Spastic paraplegia
Classification according to ICD-10 | |
---|---|
G11.4 | Hereditary spastic paraplegia |
ICD-10 online (WHO version 2019) |
The spastic paraplegia (SPG) , also called spastic spinal paralysis , represent a group of neurodegenerative diseases that occur sporadically or hereditary (hereditary). The hereditary spastic paraplegia (short HSP , also Strümpell Lorrain syndrome ) are genetically heterogeneous because mutations may trigger the disease in different genes. The inheritance is autosomal - dominant , autosomal recessive or X-linked recessive.
The spastic paraplegia are characterized by increasing spastic paralysis in the legs. At a very advanced stage, the person concerned may be dependent on using a wheelchair for the following lifetime .
Synonyms
Spastic spinal paralysis is synonymous with Erb-Charcot syndrome or Erb-Charcot disease . Both names refer to Wilhelm Heinrich Erb , who first described the disease in 1875, and to Jean-Martin Charcot with his description from 1876. Another description comes from Adolf von Strümpell from 1886. Hence the synonym Strümpell- Lorrain syndrome.
classification
Hereditary disease | Synonyms | clinic | Inheritance | OMIM | gene | Locate | Gene product | frequency |
---|---|---|---|---|---|---|---|---|
SPG1 | MASA syndrome | complicated HSP with mental retardation, hypoplasia of the corpus callosum , adducted thumb, and hydrocephalus | X-linked | 303350 | L1CAM | Xq28 | Neural cell adhesion molecule L1 | > 100 families |
SPG2 | Pelizaeus Merzbacher's disease | complicated HSP with quadriplegia, nystagmus, mental retardation and epileptic seizures | X-linked | 312920 | PLP1 | Xq22.2 | Myelin proteolipid protein | <100 families |
SPG3 | SPG3A | pure HSP, early onset, slow progression | autosomal dominant | 182600 | ATL1 | 14q22.1 | Atlastin-1 | <10% of autosomal dominant HSPs |
SPG4 | mainly pure HSP, variable age of onset | autosomal dominant | 182601 | SPAST | 2p22.3 | Spastin | 40% of pure autosomal dominant HSPs | |
SPG5A | pure HSP, variable age of onset, first possibly treatable form | autosomal recessive | 270800 | CYP7B1 | 8q12.3 | 25-hydroxycholesterol 7-alpha-hydroxylase | ~ 80 families
(second most common recessive form) |
|
SPG6 | pure HSP, manifestation adults | autosomal dominant | 600363 | NIPA1 | 15q11.2 | Magnesium transporter NIPA1 | ~ 10 families | |
SPG7 | Complicated HSP with cerebellar symptoms, optic atrophy and neuropathy, variable age of onset | autosomal recessive | 607259 | SPG7 | 16q24.3 | Paraplegin | > 400 families | |
SPG8 | pure HSP, manifestation adults | autosomal dominant | 603563 | KIAA0196 | 8q24.13 | WASH complex subunit strumpellin | <10 families | |
SPG9 | complicated HSP with cataract , motor neuropathy, skeletal abnormalities, and gastroesophageal reflux | autosomal dominant | 601162 | unknown | 10q23.3-q24.1 | unknown | 1 family | |
SPG10 | pure HSP, possibly complicated by muscle atrophy | autosomal dominant | 604187 | KIF5A | 12q13.3 | Kinesin heavy chain isoform 5A | <10 families | |
SPG11 | complicated HSP with narrow corpus callosum, cognitive impairment and neuropathy, early onset | autosomal recessive | 604360 | SPG11 | 15q21.1 | Spatacsin | many families | |
SPG12 | pure HSP, early manifestation | autosomal dominant | 604805 | unknown | 19q13 | unknown | <10 families | |
SPG13 | pure HSP, manifestation adults | autosomal dominant | 605280 | HSPD1 | 2q33.1 | Heat shock protein 60 | <10 families | |
SPG14 | Complicated HSP with motor neuropathy and mental retardation, variable age of onset | autosomal recessive | 605229 | unknown | 3q27-q28 | unknown | 1 family | |
SPG15 | Kjellin's syndrome | Complicated HSP with retinopathia pigmentosa , cerebellar symptoms and mental retardation, manifestation adolescence | autosomal recessive | 270700 | ZFYVE26 | 14q24.1 | Spasticity | <10 families |
