Coexistence of neurofibromatosis type I, multiple sclerosis, and ischemic stroke: A case report and literature review.

Neurofibromatosis type I and multiple sclerosis, when considered separately, are associated with a higher risk of cerebrovascular accident. The coexistence of neurofibromatosis type I and multiple sclerosis may lead to a further increase in cerebrovascular risk; however, this has not been reported in the literature. We report the case of a 37-year-old woman affected by both neurofibromatosis type I and multiple sclerosis: she was referred to our rehabilitation department because of a recent event of ischemic stroke. Moreover, we provide a comprehensive and updated review of all published cases reporting the coexistence of neurofibromatosis type I and multiple sclerosis to gather information regarding their association with cerebrovascular accidents.

Fatigue may improve equally after balance and endurance training in multiple sclerosis: a randomised, crossover clinical trial.

Introduction: Fatigue and poor balance are frequent and severe problems in multiple sclerosis (MS) that may interact. Endurance training is known to be effective on fatigue. This study aims to test if balance training is more effective against MS fatigue. Methods: A randomised crossover trial was run, recruiting 31 MS people (21 women; median age: 46 years, range: 30-64; median EDSS: 4, range: 2.5-5). Participants received balance and endurance training alternately (15 one-to-one sessions, 5 days/week) and were assessed before (T0), after (T1), and 30 days after treatment ended (T2). The Modified Fatigue Impact Scale (MFIS) with scores linearised through Rasch analysis was the primary outcome (the lower the measure, the better the condition, i.e., the lower the fatigue symptoms). The Equiscale balance scale and posturography (EquiTest) were used to assess balance. Linear mixed-effects models with ANOVA were used for significance testing. Results: Thirteen participants had no carryover effect and were included in the primary analysis. Fatigue significantly changed across the three time points (F2,58 = 16.0; p < 0.001), but no difference across treatments was found. Altogether, both treatments significantly improved the MFIS measure at T1 (95%CI: -1.24 logits; mean: -1.67 to -0.81 logits) and T2 (95%CI: -1.04; mean: -1.49 to -0.60) compared to T0 (95%CI: -0.51; mean: -0.95 to -0.08; p ≤ 0.001). Equiscale and posturography highlighted balance improvement after balance training but not after endurance training. Conclusion: Balance and endurance training could similarly reduce fatigue in MS patients in the short term. However, only balance training also improved balance in MS.

The Telephone Language Screener (TLS): standardization of a novel telephone-based screening test for language impairment.

BACKGROUND: This study aimed at developing and standardizing the Telephone Language Screener (TLS), a novel, disease-nonspecific, telephone-based screening test for language disorders. METHODS: The TLS was developed in strict pursuance to the current psycholinguistic standards. It comprises nine tasks assessing phonological, lexical-semantic and morpho-syntactic components, as well as an extra Backward Digit Span task. The TLS was administered to 480 healthy participants (HPs), along with the Telephone-based Semantic Verbal Fluency (t-SVF) test and a Telephone-based Composite Language Index (TBCLI), as well as to 37 cerebrovascular/neurodegenerative patients-who also underwent the language subscale of the Telephone Interview for Cognitive Status (TICS-L). An HP subsample was also administered an in-person language battery. Construct validity, factorial structure, internal consistency, test-retest and inter-rater reliability were tested. Norms were derived via Equivalent Scores. The capability of the TLS to discriminate patients from HPs and to identify, among the patient cohort, those with a defective TICS-L, was also examined. RESULTS: The TLS was underpinned by a mono-component structure and converged with the t-SVF (p < .001), the TBCLI (p < .001) and the in-person language battery (p = .002). It was internally consistent (McDonald's ω = 0.67) and reliable between raters (ICC = 0.99) and at retest (ICC = 0.83). Age and education, but not sex, were predictors of TLS scores. The TLS optimally discriminated patients from HPs (AUC = 0.80) and successfully identified patients with an impaired TICS-L (AUC = 0.92). In patients, the TLS converged with TICS-L scores (p = 0.016). DISCUSSION: The TLS is a valid, reliable, normed and clinically feasible telephone-based screener for language impairment.

