Content overlap of 91 dystonia symptoms among the seven most commonly used cervical dystonia scales.

INTRODUCTION: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions. Cervical dystonia (CD) is the most common focal dystonia. There are several instruments assessing the symptoms of CD. However, different scales assess different features which may lead to poor patient evaluation. AIM: The aim of the study was to evaluate the degree of overlap of most often used CD rating scales identified by the literature review. METHODS: A thorough search of the Medline database was conducted in September 2021. Then the frequency of each scale was calculated, and 7 most common scales were included in the content overlap analysis using Jaccard index (0 - no overlap, 1 - full overlap). RESULTS: Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), Tsui score, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Cervical Dystonia Impact Profile 58 (CDIP-58), Craniocervical Dystonia Questionnaire 24 (CDQ-24), Cervical Dystonia Severity Rating Scale (CDSS), Cervical Dystonia Severity Rating Scale (DDS) and The Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest) were the most common scales. 91 CD symptoms were distinguished from 134 items used in the scales. The mean overlap among all scales was 0.17. 52 (62%) symptoms were examined by more than one scale. The CIDP-58 captured the highest number of symptoms (63.0%), while the CDSS captured the lowest number (8.0%). None of the symptoms were examined by seven instruments. CONCLUSIONS: There was a very weak overlap among scales. High inconsistency between the scales may lead to highly different dystonia severity assessment in clinical practice. Thus, the instruments should be combined.

A Narrative Review on Multi-Domain Instrumental Approaches to Evaluate Neuromotor Function in Rehabilitation.

In clinical scenarios, the use of biomedical sensors, devices and multi-parameter assessments is fundamental to provide a comprehensive portrait of patients' state, in order to adapt and personalize rehabilitation interventions and support clinical decision-making. However, there is a huge gap between the potential of the multidomain techniques available and the limited practical use that is made in the clinical scenario. This paper reviews the current state-of-the-art and provides insights into future directions of multi-domain instrumental approaches in the clinical assessment of patients involved in neuromotor rehabilitation. We also summarize the main achievements and challenges of using multi-domain approaches in the assessment of rehabilitation for various neurological disorders affecting motor functions. Our results showed that multi-domain approaches combine information and measurements from different tools and biological signals, such as kinematics, electromyography (EMG), electroencephalography (EEG), near-infrared spectroscopy (NIRS), and clinical scales, to provide a comprehensive and objective evaluation of patients' state and recovery. This multi-domain approach permits the progress of research in clinical and rehabilitative practice and the understanding of the pathophysiological changes occurring during and after rehabilitation. We discuss the potential benefits and limitations of multi-domain approaches for clinical decision-making, personalized therapy, and prognosis. We conclude by highlighting the need for more standardized methods, validation studies, and the integration of multi-domain approaches in clinical practice and research.

Perfil de personalidad en el trastorno del espectro autista mediante el Inventario Multifásico de Personalidad de Minnesota / Personality profiles in autism spectrum disorder obtained with the Minnesota Multiphasic Personality Inventory (MMPI)

Desde la publicación de DSM-5, se ha vuelto más importante llevar a cabo un diagnóstico diferencial para distinguir a las personas con TEA de los trastornos de personalidad del grupo C. El objetivo de la presente investigación fue identificar un perfil de personalidad de sujetos con trastorno del espectro autista (TEA) utilizando el Inventario de Personalidad Multifásico de Minnesota (MMPI) para llevar a cabo dicho diagnóstico diferencial. La muestra del estudio consistió en un total de 178 sujetos divididos en cuatro grupos de comparación. El grupo TEA obtuvo un perfil de personalidad MMPI con un código característico 2-0 que era específico para esta muestra de personas con TEA leve, y puntuaciones más altas en las escalas 6, 7 y 8 en relación con las otras puntuaciones de la escala. Se identificó un perfil de personalidad MMPI específico para los sujetos con TEA que diferenció a este grupo de los otros grupos estudiados. (AU)

Since the publication of DSM-5, it has become more important to carry out a differential diagnosis to distinguish people with autism spectrum disorder (ASD) from cluster C personality disorders. The aim of the present research study was to identify a personality profile of adults with ASD using the Minnesota Multiphasic Personality Inventory (MMPI) in order to carry out this differential diagnosis. The study sample consisted of a total of 178 subjects divided into four groups for comparison purposes. The ASD group obtained a MMPI personality profile with a characteristic 2-0 code that was specific to this sample of people with mild ASD, and higher scores in scales 6, 7 and 8 relative to the other scale scores. A specific MMPI personality profile was identified for ASD subjects, which differentiated this group from the other groups studied. (AU)

The dilemma between milestones of progression versus clinical scales in Parkinson's disease.

