Hereditary spastic paraplegia

　　First, the cause of the disease

　　This disease is a genetic disorder with high genetic heterogeneity. Twenty gene loci have been found, named SPG1 to SPG20 in the order of discovery, among which five genes have been cloned.

　　1, Autosomal dominant inheritance is associated with chromosomes 2p, 8q, 14q, and 15q. The pathogenic gene for SPG4 is located at 2p21-24 and is a CAG repeat dynamic mutation. The protein product spastin protein is associated with transfection cell microtubules, causing damage to the long-axis microtubule cytoskeleton regulation, which is the most common and associated with dementia. The clinical manifestations of 2p common variants are significantly different.

　　2, Autosomal recessive inheritance is associated with 8p, 15q, and 16q, with 15q being the most common. SPG5, SPG7, and Sj?gren-Larsson syndrome are located at 8p12-13, 16q24.3, and 17p11.2, respectively. The gene products of SPG5 and Sj?gren-Larsson syndrome are paraplegin and FAIDH, respectively. SPG5 gene mutations can be in the form of deletions and insertions. Paraplegin protein is a mitochondrial inner membrane metalloproteinase associated with 16q variants. Oxidative phosphorylation defects have been confirmed in patients.

　　3. X-linked recessive inheritance is rare, the SPG1 pathogenic gene is located at Xq28, the gene product is cell adhesion molecule L1 (CAM-L1), and pathogenic mutations have been found including point mutations (Ile179Ser, Gly370Arg) and small deletions in exons 3, 26, and 28; SPG2 pathogenic gene Xq21-22, the gene product is lipid protein (PLP), and 5 pathogenic point mutations have been found (His139Tyr, Trp144Term, Ser169Phe, Ile186Thr, Phe236Ser).

　　Second, pathogenesis

　　Currently, there are only a few pathological studies, mainly seen in autosomal dominant simple type. The main pathological change is the mutation of the longest ascending and descending nerve conduction tract axons, including the corticospinal tract, fasciculus, a small amount of fasciculus, and spinal-cerebellar tract that支配 the lower limbs. The thoracic spinal cord is more severe, and the nerve cells of the degenerated axons are still retained. The anterior horn cells of the spinal cord may have a small loss. The posterior root ganglion and posterior root, and peripheral nerves are normal, without demyelinating changes. The basal ganglia, cerebellum, brainstem, and optic nerve are often involved.

　　For patients with SPG7 caused by paraplegin gene mutation, muscle biopsy can find bristle-like red fibers (RRF).

　　Attention should be paid to complications caused by long-term bed rest, such as pulmonary infection, bedsores, etc. Long-term bedridden patients, due to extreme physical weakness or loss of sensory and motor function, are unable to change their position. In addition, improper care can lead to ulcers formed by the skin tissue located between the body surface bony prominence and the bed mattress, even muscle, due to continuous pressure, local hypoxia, vascular thrombosis, tissue necrosis, and corruption.

　　This disease is characterized by slowly progressive spastic weakness in both lower limbs, often occurring in childhood or adolescence, with a slight male predominance. Clinically, it can be divided into 2 types:

　　First, simple type:More common, only showing spastic paraplegia. Patients may feel stiffness in both lower limbs at the onset of the disease, easily fall while walking, have difficulty climbing stairs, and may show scissor gait. Both lower limbs have increased muscle tone, hyperreflexia, and pathological signs. In some cases, arch foot deformity can be seen in childhood onset, accompanied by gastrocnemius shortening (pseudocontracture), and the child can only walk on the tips of their feet. Both legs are underdeveloped and thin. As the disease progresses, the upper limbs show pyramidal tract signs. Sensory and autonomic functions are generally normal. Some reports suggest that fine sensation in the feet may be missing. Some patients have stiffness in their hands, awkward movements, and mild dysphonia.

　　Second, variant type:Spastic paraplegia accompanied by other impairments, forming various syndromes.

　　1. HSP with spinal-cerebellar and ocular symptoms (Ferguson-Critchley syndrome):Spinal-cerebellar ataxia manifestations appear between 30 to 40 years old, with spastic muscle weakness in both legs, possible distal deep sensation impairment in both lower limbs, accompanied by optic nerve atrophy, diplopia, horizontal nystagmus, lateral and vertical gaze restriction, and dysphonia, resembling multiple sclerosis. It can appear in several generations of a family, and can be accompanied by extrapyramidal symptoms such as rigidity of the limbs, facial expressionlessness, propulsive gait, and involuntary movements.

　　2, HSP with extrapyramidal signs:Including static tremor, parkinsonian rigidity, hypotonic tongue movement, and athetosis of hands and feet, the most common being Parkinson's syndrome with spastic weakness and corticospinal tract signs.