The predictive role of fatigue and neuropsychological components on functional outcomes in COVID-19 after a multidisciplinary rehabilitation program.

OBJECTIVE: To verify the impact of altered cognitive functioning and higher levels of mental fatigue, both reported after coronavirus disease 2019 (COVID-19), on rehabilitation treatment outcomes. METHODS: In this real-practice retrospective pre-post intervention cohort study, cognitive functioning, measured through standardized neuropsychological measures, and individual levels of fatigue, depression and anxiety symptoms, were evaluated at admission to a rehabilitation program in individuals who had been hospitalized for COVID-19. The rehabilitation program effectiveness was measured through the Functional Independence Measure. RESULTS: Among the patient sample (n = 66), 87.88% reported experiencing high levels of fatigue at admission, while 16.67% reported depressive symptoms, and 22.73% reported anxiety symptoms. After rehabilitation, the sample displayed a significant decrease in the level of disability, in both the motor and cognitive subscales. Neuropsychological and psychological functioning did not play a predictive role. The 45 patients who received mechanical ventilation during intensive care, representing 68.18% of the sample, benefited more from rehabilitation treatment. CONCLUSIONS: The results support the importance of an early rehabilitation program after COVID-19 infection, independent of the initial neuropsychological and psychological functioning. Respiratory assistance may represent a crucial factor for short-term neuropsychological disease after-effects. Future studies on the long-term neuropsychological effect of COVID-19 infection on individual levels of disability are necessary.

Evaluation of the predictive factors of the short-term effects of a multidisciplinary rehabilitation in COVID-19 survivors.

OBJECTIVE: Functional impairments after coronavirus disease 2019 (COVID-19) constitute a major concern in rehabilitative settings; however, evidence assessing the efficacy of rehabilitation programs is lacking. The aim of this study was to verify the clinical characteristics that may represent useful predictors of the short-term effectiveness of multidisciplinary rehabilitation. METHODS: In this real-practice retrospective pre-post intervention cohort study, the short-term effectiveness of a multidisciplinary patient-tailored rehabilitation program was assessed through normalized variations in the Functional Independence Measure in post-acute care patients who had overcome severe COVID-19. Biochemical markers, motor and nutritional characteristics, and the level of comorbidity were evaluated as predictors of functional outcome. Length of stay in the rehabilitation ward was also considered. RESULTS: Following rehabilitation, all participants (n = 53) reported a significant decrease in the level of disability in both motor and cognitive functioning. However, neither motor and nutritional characteristics nor comorbidities played a significant role in predicting the overall positive change registered after rehabilitation. CONCLUSIONS: The results support the existing sparse evidence addressing the importance of an early rehabilitation program for patients who received intensive care and post-acute care due to severe COVID-19.

Balance Impairment in Fahr's Disease: Mixed Signs of Parkinsonism and Cerebellar Disorder. A Case Study.

Fahr's disease is a rare idiopathic degenerative disease characterized by calcifications in the brain, and has also been associated with balance impairment. However, a detailed analysis of balance in these patients has not been performed. A 69-year-old woman with Fahr's disease presented with a long-lasting subjective imbalance. Balance was analyzed using both clinical (EquiScale, Timed Up and Go test, and Dizziness Handicap Inventory-short form) and instrumented tests (the sway of the body center of mass during quiet, perturbed, and self-perturbed stance, and the peak curvature of the center of mass during single stance while walking on a force-treadmill). The patient's balance was normal during clinical tests and walking. However, during standing, a striking impairment in vestibular control of balance emerged. The balance behavior displayed mixed parkinsonian (e.g., slowness and reduced amplitude of movement) and cerebellar (e.g., increased sway during standing in all conditions and decomposition of movement) features, with a discrepancy between the high severity of the static and the low severity of the dynamic balance impairment. The balance impairment characteristics outlined in this study could help neurologists and physiatrists detect, stage, and treat this rare condition.

Abnormal multisensory integration in relapsing-remitting multiple sclerosis.