There are significant challenges in accurately documenting the progression of Parkinson's disease (PD). The disease course is highly heterogeneous, there are no validated biomarkers, and we are reliant on repeated clinical measures to assess disease state over time. Yet, the ability to chart disease progression accurately is vital in both observational and interventional study designs, where reliable measures are critical to determine whether an outcome has been met. In this chapter, we first discuss the natural history of PD, including the spectrum of clinical presentation and expected developments through the course of the disease. We then explore in detail the current strategies for measuring disease progression, which can be broadly divided into: (i) the use of quantitative clinical scales; and (ii) determination of the onset time of key milestones. We discuss the strengths and limitations of these approaches for use in clinical trials, with a particular focus on disease modification trials. The selection of outcome measures for a particular study will depend on multiple factors, but trial duration is an important determinant. Milestones are reached over a course of years rather than months, and hence clinical scales with sensitivity to change are needed for short-term studies. However, milestones represent important markers of disease stage which are not confounded by symptomatic therapies and are of critical relevance to the patient. Prolonged but low intensity follow-up beyond a limited period of treatment with a putative disease-modifying agent may allow milestones to be incorporated into evaluation of efficacy in a practical and cost-effective way.

Progression of Clinical and Eye Movement Markers in Preataxic Carriers of Machado-Joseph Disease.

BACKGROUND: Little is known about preclinical stages of Machado-Joseph disease, a polyglutamine disorder characterized by progressive adult-onset ataxia. OBJECTIVE: We aimed to describe the longitudinal progression of clinical and oculomotor variables in the preataxic phase of disease. METHODS: Carriers and noncarriers were assessed at three visits. Preataxic carriers (Scale for Assessment and Rating of Ataxia score < 3) expected to start ataxia in ≤4 years were considered near onset (PAN). Progressions of ataxic and preataxic carriers, considering status at the end of the study, were described according to the start (or its prediction) of gait ataxia (TimeToAfterOnset) and according to the study time. RESULTS: A total of 35 ataxics, 38 preataxics, and 22 noncarriers were included. The "TimeToAfterOnset" timeline showed that Neurological Examination Scale for Spinocerebellar Ataxias (NESSCA; effect size, 0.09), Inventory of Non-Ataxia Symptoms (INAS0.07), and the vestibulo-ocular reflex gain (0.12) progressed in preataxic carriers, and that most slopes accelerate in PAN, turning similar to those of ataxics. In the study time, NESSCA (1.36) and vertical pursuit gain (1.17) significantly worsened in PAN, and 6 of 11 PANs converted to ataxia. For a clinical trial with 80% power and 2-year duration, 57 PANs are needed in each study arm to detect a 50% reduction in the conversion rate. CONCLUSIONS: NESSCA, INAS, vestibulo-ocular reflex, and vertical pursuit gains significantly worsened in the preataxic phase. The "TimeToAfterOnset" timeline unveiled that slopes of most variables are small in preataxics but increase and reach the ataxic slopes from 4 years before the onset of ataxia. For future trials in preataxic carriers, we recommend recruiting PANs and using the conversion rate as the primary outcome. © 2022 International Parkinson and Movement Disorder Society.

Resting-state electroencephalogram microstate to evaluate post-stroke rehabilitation and associate with clinical scales.

