVID-19 cognitive disfunction: strain-specific effects on 452 subjects (S21.010)

<h3>Objective:</h3> Evaluate the effect of COVID-19 presumed viral strains on different cognitive domains. <h3>Background:</h3> Cognitive dysfunction (CD) is a frequent and debilitating symptom of long-COVID syndrome with a negative impact on survivors’ productivity and quality of life. It is unknown whether there are strain-specific effects on cognition. <h3>Design/Methods:</h3> We used the Fiocruz database (http://www.genomahcov.fiocruz.br) to separate 452 subjects (15 years of education; 88 days after diagnosis) according to the prevalent viral strain at the time of the positive COVID-19 test. Subjects completed a neuropsychological evaluation consisting of phonetic fluency (FAS), semantic fluency (SF: animals), logic memory (immediate and late recall), Rey-Osterrieth complex figure test (copy and recall), colored trails test A and B, 9-hole peg test (dominant and non-dominant hand) and the five digits test (reading, counting, choice, alternation, inhibition, and flexibility). Test scores were converted to Z-scores using normative Brazilian tables. Global strain effects were tested using MANOVA, followed by one-way ANOVAs for each test. <h3>Results:</h3> Subjects were classified into five presumed strain groups: original (247), original+P2 (36), P2 (86), gamma+P2 (50), and delta (6). Full testing data were available for 141 subjects. MANOVA showed significant strain effects (p=0.046). However, post-hoc tests showed no strain effects on any of the cognitive tests. SF showed a marginally significant effect (n=392, p=0.056) due to better performances in the original+P2 and P2 groups. FDT reading subtest was marginally significant (n=323, p=0.073) due to better test performances in the P2 and delta groups. <h3>Conclusions:</h3> Despite the small groups with non-original strains, we suppose neurotropism regardless of different strains. As millions of survivors may present CD, there is an urgent need for health policies to provide multidisciplinary treatment and rehabilitation to improve workability and quality of life. Further studies with larger samples may disclose the protective role of vaccination in preventing CD. <b>Disclosure:</b> Dr. Karmann Aventurato has received research support from Coordenadoria de Aperfeiçoamento de Pessoal de Ensino Superior (CAPES). Mateus Nogueira has nothing to disclose. Lucas Silva has nothing to disclose. Prof. João has received research support from FAPESP. Mr. Becchelli has nothing to disclose. Alan Ferreira dos Santos has nothing to disclose. Leila Camila Santos Silva has nothing to disclose. Mariana Brito has nothing to disclose. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB Biopharma. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for United Medical – Brazil. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Zodiac Pharma . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma – Brazil . Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Epilepsia. Dr. Cendes has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology - Epilepsy. The institution of Dr. Cendes has received research support from São Paulo Research Foundation - FAPESP. The institution of Dr. Cendes has received research support from Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil . The institution of Dr. Cendes has received research support from NIH. Clarissa Yasuda has nothing to disclose.