hereditary spastic paraplegia
Introduction
Introduction to hereditary spastic paraplegia Hereditary spastic paraplegia (HSP) was first reported by Seeligmuller (1874). It is characterized by progressive muscle tone, muscle weakness and scissor gait in both lower extremities. The clinical manifestations are slow progression of spastic paraplegia. The symptoms are diverse, and most scholars attribute it to the hereditary ataxia category, accounting for about a quarter of the total number of cases. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: multiple lung infections acne
Cause
Hereditary spastic paraplegia
Autosomal dominant inheritance (25%):
Autosomal dominant inheritance is related to chromosomes 2p, 8q, 14q and 15q. The SPG4 pathogenic gene is located at 2p2l-24, which is a CAG repeat dynamic mutation. The protein product spastin protein is connected with the microtubule of transfected cells to cause long-axis microtubule cytoskeleton regulation. Impaired, the most common, and related to dementia, 2p common variation clinical manifestations are significantly different.
Autosomal recessive inheritance (25%):
Autosomal recessive inheritance is associated with 8p, 15q and 16q, 15q is the most common, SPG5, SPG7 and Sjögren-Larsson syndrome are located at 8p12-13, 16q24.3 and 17p11.2, respectively; SPG5 and Sjögren-Larsson syndrome genes The products are paraplegin and FAIDH, and the SPG5 gene has deletions and insertions. The paraplegin protein is a metalloproteinase in the mitochondrial inner membrane, which is related to the 16q variation. It has been confirmed that the patient has oxidative phosphorylation defects.
X-linked recessive inheritance (5%):
X-linked recessive inheritance is rare. The SPG1 pathogenic gene is located in Xq28, and the gene product is the cell adhesion molecule L1 (CAM-L1). Pathogenic mutations including point mutations (Ile179Ser, Gly370Arg) and 3, 26, 28 have been revealed. Sub-small deletion; SPG2 pathogenic gene Xq21-22, the gene product is a lipid-containing protein (PLP), and five pathogenic point mutations (His139Tyr, Trp144Term, Ser169Phe, Ile186Thr, Phe236Ser) have been found.
Pathogenesis
At present, there are only a few pathological studies, mainly in the simple type of autosomal dominant inheritance. The main pathological changes are the longest up and down nerve conduction beam axis mutations, including corticospinal bundles that control the lower extremities, thin bundles, and small amounts. Wedge bundle, spinal cord cerebellar tract, heavier thoracic cord, nerve cells of degenerated axon remain, spinal cord anterior horn cells may have a small amount of deletion, posterior root ganglia and posterior root, peripheral nerves are normal, no demyelinating changes, base The nucleus, cerebellum, brainstem, and optic nerve are often involved.
Muscle biopsy of SPG7 patients caused by paraplegin gene mutations can be found in the hairy red fiber (RRF).
Prevention
Hereditary spastic paraplegia prevention
Neurological genetic diseases are difficult to treat, and the efficacy is not satisfactory. Prevention is more important. Preventive measures include avoiding marriage of close relatives, conducting genetic counseling, genetic testing of carriers, prenatal diagnosis and selective abortion to prevent the birth of children.
Complication
Hereditary spastic paraplegia Complications multiple lung infections acne
Should pay attention to lung infection caused by prolonged bed rest, hemorrhoids and so on.
Symptom
Hereditary spastic paraplegia symptoms Common symptoms Traumatic low paraplegia easy to fall involuntary movement muscle tension reduction reflex hyperthyroidism urinary incontinence deafness ataxia dementia
The disease is characterized by slow progressive lower extremity spasm weakness, mostly in children or puberty, males are slightly more, clinically can be divided into 2 types:
1. Simple type is more common, only showing paralytic paraplegia. The patient feels stiff in both lower limbs at the beginning of the disease. It is easy to fall on the road and difficult to go upstairs. It can be seen that the scissors gait, the muscle tension of both lower limbs, the hyperreflexia and pathological signs, etc. In childhood onset, bow-shaped foot deformity can be seen, accompanied by shortening of the gastrocnemius muscle (pseudo-collapse). The child can only walk with the toe, and the legs are less developed and thinner. As the disease progresses, the upper limbs appear pyramidal tract sign, feeling and autonomy. The neurological function is generally normal. It is reported that the fine feeling of the foot can be absent. Some patients have stiff hands, awkward movements, and mild dysarthria.
