Spastic paraplegia

from Wikipedia, the free encyclopedia
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
Genetic classification of hereditary spastic spinal paralyses

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

  1. P. Berlit: Clinical Neurology. 2nd Edition. Springer, 2005, ISBN 3-540-01982-0 , pp. 550-551.
  2. Peter Reuter: Springer Lexicon Medicine. Springer, Berlin a. a. 2004, ISBN 3-540-20412-1 (Lemma Spastic Spinal Paralysis).
  3. Who named it
  4. ^ WH Erb: Spinal symptom complex. In: Berliner Zeitschrift Psych. 32, 1875. On spastic spinal paralysis (tabès dorsal spasmodique Charcot)
  5. JM Charcot: You spasmodique tabes dorsal. In: Progrés médical. 5, Paris 1876, pp. 737-737.
  6. 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.
  7. 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]).
  8. a b c d e SPG18.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  9. SPG19.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  10. SPG20.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  11. SPG21.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  12. a b c SPG30.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  13. SPG31.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  14. a b c d e f g h SPG33.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  15. a b c d e f g SPG34.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  16. 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]).
  17. a b c SPG35.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  18. a b SPG36.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  19. a b SPG37.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  20. a b SPG41.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  21. a b c d e f g h SPG42.  In: Online Mendelian Inheritance in Man . (English), last accessed October 3, 2011.
  22. ^ 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).
  23. ^ W. Hacke: Neurology. 13th edition. Springer-Verlag, 2010, ISBN 978-3-642-12381-8 , p. 718.
  24. R. Schüle, L. Schöls: Differential diagnosis of spastic paresis. In: Neurology & Psychiatry. 13 (1), 2011, pp. 30-36.
  25. a b c d A. Visbeck, HC Hopf: The hereditary spastic spinal paralyses. In: Akt Neurol. 28, 2001, pp. 153-160.
  26. Ludger Schöls et al .: Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain 2017; 140: 3112-3127.
  27. Neurological movement disorders
  28. Jürgen Heisel: Neurological differential diagnosis. 1st edition. Thieme-Verlag 2007, ISBN 978-3-13-140861-7 , p. 214.