spastic paraplegia

痙性対麻痺

関

paraplegia、spastic paraparesis

WordNet

1. suffering from spastic paralysis; "a spastic child"
2. a person suffering from spastic paralysis
3. relating to or characterized by spasm; "a spastic colon"; "spastic paralysis is a spastic form of cerebral palsy"
4. paralysis of the lower half of the body (most often as a result of trauma)

PrepTutorEJDIC

1. けいれん性麻痺患者
2. 対麻痺(ついまひ)(病気による両下肢(し)の麻痺)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/08 18:10:43」(JST)

wiki en

[Wiki en表示]

Hereditary spastic paraplegia
Classification and external resources
Specialty	neurology
ICD-10	G11.4
ICD-9-CM	334.1
OMIM	312920 PS303350
DiseasesDB	33207
eMedicine	pmr/45
MeSH	D015419

Hereditary spastic paraplegia (HSP), also known as hereditary spastic paraparesis, familial spastic paraplegias, French settlement disease, or Strumpell-Lorrain disease, is a group of inherited diseases whose main feature is progressive stiffness and contraction (spasticity) in the lower limbs, as a result of damage to or dysfunction of the nerves.

HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as, for example, spastic diplegia. The origins of HSP are entirely separate phenomena from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to try to treat HSP symptomatology.

The condition sometimes also affects the optic nerve and retina of the eye, causes cataracts, ataxia (lack of muscle coordination), epilepsy, cognitive impairment, peripheral neuropathy, and deafness. HSP is caused by defects in the mechanisms that transport proteins and other substances through the cell. Long nerves are affected because they have to transport cellular material through long distances, and are particularly sensitive to defects of cellular transport.

Hereditary spastic paraplegia was first described in 1883 by Adolph Strümpell, a German neurologist, and was later described more extensively in 1888 by Maurice Lorrain, a French physician.

Neuropathology

The major neuropathologic feature of HSP is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent. Neuronal cell bodies of degenerating fibers are preserved and there is no evidence of primary demyelination. Loss of anterior spinal horn is observed in some cases. Dorsal root ganglia, posterior roots and peripheral nerves are normal.

Classification

Hereditary spastic paraplegias are classified based on the symptoms; on their mode of inheritance; on the patient’s age at onset; and, ultimately, on the gene associated with the condition.

Based on symptoms

Spasticity in the lower limbs alone is described as pure HSP. On the other hand, HSP is classified as complex or complicated when associated with other neurological signs, including ataxia, mental retardation, dementia, extrapyramidal signs, visual dysfunction or epilepsy, or with extraneurological signs. Complicated forms are diagnosed as HSPs when pyramidal signs are the predominant neurological characteristic. This classification, however, is subjective and patients with complex HSPs are sometimes diagnosed as having cerebellar ataxia, mental retardation or leukodystrophy.

Based on mode of inheritance

HSP being a group of genetic disorders, they follow general inheritance rules and can be inherited in an autosomal dominant, autosomal recessive or x-linked recessive manner. The mode of inheritance involved has a direct impact on the chances of inheriting the disorder. Over 70 genotypes have been described.

At least 48 genetic loci have been linked to this condition. Ten genes have been identified with autosomal dominant inheritance. One of these SPG4 accounts for ~50% of all cases. Twelve genes are known to be inherited in an autosomal recessive fashion. Collectively this latter group account for ~1/3 cases.

The functions of a number of these genes are known: spastin (SPG4) and paraplegin (SPG7) are both AAA ATPases. Spastizin (ZFYVE26) is zinc finger transcription factor: mutations in this gene cause SPG15. The inheritance of SPG15 is autosomal recessive.

Summary of genotypes

The genes are designated SPG (Spastic gait gene). The gene locations are in the format: chromosome - arm (short or p: long or q) - band number. These designations are for the human genes only. The locations may (and probably will) vary in other organisms.