Temporal Binding Window (TBW) represents a reliable index of efficient multisensory integration process, which allows individuals to infer which sensory inputs from different modalities pertain to the same event. TBW alterations have been reported in some neurological and neuropsychiatric disorders and seem to negatively affects cognition and behavior. So far, it is still unknown whether deficits of multisensory integration, as indexed by an abnormal TBW, are present even in Multiple Sclerosis. We addressed this issue by testing 25 participants affected by relapsing-remitting Multiple Sclerosis (RRMS) and 30 age-matched healthy controls. Participants completed a simultaneity judgment task (SJ2) to assess the audio-visual TBW; two unimodal SJ2 versions were used as control tasks. Individuals with RRMS showed an enlarged audio-visual TBW (width range = from - 166 ms to + 198 ms), as compared to healthy controls (width range = - 177/ + 66 ms), thus showing an increased tendency to integrate temporally asynchronous visual and auditory stimuli. Instead, simultaneity perception of unimodal (visual or auditory) events overall did not differ from that of controls. These results provide first evidence of a selective deficit of multisensory integration in individuals affected by RRMS, besides the well-known motor and cognitive impairments. The reduced multisensory temporal acuity is likely caused by a disruption of the neural interplay between different sensory systems caused by multiple sclerosis.

Normative Data for the NeuroCom® Sensory Organization Test in Subjects Aged 80-89 Years.

Aging is known to increase the risk of falling. In older people, whose share in the total population is rising sharply, the Sensory Organization Test (SOT, Equitest NeuroCom) is a useful tool during rehabilitation and in clinical research for assessing postural stability, risk of falling, and balance improvement. Normative data for the SOT in the healthy population older than 79 years have not been previously published. We recruited 53 recreationally active healthy subjects aged 80 years and older from the general population in a cross-sectional study. We presented the normative data for SOT for the 80-84 and 85-89 years groups. Our results showed that the "vestibular" balance control tended to be affected by aging more than the vision and proprioception-based systems. A striking reduction in performance after the age of 85 years was observed. These findings will be useful for clinical and research purposes.

Explicit motor sequence learning after stroke: a neuropsychological study.

Motor learning interacts with and shapes experience-dependent cerebral plasticity. In stroke patients with paresis of the upper limb, motor recovery was proposed to reflect a process of re-learning the lost/impaired skill, which interacts with rehabilitation. However, to what extent stroke patients with hemiparesis may retain the ability of learning with their affected limb remains an unsolved issue, that was addressed by this study. Nineteen patients, with a cerebrovascular lesion affecting the right or the left hemisphere, underwent an explicit motor learning task (finger tapping task, FTT), which was performed with the paretic hand. Eighteen age-matched healthy participants served as controls. Motor performance was assessed during the learning phase (i.e., online learning), as well as immediately at the end of practice, and after 90 min and 24 h (i.e., retention). Results show that overall, as compared to the control group, stroke patients, regardless of the side (left/right) of the hemispheric lesion, do not show a reliable practice-dependent improvement; consequently, no retention could be detected in the long-term (after 90 min and 24 h). The motor learning impairment was associated with subcortical damage, predominantly affecting the basal ganglia; conversely, it was not associated with age, time elapsed from stroke, severity of upper-limb motor and sensory deficits, and the general neurological condition. This evidence expands our understanding regarding the potential of post-stroke motor recovery through motor practice, suggesting a potential key role of basal ganglia, not only in implicit motor learning as previously pointed out, but also in explicit finger tapping motor tasks.

Short-Term Repeatability of Stabilometric Assessments.

The authors evaluated the short-term (within-day, between-days) repeatability of center of pressure (COP) displacements. COP sway area and speed were obtained in the morning and afternoon of two separate days, both with open (EO) and closed (EC) eyes, in 10 healthy adults. Agreement and variability among conditions were tested by ANOVA and Bland-Altman plots. Mode (EO/EC, area: p = .032; speed: p < .004), and day (day1/day2, area: p = .006; speed: p = .02) showed significant differences. The EC condition and the second test day showed the largest values, with medium-large effect sizes. Time-of-day did not influence COP displacements. Speed had better agreement than area (Bland-Altman plots). COP displacements were well reproducible within-day, but had significant between-days variations. COP assessments should be performed in the same session.

