**4. Hereditary spastic paraplegia (HSP)**

HSP is a genetic neurodegenerative disorder that involves bilateral leg spasticity with additional features: mental impairment, peripheral neuropathy, cerebellar ataxia, retinal degeneration, etc. [5]. Its progression is slower than that of ALS. We have encountered and described several cases who suffered from HSPs. First, I present a SPG3A case. SPG3A is an autosomal dominant, early-onset pure spastic paraplegia caused by an *Atlastin1* (*ATL1*) gene mutation [13].

A 52-year-old man visited our clinic because of early-onset gait disturbance at age two (**Figure 2**, IV-7). He had been diagnosed as having cerebral palsy by a doctor at another hospital. He underwent bilateral Achilles tendon lengthening in his early childhood. His older brother suffered from late-onset gait disturbance (**Figure 2**, IV-6).

On examination, his gait was spastic. Muscle weakness and atrophy of his lower extremities were observed. Exaggerated DTRs except for a diminished Achilles tendon reflex and pathological reflexes of his legs were noted (**Table 1**). MRI of his brain revealed no abnormal findings, whereas his spinal cord was slightly atrophic. Serum HTLV-1 antibody was positive, but he refused a lumbar puncture. Whole-exome sequencing analysis allowed the diagnosis of SPG3A. He had a reported heterozygous missense mutation (c.1239T>C, p.F413L) of the *ATL1* gene [14] (**Figure 3**).

A 31-year-old man was admitted to our hospital because of standing difficulty and bilateral leg pain. He noticed gait disturbance at age 13. His gait disturbance gradually worsened and he became wheel-chair bound at age 23. He has mental impairment. On examination, exaggerated DTRs and marked spasticity with sustained clonus of both legs were observed. Brain MRI showed a thin corpus callosum. Genetic analysis disclosed compound heterozygous mutations of the *SPG11* gene [16]. We tried intrathecal low-dose baclofen administration, which dramatically alleviated his spasticity (from 4 to 2, modified Ashworth score) and pain with leg clonus. Then an intrathecal baclofen infusion pump was implanted by a neurosurgeon. He became almost free from leg clonus pain with intrathecal baclofen and the modified

**Figure 3.** Gene analysis of the SPG3A patient. A. Whole-exome sequencing revealed the c.1239T>C (p.F413L) variant of the *Atlastin1* (*ATL1*) gene. B. Sanger sequencing confirmed the c.1239T>C (p.F413L) mutation of the *ATL1* gene.

**IV-6 (HAM) IV-7 (SPG3A)**

Spastic Paraplegias Due to Non-Traumatic Spinal Cord Disorders

http://dx.doi.org/10.5772/intechopen.71457

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Age at examination 54 52 Age at onset 42 2

Babinski reflex + + Leg atrophy − + Sensory disturbance + −

DTR of legs ↑ PTR↑, ATR↓

Spinal MRI Normal Mild atrophy

Ashworth score decreased to 2 or 3.

**Table 1.** Clinical symptoms of the HAM and SPG3A cases.

This mutation was not detected in DNA from his father (III-1) or older brother (IV-6). We prescribed muscle relaxants (tizanidine and dantrolene), but he could not continue to take them due to their side effects (nausea and sleepiness).

Next, I present a SPG11 case. SPG11 is an autosomal recessive, complicated SPG accompanied by mental impairment, peripheral neuropathy and a thin corpus callosum. This disease is caused by mutations of the *SPG11* gene encoding spatacsin protein [15].

**Figure 2.** Family tree including the SPG3A/HAM cases. Proband (IV-7): SPG3A patient, HTLV-1 carrier. Older brother (IV-6): HAM patient. Father (III-1): Healthy HTLV-1 carrier. Diamonds indicate positive anti-HTLV-1 antibodies.


**Table 1.** Clinical symptoms of the HAM and SPG3A cases.

degeneration, etc. [5]. Its progression is slower than that of ALS. We have encountered and described several cases who suffered from HSPs. First, I present a SPG3A case. SPG3A is an autosomal dominant, early-onset pure spastic paraplegia caused by an *Atlastin1* (*ATL1*) gene

A 52-year-old man visited our clinic because of early-onset gait disturbance at age two (**Figure 2**, IV-7). He had been diagnosed as having cerebral palsy by a doctor at another hospital. He underwent bilateral Achilles tendon lengthening in his early childhood. His older brother suf-

On examination, his gait was spastic. Muscle weakness and atrophy of his lower extremities were observed. Exaggerated DTRs except for a diminished Achilles tendon reflex and pathological reflexes of his legs were noted (**Table 1**). MRI of his brain revealed no abnormal findings, whereas his spinal cord was slightly atrophic. Serum HTLV-1 antibody was positive, but he refused a lumbar puncture. Whole-exome sequencing analysis allowed the diagnosis of SPG3A. He had a reported heterozygous missense mutation (c.1239T>C, p.F413L) of the *ATL1*

This mutation was not detected in DNA from his father (III-1) or older brother (IV-6). We prescribed muscle relaxants (tizanidine and dantrolene), but he could not continue to take them

Next, I present a SPG11 case. SPG11 is an autosomal recessive, complicated SPG accompanied by mental impairment, peripheral neuropathy and a thin corpus callosum. This disease is

**Figure 2.** Family tree including the SPG3A/HAM cases. Proband (IV-7): SPG3A patient, HTLV-1 carrier. Older brother (IV-6): HAM patient. Father (III-1): Healthy HTLV-1 carrier. Diamonds indicate positive anti-HTLV-1 antibodies.

caused by mutations of the *SPG11* gene encoding spatacsin protein [15].

fered from late-onset gait disturbance (**Figure 2**, IV-6).

due to their side effects (nausea and sleepiness).

mutation [13].

60 Essentials of Spinal Cord Injury Medicine

gene [14] (**Figure 3**).

A 31-year-old man was admitted to our hospital because of standing difficulty and bilateral leg pain. He noticed gait disturbance at age 13. His gait disturbance gradually worsened and he became wheel-chair bound at age 23. He has mental impairment. On examination, exaggerated DTRs and marked spasticity with sustained clonus of both legs were observed. Brain MRI showed a thin corpus callosum. Genetic analysis disclosed compound heterozygous mutations of the *SPG11* gene [16]. We tried intrathecal low-dose baclofen administration, which dramatically alleviated his spasticity (from 4 to 2, modified Ashworth score) and pain with leg clonus. Then an intrathecal baclofen infusion pump was implanted by a neurosurgeon. He became almost free from leg clonus pain with intrathecal baclofen and the modified Ashworth score decreased to 2 or 3.

**Figure 3.** Gene analysis of the SPG3A patient. A. Whole-exome sequencing revealed the c.1239T>C (p.F413L) variant of the *Atlastin1* (*ATL1*) gene. B. Sanger sequencing confirmed the c.1239T>C (p.F413L) mutation of the *ATL1* gene.