Introduction: Stroke is usually accompanied by a range of complications, like post-stroke motor disorders. So far, its evaluation of motor function is developed on clinical scales, such as Fugl-Meyer Assessment (FMA), Instrumental Activities of Daily Living (IADL), etc. These scale results from behavior and kinematic assessment are inevitably influenced by subjective factors, like the experience of patients and doctors, lacking neurological correlations and evidence. Methods: This paper applied a microstate model based on modified k-means clustering to analyze 64-channel electroencephalogram (EEG) from 12 stroke patients and 12 healthy volunteers, respectively, to explore the feasibility of applying microstate analysis to stroke patients. We aimed at finding some possible differences between stroke and healthy individuals in resting-state EEG microstate features. We further explored the correlations between EEG microstate features and scales within the stroke group. Results and discussion: By statistical analysis, we obtained significant differences in EEG microstate features between the stroke and healthy groups and significant correlations between microstate features and scales within the stroke group. These results might provide some neurological evidence and correlations in the perspective of EEG microstate analysis for post-stroke rehabilitation and evaluation of motor disorders. Our work suggests that microstate analysis of resting-state EEG is a promising method to assist clinical and assessment applications.

Responsiveness of UMSARS and other clinical measures in a longitudinal structured care clinic for multiple system atrophy.

PURPOSE: As understanding of multiple system atrophy (MSA) pathophysiology improves, clinical trials of disease-modifying therapies are starting. Outcome measures responsive to disease progression will be critical, but the United MSA Rating Scale (UMSARS) has limitations. The MSA multidisciplinary clinic at the University of Texas Southwestern is a longitudinal clinic with structured assessments performed at fixed time intervals. The objective of this study was to evaluate the performance of clinical measures in assessing MSA progression over time. METHODS: Data from 73 subjects with clinically diagnosed MSA were analyzed using repeated measures correlation models. Observations were made every 4 months, with up to 3 years of data included for each patient. RESULTS: UMSARS-I and UMSARS-II correlated positively with the MSA Quality of Life (QOL) scale. The rate of change was 3.12 points per year (ppy) for UMSARS-I and 5.55 ppy for UMSARS-II. Some individual UMSARS questions contributed more significantly than others to overall UMSARS rate of change. Based on this finding, and using repeated measures correlations between question combinations and QOL, an optimization of UMSARS parts I and II was curated. The amended UMSARS-I included 8 of the 12 subquestions, and the amended UMSARS-II included 10 of the 14 subquestions. CONCLUSIONS: Data from a longitudinal MSA clinic allows better characterization of the performance of UMSARS as a clinical outcome measure. A curated set of UMSARS questions appears more responsive to change and accounts for correlation with QOL, and could be the starting point for an improved MSA outcome measure.

Measurement tools to assess activities of daily living in patients with Parkinson's disease: A systematic review.

Introduction: Parkinson's disease (PD) is associated with a progressive inability to accomplish essential activities of daily living (ADL) resulting in a loss of autonomy and quality of life. Accurate measurement of ADL in PD is important to monitor disease progression and optimize care. Despite its relevance, it is still unclear which measurement instruments are the most suitable for evaluating ADL in people with PD. Objective: To identify and critically appraise which measurement instruments have been used to assess ADL in PD. Methods: A systematic review was conducted using the databases CENTRAL, MEDLINE, and PEDro from their inception to October 2021 to identify all observational and experimental studies conducted in PD or atypical parkinsonism that included an ADL assessment. Titles and abstracts were screened independently by two authors. The clinimetric properties of the measurement instruments were assessed, and the instruments were classified as "recommended," "suggested," or "listed." Results: A total of 129 articles were included, with 37 measurement instruments used. The Unified Parkinson's Disease Rating Scale (UPDRS), the Schwab & England ADL scale (S&E scale), the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Barthel Index, the Lawton-Brody Instrumental Activities of Daily Living Scale, the Functional Independence Measure (FIM) and the Alzheimer's Disease Cooperative Study - ADL (ADCS-ADL) scale were the seven most frequently cited measurement instruments. Of these, only two included an assessment of basic and instrumental ADL. Conclusion: MDS-UPDRS and the S&E scale were the only two scales that could be classified as recommended. For the MDS-UPDRS, either the full version or only Part II, which is focused on ADL, can be used. Future studies should explore the use of wearable devices to assess ADL remotely and more continuously.

