Background

Accurate assessment of mobility is critical for the clinical management of people with MS (pwMS), and as a biomarker in clinical trials. Small, body worn sensors hold the possibility to provide greater reliability and accuracy than existing clinical tools. Since these sensors can provide a variety of metrics, they have the potential to provide a richer and more holistic assessment of gait impairment than existing clinical tools. Paradoxically however, the sheer number and partial overlap between the metrics provided by these sensors has led to confusion and impeded their clinical translation and acceptability.

Objectives

This study in the first to establish a data driven conceptual model of factors contributing to gait disturbance in pwMS using data obtained from body worn sensors. We then tested the model for its ability to quantify gait differences across different levels of disability and clinical courses of MS.

Methods

We studied 114 pwMS, divided in three groups according to their Expanded Disability Status Scale (EDSS) score. (mild, EDSS ≤ 3.5, moderate, 4.0 ≤ EDSS ≤ 5.5, and severe EDSS ≥ 6), as well as the clinical course of their illness (relapsing remitting or progressive), and 24 healthy controls. Gait was assessed with inertial sensors (OPAL, APDM), located on the lower shanks and on the lower back while they walked for 6 minutes at their self-selected speed along a 10-m path in a hospital corridor.

Results

Thirty-six metrics were initially computed from the sensor data. Twenty of these met quality criteria for exploratory factor analysis, which revealed a gait model consisting of five factors: rhythm/variability, pace, asymmetry, and forward and lateral dynamic balance. After confirming overall goodness with a confirmatory factor analysis, the model was used to investigate differences in gait features across pwMS with different levels of disability. We found significant alterations in rhythm/variability, asymmetry, and pace domains in the mild disability group, which further progressed in the moderate and severe disability group. Dynamic balance, conversely, appeared to be conserved in mild and moderate disability groups, only deteriorating in the severe disability group.

Conclusions

This model of gait in pwMS highlights clinically relevant and differential gait impairment across different clinical disease course and disability levels. The data can be obtained from small body worn sensors in a clinical setting. This approach has potential as an accurate and responsive clinical biomarker in clinical trials and more widely in clinical practise.

Background

Balo’s concentric sclerosis is often regarded as a rare variant of multiple sclerosis (MS) and is characterised by concentrically multi-layered ring-like lesions in the cerebral white matter. Despite pathological overlap with MS, the effect of disease modifying therapies is unclear.

The only existing case report of Alemtuzumab in Balo’s concentric sclerosis described a lack of clinical response in a patient with Balo’s concentric sclerosis who had previously not responded to corticosteroids, plasma exchange and cyclophosphamide. The authors did speculate that Alemtuzumab may have been more effective if started earlier in the disease process.

Objectives

We present the imaging and clinical outcomes of a patient with Balo’s concentric sclerosis who was successfully treated with Alemtuzumab over a period of 3 years.

Methods

A 54 year old nurse with no prior history of neurological symptoms presented with a 2 day history of expressive dysphasia and subacute onset of right hemiplegia. MRI of the brain revealed a large enhancing lesion in the white matter of the posterior temporal lobe measuring 29.5mm in maximal diameter with a complex layered enhancement pattern. There were also non-enhancing lesions present in the periventricular and deep white matter with an appearance typical of demyelination due to multiple sclerosis. CSF examination revealed positive oligoclonal bands. Anti-aquaporin-4 IgG and MOG-IgG were negative. A diagnosis of Balo’s concentric sclerosis was made, and she was treated with intravenous and oral steroids, followed by Alemtuzumab.

Results

Clinically her speech and weakness gradually improved and she is now symptom free. She has had no further relapses. Radiologically the Balo’s lesion ceased to enhance and reduced in size and T2 hyperintensity gradually. She has had no new or enlarging T2 lesions.

Conclusions

We present the second case report of the use of Alemtuzumab in Balo’s concentric sclerosis. Our patient has enjoyed a good outcome with resolution of symptoms, and a period of freedom from relapse and radiological activity. Alemtuzumab may be effective in the treatment of Balo’s concentric sclerosis if started early.