SPG16 | Complicated HSP with aphasia, sphincter disorder and mental retardation, manifestation in childhood | X-linked | 300266 | unknown | Xq11.2 | unknown | 1 family | |
SPG17 | Silver Syndrome | Complicated HSP with distal muscular atrophy of the arms> legs, variable age of onset | autosomal dominant | 270685 | BSCL2 | 11q12.3 | Seipin | <20 families |
SPG18 | Complicated HSP with mental retardation and hypoplasia or agenesis of the corpus callosum, manifestation in childhood | autosomal recessive | 611225 | unknown | 8p12-p11.21 | unknown | 2 families | |
SPG19 | pure HSP, manifestation of adulthood | autosomal dominant | 607152 | unknown | 9q | unknown | 1 family | |
SPG20 | Troyer syndrome | Complicated HSP with muscular atrophy, cerebellar symptoms and developmental delay, manifestation in childhood | autosomal recessive | 275900 | SPG20 | 13q13.3 | Spartin | Founder Mutation in Amish |
SPG21 | Mast Syndrome | Complicated HSP with narrow corpus callosum, cognitive decline, cerebellar and extrapyramidal motor symptoms, manifestation of early adulthood | autosomal recessive | 248900 | SPG21 | 15q22.31 | Maspardin | Founder Mutation in Amish |
SPG23 | Lison syndrome | complicated HSP with pigment anomalies, facial and skeletal dysmorphisms, cognitive decay and tremor, manifestation in childhood | autosomal recessive | 270750 | unknown | 1q24-q32 | unknown | 1 family |
SPG24 | pure HSP, pseudobulbar symptoms | autosomal recessive | 607584 | unknown | 13q14 | unknown | 1 family | |
SPG25 | complicated HSP with cataracts and herniated discs, manifestation in adulthood | autosomal recessive | 608220 | unknown | 6q23-q24.1 | unknown | 1 family | |
SPG26 | Complicated HSP with neuropathy, distal muscular atrophy and intellectual impairment, manifestation in adulthood | autosomal recessive | 609195 | unknown | 12p11.1-q14 | unknown | 2 families | |
SPG27 | Complicated HSP with cerebellar symptoms, neuropathy, mental retardation and microcephaly, variable age of onset | autosomal recessive | 609041 | unknown | 10q22.1-q24.1 | unknown | 2 families | |
SPG28 | pure HSP, early manifestation | autosomal recessive | 609340 | unknown | 14q21.3-q22.3 | unknown | 1 family | |
SPG29 | complicated HSP with deafness, hiatal hernia , arches feet, and hyperbilirubinemia | autosomal dominant | 609727 | unknown | 1p31.1-p21.1 | unknown | 1 family | |
SPG30 | pure HSP, sensitive neuropathy, manifestation adolescence | autosomal recessive | 610357 | KIF1A | 2q37.3 | Kinesin-like protein KIF1A | 1 family | |
SPG31 | pure HSP, variable age of onset | autosomal dominant | 610250 | REEP1 | 2p11.2 | Receptor expression-enhancing protein 1 | 8% of pure autosomal dominant HSPs | |
SPG32 | Complicated HSP with mental retardation, narrow corpus callosum and pontine dysraphism , manifestation in childhood | autosomal recessive | 611252 | unknown | 14q12-q21 | unknown | 1 family | |
SPG33 | pure HSP, manifestation of adulthood | autosomal dominant | 610244 | ZFYVE27 | 10q24.2 | Protrudin | 1 family | |
SPG34 | pure HSP, early manifestation | X-linked | 300750 | unknown | Xq24-q25 | unknown | 1 family | |
SPG35 | Complicated HSP with intellectual decline, hair abnormalities and specific signs in the cMRI picture "WHAT", manifestation mainly in childhood | autosomal recessive | 612319 | FA2H | 16q23.1 | Fatty acid 2-hydroxylase | > 55 families | |
SPG36 | complicated HSP, age of manifestation variable | autosomal dominant | 613096 | unknown | 12q23-q24 | unknown | 1 family | |
SPG37 | variable age of onset | autosomal dominant | 611945 | unknown | 8p21.1-q13.3 | unknown | 1 family | |
