title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Martinuzzi
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Unit of Neuroradiology, Pisa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Montanaro
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Marinela
authors.initials: M
authors.lastname: Vavla
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Paparella
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonanni
authors.affiliation: University of Messina, Department of Neurosciences, Messina, Italy.
authors.forename: Olimpia
authors.initials: O
authors.lastname: Musumeci
authors.affiliation: IRCCS E. Medea, Neurorehabilitation Department, Bosisio Parini (LC), Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Brighina
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Unit of Neuroradiology, Pisa, Italy.
authors.forename: Hana
authors.initials: H
authors.lastname: Hlavata
authors.affiliation: Institute of Clinical Physiology, National Council of Research, Unit of Epidemiology and Biostatistics, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Fondazione CNR/Regione Toscana G. Monasterio, Unit of Neuroradiology, Pisa, Italy.
authors.forename: Gayane
authors.initials: G
authors.lastname: Aghakhanyan
authors.affiliation: ULSS 7-Pieve di Soligo, Department of Imaging, Conegliano (TV), Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Martino
authors.affiliation: ULSS 7-Pieve di Soligo, Department of Imaging, Conegliano (TV), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baratto
authors.affiliation: IRCCS E. Medea, Neurorehabilitation Department, Bosisio Parini (LC), Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: D'Angelo
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Peruch
authors.affiliation: IRCCS E. Medea, Polo Regionale di Conegliano, Conegliano (TV), Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Fantin
authors.affiliation: IRCCS E. Medea, Laboratory of Molecular Biology, Bosisio Parini (LC), Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Arnoldi
authors.affiliation: IRCCS E. Medea, Laboratory of Molecular Biology, Bosisio Parini (LC), Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Citterio
authors.affiliation: IRCCS E. Medea, Laboratory of Molecular Biology, Bosisio Parini (LC), Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Vantaggiato
authors.affiliation: University of Messina, Department of Neurosciences, Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Rizzo
authors.affiliation: University of Messina, Department of Neurosciences, Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.affiliation: IRCCS Fondazione Policlinico, University of Milano, Department of Neuroscience, Milano, Italy.
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.affiliation: IRCCS E. Medea, Laboratory of Molecular Biology, Bosisio Parini (LC), Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002531:Cerebellum / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D035002:Lower Extremity / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010865:Pilot Projects; D012026:Reflex, Stretch / Q000502:physiology*; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D000074181:Spastin; D013710:Tendons / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human