Klinische Validierung der sensorbasierten Ganganalyse bei Patientinnen und Patienten mit hereditärer spastischer Paraplegie

Background: Hereditary spastic paraplegia (HSP) is a rare neurodegenerative disorder which is characterized by a progressive spasticity and weakness of the lower limbs. These symptoms lead to abnormal gait. Measurement of the spatio-temporal gait parameters have made it possible to perform a more standardized gait analysis. Especially the use of sensor-based gait analysis has the benefit of being cost-efficient and easy to use while being able to monitor disease progression and the effects of therapeutic approaches. Objective: The aim of this study was to perform a clinical validation of sensor-based gait analysis in patients with HSP. The main questions were if the gait impairment correlates with the severity of the disease and if specific spatio-temporal gait parameters characterize specific genotypes. Methods: Patients (n = 36) with a diagnosis of manifest HSP were included into the study if they were still able to complete the defined gait test of 4x10m walking. Controls (n = 36) were matched to cases for age and gender. Gait was recorded by two sensors on the shoes, and spatio-temporal gait parameters were extracted using a pattern recognition algorithm. The severity of the disease was graded on the ‘Spastic Paraplegia Rating Scale’ (SPRS). Results: In comparison to the controls, the group of HSP patients showed prolonged stride and stance times as well as an increased gait variability. Swing duration, in contrast, was decreased in HSP. The spatio-temporal gait parameters correlated with disease severity. The highest correlation was shown for the coefficients of variation (CV) of stride time (r = 0,747; p < 0,001), stance time (r = 0,702; p < 0,001) and swing duration (r = 0,709; p <0,001). Conclusion: Sensor-based gait analysis can determine spatio-temporal gait parameters in HSP, which are associated with disease severity. Highest correlations were shown for parameters of stride variability. In the future, these findings should be used to monitor the disease and its progression more closely, and to evaluate therapeutic approaches.Hintergrund: Die hereditäre spastische Paraplegie (HSP) ist eine seltene neurodegenerative Erkrankung, die sich durch eine progrediente Spastik und Schwäche der unteren Extremitäten äußert. Diese Beeinträchtigungen bedingen ein pathologisches Gangbild. Objektiv gemessene Weg-Zeit-Gangparameter ermöglichen eine standardisierte Ganganalyse der Patientinnen und Patienten. Besonders die Entwicklung der sensorbasierten Ganganalyse bringt dabei den Vorteil einer kostengünstigen und schnellen Methode, um Krankheitsprogression und Therapieerfolg zu überwachen. Ziel und Fragestellung: Die klinische Validierung der sensorbasierten Ganganalyse bei Patientinnen und Patienten mit HSP war das Ziel der vorliegenden Studie. Dabei wurde die Fragestellung untersucht, ob ein Zusammenhang zwischen der Gangeinschränkung und der Krankheitsschwere hergestellt werden kann und ob bestimmte Weg-Zeit-Gangparameter charakteristisch für spezifische Genotypen sind. Methoden: Probandinnen und Probanden mit einer bestätigten HSP-Diagnose (n = 36) und erhaltener Gehfähigkeit wurden in die Studie eingeschlossen. Diesen wurden Kontrollen (n = 36) entsprechend der Alters- und Geschlechtsverteilung zugeordnet. Teil der Untersuchung war ein 4x10 m Gangtest, welcher mit Hilfe von Inertialsensoren an den Schuhen durchgeführt und woraus mit Hilfe eines Musterekennungsalgorithmus die Weg-Zeit-Gangparameter extrahiert wurden. Der Schweregrad der Erkrankung wurde anhand der ‚Spastic Paraplegia Rating Scale‘ (SPRS) bestimmt. Ergebnisse: Im Vergleich zu den Kontrollpersonen wiesen die HSP-Probandinnen und Probanden eine Verlängerung der absoluten Doppelschritt-Zeit, der Zeit der Standphase und eine erhöhte Gangvariabilität sowie eine geringere normierte Schwungdauer auf. Die Korrelationsanalyse nach Spearman zeigte einen Zusammenhang zwischen dem Schweregrad der Erkrankung und den Weg-Zeit-Parametern. Die Gangparameter mit der größten Korrelation zum SPRS-Wert waren die Variationskoeffizienten der Doppelschritt-Zeit (r = 0,747; p < 0,001), der Zeit der Standphase (r = 0,702; p < 0,001) und der Schwungdauer (r = 0,709; p < 0,001). Fazit: Die sensorbasierte Ganganalyse identifiziert Weg-Zeit-Gangparameter, welche im Zusammenhang mit dem Schweregrad der Erkrankung stehen. Die höchste Korrelation zeigte dabei die Variabilität des Doppelschrittes. Mit dieser Methode können in Zukunft die Progression der Erkrankung und Therapieansätze besser überwacht werden

Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia

Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11

Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia

Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking. Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI. Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients. Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11