Dataset Information

Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

ABSTRACT: BACKGROUND:Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms). The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. METHODS:We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. RESULTS:Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The "complicated" forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. CONCLUSION:We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping.

SUBMITTER: Martinuzzi A

PROVIDER: S-EPMC4831837 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

Martinuzzi Andrea A Montanaro Domenico D Vavla Marinela M Paparella Gabriella G Bonanni Paolo P Musumeci Olimpia O Brighina Erika E Hlavata Hana H Rossi Giuseppe G Aghakhanyan Gayane G Martino Nicola N Baratto Alessandra A D'Angelo Maria Grazia MG Peruch Francesca F Fantin Marianna M Arnoldi Alessia A Citterio Andrea A Vantaggiato Chiara C Rizzo Vincenzo V Toscano Antonio A Bresolin Nereo N Bassi Maria Teresa MT

PloS one 20160414 4

<h4>Background</h4>Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system ("pure" forms). The involvement of other components of the central nervous system or of other systems is described in the "complicate" forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would h ...[more]

PMID: 27077743

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Project description:Background: Hereditary Spastic Paraplegia (HSP) is a slowly progressive neurodegenerative disorder with no disease modifying treatment. Potential therapeutic approaches are emerging and large-scale clinical drug trials for patients with HSP are imminent. A sensitive biomarker to measure the drug efficacy in these trials is required. Motor evoked potentials (MEPs) are a potential biomarker for HSP as they assess the central motor pathways and can be standardized with set protocols and guidelines. Objectives: We performed a systematic review to investigate the utility of MEPs as a diagnostic and disease severity biomarker for HSP. Search Methods: Systematic searches of PubMed, Embase, Medline, and Scopus were performed. Selection Criteria: Studies reporting on central motor conduction time measured with MEPs in adult and pediatric patients with HSP were included. We excluded studies in non-HSP patient cohorts, not in English, not original research, and unpublished journal articles. Data Collection and analysis: Search results were de-duplicated and screened according to the inclusion and exclusion criteria. The included papers were reviewed independently by two reviewers and data was collected on patient cohorts, test methods, results, and study quality. Results were analyzed using descriptive methods. Results: Of the 882 search results, 32 studies were included in the review. The most common finding was absent or prolonged lower limb (LL) central motor conduction time (CMCT) in patients with HSP (78% of patients studied). Quality assessment revealed variability in study methodology and reporting of results. Variations included patient cohorts of various genotypes as well as variations in equipment and techniques used. Aside from CMCT, none of the MEP parameter measures correlated with disease severity and many did not show significant difference between HSP patients and controls. Conclusion: Systematic review of MEP studies in HSP patient cohorts demonstrated mixed findings. Lower limb CMCT was the most promising parameter in terms of differentiating HSP patients from controls, with one study demonstrating a weak correlation with clinical disease severity. It is possible that the lack of consistency in study methodologies and small patient cohorts have contributed to the variable findings. A longitudinal study of MEPs in a large cohort of HSP patients with the same genotype will help clarify the utility of MEPs as a biomarker for disease severity and use in clinical trials.

Project description:BackgroundTo analyze the clinical phenotype of hereditary spastic paraplegia (HSP) caused by SPG11 mutations (SPG11-HSP).MethodsAmong the 17 patients with sporadic HSP who performed whole exome sequencing analysis, six were diagnosed with SPG11-HSP. The clinical and radiologic findings and the results of the electrodiagnostic and neuropsychologic tests were reviewed retrospectively.ResultsThe median age at onset was 16.5 years (range, 13-38 years). Progressive spastic paraparesis was a core feature, and the median spastic paraplegia rating scale score was 24/52 (range, 16-31 points). Additional major symptoms were pseudobulbar dysarthria, intellectual disability, bladder dysfunction, and being overweight. Minor symptoms included upper limbs rigidity and sensory axonopathy. The median body mass index was 26.2 kg/m2 (range, 25.2-32.3 kg/m2). The thin corpus callosum (TCC) was predominant at the rostral body or anterior midbody, and the ears of the lynx sign was seen in all. The follow-up MRI showed the worsening of periventricular white matter (PVWM) signal abnormalities with ventricular widening or the extension of the TCC. Motor evoked potentials (MEP) to the lower limbs showed an absent central motor conduction time (CMCT) in all subjects. The upper limb CMCT was initially absent in three subjects, although it became abnormal in all at the follow-up. The mini-mental state examination median score was 27/30 (range, 26-28) with selective impairment of the attention/calculation domain. The median score of the full-scale intelligence quotient was 48 (range, 42-72) on the Wechsler Adult Intelligence Scale test.ConclusionAttention/calculation deficits and being overweight as well as pseudobulbar dysarthria were common additional symptoms in patients with SPG11-HSP. The rostral body and anterior midbody of the corpus callosum were preferentially thinned, especially in the early stage of the disease. The TCC, PVWM signal changes, and MEP abnormality worsened as the disease progressed.

Dataset Information

Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

Publications

Clinical and Paraclinical Indicators of Motor System Impairment in Hereditary Spastic Paraplegia: A Pilot Study.

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