Improving left spatial neglect through music scale playing.

The study assessed whether the auditory reference provided by a music scale could improve spatial exploration of a standard musical instrument keyboard in right-brain-damaged patients with left spatial neglect. As performing music scales involves the production of predictable successive pitches, the expectation of the subsequent note may facilitate patients to explore a larger extension of space in the left affected side, during the production of music scales from right to left. Eleven right-brain-damaged stroke patients with left spatial neglect, 12 patients without neglect, and 12 age-matched healthy participants played descending scales on a music keyboard. In a counterbalanced design, the participants' exploratory performance was assessed while producing scales in three feedback conditions: With congruent sound, no-sound, or random sound feedback provided by the keyboard. The number of keys played and the timing of key press were recorded. Spatial exploration by patients with left neglect was superior with congruent sound feedback, compared to both Silence and Random sound conditions. Both the congruent and incongruent sound conditions were associated with a greater deceleration in all groups. The frame provided by the music scale improves exploration of the left side of space, contralateral to the right hemisphere, damaged in patients with left neglect. Performing a scale with congruent sounds may trigger at some extent preserved auditory and spatial multisensory representations of successive sounds, thus influencing the time course of space scanning, and ultimately resulting in a more extensive spatial exploration. These findings offer new perspectives also for the rehabilitation of the disorder.

The diagnostic challenge of Divry van Bogaert and Sneddon Syndrome: Report of three cases and literature review.

Divry van Bogaert Syndrome (DBS) is a familial juvenile-onset disorder characterized by livedo racemosa, white matter disease, dementia, epilepsy and angiographic finding of "cerebral angiomatosis". A similar syndrome including livedo racemosa and cerebrovascular disease, often associated with anticardiolipin antibodies, has been described as Sneddon Syndrome (SS) highlighting the question whether these two conditions have to be considered different entities or indeed different features of a unique syndrome. Herein, we report the clinical, neuroradiological, histopathological findings and follow up of three cases diagnosed as Divry-van Bogaert Syndrome, including an updated review of literature of both DBS and SS cases. Our findings support the assumption that DBS and SS are different disease entities. DBS is characterized by the typical angiographic feature of angiomatosis, a hereditary trait and a juvenile onset of cognitive impairment and leukoaraiosis, whereas SS has less severe manifestations of cerebrovascular disease associated with livedo racemosa but without the characteristic cerebral angiography. The report of our cases and the literature review underline the necessity of a detailed work-up and the collection of larger series to better clarify the DBS and SS phenotype and course.

Bimanual dexterity assessment: validation of a revised form of the turning subtest from the Minnesota Dexterity Test.

Bimanual coordination underlies many daily activities. It is tested by various versions of the old Minnesota Dexterity Test (dating back to 1931, 'turning' subtest). This, however, is ill standardized, may be time-consuming, and has poor normative data. A timed-revised form of the turning subtest (MTTrf) is presented. Age-related norms and test-retest reliability were computed. Sixty-four healthy individuals, 24-79 years, comprising 34 women, were required to pick up 60 small plastic disks from wells, rotate each disk, and transfer it to the other hand, which must replace it, as quickly as possible. Two trials were requested for each hand (ABBA sequence). The average time (seconds) across the 4 trials gave the test score. Participants were grouped (CART algorithm) into 3 statistically distinct (P<0.05) age×score strata, with cutoff 53+ and 73+ years, and tested at baseline and after 1 week. Test-retest reliability was measured both as consistency [intraclass correlation coefficient (ICCs) model 2.1] and as agreement (Bland-Altman plot). From the ICCs, the individual test-retest minimal real difference (in seconds) was computed. The whole MTTrf took less than 4 min to administer. Baseline scores ranged from 40 to 78 s. The ICCs ranged from 0.45 to 0.81 and the minimal real difference ranged from 6.68 to 13.40 s across the age groups. Fifty-nine out of 64 observations (92%) fell within the confidence limits of the Bland-Altman plot. The MTTrf is a reliable and practical test of bimanual coordination. It may be a useful addition to protocols of manual testing in occupational therapy.