2. Variant sputum paraplegia with other damages constitute various syndromes.
(1) HSP with spinal cerebellum and ocular symptoms (Ferguson-Critchley syndrome): 30- to 40-year-old cerebellar cerebellar ataxia, bilateral leg muscle weakness, may have deep lower extremity sensation of the lower extremities, with optic nerve Atrophy, diplopia, horizontal nystagmus, lateral and vertical gaze limitation, and dysarthria, similar to multiple sclerosis, can occur in a family of generations, with extrapyramidal symptoms, such as stiff limbs, face Expressionless, forward gait and involuntary movement.
(2) HSP with extrapyramidal signs: such as resting tremor, Parkinson-like muscle rigidity, muscle tension reduced tongue movement and hand and foot hyperactivity, etc., the most common Parkinson's syndrome with spastic weakness and pyramidal tract signs.
(3) HSP with optic atrophy (Behr syndrome): usually combined with cerebellar signs, also known as optic atrophy - ataxia syndrome, is autosomal recessive inheritance, gradually decreased visual acuity before the age of 10, the fundus of the fundus is pale, The nipple macular bundle atrophy, combined with lower extremity paralysis, cleft palate, unclear speech, distal muscle atrophy, deformed foot, ataxia and hydrocephalus, etc., complete type often died before the age of 20, the life of the setback can be normal, only vision Mild decline.
(4) HSP with macular degeneration (Kjellin syndrome): about 25 years old, sputum weakness with progressive atrophy of hands and small muscles of the legs, mental retardation and central retinal degeneration; combined with ophthalmoplegia called Barnard- Scholz syndrome.
(5) HSP with mental retardation or dementia: also known as ichthyosis-like erythroderma - spastic paraplegia - mental retardation (Sjögren-Larsson) syndrome, autosomal recessive inheritance, early childhood onset or soon after birth The skin, diffuse flushing and thickening of the neck, armpits, elbow fossa, lower abdomen and groin, followed by skin keratosis and desquamation, dark red scales, spastic paraplegia or quadriplegia (lower limb weight), often accompanied by pseudobulbar Paralysis, epileptic seizures or small episodes, hand and foot movements, mild to severe mental retardation; 1/3 of cases of retinal macular degeneration cause visual impairment, visible optic atrophy or optic neuritis, but not blind; children are short, Enamel dysplasia, finger (toe) growth is not neat, poor prognosis, mostly died soon after the onset, rarely survive to childhood.
(6) HSP with polyneuropathy: manifested as sensory motor polyneuropathy with signs of corticospinal tract lesions, childhood or adolescent onset, until the early adult can not walk when the lesions stop progress, sural nerve biopsy is typical hyperplastic multiple Sexual neuropathy.
(7) HSP with distal muscle atrophy (Tyorer syndrome): autosomal recessive inheritance, early childhood onset, with hand muscle atrophy, followed by lower extremity paralysis or contracture, short stature, mild cerebellar symptoms, finger Xu Some cases are involuntarily laughing and dysfunctional, and they are still unable to walk until 20 to 30 years old.
(8) HSP with Alzheimer's disease (Mast syndrome): 11 to 20 years old, with explosive language, mask face, hand and foot, and ataxia.
(9) Charlevoix-Sageunay syndrome: more in children, manifested as paralytic paraplegia, ataxia, mental retardation, mitral valve prolapse, both hands muscle atrophy and urinary incontinence.
Examine
Hereditary spastic paraplegia
The disease, blood, urine, stool, cerebrospinal fluid routine tests are normal.
1. CT and MRI may have spinal cord thinning and atrophy.
2. Due to the damage of the posterior cord of the spinal cord, the somatosensory evoked potential of the lower limb cortex is abnormal, the latency is prolonged, and the amplitude is decreased, indicating that the nerve conduction velocity is slowed down.
Diagnosis
Diagnosis and differentiation of hereditary spastic paraplegia
According to family history, childhood (a few 20 to 30 years old) onset, slow progressive lower extremity paralysis, scissors gait, with optic atrophy, extrapyramidal symptoms, ataxia, muscle atrophy, dementia and skin lesions .
The disease must be differentiated from Arnold-Chiari malformation, multiple sclerosis, cerebral palsy, hereditary motor neuron disease, multiple system atrophy, cerebellar ataxia, subacute combined degeneration, and spinal cord compression.