Infusion-related side-effects during convection enhanced delivery for brainstem-diffuse midline glioma/diffuse intrinsic pontine glioma.

INTRODUCTION: Side-effects during convection enhanced delivery (CED) are poorly understood. We intended to determine the frequency of side-effects during brain stem infusion and determine risk factors for side-effects persisting longer than 24 h. METHODS: Children with a radiological diagnosis of brain stem diffuse midline glioma/Diffuse Intrinsic Pontine Glioma were treated on compassionate grounds with awake infusion of carboplatin and sodium valproate into the brain stem using the 4-catheter (2 trans-cerebellar 2 trans-frontal) chronic, intermittent Renishaw Drug Delivery System. We used change in the Pontine Neurological Observation Score (PONScore), a standardised neurological assessment tool, to identify side-effects during infusion. Recovery was determined by retrospective chart review. RESULTS: 55 infusions were performed in 8 children (3-11 years). Mean PONScore increased during infusion from 3.3 to 5.7 (p-value > 0.001). One hundred and fifty-seven infusion-related side-effects were identified including headache (33/157) and limb weakness (49/157). Fifty-four side-effects persisted > 24 h. Side-effects that had occurred during a previous infusion and those that occurred during infusion via trans-cerebellar catheters were more likely to be persistent with OR 2.333 (95% CI 1.094-4.976; p-value = 0.028) and 2.155 (1.029-4.513; p-value = 0.042) respectively. If infusion was stopped or titrated at onset rather than continued, the side-effect was less likely to persist > 24 h, OR 0.473 (95% CI 0.177-0.948; p-value = 0.037). Most side-effects developed within the first three millilitre of infusion. CONCLUSIONS: Side-effects during brainstem infusion are common, can be transient or persist longer than 24 h. Neurological injury during infusion may be time dependent and accumulative rather than volume dependent.

Foot Assessment Clinical Scales in Charcot-Marie-Tooth Patients: A Scoping Review.

Introduction: Charcot-Marie-Tooth disease (CMT) is a slow and progressive peripheral motor sensory neuropathy frequently associated with the cavo-varus foot deformity. We conducted a scoping review on the clinical scales used to assess foot deviations in CMT patients and analyzed their metric properties. Evidence Acquisition: A first search was conducted to retrieve all scales used to assess foot characteristics in CMT patients from the Medline, Web of Science, Google Scholar, Cochrane, and PEDro databases. A second search was conducted to include all studies that evaluated the metric properties of such identified scales from the same databases. We followed the methodologic guidelines specific for scoping reviews and used the PICO framework to set the eligibility criteria. Two independent investigators screened all papers. Evidence Synthesis: The first search found 724 papers. Of these, 41 were included, using six different scales: "Foot Posture Index" (FPI), "Foot Function Index", "Maryland Foot Score", "American Orthopedic Foot & Ankle Society's Hindfoot Evaluation Scale", "Foot Health Status Questionnaire", Wicart-Seringe grade. The second search produced 259 papers. Of these, 49 regarding the metric properties of these scales were included. We presented and analyzed the properties of all identified scales in terms of developmental history, clinical characteristics (domains, items, scores), metric characteristics (uni-dimensionality, inter- and intra-rater reliability, concurrent validity, responsiveness), and operational characteristics (normative values, manual availability, learning time and assessors' characteristics). Conclusions: Our results suggested the adoption of the six-item version of the FPI scale (FPI-6) for foot assessment in the CMT population, with scoring provided by Rasch Analysis. This scale has demonstrated high applicability in different cohorts after a short training period for clinicians, along with good psychometric properties. FPI-6 can help health professionals to assess foot deformity in CMT patients over the years.

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study.

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients.

Brain magnetic resonance imaging and severity of neurological disease in Wilson's disease - the neuroradiological correlations.

