Autosomal dominant pure spastic paraplegia: a clinical, paraclinical, and genetic study

Abstract

Objectives-At least three clinically indistinguishable but genetically diVerent types of autosomal dominant pure spastic paraplegia (ADPSP) have been described. In this study the clinical, genetic, neurophysiological, and MRI characteristics of ADPSP were investigated. Methods-Sixty three at risk members from five families were clinically evaluated. A diagnostic index was constructed for the study. Microsatellite genotypes were determined for chromosomes 2p, 14q, and 15q markers and multipoint linkage analyses were performed. Central motor conduction time studies (CMCT), somatosensory evoked potential (SSEP) measurement, and MRI of the brain and the total spinal cord were carried out in 16 patients from four families. Results-The clinical core features of ADPSP were homogeneously expressed in all patients but some features were only found in some families and not in all the patients within the family. In two families non-progressive "congenital" ADPSP was seen in some aVected members whereas adult onset progressive ADPSP was present in other aVected family members. As a late symptom not previously described low backache was reported by 47%. Age at onset varied widely and there was a tendency for it to decline in successive generations in the families, suggesting anticipation. Genetic linkage analysis confined the ADPSP locus to chromosome 2p21-p24 in the five families. The lod scores obtained by multipoint linkage analysis were positive with a combined maximum lod score of Z=8.60. The neurophysiological studies only showed minor and insignificant prolongation of the central motor conduction time and further that peripheral conduction and integrity of the dorsal columns were mostly normal. Brain and the total spinal cord MRI did not disclose any significant abnormalities compared with controls. Conclusions-ADPSP linked to chromosome 2p21-p24 is a phenotypic heterogeneous disorder characterised by both interfamilial and intrafamilial variation. In some families the disease may be "pure" but the existence of "pure plus" families is suggested in others. The neurophysiological and neuroimaging investigations did not show any major abnormalities.(J Neurol Neurosurg Psychiatry 1998;64:61-66)

MR Imaging Findings in Autosomal Recessive Hereditary Spastic Paraplegia

“…However, they did speculate that the atrophy is predominantly secondary to the degeneration of the descending pyramidal tract, resulting in marked atrophy at the thoracic and not at the cervical level. 4 Mild atrophy of the cervical and thoracic spinal cord (not quantified) was also reported by Durr et al, 3 Lesca et al, 5 Nicolau et al, 10 and Nielsen et al 35 In our study, patient 1 had mild atrophy of the cervical spinal cord and 2 patients of family II presented an unusual finding, namely the round T2 high signal intensity in the posterior aspect of the spinal cord representing either an enlarged and posteriorly displaced ependymal canal or a direct high signal intensity along the dorsal columns of the cord (Fig 3A, -B); in both cases, it reflects the neuropathologic finding of degeneration and atrophy of the dorsal columns of the spinal cord. Although this finding is not very conclusive in confirming the diagnosis of HSP, it may be useful in the evaluation of dorsal column degeneration.…”

The hereditary spastic paraplegias

“…The most frequent abnormality on magnetic resonance imaging (MRI) is spinal cord atrophy, particularly in the cervical and thoracic regions. Quantitative MRI investigations have suggested that the corpus callosum may be smaller than normal [8,12,23,24]. Several MRI studies have identified a trend for white matter lesions to be more common than in controls, although individually none of these studies has found this statistically significant [23,24].…”

“…Quantitative MRI investigations have suggested that the corpus callosum may be smaller than normal [8,12,23,24]. Several MRI studies have identified a trend for white matter lesions to be more common than in controls, although individually none of these studies has found this statistically significant [23,24]. Peripheral nerve conduction studies are almost always normal [4, 24,25].…”

“…Several MRI studies have identified a trend for white matter lesions to be more common than in controls, although individually none of these studies has found this statistically significant [23,24]. Peripheral nerve conduction studies are almost always normal [4, 24,25]. Cervical somatosensory evoked potentials and central motor conduction studies may be abnormal in the majority of cases, although the validity of some motor conduction studies has been questioned because of methodological concerns [24,[26][27][28][29].…”

Motor system abnormalities in hereditary spastic paraparesis type 4 (SPG4) depend on the type of mutation in the spastin gene

“…6 The results of electrophysiological investigations vary between studies and have not contributed significantly to the elucidation of possible differences in the aetiology and pathogenesis of the disorder. TMS studies have demonstrated that CMCTs to lower extremities are delayed in most but not all patients [7][8][9][10] ; CMCTs to upper extremities are usually normal but may be prolonged in a minority of patients, 8 11 and intracortical facilitation may be increased. 12 In none of these studies, electrophysiological findings have been combined with genotypes.…”