031 Investigating motor evoked potentials as a biomarker for disease severity in hereditary spastic paraplegia

IntroductionHereditary spastic paraplegia (HSP) encompasses a diverse group of neurodegenerative disorders that results in significant disability with no curative or disease-modifying treatment. The lack of standardised biomarkers of disease severity has limited the evaluation of potential therapeutic agents. Our aim is to investigate motor evoked potentials (MEPs) as a marker of HSP disease severity.MethodsWe studied 21 subjects (10 male, 11 female; mean age 54.3±13.8 years) with a clinical diagnosis of HSP (10 SPG4, 4 SPG7, 1 SPG3A, 1 SPG 30, 5 genetically undetermined). All patients underwent transcranial magnetic stimulation to measure central motor conduction time (CMCT), resting motor threshold (rMT) and MEP amplitude from the tibialis anterior (TA), abductor hallucis (AH) and abductor digiti minimi (ADM). Clinical disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Pearson correlation coefficient was used to assess correlation between variables, significance was defined as P value<0.05.ResultsTA CMCT was prolonged in 16/21 subjects (76%). AH CMCT was absent in 3/18 subjects (16.7%) and prolonged in 9/18 subjects (50%). ADM CMCT was measured in 19 subjects; all were normal. There was no significant correlation between SPRS scores and MEP amplitude, rMT or CMCT for TA or AH. There was also no significant correlation between these MEP measures and disease duration or patient age. Subgroup analysis of SPG4 HSP (10 subjects) revealed significant correlation between TA and AH CMCT with disease duration (r=0.841, p=0.001; r=0.930, p=0.001) but not SPRS scores.ConclusionLower limb CMCT was absent or prolonged in the majority of subjects. Despite being potentially useful as a diagnostic biomarker for HSP, this study only showed a correlation between lower limb CMCT and disease duration in the SPG4 subgroup. Further genotype-specific studies utilising larger numbers may clarify the relationship between MEP markers and clinical features.

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Motor Evoked Potentials in Hereditary Spastic Paraplegia—A Systematic Review

Frontiers in Neurology ◽

10.3389/fneur.2019.00967 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 2

Author(s):

Sue-Faye Siow ◽

Ruaridh Cameron Smail ◽

Karl Ng ◽

Kishore R. Kumar ◽

Carolyn M. Sue

Keyword(s):

Systematic Review ◽

Evoked Potentials ◽

Hereditary Spastic Paraplegia ◽

Motor Evoked Potentials ◽

Spastic Paraplegia

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Motor Evoked Potentials and Disability in Secondary Progressive Multiple Sclerosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100033011 ◽

1997 ◽

Vol 24 (04) ◽

pp. 332-337 ◽

Cited By ~ 22

Author(s):

D. Facchetti ◽

R. Mai ◽

A. Micheli ◽

N. Marcianó ◽

R. Capra ◽

...

Keyword(s):

Evoked Potentials ◽

Lower Limb ◽

Evoked Potential ◽

Motor Evoked Potentials ◽

Functional System ◽

Conduction Time ◽

Lesion Load ◽

Secondary Progressive ◽

Spinal Motor ◽

Relapsing Remitting

ABSTRACT:Background:To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitative estimate of the total lesion load of the brain.Results:Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 ± 3719.0 mm2) and the total number of lesions (67.7 ± 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001).Conclusions:These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

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Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients

Nutrients ◽

10.3390/nu13051530 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1530

Author(s):

Francesco Fisicaro ◽

Giuseppe Lanza ◽

Carmela Cinzia D’Agate ◽

Raffaele Ferri ◽

Mariagiovanna Cantone ◽

...

Keyword(s):

Celiac Disease ◽

Transcranial Magnetic Stimulation ◽

Magnetic Stimulation ◽

Rating Scale ◽

De Novo ◽

Motor Evoked Potentials ◽

Silent Period ◽

Cross Sectional ◽

Transcallosal Inhibition ◽

Resting Motor Threshold

Background: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. Methods: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). Results: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. Conclusions: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

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Conditioning effects of sural nerve stimulation on short and long latency motor evoked potentials in lower limb muscles

Electroencephalography and Clinical Neurophysiology/Electromyography and Motor Control ◽

10.1016/0924-980x(94)00239-4 ◽

1995 ◽

Vol 97 (1) ◽

pp. 11-17 ◽

Cited By ~ 13

Author(s):

D.L. Wolfe ◽

K.C. Hayes

Keyword(s):

Evoked Potentials ◽

Nerve Stimulation ◽

Lower Limb ◽

Sural Nerve ◽

Motor Evoked Potentials ◽

Lower Limb Muscles ◽

Long Latency ◽

Limb Muscles

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P155 Fluctuation of motor evoked potentials and resting motor threshold over time

Clinical Neurophysiology ◽

10.1016/j.clinph.2016.10.276 ◽

2017 ◽

Vol 128 (3) ◽

pp. e92-e93

Author(s):

C. Havill ◽

G. Samusyte ◽

M. Koltzenburg

Keyword(s):

Evoked Potentials ◽

Motor Evoked Potentials ◽

Motor Threshold ◽

Resting Motor Threshold ◽

Over Time

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Camptocormia in patients with multiple system atrophy at different disease durations: frequency and related factors

BMC Neurology ◽

10.1186/s12883-021-02210-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ling Yu Zhang ◽

Bei Cao ◽

Qian-Qian Wei ◽

Ru Wei Ou ◽

Bi Zhao ◽

...

Keyword(s):

Multiple System Atrophy ◽

Disease Severity ◽

Disease Duration ◽

Rating Scale ◽

Cox Regression ◽

Age Of Onset ◽

Older Age ◽

Related Factors ◽

Cox Regression Analysis ◽

The Impact

Abstract Background Camptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated. Methods A total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3–5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used. Results In the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3–5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3–5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463). Conclusion The frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.

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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia

Brain ◽

10.1093/brain/awz307 ◽

2020 ◽

Cited By ~ 1

Author(s):

Darius Ebrahimi-Fakhari ◽

Julian Teinert ◽

Robert Behne ◽

Miriam Wimmer ◽

Angelica D'Amore ◽

...

Keyword(s):

Disease Severity ◽

Protein Complex ◽

Hereditary Spastic Paraplegia ◽

Adaptor Protein ◽

Allelic Loss ◽

Foot Deformities ◽

Periventricular White Matter ◽

Spastic Paraplegia ◽

Clinical Imaging ◽

The Mean

Abstract Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0–49.3 years). While the mean age at symptom onset was 0.8 ± 0.6 years [standard deviation (SD), range 0.2–5.0], the mean age at diagnosis was 10.2 ± 8.5 years (SD, range 0.1–46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 ± 5.1 years, SD) and later tetraplegia (mean age: 16.1 ± 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 ± 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 ± 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an ‘AP-4 deficiency syndrome’. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.

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