Genotype	Gene name	Gene function	Inheritance	Age of onset	Gene location
SPG1	L1 cell adhesion molecule	Glycoprotein	X linked recessive	Early	Xq28
SPG2	Myelin protein	Transmembrane protein	X linked recessive	Variable	Xq22.2
SPG3A	Atlastin	Membrane anchored GTPase	Autosomal dominant	Early	14q22.1
SPG4	Spastin	AAA ATPase	Autosomal dominant	Variable	2p22.3
SPG5	25-hydroxycholesterol 7-alpha-hydroxylase	Cytochrome P45	Autosomal recessive	Variable	8q12.3
SPG6	Non-imprinted in Prader-Willi/Angelman syndrome region protein 1	Transmembrane protein	Autosomal dominant	Teenage	15q11.2
SPG7	Paraplegin	AAA ATPase	Autosomal dominant	Variable	16q24.3
SPG8	Strumpellin	Valosin containing endoplasmic reticulum protein	Autosomal dominant	Adult	8q24.13
SPG9	Not currently known		Autosomal dominant	Teenage	10q23.3–24.2
SPG10	Kinesin heavy chain isoform 5A	Kinesin chain	Autosomal dominant	Early	12q13.3
SPG11	Spatacsin	Lysosomal protein	Autosomal recessive	Variable	15q21.1
SPG12	Reticulon 2	Endoplasmic reticulum protein	Autosomal dominant	Early	19q13.32
SPG13	Chaperonin 60/Heat shock protein 60	Heat shock protein	Autosomal dominant	Variable	2q33.1
SPG14	Not currently known		Autosomal recessive	Adult	3q27–q28
SPG15	Spastizin	Zinc finger containing protein	Autosomal recessive	Early	14q24.1
SPG16	Not currently known		X linked recessive	Early	Xq11.2
SPG17	Seipin	Integral membrane protein of the endoplasmic reticulum	Autosomal dominant	Teenage	11q12.3
SPG18	ERLIN2	Endoplasmic reticulum protein	Autosomal recessive	Early	8p11.23
SPG19	Not currently known		Autosomal dominant	Adult onset	9q
SPG20	Spartin	FK506-binding protein	Autosomal recessive	Early onset	13q13.3
SPG21	Acidic cluster protein 33/Maspardin	Membrane protein	Autosomal recessive	Early onset	15q22.31
SPG22	Monocarboxylate transporter 8	Transmembrane transport protein	X linked recessive	Early onset	Xq13.2
SPG23	Not currently known		Autosomal recessive	Early onset	1q24–q32
SPG24	Not currently known		Autosomal recessive	Early onset	13q14
SPG25	Not current known		Autosomal recessive	Adult	6q23–q24.1
SPG26	Beta-1,4 N-acetylgalactosaminyltransferase 1		Autosomal recessive	Early onset	12p11.1–q14
SPG27	Not currently known		Autosomal recessive	Variable	10q22.1–q24.1
SPG28	DDHD1/Phosphatidic acid phospholipase A1		Autosomal recessive	Early onset	14q22.1
SPG29	Not currently known		Autosomal dominant	Teenage	1p31.1–p21.1
SPG30	Kinesin 3	Kinesin protein	Autosomal recessive	Teenage	2q37.3
SPG31	Receptor expression-enhancing protein 1	Endoplasmic reticulum protein	Autosomal dominant	Early onset	2p11.2

Based on patient's age at onset

In the past, HSP also has been classified as type I or type II on the basis of the patient's age at the onset of symptoms, which influences the amount of spasticity versus weakness. Type I is characterized by age onset below 35 years, whereas Type II is characterized by onset over 35 years. In the type I cases, delay in walking is not infrequent and spasticity of the lower limbs is more marked than weakness. In the type II muscle weakness, urinary symptoms and sensory loss are more marked. Furthermore, type II form of HSP usually evolves more rapidly.

Symptoms

Symptoms depend on the type of HSP inherited. The main feature of the disease is progressive spasticity in the lower limbs, due to pyramidal tract dysfunction. This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. Furthermore, among the core symptoms of HSP are also included abnormal gait and difficulty in walking, decreased vibratory sense at the ankles, and paresthesia. Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. Symptoms of HSP may begin at any age, from infancy to older than 60 years. If symptoms begin during the teenage years or later, then spastic gait disturbance usually progresses insidiously over many years. Canes, walkers, and wheelchairs may eventually be required, although some people never require assistance devices. More specifically, patients with the autosomal dominant pure form of HSP reveal normal facial and extraocular movement. Although jaw jerk may be brisk in older subjects, there is no speech disturbance or difficulty of swallowing. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles. In the complex form of the disorder, additional symptoms are present. These include: peripheral neuropathy, amyotrophy, ataxia, mental retardation, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.

Diagnosis

Initial diagnosis of HSPs relies upon family history, the presence or absence of additional signs and the exclusion of other nongenetic causes of spasticity, the latter being particular important in sporadic cases.

Cerebral and spinal MRI is an important procedure performed in order to rule out other frequent neurological conditions, such as multiple sclerosis, but also to detect associated abnormalities such as cerebellar or corpus callosum atrophy as well as white matter abnormalities. Differential diagnosis of HSP should also exclude spastic diplegia which presents with nearly identical day-to-day effects and even is treatable with similar medicines such as baclofen and orthopedic surgery; at times, these two conditions may look and feel so similar that the only perceived difference may be HSP's hereditary nature versus the explicitly non-hereditary nature of spastic diplegia (however, unlike spastic diplegia and other forms of spastic cerebral palsy, HSP cannot be reliably treated with selective dorsal rhizotomy).

Ultimate confirmation of HSP diagnosis can only be provided by carrying out genetic tests targeted towards known genetic mutations.

Prognosis

Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. Some cases are seriously disabling while others are less disabling and are compatible with a productive and full life. The majority of individuals with HSP have a normal life expectancy.

Treatment

No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. Therapeutics offered to HSP patients include:

• Baclofen – a voluntary muscle relaxant to relax muscles and reduce tone
• Tizanidine – to treat nocturnal or intermittent spasms
• Diazepam and Clonazepam – to decrease intensity of spasms
• Oxybutynin chloride – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
• Tolterodine tartate – an involuntary muscle relaxant and spasmolytic agent, used to reduce spasticity of the bladder in patients with bladder control problems
• Botulinum toxin – to reduce muscle overactivity
• Antidepressants (such as selective serotonin re-uptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors) – for patients experiencing clinical depression
• Physical Therapy – to restore and maintain the ability to move; to reduce muscle tone; to maintain or improve range of motion and mobility; to increase strength and coordination; to prevent complications, such as frozen joints, contractures, or bedsores.