Background

Accurate assessment of mobility is critical for the clinical management of people with MS (pwMS), and as a biomarker in clinical trials. Small, body worn sensors hold the possibility to provide greater reliability and accuracy than existing clinical tools. Since these sensors can provide a variety of metrics, they have the potential to provide a richer and more holistic assessment of gait impairment than existing clinical tools. Paradoxically however, the sheer number and partial overlap between the metrics provided by these sensors has led to confusion and impeded their clinical translation and acceptability.

Objectives

This study in the first to establish a data driven conceptual model of factors contributing to gait disturbance in pwMS using data obtained from body worn sensors. We then tested the model for its ability to quantify gait differences across different levels of disability and clinical courses of MS.

Methods

We studied 114 pwMS, divided in three groups according to their Expanded Disability Status Scale (EDSS) score. (mild, EDSS ≤ 3.5, moderate, 4.0 ≤ EDSS ≤ 5.5, and severe EDSS ≥ 6), as well as the clinical course of their illness (relapsing remitting or progressive), and 24 healthy controls. Gait was assessed with inertial sensors (OPAL, APDM), located on the lower shanks and on the lower back while they walked for 6 minutes at their self-selected speed along a 10-m path in a hospital corridor.

Results

Thirty-six metrics were initially computed from the sensor data. Twenty of these met quality criteria for exploratory factor analysis, which revealed a gait model consisting of five factors: rhythm/variability, pace, asymmetry, and forward and lateral dynamic balance. After confirming overall goodness with a confirmatory factor analysis, the model was used to investigate differences in gait features across pwMS with different levels of disability. We found significant alterations in rhythm/variability, asymmetry, and pace domains in the mild disability group, which further progressed in the moderate and severe disability group. Dynamic balance, conversely, appeared to be conserved in mild and moderate disability groups, only deteriorating in the severe disability group.

Conclusions

This model of gait in pwMS highlights clinically relevant and differential gait impairment across different clinical disease course and disability levels. The data can be obtained from small body worn sensors in a clinical setting. This approach has potential as an accurate and responsive clinical biomarker in clinical trials and more widely in clinical practise.

Background

Balo’s concentric sclerosis is often regarded as a rare variant of multiple sclerosis (MS) and is characterised by concentrically multi-layered ring-like lesions in the cerebral white matter. Despite pathological overlap with MS, the effect of disease modifying therapies is unclear.

The only existing case report of Alemtuzumab in Balo’s concentric sclerosis described a lack of clinical response in a patient with Balo’s concentric sclerosis who had previously not responded to corticosteroids, plasma exchange and cyclophosphamide. The authors did speculate that Alemtuzumab may have been more effective if started earlier in the disease process.

Objectives

We present the imaging and clinical outcomes of a patient with Balo’s concentric sclerosis who was successfully treated with Alemtuzumab over a period of 3 years.

Methods

A 54 year old nurse with no prior history of neurological symptoms presented with a 2 day history of expressive dysphasia and subacute onset of right hemiplegia. MRI of the brain revealed a large enhancing lesion in the white matter of the posterior temporal lobe measuring 29.5mm in maximal diameter with a complex layered enhancement pattern. There were also non-enhancing lesions present in the periventricular and deep white matter with an appearance typical of demyelination due to multiple sclerosis. CSF examination revealed positive oligoclonal bands. Anti-aquaporin-4 IgG and MOG-IgG were negative. A diagnosis of Balo’s concentric sclerosis was made, and she was treated with intravenous and oral steroids, followed by Alemtuzumab.

Results

Clinically her speech and weakness gradually improved and she is now symptom free. She has had no further relapses. Radiologically the Balo’s lesion ceased to enhance and reduced in size and T2 hyperintensity gradually. She has had no new or enlarging T2 lesions.

Conclusions

We present the second case report of the use of Alemtuzumab in Balo’s concentric sclerosis. Our patient has enjoyed a good outcome with resolution of symptoms, and a period of freedom from relapse and radiological activity. Alemtuzumab may be effective in the treatment of Balo’s concentric sclerosis if started early.