RESUMEN
PURPOSE: To provide an overview of outcome and complications of selective dorsal rhizotomy (SDR) and intrathecal baclofen pump implantation (ITB) for spasticity treatment in children with hereditary spastic paraplegia (HSP). METHODS: Retrospective study including children with HSP and SDR or ITB. Gross motor function measure (GMFM-66) scores and level of spasticity were assessed. RESULTS: Ten patients were included (most had mutations in ATL1 (n = 4) or SPAST (n = 3) genes). Four walked without and two with walking aids, four were non-walking children. Six patients underwent SDR, three patients ITB, and one both. Mean age at surgery was 8.9 ± 4.5 years with a mean follow-up of 3.4 ± 2.2 years. Five of the SDR patients were walking. Postoperatively spasticity in the legs was reduced in all patients. The change in GMFM-66 score was + 8.0 (0-19.7 min-max). The three ITB patients treated (SPAST (n = 2) and PNPLA6 (n = 1) gene mutation) were children with a progressive disease course. No complications of surgery occurred. CONCLUSIONS: SDR is a feasible treatment option in carefully selected children with HSP, especially in walking patients. The majority of patients benefit with respect to gross motor function, complication risk is low. ITB was used in children with severe and progressive disease.
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Parálisis Cerebral , Paraplejía Espástica Hereditaria , Niño , Humanos , Adolescente , Preescolar , Estudios Retrospectivos , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/cirugía , Paraplejía Espástica Hereditaria/complicaciones , Parálisis Cerebral/complicaciones , Espasticidad Muscular/genética , Espasticidad Muscular/cirugía , Baclofeno/uso terapéutico , Rizotomía/métodos , Resultado del Tratamiento , EspastinaRESUMEN
Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.
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Parálisis Cerebral , Relajantes Musculares Centrales , Paraplejía Espástica Hereditaria , Traumatismos de la Médula Espinal , Humanos , Baclofeno/efectos adversos , Parálisis Cerebral/complicaciones , Parálisis Cerebral/tratamiento farmacológico , Relajantes Musculares Centrales/efectos adversos , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/tratamiento farmacológico , Bombas de Infusión Implantables/efectos adversos , Espasticidad Muscular/etiología , Espasticidad Muscular/inducido químicamente , Traumatismos de la Médula Espinal/etiología , Inyecciones Espinales/efectos adversosRESUMEN
Spastic paraplegia is a neurodegenerative disorder characterized by progressive leg weakness and spasticity due to degeneration of corticospinal axons. SPG7 encodes paraplegin, and pathogenic variants in the gene cause hereditary spastic paraplegia as an autosomal recessive trait. Various ophthalmological findings including optic atrophy, ophthalmoplegia, or nystagmus have been reported in patients with spastic paraplegia type 7. We report a 15-year-old male patient with a novel heterozygous variant, c.1224T>G:p.(Asp408Glu) in SPG7 (NM_003119.3) causing early onset isolated optic atrophy and infantile nystagmus prior to the onset of neurological symptoms. Therefore, SPG7 should be considered a cause of infantile nystagmus with optic atrophy.
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Atrofia Óptica Autosómica Dominante , Atrofia Óptica , Paraplejía Espástica Hereditaria , Humanos , Masculino , ATPasas Asociadas con Actividades Celulares Diversas/genética , Metaloendopeptidasas/genética , Mutación , Atrofia Óptica/diagnóstico , Atrofia Óptica/genética , Atrofia Óptica/patología , Paraplejía/genética , Fenotipo , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genética , AdolescenteRESUMEN
BACKGROUND: Hereditary spastic paraplegia (HSP) include various sporadic and hereditary neurodegenerative disorders, characterized by progressive spasticity and weakness of lower limbs, possibly associated to additional features. CASE PRESENTATION: We report a male HPS patient in his 40 s, showing mental retardation associated with language impairment, dysarthria, and increased urinary frequency. Three months after treatment with electric chronic high-frequency cervical spinal cord stimulation (HF-SCS), he showed an amelioration of motor symptoms (lower limbs spasticity and gait), dysarthria, cognitive functioning (language and constructive praxic abilities), and urinary symptoms (decreased urinary frequency). Single-photon emission computed tomography (SPECT) showed a postoperative increase of cerebral perfusion in right frontal cortex and temporal cortex bilaterally. CONCLUSION: In our patient, HF-SCS might have induced an activation of ascending neural pathways, resulting in changes in activity in various cortical areas (including sensory-motor cortical areas), which may give rise to a modulation of activity in spared descending motor pathways and in neural networks involved in cognitive functions, including language. Although further studies in patients with HPS are needed to clarify whether HF-SCS can be a suitable treatment option in HSP, our observation suggests that HF-SCS, a minimally invasive neurosurgical procedure, might induce beneficial effects of on various symptoms of such orphan disease.
