Widespread thalamic and cerebellar degeneration in a patient with a complicated hereditary spastic paraplegia (HSP)

Seidel, Kay; Vos, R. de; Derksen, Laura; Bauer, Péter; Rieß, Olaf; Dunnen, Wilfred F. A. den; Deller, Thomas; Hageman, G.; Rüb, Udo

doi:10.1016/j.aanat.2008.11.003

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…This result was also confirmed in genetically proven cases of SPG4 [40,41]. In complicated forms pathology shows more widespread neurodegeneration also affecting the thalamus, brainstem nuclei and the cerebellum [42]. …”

Section: Discussionmentioning

confidence: 58%

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)

Karle

Schüle

Klebe

et al. 2013

Orphanet J Rare Dis

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BackgroundHereditary spastic paraplegias (HSPs) are characterised by lower limb spasticity due to degeneration of the corticospinal tract. We set out for an electrophysiological characterisation of motor and sensory tracts in patients with HSP.MethodsWe clinically and electrophysiologically examined a cohort of 128 patients with genetically confirmed or clinically probable HSP. Motor evoked potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and radial nerves were assessed.ResultsWhereas all patients showed clinical signs of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad spectrum with axonal or demyelinating features in the others. This heterogeneity can at least in part be explained by different underlying genotypes, hinting for distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an axonal type of damage was evident. Comprehensive electrophysiological testing disclosed a more widespread affection of long fibre tracts involving peripheral nerves and the sensory system in 40%, respectively. Electrophysiological abnormalities correlated with the severity of clinical symptoms.ConclusionsWhereas HSP is primarily considered as an upper motoneuron disorder, our data suggest a more widespread affection of motor and sensory tracts in the central and peripheral nervous system as a common finding in HSP. The distribution patterns of electrophysiological abnormalities were associated with distinct HSP genotypes and could reflect different underlying pathomechanisms. Electrophysiological measures are independent of symptomatic treatment and may therefore serve as a reliable biomarker in upcoming HSP trials.

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Section: Discussionmentioning

confidence: 58%

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)

Karle

Schüle

Klebe

et al. 2013

Orphanet J Rare Dis

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“…According to previous reports, the core neuropathological features of pure HSP consist of damage to the longest descending and ascending tracts of the spinal cord and degeneration in layer V of the primary motor cortex, cerebellum, and spinocerebellar tracts. Patients with complicated HSP display widespread degenerative changes in the cerebellum, cerebral cortex, thalamus, and brainstem ( 21 , 22 ). Kuru and colleagues ( 23 ) reported neurodegeneration in the corticospinal tract, thalamus, cerebral white matter, substantia nigra, and anterior horn and in the posterior column of the spinal cord in a spastic paraplegia patient with a thin corpus callosum.…”

Section: Discussionmentioning

confidence: 99%

Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism

Kim

et al. 2013

J Korean Med Sci

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Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.

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“…In these patients, lesions in the cortical or subcortical structures as part of a widespread neurodegenerative process not restricted to the corticospinal tract involvement responsible for spastic paraparesis has been suggested. In SPG11 patients, in addition to the thinning of the corpus callosum, progressive cortical and thalamic hypometabolism in the 18 F-fl uorodeoxyglucose PET [10] , extensive subcortical neurodegeneration revealed by neuropathological examination [6] , and widespread changes involving corpus callosum and subcortical white matter identifi ed by diff usor tensor imaging [2] have been reported, suggesting that cortico-subcortical structures linked to the executive dysfunction may be involved.…”

Section: Discussion ▼mentioning

confidence: 99%

Cognitive Profile in Spastic Paraplegia with Thin Corpus Callosum and Mutations inSPG11

et al. 2010

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Autosomal recessive hereditary spastic paraplegia with thinning of the anterior corpus callosum (ARHSP-TCC) due to mutations in SPG11 on chromosome 15q (MIM610844) is the single most common cause of ARHSP. It is characterized by slowly progressive paraparesis and peripheral neuropathy. Although cognitive impairment, sometimes diagnosed as mental retardation, is an almost invariable feature, the extent and specific neuropsychological features are not fully understood. We report a comprehensive neuropsychological assessment in two ARHSP-TCC patients harbouring mutations in SPG11. A specific impairment in executive functions occurring even before cognitive decline, may be considered the core of the neuropsychological profile of patients harbouring mutations in SPG11.

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Widespread thalamic and cerebellar degeneration in a patient with a complicated hereditary spastic paraplegia (HSP)

Cited by 12 publications

References 36 publications

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)

Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)

Striatal Dopaminergic Functioning in Patients with Sporadic and Hereditary Spastic Paraplegias with Parkinsonism

Cognitive Profile in Spastic Paraplegia with Thin Corpus Callosum and Mutations inSPG11

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