Hereditary spastic paraplegia is a degenerative hereditary myelopathy with bilateral lesion of the lateral and anterior spinal columns mainly at the lumbar level. The basic clinical symptom is central paraparesis of the lower extremities. Typical symptoms, the presence of a family history, ENMG data, studies of evoked potentials, MRI and genetic analyses allow to diagnose hereditary spastic paraplegia. Treatment is based on constant intake, intramuscular or endolumbal administration of muscle relaxants in combination with physical therapy and physiotherapy.
G11.4 Hereditary spastic paraplegia
Hereditary spastic paraplegia (Strumpel’s disease) was first described in 1883 by the German clinician A. Strumpel. In the future, M. Loren was engaged in the study of this pathology. In honor of these researchers, an eponymous name was introduced into medical practice — Strumpel-Loren disease, which in modern neurology is more often used as hereditary spastic paraplegia. The pathogenetic substrate of the disease is the progressive glial degeneration of the pyramidal tracts of the anterior and lateral pillars at the level of the thoracic and lumbar segments of the spinal cord. Along with this, there may be atrophic processes in the anterior horns, degeneration of the cerebellar pathways, a decrease in the number of neurons in the motor cortex, gliosis of the pyramidal tracts at the level of the brain stem.
Data on the prevalence of hereditary spastic paraplegia vary, on average it is about 3.8 cases per 100 thousand population. The age period of the clinical picture debut is very wide: from 1 to 80 years. However, most often hereditary spastic paraplegia manifests at the age of 10-30 years. As a result of the rapid development of genetics in recent years, many genetic variants of hereditary spastic paraplegia have been identified and continue to be discovered. Currently, there are at least 17 chromosomal loci, defects in which cause hereditary spastic paraplegia with autosomal dominant inheritance, 29 loci responsible for autosomal recessive types of the disease, and 4 loci associated with inherited X-linked forms.
In clinical practice, the classification of hereditary spastic paraplegia is used, taking into account several different aspects at once. Depending on the mechanism of inheritance, autosomal dominant, autosomal recessive and X-linked forms are distinguished. In the first case, if one of the parents has hereditary spastic paraplegia, then the probability of the disease in the descendants is 50%. In the second case, the child’s disease is possible if both parents are carriers of a defective gene, the risk of having a sick child is 25%. With inheritance linked to the X chromosome, only males get sick, women are carriers of the pathological gene.
According to clinical manifestations, hereditary spastic paraplegia is classified into uncomplicated (simple) and complicated (complex) forms. The former are not accompanied by other leading symptoms, except for spastic lower paraparesis, the latter are its combination with other neurological disorders (epilepsy, mental retardation, hearing disorder, optic nerve atrophy, retinopathy, cerebellar ataxia, dysarthria). There are also hereditary spastic paraplegiae with onset in childhood, adolescence and adulthood.
According to the type of gene defect, the classification is constructed in the form of a numerical sequence. The English—language abbreviation of the hereditary spastic paraplegia gene is used – SPG, followed by a number from 1 to 56 or more (due to the constant detection of new types of mutations). Studies have shown that the most common type is SPG4, which accounts for up to 40% of cases of the disease.
With the early onset of the disease, the first symptoms are a delay in the formation of walking skills and walking on tiptoe. At the beginning at an older age, the clinic manifests difficulties when walking with frequent falls. Often, the first complaint of patients is “poor foot support when walking”, “stiffness in the legs”. Increased muscle tone in the legs is present from the very beginning of the disease. During the debut period, it can be transient in nature: it increases when walking and disappears at rest. Spasticity prevails in the soleus muscles of the lower leg, adductor and posterior thigh muscles. It may have an asymmetric character. In some cases, the patient complains of problems with only one leg. However, a neurological examination reveals a bilateral increase in tone and hyperreflexion of both legs with the presence of pyramidal stop signs (Oppenheim, Babinsky, Bekhterev, Rossolimo, etc.), clonus of the feet may be caused.