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Discapacidad Intelectual , Paraplejía Espástica Hereditaria , Estimulación de la Médula Espinal , Humanos , Masculino , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/terapia , Paraplejía Espástica Hereditaria/diagnóstico , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/terapia , Disartria , Cognición , Espasticidad Muscular , MarchaRESUMEN
INTRODUCTION: Hereditary spastic paraplegia refers to a group of conditions characterized by a slow progression of spasticity in lower limbs resulting in gait abnormalities. Current treatment options have proven to be insufficient in terms of symptom alleviation. In this study, we tested the effectiveness of repetitive transcranial magnetic stimulation (rTMS) on lower limb spasticity in patients with hereditary spastic paraplegia. METHODS: Eight patients were randomly assigned to receive either five sessions of active 5 Hz-rTMS ( n = 4) or sham rTMS ( n = 4). The primary outcome was a change in spasticity assessed by the modified Ashworth scale. Secondary outcomes were change in 10 m walking test, Fugl-Meyer assessment of lower extremity motor function, and quality-of-life short-form survey scores. Assessment of the outcomes was done before, upon completion, and 1 month after the intervention. We analyzed the data using repeated-measure analysis of variance. RESULTS: Mean age of the participants was 38.5 (SD = 5.4) years, and 50% were women. Compared with sham rTMS, real rTMS was effective in decreasing modified Ashworth scale (rTMS × time: F [df = 2] = 7.44; P = 0.008). Real rTMS group had lower modified Ashworth scale scores at the end of rTMS sessions (estimate = -0.938; SE = 0.295; P = 0.019) and at the end of follow-up (estimate = -0.688; SE = 0.277; P = 0.048) compared with the sham rTMS group. Real and sham rTMS groups were not different in the secondary outcomes. CONCLUSIONS: Repetitive transcranial magnetic stimulation is an effective method in reducing lower limb spasticity of patients with hereditary spastic paraplegia.
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Corteza Motora , Paraplejía Espástica Hereditaria , Accidente Cerebrovascular , Humanos , Femenino , Adulto , Masculino , Estimulación Magnética Transcraneal/métodos , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/terapia , Resultado del Tratamiento , Espasticidad Muscular/terapia , Espasticidad Muscular/complicaciones , Extremidad Inferior , Accidente Cerebrovascular/complicacionesRESUMEN
Kjellin's syndrome is a rare autosomal recessive hereditary neuro-ophthalmologic syndrome. The diagnosis of Kjellin's syndrome is based on the retinal appearance in a patient with spastic paraplegia, learning difficulties, amyotrophy and thin corpus callosum. We present the case of a 42-years-old man without visual symptoms, referred to study from the Neurology Service due to a degenerative condition. On ophthalmologic examination is found a multifocal pattern dystrophy simulating fundus flavimaculatus and a delay in the visual evoked potential responses. The performed tests are reviewed and a genetic analysis for subtypes 11 and 15 of hereditary spastic paraplegia are requested. These subtypes are associated with macular changes. A pathogenic variant in the SPG 11 gene is identified, which explains the patient's clinical manifestations. Ophthalmological findings were key in the diagnosis of this rare syndrome.