　　3, HSP with optic atrophy (Behr syndrome):It is often associated with cerebellar signs, also known as the optic atrophy-ataxia syndrome, an autosomal recessive inheritance, with gradual vision loss before the age of 10, fundus disc pallor in the temporal side, atrophy of the papillomacular bundle, accompanied by bilateral lower limb spasm, cleft palate, unclear speech, distal muscle atrophy, deformed feet, ataxia, and hydrocephalus, etc. The complete type often dies before the age of 20, while the abortive type can have a normal lifespan, with only slight vision loss.

　　4, HSP with macular degeneration (Kjellin syndrome):Onset around 25 years old, with spastic weakness accompanied by progressive atrophy of small muscles in the hands and legs, intellectual disability, and central retinal degeneration, etc.; when combined with ophthalmoplegia, it is called the Barnard-Scholz syndrome.

　　5, HSP with intellectual disability or dementia:Also known as ichthyosis-like erythroderma-spastic paraplegia-intellectual disability (Sjgren-Larsson) syndrome, it is an autosomal recessive inheritance, with onset in infancy or shortly after birth, presenting with generalized erythema and thickening of the skin over the neck, axilla, elbow, lower abdomen, and inguinal regions, followed by skin keratosis and desquamation, appearing as dark red ichthyosis. Spastic paraplegia or quadriplegia (more severe in the lower limbs), often accompanied by pseudobulbar palsy, grand mal or petit mal seizures, athetosis, mild to severe intellectual disability, etc.; 1/3 of the cases have macular degeneration of the retina, leading to visual impairment, with optic atrophy or optic neuritis, but not blindness; children are short in stature, with incomplete enamel development, irregular growth of fingers (toes), poor prognosis, and most die soon after onset, rarely surviving to childhood.

　　6, HSP with polyneuropathy:Manifested as sensory motor polyneuropathy with signs of corticospinal tract lesions, onset in childhood or adolescence, and the lesions stop progressing when unable to walk in early adulthood, with a biopsy of the popliteal nerve showing typical hyperplastic polyneuropathy.

　　7, HSP with distal muscle atrophy (Tyorer syndrome):It is an autosomal recessive inheritance, with onset in early childhood, accompanied by hand muscle atrophy, followed by lower limb spasm or contracture, short stature, mild cerebellar symptoms, finger athetosis, and deafness, etc. Some cases have involuntary smiling, dysphonia, and cannot walk until 20 to 30 years old.

　　8, HSP with presenile dementia (Mast syndrome):Onset between 11 to 20 years old, with symptoms such as explosive language, mask-like face, athetosis of hands and feet, and ataxia, etc.

　　9, Charlevoix-Sageunay syndrome:Mostly occur in children, with symptoms such as spastic paraplegia, ataxia, intellectual disability, mitral valve prolapse, hand muscle atrophy, and urinary incontinence, etc.

　　The treatment of neurological genetic diseases is difficult, the efficacy is not satisfactory, and prevention is more important. Prevention measures include avoiding close relatives' marriage, promoting genetic counseling, carrier gene detection, prenatal diagnosis, and selective induced abortion, etc., to prevent the birth of children. Decubitus ulcers are prone to occur at the sacrum, ischial tuberosity, greater trochanter of the femur, etc., followed by calcaneus, occipital bone, anterior superior iliac spine, medial and lateral malleoli, etc., which are the most common complications of the disease. Pay attention to active prevention.

　　The routine blood, urine, stool, and cerebrospinal fluid tests of this disease are all normal.

　　1. CT and MRI may show thinning and atrophy of the spinal cord.

　　2. Due to the damage of the posterior column of the spinal cord, the somatosensory evoked potential of the lower limbs is abnormal, the latency is prolonged, and the amplitude is reduced, indicating that the conduction speed of the nerve is slowed down.

　　Diet should be light and nutritious, pay attention to dietary balance. Avoid spicy and刺激性 foods. In order to avoid the recurrence of the disease, such as seafood, chicken, dog meat, etc. At the same time, do not ban spicy foods. Eat more fresh vegetables and fruits. Fresh vegetables and fruits contain a large number of nutrients needed by the human body. Eat more foods that enhance immunity: postoperative patients have poor physical condition and low immunity, so they should eat more foods that can enhance immunity, such as yam, turtle, mushroom, kiwi, fig, apple, sardine, honey, milk, pork liver, etc., to improve the body's resistance to diseases.

　　I. Treatment

　　To date, there is no effective prevention and treatment method for this disease, nor any method to delay its progression. The main approach is symptomatic treatment, levodopa and baclofen can alleviate symptoms, physical therapy and appropriate exercise are also helpful.

　　II. Prognosis

　　The condition progresses slowly, eventually leading to bedridden, and death due to the complication of other diseases.

　　Primarily based on careful nursing. Treatment includes non-surgical treatment and surgical treatment. Surgical treatment, in addition to the complete excision of ulcers, often uses skin flaps and other methods to repair the wound.