INTRODUCTION: Wilson's disease (WD) is a genetic disorder with pathological copper accumulation and associated clinical symptoms in various organs, particularly the liver and brain. Neurological disease is assessed with the clinical Unified Wilson's Disease Rating Scale (UWDRS). There is a lack of quantitative objective markers evaluating brain involvement. Recently, a semiquantitative brain magnetic resonance imaging (MRI) scale has been proposed, which combines acute toxicity and chronic damage measures into a total score. The relationship between MRI brain pathology and the MRI scale with disease form and neurological severity was studied in a large cohort. METHODS: We retrospectively assessed 100 newly diagnosed treatment-naïve patients with WD with respect to brain MRI pathology and MRI scores (acute toxicity, chronic damage, and total) and analyzed the relationship with disease form and UWDRS part II (functional impairment) and part III (neurological deficits) scores. RESULTS: Most patients had the neurological form of WD (55%) followed by hepatic (31%) and presymptomatic (14%). MRI examination revealed WD-typical abnormalities in 56% of patients, with higher pathology rates in neurological cases (83%) than in hepatic (29%) and presymptomatic (7%) cases. UWDRS part II and III scores correlated with the MRI acute toxicity score (r = 0.55 and 0.55, respectively), chronic damage score (r = 0.39 and 0.45), and total score (0.45 and 0.52) (all P < 0.01). CONCLUSIONS: Brain MRI changes may be present even in patients without neurological symptoms, although not frequently. The semiquantitative MRI scale correlated with the UWDRS and appears to be a complementary tool for severity of brain injury assessment in WD patients.

Circulating Endocannabinoids in Huntington's Disease: An Exploratory Cross-Sectional Study.

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive and behavioral deficits. Some evidence suggests that the endocannabinoid system participates in the pathophysiology of HD. We conducted a cross-sectional study comparing plasma levels of anandamide and 2-arachidonoylglycerol in manifest HD gene-expansion carriers (HDGEC) and healthy controls, finding no difference in endocannabinoid levels between the groups. Correlations between endocannabinoid levels and clinical scales (Mini-Mental State Examination, Hospital Anxiety and Depression Scale, Unified Huntington Disease Rating Scale) were non-significant. We found a significant association between body mass index and anandamide levels in healthy controls but not in HDGEC.

Quantifying the Changes of Mechanical and Electrical Properties of Paralyzed Muscle in Survivors With Cervical Spinal Cord Injury.

Background: Survivors with spinal cord injury (SCI) have neuromuscular deficits such as muscle atrophy that lead to functional impairments. This study utilized myotonometry and electrical impedance myography (EIM) to quantitatively evaluate the changes in muscle mechanical properties and compositions after SCI. Methods: This study adopted a cross-sectional design. Eighteen SCI patients and 18 healthy individuals were recruited. The outcome measures were: (1) The myotonometer measured muscle mechanical parameters of oscillation frequency (freq), dynamic stiffness, logarithmic decrement (decr), mechanical stress relaxation time, and indication of creep. (2) The electrical impedance myography measured parameters of resistance (R), reactance (X), and phase angle (θ). (3) muscle strength (maxForce); (4) clinical scales of Manual Muscle Testing (MMT) and modified Ashworth scale (MAS). All outcome measures were compared between the bicep brachii muscle of the weaker side of the SCI group and the non-dominate side of the healthy group. Correlation analysis was performed at quantitative data and clinical scales. Results: Freq, stiffness, and maxForce of the SCI group were significantly lower (p < 0.01) than those of the healthy control. The relaxation time and creep were significantly higher in the SCI group than in the control group. Significant differences of R and Xc were observed between the two groups. Significant correlation was observed between freq, stiffness, and months past injury, and between Xc, creep, and relaxation time. Conclusions: Reduced muscle tone and stiffness might relate to muscle atrophy, and higher relax time and creep may be caused by poor contractile ability. The changes in EIM parameters could indirectly reflect the muscle cell size, and fatty and connective tissue alterations. These findings support the feasibility of myotonometer and EIM to quantify muscle mechanical and intrinsic properties in patients with SCI. The results could facilitate the understanding of neuromuscular changes that are related to functional impairments.

Biomarkers for alcohol abuse/withdrawal and their association with clinical scales and temptation to drink. A prospective pilot study during 4-week residential rehabilitation.