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Distrofias Retinianas , Paraplejía Espástica Hereditaria , Masculino , Humanos , Adulto , Potenciales Evocados Visuales , Enfermedad de Stargardt , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía/complicaciones , Paraplejía/diagnóstico , SíndromeRESUMEN
OBJECTIVES: The term hereditary spastic paraplegia comprises an ever-expanding array of neurological disorders with distinct aetiologies. Spastic paraplegia gene 39 is one of the many genetically defined types with features of other organs and neurological systems in addition to paraspasticity. We describe a large kindred with a novel clinical phenotype as, in addition to spastic paraplegia, affected subjects suffered from a prominent cerebellar oculomotor dysfunction with two hitherto undescribed mutations of PNPLA6. METHODS: Three of five genetically tested family members of a large kindred were affected by spastic gait and a unique and prominent cerebellar oculomotor dysfunction. Further clinical, imaging, laboratory and videonystagmographic data were analyzed. Genetic analysis was done using next-generation sequencing. RESULTS: The most salient clinical feature, in addition to paraspasticity, in three of five subjects was cerebellar oculomotor dysfunction with an upbeating nystagmus provoked by downward gaze. Genetic analysis revealed two hitherto unknown sequence variants in the PNPLA6 gene, a splice-site variant c.1635 + 3G > T and a missense variant c.3401A > T, p.(Asp1134Val). In addition to cerebellar oculomotor dysfunction, compound-heterozygous siblings presented with paraspasticity and a moderate hypogonadotropic hypogonadism in the female. A paternal uncle being homozygous for the splice-site variant of PNPLA6 presented with increased lower limb reflexes and an unstable gait. Treatment with 4-aminopyridine, a potassium channel blocker, lead to meaningful improvement of clinical symptoms. CONCLUSIONS: The unique and prominent cerebellar ocular motor disorder in our family broadens the spectrum of clinical phenotypes associated with variations in the PNLA6 gene. The finding of paraspasticity with cerebellar oculomotor dysfunction alongside inconspicuous brainstem imaging may raise suspicion of complex HSP with PNPLA6 mutations.
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Enfermedades Cerebelosas , Paraplejía Espástica Hereditaria , Femenino , Humanos , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Paraplejía Espástica Hereditaria/genética , Fenotipo , Paraplejía/genética , Mutación/genética , LinajeRESUMEN
INTRODUCTION: An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP and features of relapsing-remitting MS (RRMS). We took this opportunity to review the current literature of co-occurring MS and HSP. METHOD: The patient underwent clinical, laboratory and neuroimaging evaluations. We performed a literature search for cases of HSP and MS. The 2017 McDonalds Criteria for MS were retrospectively applied to the selected cases. RESULTS: A 34-year-old woman, presenting a molecular diagnosis of SPG3A, complained subacute sensory-motor symptoms. Spinal MRI disclosed T2-hyperintense lesions at C2, T6 and T4 level, the latter presenting contrast-enhancement. CSF analysis showed oligoclonal bands. She was treated with intravenous high-dose steroids, with symptom resolution. The literature review yielded 13 papers reporting 20 possible cases of MS and HSP. Nine patients (5 M, median age 34) met the 2017 McDonald criteria. Five (25%) received a diagnosis of RRMS and four (20%) of primary progressive MS. Brain MRI showed multiple WM lesions, mostly periventricular. Six of seven cases (85.7%) had spinal cord involvement. Oligoclonal bands were found in 6/8 (75%) patients. Seven patients (77.7%) improved/stabilized on immunotherapy. CONCLUSION: This is the first description on the association between SPG3A type of HSP and MS. This report adds to the other reported cases of co-occurring HSPs and MS. Although it remains unclear if this association is casual or causal, clinicians should be aware that an HSP diagnosis does not always exclude a concomitant MS.
