Strumpell's familial spastic paraplegia: genetics and neuropathology

Behan, W. M. H.; Maia, Maria de Lourdes de Sousa

doi:10.1136/jnnp.37.1.8

Cited by 190 publications

(92 citation statements)

References 19 publications

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“…The degenerative process initially affects the distal ends of these axons and then proceeds proximally toward the cell body. 2,3 On the basis of clinical features, HSP can be classified into two forms: the pure and the complex HSP. In pure HSP, spasticity occurs in relative isolation; however, when additional neurological or non-neurological symptoms are associated with spasticity then it is termed as complex HSP.…”

Section: Introductionmentioning

confidence: 99%

Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia

et al. 2008

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The SPAST gene encoding for spastin plays a central role in the genetically heterogeneous group of diseases termed hereditary spastic paraplegia (HSP). In this study, we attempted to expand and refine the genetic and phenotypic characteristics of SPAST associated HSP by examining a large cohort of HSP patients/families. Screening of 200 unrelated HSP cases for mutations in the SPAST gene led to detection of 57 mutations (28.5%), of which 47 were distinct and 29 were novel mutations. The distribution analysis of known SPAST mutations over the structural domains of spastin led to the identification of several regions where the mutations were clustered. Mainly, the clustering was observed in the AAA (ATPases associated with diverse cellular activities) domain; however, significant clustering was also observed in the MIT (microtubule interacting and trafficking), MTBD (microtubule-binding domain) and an N-terminal region (228 -269 residues). Furthermore, we used a previously generated structural model of spastin as a framework to classify the missense mutations in the AAA domain from the HSP patients into different structural/functional groups. Our data also suggest a tentative genotype-phenotype correlation and indicate that the missense mutations could cause an earlier onset of the disease.

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Section: Introductionmentioning

confidence: 99%

Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia

et al. 2008

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“…Indeed, neuropathological studies of patients with pure HSP have documented axonal degeneration of selected motor (corticospinal tracts) and sensory (dorsal column) fibers within the spinal cord. 18,19 As hypothesized by Bushmann et al, 12 this apparent lack of supporting histopathological evidence could mean a selective loss of neurotransmitter expression or release, or that a small subgroup of neurons involved in micturition and urine storage might have been missed by the histopathological examination. On the other hand, DSD may be aggravated by pelvic floor spasticity that generally accompanies lower limb spasticity in paraplegic patients.…”

Section: Discussionmentioning

confidence: 98%

Bladder dysfunction in hereditary spastic paraplegia: a clinical and urodynamic evaluation

et al. 2012

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Objectives: Hereditary spastic paraplegia (HSP) is a degenerative central nervous system disorder characterized by progressive spasticity and hyperreflexia of the lower limbs. Often, patients with HSP experience symptoms of voiding dysfunction. Urodynamic evaluations of these patients are rarely reported in the literature and the etiology of voiding dysfunction remains unclear. The present study characterizes lower urinary tract dysfunction in a large series of patients. Methods: The medical records of 29 HSP patients who underwent urodynamic evaluation were retrospectively analyzed. The history of lower urinary tract symptoms was noted and the urodynamic findings analyzed. Results: Urgency was the most dominant complaint (72.4%), followed by frequency (65.5%), urinary incontinence (55.2%) and hesitancy (51.7%). The urodynamic findings showed signs of central neurogenic bladder in 24 patients (82.7%), with detrusor overactivity (DO) in 15 patients (51.7%) and detrusor sphincter dyssynergia (DSD) in 19 (65.5%). Post-void residual (PVR) of 410% of the voided volume was found in 12 patients (41.4%). There were significant relationships between detrusor overactivity and PVR (P¼0.005), frequency (P¼0.046) and nocturia (P¼0.045). Ultrasound examination revealed no upper urinary tract complications. Conclusion: Despite the presence of DO and DSD, HSP patients do not seem to have a high risk of developing ultrasonographicallyassessed upper urinary tract complications after a mean follow-up of 22 years, contrary to spinal cord injury population. These results may guide practitioners in their decision-making about the appropriate evaluation and treatment of bladder disturbances that accompany hereditary spastic paraplegia.

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“…1 The main clinical feature is progressive spasticity due to slowly progressing "dying back" axonal degeneration, which is maximal in the terminal portions of the longest descending and ascending tracts. 2 On the basis of clinical symptoms, HSPs are classified into pure or uncomplicated, in which the spastic paraplegia is the major clinical manifestation; and complex or complicated forms, presenting with additional neurologic signs, such as intellectual disability or cognitive decline, deafness, cerebellar ataxia, epilepsy, dysarthria, peripheral neuropathy, optic atrophy, and visual dysfunction. 3 Autosomal dominant, autosomal recessive, or X-linked inheritance is associated with multiple genes or loci and leads to genetic heterogeneity of this disorder.…”

mentioning

confidence: 99%

Brain White Matter Involvement in Hereditary Spastic Paraplegias: Analysis with Multiple Diffusion Tensor Indices

Aghakhanyan

Martinuzzi²,

Frijia

et al. 2014

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:The hereditary spastic paraplegias are a group of genetically heterogeneous neurodegenerative disorders, characterized by progressive spasticity and weakness of the lower limbs. Although conventional brain MR imaging findings are normal in patients with pure hereditary spastic paraplegia, microstructural alteration in the cerebral WM can be revealed with DTI. Concomitant investigation of multiple intrinsic diffusivities may shed light on the neurobiologic substrate of the WM degeneration pattern in patients with pure hereditary spastic paraplegia across the whole brain.

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Strumpell's familial spastic paraplegia: genetics and neuropathology

Cited by 190 publications

References 19 publications

Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia

Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia

Bladder dysfunction in hereditary spastic paraplegia: a clinical and urodynamic evaluation

Brain White Matter Involvement in Hereditary Spastic Paraplegias: Analysis with Multiple Diffusion Tensor Indices

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