A bulk of evidence in the field of translational medicine applied to clinical toxicology and rehabilitation has highlighted the possibility of using biomarkers as a support in the diagnosis of alcohol-related diseases and in monitoring of alcohol withdrawal. In a cohort of 55 subjects admitted to a 4-week residential rehabilitation period for alcohol detoxification, we applied a complementary approach correlating novel and conventional peripheral blood and urine parameters in combination with clinical and functional evaluation, contextually considered with the patient's history. Biomarkers of oxidative, inflammatory, hepatic, and neurochemical effects paralleled by alcohol craving and clinical scale measurements were determined at two specific time points, i.e., admission and discharge. Concerning the post-discharge assessment (i.e., relapse evaluation one month after discharge), a follow-up oral interview during a clinical examination was applied to evaluate alcohol abstinence.Selected biomarkers, i.e., MCP1, F2-IsoPs, and SOD1, were altered in chronic alcoholics at admission, and then showed a clearly changing trend during hospitalization. Our findings demonstrated that these specific non-traditional biomarkers, measured together with more conventional ones (e.g., CDT, EtG, IL8, ALT, AST, GGT), could represent novel key parameters for monitoring alcohol use disorders and withdrawal, being also suggestive of the complexity of the psychoneuroimmune response to alcohol. A general improvement in psychological functioning (i.e., decreases in anxiety, depression, and psychological distress) was also revealed during the 4-week rehabilitation treatment, paralleled by an increase of well-being and positive changes in terms of scores. Moreover, a positive association between SOD1 and drink craving at admission was evidenced. Notably, both SOD1 and well-being displayed a significant relation with lower risk of alcohol relapse one month after discharge, indicating that SOD1 is a good predictor of reduced relapse probability. This 4-week residential rehabilitation protocol represents a sound strategy enabling identification of alcohol use disorders and monitoring of alcohol addiction state and withdrawal. However, it has to be emphasized that results derived from this pilot study need to be extensively validated in large and independent cohorts of subjects.

Developing Clinically Relevant Scales of Breathy and Rough Voice Quality.

The most common measurement tools used in the perceptual evaluation of voice quality yield ordinal data and thus do not support the establishment of mathematical relationships among different measurement values. This makes their interpretation challenging. Among the many desirable features of any psychophysical measurement tool is the ability to quantify the difference between two or more measurements and the ability to interpret the measurements in a manner that is related to the experience of the observer. The former allows one to compare among measurements using simple mathematics, while the latter allows that comparison to be interpreted in constructive ways. In this paper we describe the development of standard measurement scales for two dimensions of voice quality, following an approach that has been applied successfully to the perception of loudness. The scales follow step-by-step procedures used to develop the sone scale of loudness, which ties physical units to the perceptual estimates of loudness magnitude. Goals of the current work include development of analogous scales for the perception of breathy and rough voice qualities. First, the relationship between perceived voice quality and physical units were established using single-variable matching tasks. Second, the relationship between a change in physical units from the single-variable matching tasks and perceived voice quality magnitude were established using magnitude estimation tasks. Third, single reference points were identified on breathy and rough continuums. Finally, all points on the newly established voice quality continuums were rescaled relative to these arbitrary reference points. The proposed breathiness and roughness scales result in ratio-level data with standard measurement units that support quantitative comparisons of perceptual judgments. Such judgments can be used, for example, to compare magnitude of change pre- and post-treatment.

Early CSF Biomarkers and Late Functional Outcomes in Spinal Cord Injury. A Pilot Study.

Although, biomarkers are regarded as an important tool for monitoring injury severity and treatment efficacy, and for predicting clinical evolution in many neurological diseases and disorders including spinal cord injury, there is still a lack of reliable biomarkers for the assessment of clinical course and patient outcome. In this study, a biological dataset of 60 cytokines/chemokines, growth factorsm and intracellular and extracellular matrix proteins, analyzed in CSF within 24 h of injury, was used for correlation analysis with the clinical dataset of the same patients. A heat map was generated of positive and negative correlations between biomarkers and clinical rating scale scores at discharge, and between biomarkers and changes in clinical scores during the observation period. Using very stringent statistical criteria, we found 10 molecules which correlated with clinical scores at discharge, and five molecules, which correlated with changes in clinical scores. The proposed methodology may be useful for generating hypotheses regarding "predictive" and "treatment effectiveness" biomarkers, thereby suggesting potential candidates for disease-modifying therapies using a "bed-to-bench" approach.