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Esclerosis Múltiple , Paraplejía Espástica Hereditaria , Adulto , Femenino , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Bandas Oligoclonales , Estudios Retrospectivos , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico por imagenAsunto(s)
Epilepsia , Enfermedades del Sistema Nervioso Periférico , Paraplejía Espástica Hereditaria , Ataxia/complicaciones , Ataxia/genética , Cuerpo Calloso/diagnóstico por imagen , Epilepsia/complicaciones , Epilepsia/genética , Humanos , Mutación/genética , Paraplejía/complicaciones , Paraplejía/genética , Enfermedades del Sistema Nervioso Periférico/complicaciones , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/genética , Espastina/genéticaRESUMEN
Progressive spastic paraplegia is the core symptom of hereditary spastic paraplegias (HSPs), a group of monogenic disorders characterized pathologically by degeneration of the corticospinal tract and dorsal column and leading to irreversible neurologic deficits. However, acquired causes, such as structural, vascular, inflammatory, infectious, metabolic, toxic, neurodegenerative, and iatrogenic causes, can also cause acquired spastic paraplegia. We describe the case of a middle-aged man presenting with progressive spastic paraplegia combined with ataxia and parkinsonism. No mutation of HSP genes was detected. After a comprehensive diagnostic workup, hyperintensities in the bilateral basal ganglia, mesencephalon, pons, and cerebellum on T1-weighted images were found, which demonstrated hypointensity on susceptibility-weighted imaging. Furthermore, an increased blood ammonia level and diffuse slow-wave activity in EEG were detected. The patient had a 7-year history of hypertension, alcoholic liver cirrhosis, and transjugular intrahepatic portosystemic shunt operation 2 years before the onset of spastic paraplegia symptoms. Current workup combined with patient history resulted in a diagnosis of acquired hepatocerebral degeneration and hepatic myelopathy.. This case provided a detailed diagnostic approach for progressive spastic paraplegias and exhaustive differential diagnoses of basal ganglia deposits. The take-home message from this case was that acquired causes, especially curable causes, should always be excluded first when dealing with patients with progressive spastic paraplegia.
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Razonamiento Clínico , Paraplejía Espástica Hereditaria , Marcha , Humanos , Masculino , Persona de Mediana Edad , Mutación , Paraplejía/genética , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genéticaAsunto(s)
Distonía/fisiopatología , Paraplejía/fisiopatología , Paraplejía Espástica Hereditaria/fisiopatología , Distonía/diagnóstico , Distonía/etiología , Distonía/genética , Femenino , Humanos , Persona de Mediana Edad , Paraplejía/complicaciones , Paraplejía/diagnóstico , Paraplejía/genética , Fenotipo , Proteínas/genética , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico , Paraplejía Espástica Hereditaria/genéticaRESUMEN
Hereditary spastic paraplegia type 11 (SPG11) is the most common subtype of autosomal recessive hereditary spastic paraplegia (HSP), to date, there are more than 181 different KIAA1840 gene mutations detected, and yet the genetic landscape of SPG11 is far from complete. To find the clinical and genetic characteristics of SPG11, we performed a reanalysis of the clinical features and genotype-phenotype correlations in all reported studies exhibiting SPG11 mutations. A total of 339 patients were collected, their mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and mental retardation (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%). The most common brain MRI abnormality is thinning of the corpus callosum (TCC) (173/190, 91.05%), followed by periventricular white matter changes (130/158, 82.28%), cerebral or cerebellar cortical atrophy (55/107, 51.40%). The mutational spectrum associated with KIAA1840 gene is wide, and frameshift mutations are the most common type followed by nonsense mutations. Our reanalysis demonstrated that SPG11 exhibited significant clinical and genetic heterogeneity, and no clear genotype-phenotype correlation was observed. There is no mutational hot spot in the KIAA1840 gene, which emphasizes the need to analyse the whole gene in clinical practice. In addition to conventional genetic testing methods, further mRNA analysis should be conducted on some cases to yield a definitive diagnosis.
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Estudios de Asociación Genética , Proteínas/genética , Paraplejía Espástica Hereditaria , Adolescente , Edad de Inicio , Niño , Femenino , Humanos , Masculino , Mutación , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/patologíaRESUMEN
BACKGROUND: ALDH18A1 mutations lead to delta-1-pyrroline-5-carboxylate-synthetase (P5CS) deficiency, which is a urea cycle-related disorder including SPG9A, SPG9B, autosomal dominant cutis laxa-3 (ADCL3), and autosomal recessive cutis laxa type 3A (ARCL3A). These diseases exhibit a broad clinical spectrum, which makes the diagnosis of P5CS deficiency difficult. We report here a rare Japanese family including both patients with an ALDH18A1 mutation (SPG9A) and ones with CMT1A. CASE PRESENTATION: A Japanese family included five patients with the CMT phenotype and five with the HSP phenotype in four generations. The patients with the HSP phenotype showed a pure or complicated form, and intrafamilial clinical variability was noted. Genetically, FISH analysis revealed that two CMT patients had a PMP22 duplication (CMT1A). Exome analysis and Sanger sequencing revealed five HSP patients had an ALDH18A1 heterozygous mutation of c.755G > A, which led to SPG9A. Haplotype analysis revealed that the ALDH18A1 mutation must have newly occurred. To date, although de novo mutations of ALDH18A1 have been described in ADCL3A, they were not mentioned in SPG9A in earlier reports. Thus, this is the first SPG9A family with a de novo mutation or the new occurrence of gonadal mosaicism of ALDH18A1. Analysis of serum amino acid levels revealed that two SPG9A patients and two unaffected family members had low citrulline levels and one had a low level of ornithine. CONCLUSIONS: Since the newly occurring ALDH18A1 mutation, c.755G > A, is the same as that in two ADHSP families and one sporadic patient with SPG9A reported previously, this genomic site might easily undergo mutation. The patients with the c.755G > A mutation in our family showed clinical variability of symptoms like in the earlier reported two families and one sporadic patient with this mutation. Further studies are required to clarify the relationship between the amino acid levels and clinical manifestations, which will reveal how P5CS deficiency influences disease phenotypes including ARCL3A, ADCL3, SPG9B, and SPG9A.