SPG38 | complicated HSP with distal muscular atrophy of the arms> legs | autosomal dominant | 612335 | unknown | 4p16-p15 | unknown | 1 family | |
SPG39 | complicated HSP distal muscular atrophy of all extremities | autosomal recessive | 612020 | PNPLA6 | 19p13.2 | Neuropathy target esterase | 2 families | |
SPG41 | pure HSP, manifestation adolescence | autosomal dominant | 613364 | unknown | 11p14.1-p11.2 | unknown | 1 family | |
SPG42 | pure HSP, variable age of onset | autosomal dominant | 612539 | SLC33A1 | 3q25.31 | Acetyl-coenzyme A transporter 1 | 1 family |
Epidemiology
The prevalence is 4–5 / 100,000 inhabitants. 75% of cases are hereditary, the rest sporadic. Male people are affected twice as often as female people.
root cause
The group of spastic spinal paralyses is genetically heterogeneous. There are 48 different loci of HSP known. They are named SPG for spastic paraplegia gene and numbered from 1–78. The inheritance is different depending on the form and can be autosomal dominant, autosomal recessive or x-linked. To date,> 50 genes affected by mutations have been identified.
Symptoms and course
The onset of the disease in hereditary spastic spinal paralysis is very variable and ranges from early childhood to the seventh decade of life. There is an increasing spastic paralysis of the legs (paraparesis).
Depending on the clinical symptoms, a distinction is made between pure and complex forms of hereditary spastic spinal paralysis. In the pure forms, the symptoms are essentially limited to spastic paraparesis. However, sensitivity disorders with disorders of depth, surface and temperature sensitivity as well as bladder disorders ( imperative urination , pollakiuria , occasionally urge incontinence ) and rarely rectal disorders can occur. Complicated hereditary spinal spinal paralyses (CHSP) are defined by the occurrence of other neurological symptoms such as ataxia , severe muscle atrophy , optic atrophy , retinopathy , impairment of the extrapyramidal motor system , mental retardation , dementia , deafness , ichthyosis , neuropathy and epilepsy . The complicated shapes are very rare. Examples are Sjogren-Larsson syndrome , Troyer syndrome , MASA syndrome , Charlevoix-Saguenay syndrome and Kjellin syndrome .
The extent of the spasticity often exceeds that of the paresis. In addition to the age of onset, progression and the degree of disability are also variable. The adductors in the hip joint are typically preferentially affected. This adductor spasticity leads to a “scissor walk”. Those affected have difficulty getting their legs past each other when walking. Increased muscle reflexes are often detectable in both the upper and lower extremities. However, the muscles of the upper extremities rarely show spastic paralysis, and when they are, these are only mildly pronounced compared to the lower extremities. Symptoms of the disease worsen over a period of 2-3 decades, and in the terminal stages, patients with spastic contractures become bedridden.
examination
The self-reflexes are significantly increased during the examination . There may be a spontaneous babinski . The abdominal skin reflexes are retained for a long time, and sensitivity is often also affected. The CSF findings should be carried out to diagnose exclusion (multiple sclerosis, infection with HTLV1 / 2) and are usually normal.
histology
Downfall of the Betz cells in the 5th layer of the precentral gyrus and continuous or discontinuous degeneration of the pyramidal tract .
therapy
The diseases are currently mostly symptomatic, but not causally treatable. Only in HSP of type 5 is it known that a gene change leads to the accumulation of 27-hydroxy-cholesterol. A cholesterol lowering drug reduces the amount of this substance that damages nerve cells.