Development of a clinical scale for assessment of patients with diffuse intrinsic pontine glioma (DIPG) receiving experimental therapy: the PONScore.

PURPOSE: Monitoring neurological side-effects in experimental therapy for diffuse intrinsic pontine glioma (DIPG) can be challenging. We aimed to develop a neurological scale that could be used by non-specialists to quantify neurological changes during experimental treatment of DIPG. METHODS: We developed the Pontine Observational Neurological Score (PONScore) to measure signs and symptoms of DIPG by adapting validated assessment scales of neurological signs and symptoms in children. We developed a prototype score, taught it to paediatric intensive care nursing staff, who used the Score to assess children receiving awake pontine infusion of chemotherapy for treatment of DIPG. We used their feedback to develop the PONScore. Points are allocated for headache, ophthalmoplegia, facial and tongue weakness, dysarthria, paraesthesia, limb weakness and dysmetria with increasing scores reflecting increasing disability. The PONScore was administered every hour during awake pontine infusion. Correlation and agreement calculations between nursing staff, as non-specialists, and a specialist rater were performed in 30 infusions in 6 children (aged 8-11). Changes in PONScore versus volume of infusion are described in a further 55 infusions in 8 children (aged 3-11). RESULTS: The PONScore demonstrated excellent intra-rater reliability with an intra-class co-efficient of 0.98 (95% CI 0.97-0.99; p-value < 0.001) between a specialist and non-specialist raters with strong correlation between scores and a Spearman correlation coefficient of 0.985 (p < 0.001). PONScores increased from 3.3 to 5.7 (p-value < 0.001) during infusion reflecting accumulation of neurological signs and symptoms during infusion. CONCLUSIONS: We describe a novel neurological scale that can be used by non-specialists to describe acute neurological changes in children receiving experimental therapy for DIPG. Prospective validation as part of a clinical trial is required.

Semiquantitative Scale for Assessing Brain MRI Abnormalities in Wilson Disease: A Validation Study.

BACKGROUND: MRI is a sensitive method for the assessment of brain abnormalities in Wilson disease, that is, T2 hyperintensities, T2 hypointensities, and atrophy, but a validated scoring system for the classification of radiological severity is lacking. The objective of this study was to develop and validate a brain MRI visual rating scale for Wilson disease. METHODS: The proposed Wilson disease brain MRI severity scale consists of acute toxicity and chronic damage subscores from predefined structures. The former, calculated by summing scores of T2 hyperintensities (excluding cavitation), is likely to be partially reversible with treatment. The latter, representing the sum of scores of T2 hypointensities and brain atrophy, reflects pathology that is not readily reversible. Validation was performed on MRI scans acquired using 1.5T system from 39 Wilson disease patients examined at baseline and after 24 months on anticopper treatment. Intraclass correlation coefficients of 5 ratings from 3 raters were calculated. Temporal evolution of the MRI severity score and its association with clinical severity, assessed using the Unified Wilson Disease Rating Scale part III, was calculated. RESULTS: Intrarater and interrater agreement were good (r > 0.93; P < 0.001; and r > 0.74; P < 0.001, respectively). In neurologic Wilson disease patients, the total MRI severity score improved over 2 years (P = 0.032), mainly because of reduced acute toxicity (P = 0.0015), whereas the chronic damage score deteriorated (P = 0.035). Unified Wilson Disease Rating Scale part III score was positively associated with chronic damage and total score at baseline (P = 0.005 and P = 0.003, respectively) and in month 24 (P < 0.001 and P = 0.001, respectively). CONCLUSIONS: The Wilson disease brain MRI severity scale is a simple, reliable, and valid instrument that allows semiquantitative assessment of radiological Wilson disease severity. © 2020 International Parkinson and Movement Disorder Society.