Mirror Movements After Stroke Suggest Facilitation From Nonprimary Motor Cortex: A Case Presentation.

When stroke occurs in adulthood, mirror movements (MMs; involuntary movements occurring in 1 hand when performing unilateral movements with the contralateral hand) in the paretic hand rarely occur. We present a case of an apparently healthy 54-year-old man presenting with MMs in his left (nondominant) hand. Further evaluation revealed diminished strength and dexterity in left hand, increased spinal excitability, decreased corticospinal excitability, occurrence of ipsilateral motor responses, enlarged cortical motor representation, and imaging findings consistent with a previously undiagnosed right-subcortical stroke. MMs and ipsilateral motor responses may reflect the increased spinal motor neurons' excitability sustained by the spared nonprimary ipsilesional motor areas.

Funding Medical Research Projects: Taking into Account Referees' Severity and Consistency through Many-Faceted Rasch Modeling of Projects' Scores.

The funding policy of research projects often relies on scores assigned by a panel of experts (referees). The non-linear nature of raw scores and the severity and inconsistency of individual raters may generate unfair numeric project rankings. Rasch measurement (many-facets version, MFRM) provides a valid alternative to scoring. MFRM was applied to the scores achieved by 75 research projects on multiple sclerosis sent in response to a previous annual call by FISM-Italian Foundation for Multiple Sclerosis. This allowed to simulate, a posteriori, the impact of MFRM on the funding scenario. The applications were each scored by 2 to 4 independent referees (total = 131) on a 10-item, 0-3 rating scale called FISM-ProQual-P. The rotation plan assured "connection" of all pairs of projects through at least 1 shared referee.The questionnaire fulfilled satisfactorily the stringent criteria of Rasch measurement for psychometric quality (unidimensionality, reliability and data-model fit). Arbitrarily, 2 acceptability thresholds were set at a raw score of 21/30 and at the equivalent Rasch measure of 61.5/100, respectively. When the cut-off was switched from score to measure 8 out of 18 acceptable projects had to be rejected, while 15 rejected projects became eligible for funding. Some referees, of various severity, were grossly inconsistent (z-std fit indexes less than -1.9 or greater than 1.9). The FISM-ProQual-P questionnaire seems a valid and reliable scale. MFRM may help the decision-making process for allocating funds to MS research projects but also in other fields. In repeated assessment exercises it can help the selection of reliable referees. Their severity can be steadily calibrated, thus obviating the need to connect them with other referees assessing the same projects.

Surgical leg rotation: cortical neuroplasticity assessed through brain mapping using transcranial magnetic stimulation.

Rotationplasty (Borggreve-Van Nes operation) is a rare limb salvage procedure, most often applied to children presenting with sarcoma of the distal femur. In type A1 operation, the distal thigh is removed and the proximal tibia is axially rotated by 180°, remodeled, grafted onto the femoral stump, and then prosthetized. The neurovascular bundle is spared. The rotated ankle then works as a knee. The foot plantar and dorsal flexors act as knee extensors and flexors, respectively. Functional results may be excellent. Cortical neuroplasticity was studied in three men (30-31 years) who were operated on the left lower limb at ages between 7 and 11 years and were fully autonomous with a custom-made prosthesis, as well as in three age-sex matched controls. The scalp stimulation coordinates, matching the patients' brain MRI spots, were digitized through a 'neuronavigation' optoelectronic system, in order to guide the transcranial magnetic stimulation coil, thus ensuring spatial precision during the procedure. Through transcranial magnetic stimulation driven by neuronavigation, the cortical representations of the contralateral soleus and vastus medialis muscles were studied in terms of amplitude of motor evoked potentials (MEPs) and centering and width of the cortical areas from which the potentials could be evoked. Map centering on either hemisphere did not differ substantially across muscles and participants. In the operated patients, MEP amplitudes, the area from which MEPs could be evoked, and their product (volume) were larger for the muscles of the unaffected side compared with both the rotated soleus muscle (average effect size 0.75) and the muscles of healthy controls (average effect size 0.89). In controls, right-left differences showed an effect size of 0.38. In no case did the comparisons reach statistical significance (P>0.25). Nevertheless, the results seem consistent with cortical plasticity reflecting strengthening of the unaffected leg and a combination of cross-education and skill training of the rotated leg.