Hereditary spastic paraplegiae is characterized by gradual development. Decreased strength in the leg muscles (paresis) it appears after a fairly long period. With autosomal recessive forms, it is several years, with dominant forms – even more. Of the sensory disorders, some patients have mild disturbances of vibrational perception, sometimes paresthesia in the shins and feet. More pronounced sensitivity disorders are observed with the addition of polyneuropathy, usually with complicated forms.
Atrophic changes in the leg muscles, as a rule, occur in the late stages of hereditary spastic paraplegia and are caused by immobility due to severe paresis. Some forms of familial hereditary paraplegia (SPG10 and SPG17) are accompanied by atrophy of the arm muscles. In the advanced stage of the disease, spastic paresis of the upper extremities and urinary incontinence may occur. The latter is more typical for elderly patients, however, with SPG19 it manifests itself at the beginning of the disease. Complex forms of the disease are accompanied by a number of additional neurological symptoms, primarily cognitive decline from mild oligophrenia to severe dementia. Epilepsy, optical neuropathy, congenital retinopathy, dysarthria, cerebellar syndrome, extrapyramidal disorders, hearing loss, pseudobulbar syndrome are possible.
The presence of lower central paraplegia as a basic symptom and its familial nature is of crucial diagnostic importance. With sporadic and complicated forms, the neurologist has to perform differential diagnosis with ALS, spinal cord tumor, spinal variant of multiple sclerosis, vascular myelopathy, neurosyphilis. In order to differentiate hereditary spastic paraplegiae from leukodystrophy, an MRI of the brain is performed. In some cases, it reveals atrophic changes in the cerebral cortex. MRI of the spine visualizes degenerative-atrophic processes in the lateral and anterior pillars at the level of the thoracic and/or lumbar segments of the spinal cord.
An auxiliary method in the diagnosis of hereditary spastic paraplegia is electroneuromyography (ENMG) and the study of evoked potentials. ENMG allows you to determine the presence and degree of neuropathy. The study of somatosensory VP demonstrates a delay in conducting along the posterior spinal columns, the study of cortical VP demonstrates a decrease in the speed of conducting along the cortical—spinal pathway. Genealogical analysis and molecular genetic studies are of great diagnostic importance. Due to the large heterogeneity of pathology, the latter are carried out only for the most common types of the disease. Prenatal diagnosis is possible.
The therapy is based on muscle relaxants (baclofen, tolperizone) and tranquilizers (tazepam, diazepam), which also have a muscle relaxing effect. Treatment starts with a minimum dosage of the drug, which gradually increases. When the effect is achieved in the form of a significant weakening of spasticity, the dose of the drug is stopped to increase. If side effects occur, the dose increase is stopped, if this does not help, it is gradually reduced. Abrupt withdrawal of the drug is dangerous withdrawal syndrome, i.e. a rapid increase in spasticity to a degree exceeding the initial manifestations. In cases where oral administration does not give the desired effect, the drugs are administered intramuscularly. Endolumbal local administration is possible. In case of severe spasticity, they resort to installing a pump for constant intrathecal infusion of baclofen. This treatment is symptomatic, it does not completely cure hereditary spastic paraplegia, but only makes it possible to reduce stiffness in the legs and, thus, improve their mobility.
An alternative method of reducing spasticity is the introduction of botulinum toxin into the posterior thigh muscles and calf muscles. Along with medical treatment, a special complex of physical therapy, physiotherapy (paraffin treatment, acupressure, therapeutic baths) is used. The consultation and supervision of an orthopedist is indicated, if necessary, the use of orthoses. According to the indications, surgical orthopedic treatment of the resulting contractures is possible.
Hereditary spastic paraplegiae does not pose a threat to the patient’s life, but reduces his ability to work. The rate of progression and the severity of symptoms varies greatly even among members of the same family. The occurrence of the disease at an early age is usually characterized by a more malignant course. With uncomplicated forms during puberty, the condition can stabilize; despite significant difficulties when walking, patients do not lose the ability to move independently. In other cases, there is a steady progression with the loss of the ability to walk.