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Aldehído Deshidrogenasa/genética , Huesos/anomalías , Catarata/complicaciones , Catarata/genética , Enfermedad de Charcot-Marie-Tooth/complicaciones , Enfermedad de Charcot-Marie-Tooth/genética , Trastornos del Crecimiento/complicaciones , Trastornos del Crecimiento/genética , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/genética , Adulto , Pueblo Asiatico/genética , Femenino , Heterocigoto , Humanos , Masculino , Mutación , Proteínas de la Mielina/genética , Linaje , FenotipoRESUMEN
BACKGROUND: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. METHODS: In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. RESULTS: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language. CONCLUSIONS: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.
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Disfunción Cognitiva/diagnóstico , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/diagnóstico , Adolescente , Adulto , Disfunción Cognitiva/genética , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Mutación , Proteínas/genética , Adulto JovenRESUMEN
INTRODUCTION: Hereditary spastic paraplegia is a heterogeneous group of genetic disorders characterized by degeneration of the corticospinal tracts, coursing with progressive weakness and spasticity of the lower limbs. To date, there are no effective treatments for progressive deficits or disease-modifying therapy for those patients. We report encouraging results for spastic paraparesis after spinal cord stimulation. METHODS: A 51-year-old woman suffering from progressive weakness and spasticity in lower limbs related to hereditary spastic paraplegia type 4 underwent spinal cord stimulation (SCS) and experienced also significant improvement in motor function. Maximum ballistic voluntary isometric contraction test, continuous passive motion test and gait analysis using a motion-capture system were performed in ON and OFF SCS conditions. Neurophysiologic assessment consisted of obtaining motor evoked potentials in both conditions. RESULTS: Presurgical Spastic Paraplegia Rating Scale (SPRS) score was 26. One month after effective SCS was initiated, SPRS went down to 15. At 12 months follow up, she experienced substantial improvement in motor function and in gait performance, with SPRS scores 23 (OFF) and down to 20 (ON). There was an increased isometric muscle strength (knee extension, OFF: 41 N m; ON: 71 N m), lower knee extension and flexion torque values in continuous passive motion test (decrease in spastic tone) and improvement in gait (for example, step length increase). CONCLUSION: Despite being a case study, our findings suggest innovative lines of research for the treatment of spastic paraplegia.
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Trastornos Neurológicos de la Marcha/rehabilitación , Actividad Motora , Paraplejía/rehabilitación , Paraplejía Espástica Hereditaria/rehabilitación , Estimulación de la Médula Espinal , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Persona de Mediana Edad , Actividad Motora/fisiología , Paraplejía/complicaciones , Paraplejía/fisiopatología , Índice de Severidad de la Enfermedad , Paraplejía Espástica Hereditaria/complicaciones , Paraplejía Espástica Hereditaria/fisiopatologíaRESUMEN
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder clinically characterized by slowly progressing spastic paraparesis. We herein report a 50-year-old Japanese woman who presented with slowly progressing spastic paraplegia and a history of Paget's disease of bone (PDB). Genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.Arg155Cys; c.436C>T). This mutation has not been reported to cause HSP with PDB.