Investigation methods
Differential diagnoses
Multiple sclerosis , cervical myelopathy , space occupying spinal process , amyotrophic lateral sclerosis , funicular myelosis , neuroborreliosis , Friedreich's ataxia , parasagittal meningioma
See also
Individual evidence
- ↑ P. Berlit: Clinical Neurology. 2nd Edition. Springer, 2005, ISBN 3-540-01982-0 , pp. 550-551.
- ↑ Peter Reuter: Springer Lexicon Medicine. Springer, Berlin a. a. 2004, ISBN 3-540-20412-1 (Lemma Spastic Spinal Paralysis).
- ↑ Who named it
- ^ WH Erb: Spinal symptom complex. In: Berliner Zeitschrift Psych. 32, 1875. On spastic spinal paralysis (tabès dorsal spasmodique Charcot)
- ↑ JM Charcot: You spasmodique tabes dorsal. In: Progrés médical. 5, Paris 1876, pp. 737-737.
- ↑ A. von Strümpell: About a certain form of the primary combined systemic diseases of the spinal cord. In: Archives for Psychiatry and Nervous Diseases. 17, Berlin 1886, pp. 217-238.
- ↑ Ludger Schöls *, Tim W Rattay *, Peter Martus, Christoph Meisner, Jonathan Baets: Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial . In: Brain . tape 140 , no. 12 , December 1, 2017, ISSN 0006-8950 , p. 3112–3127 , doi : 10.1093 / brain / awx273 , PMID 29126212 , PMC 5841036 (free full text) - ( oup.com [accessed September 1, 2019]).
- ↑ a b c d e SPG18. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ SPG19. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ SPG20. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ SPG21. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b c SPG30. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ SPG31. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b c d e f g h SPG33. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b c d e f g SPG34. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b Tim Rattay W, Tobias Lindig, Jonathan Baets, Katrien Smets, Tine Deconinck: FAHN / SPG35: a narrow phenotypic spectrum across disease classifications . In: Brain . tape 142 , no. 6 , June 1, 2019, ISSN 0006-8950 , p. 1561–1572 , doi : 10.1093 / brain / awz102 , PMID 31135052 , PMC 6536916 (free full text) - ( oup.com [accessed September 1, 2019]).
- ↑ a b c SPG35. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b SPG36. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b SPG37. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b SPG41. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ↑ a b c d e f g h SPG42. In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
- ^ A b S. Salinas, C. Proukakis, A. Crosby, TT Warner: Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. In: The Lancet Neurology . Volume 7, Number 12, December 2008, pp. 1127-1138, ISSN 1474-4422 . doi: 10.1016 / S1474-4422 (08) 70258-8 . PMID 19007737 . (Review).
- ^ W. Hacke: Neurology. 13th edition. Springer-Verlag, 2010, ISBN 978-3-642-12381-8 , p. 718.
- ↑ R. Schüle, L. Schöls: Differential diagnosis of spastic paresis. In: Neurology & Psychiatry. 13 (1), 2011, pp. 30-36.
- ↑ a b c d A. Visbeck, HC Hopf: The hereditary spastic spinal paralyses. In: Akt Neurol. 28, 2001, pp. 153-160.
- ↑ Ludger Schöls et al .: Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain 2017; 140: 3112-3127.
- ↑ Neurological movement disorders
- ↑ Jürgen Heisel: Neurological differential diagnosis. 1st edition. Thieme-Verlag 2007, ISBN 978-3-13-140861-7 , p. 214.