Epidemiology

Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. A Norwegian study of more than 2.5 million people published in March 2009 has found an HSP prevalence rate of 7.4/100,000 of population – a higher rate, but in the same range as previous studies. No differences in rate relating to gender were found, and average age at onset was 24 years. In the United States, Hereditary Spastic Paraplegia is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health which means that the disorder affects less than 200,000 people in the US population.

See also

• Genetics

References

External links

• GeneReviews/NCBI/NIH/UW entry on Spastic Paraplegia 3A
• Hereditary spastic paraplegia at DMOZ
• GeneReviews/NCBI/NIH/UW entry on Hereditary Spastic Paraplegia Overview
• Warner, Tom (January–February 2007). "Hereditary Spastic Paraplegia" (PDF). Advances in Clinical Neuroscience & Rehabilitation 6 (6): 16–17. 
• Hereditary Spastic Paraplegia Support Group
• Hereditary Spastic Paraplegia multi-language communication platform

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 遺伝性痙性対麻痺 hereditary spastic paraplegia
• 2. ペリツェウス・メルツバッハー病 pelizaeus merzbacher disease
• 3. 脊髄に影響を与える疾患 disorders affecting the spinal cord
• 4. 脊髄障害の解剖学および局在性 anatomy and localization of spinal cord disorders
• 5. 筋萎縮性側索硬化症およびその他の運動ニューロン疾患の診断 diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease

English Journal

• Determinants of handbike use in persons with spinal cord injury: results of a community survey in Switzerland.

• Arnet U1,2, Hinrichs T1,2, Lay V1, Bertschy S1,2, Frei H3, Brinkhof MW1,2; SwiSCI study group.
• Disability and rehabilitation.Disabil Rehabil.2016 Jan;38(1):81-6. doi: 10.3109/09638288.2015.1024339. Epub 2015 Mar 18.
• PURPOSE: To examine the prevalence and determinants of handbike use in persons living with spinal cord injury in Switzerland.METHOD: A population-based cross-sectional survey in Switzerland.RESULTS: The crude prevalence of handbike use among the 1549 participants was 22.6%, varying between 25.3% in
• PMID 25784201

• Modeling Axonal Phenotypes with Human Pluripotent Stem Cells.

• Denton KR1, Xu CC1, Li XJ2,3.
• Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2016;1353:309-21. doi: 10.1007/7651_2014_167.
• Impaired axonal development and degeneration are implicated in many debilitating disorders, such as hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and periphery neuropathy. Human pluripotent stem cells (hPSCs) have provided researchers with an excellent resource for modeli
• PMID 25520289

• Overexpression of KLC2 due to a homozygous deletion in the non-coding region causes SPOAN syndrome.

• Melo US1, Macedo-Souza LI1, Figueiredo T2, Muotri AR3, Gleeson JG4, Coux G5, Armas P5, Calcaterra NB5, Kitajima JP6, Amorim S7, Olávio TR1, Griesi-Oliveira K1, Coatti GC1, Rocha CR8, Martins-Pinheiro M8, Menck CF8, Zaki MS9, Kok F10, Zatz M11, Santos S2.
• Human molecular genetics.Hum Mol Genet.2015 Dec 15;24(24):6877-85. doi: 10.1093/hmg/ddv388. Epub 2015 Sep 18.
• SPOAN syndrome is a neurodegenerative disorder mainly characterized by spastic paraplegia, optic atrophy and neuropathy (SPOAN). Affected patients are wheelchair bound after 15 years old, with progressive joint contractures and spine deformities. SPOAN patients also have sub normal vision secondary
• PMID 26385635

Japanese Journal

• SPAST mutation spectrum and familial occurrence among Czech patients with pure hereditary spastic paraplegia

• Journal of human genetics 61(10), 845-850, 2016-10
• NAID 40020966111

• Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia

• Journal of human genetics 61(6), 571-573, 2016-06
• NAID 40020857183

• 遺伝性痙性対麻痺 (第1土曜特集 小脳の最新知見 : 基礎研究と臨床の最前線) -- (小脳の病態 : 小脳疾患の診療の最前線)

• 医学のあゆみ 255(10), 1055-1061, 2015-12-05
• NAID 40020666594

Related Pictures

---

★リンクテーブル★

リンク元	「痙性対麻痺」「spastic paraparesis」
関連記事	「spastic」

「痙性対麻痺」

　　[★]

英

spastic paraparesis、spastic paraplegia

関

対麻痺

「spastic paraparesis」

　　[★]

痙性対麻痺

関

spastic paraplegia

「spastic」

　　[★]

• adj.

• 痙性の、痙直の、痙攣性の、けいれん性の、痙縮性の

関

convulsive、cramp、muscle spasticity、spasmodic、spasticity