Electromyographic latency of postural evoked responses from the leg muscles during EquiTest Computerised Dynamic Posturography: Reference data on healthy subjects.

No normative data are available for the latencies of the EMG signals from the ankle muscles in response to sudden sagittal tilt (toes-UP or toes-DOWN) or shift (shift-FOR or shift-BACK) of the support surface during standing. In this study the postural evoked response (PER) paradigm on the EquiTest™ force platform was applied to 31 healthy adults (18 women and 13 men; mean age 29 years). The EMG latencies (PEREMG) were computed both through the standard manual procedure and through a specially designed automated algorithm. The manually computed PEREMG onset yielded a 95% tolerance interval between 82ms and 148ms after toes-UP perturbation, between 93ms and 182ms after toes-DOWN perturbation, between 67ms and 107ms after shift-BACK perturbation, and between 73ms and 113ms after shift-FOR perturbation. When comparing the two methods, paired t-tests showed no significant mean difference (Bonferroni-adjusted p-values ranged from 0.440 to 1.000) and all Bland-Altman plots included zero difference within the limits of agreement. Therefore, the manual and the automated methods appear to be sufficiently consistent. These results foster the clinical application of PEREMG testing on the EquiTest platform.

Walk ratio (step length/cadence) as a summary index of neuromotor control of gait: application to multiple sclerosis.

In healthy adults, the step length/cadence ratio [walk ratio (WR) in mm/(steps/min) and normalized for height] is known to be constant around 6.5 mm/(step/min). It is a speed-independent index of the overall neuromotor gait control, in as much as it reflects energy expenditure, balance, between-step variability, and attentional demand. The speed independence of the WR in patients with multiple sclerosis (MS), and its capacity to discriminate (a) across patients with MS and controls and (b) among disability levels in MS were tested. The WR was computed in 30 outpatients with MS [20 women, 10 men; Extended Disability Status Scale (potential range: 0-10, observed median 3.5, range 2.5-5.0)] walking at free speed (range: 0.43-1.67 ms), and in 30 healthy controls (20 women, 10 men) at free and slow speed (range: 0.55-1.67 ms). The WR was 6.38±0.66 in controls versus 5.36±0.86 in patients with MS (P<0.000), independent of age, sex, and walking speed. The WR was 5.95±0.69 and 4.90±0.70 in patients with an Extended Disability Status Scale score (P<0.001) below or above the median, respectively, independent of the disease duration (P<0.000). In patients with MS, the WR is a disability-sensitive index of neuromotor control of gait, and thus a promising outcome measure for treatments aimed at improving motor coordination.

Generic ABILHAND questionnaire can measure manual ability across a variety of motor impairments.

ABILHAND is, in its original version, a 46-item, 4-level questionnaire. It measures the difficulty perceived by patients with rheumatoid arthritis as they do various daily manual tasks. ABILHAND was originally built through Rasch analysis. In a later study, it was simplified to a generic 23-item, three-level questionnaire, showing both cross-cultural (Belgium vs. Italy) and cross-impairment (rheumatoid arthritis vs. stroke) validity. Later research returned to the development of impairment-specific versions, with modified item sets and levels. Each version has its own Rasch-derived item difficulty calibrations, which are required to extract the patient's measure from the individual string of responses, through computerized algorithms. All of these hamper the practical application of the scale in rehabilitation units, where patients with diverse conditions may share similar impairments and treatment approaches. In this study through Rasch analysis the 'generic' scale was applied to 126 chronic patients with different upper limb impairments, and to 24 healthy controls. It was supported that the generic questionnaire remains valid across a variety of motor impairments. To further facilitate clinical application, a normative cut-off (>79 of 100) is suggested. Rasch-based item calibrations are provided together with a software routine designed to calculate, on individual patients, linear 0-100 measures and error estimates from the raw scores.