The few available pathologic studies have shown that, in addition to degeneration of the corticospinal tracts throughout the spinal cord, there is thinning of the columns of Goll, mainly in the lumbosacral regions, and of the spinocerebellar tracts, even when no sensory abnormalities had been detected during life. These were the pathologic findings described by Strümpell in his original (1880) report of 2 brothers with spastic paraplegia; one of them, in addition, had a cerebellar syndrome, but again, there were no sensory abnormalities. A reduction in the number of Betz and anterior horn cells has also been reported.
Genetic aspects of hereditary spastic paraplegia
Numerous genetic mutations have given rise to this disease. As of this writing, there were at least 52 hereditary spastic paraplegia (HSP) loci some of which are shown in Table 38-8. The disease types have been renamed under the designation “SPG” (for spastic paraplegia) and numbered in order of discovery of the associated gene. The common uncomplicated autosomal dominant form of disease has been linked to mutations in many proteins, the most common being (proteins in parentheses) SPAST (spastin) and ALT1 (atlastin); and the common recessive varieties, are in SPG7 (paraplegin); and X-linked in L1CAM and PLP1 (proteolipid protein). The common spastin variety, associated with a mutation on chromosome 2p, results in great variability of clinical presentation within and among families (see Nielsen et al). A high frequency of partial deletions of the SPAST gene has been found. The possible subcellular mechanisms by which these mutations cause degeneration of the corticospinal tracts have been reviewed by Blackstone.
Differential diagnosis In the diagnosis of this disorder, one should consider an indolent spinal cord or foramen magnum tumor, cervical spondylosis, a spinal from of multiple sclerosis (this was the clinical diagnosis in Strümpell’s original cases), Chiari malformation, compression of the cord by a variety of congenital bony malformations at the craniocervical junction, and a number of chronic myelitides, among them, lupus erythematosus, sarcoidosis, HIV myelopathy, adrenomyeloneuropathy, primary lateral sclerosis (described earlier in this chapter), hypocupric myelopathy, spinal arteriovenous dural fistula, and especially, tropical spastic paraparesis (caused by the HTLV-1 virus as discussed in Chap. 32).
Variants of Familial Spastic Paraplegia