HEREDITARY SPASTIC PARAPLEGIA: CLINICAL OBSERVATIONS

Pinchuk V. A., Kryvchun A. M., Sylenko G. Ya., Pinchuk V. V., Verevka O. A.

LITERATURE REVIEWS

Scentific article

The article presents examples of own clinical observation of two cases of sporadic hereditary spastic paraplegia. Discussed clinical and diagnostic criteria of this pathology. The features of the course, clinical picture, heredity and additional methods of research of hereditary spastic paraplegia are noted. Knowledge of this form will help neurologists not only properly formulate the diagnosis, but also to predict its course. In the article examples of the clinical observation of two cases of sporadic hereditary spastic paraplegia (HSP) are given. HSP is a group of clinically and genetically diverse disorders that manifest themselves with severe weakness and spasticity of the lower extremities, and the recovery of tendon reflexes in the absence of susceptible disorders. The prevalence of HSP varies from 1,0-4,0 per 100 000 people. Several mechanisms have been identified in the pathogenesis of HSP: the transport of cell membranes, in particular axonal transport of macromolecules and organelles; mitochondrial dysfunction; defects in the functioning of oligodendroglia for the SPG2 gene. The degenerative process is observed in the lateral and posterior pins of the spinal cord. Currently more than 80 genetic loci have been identified. There are families with autosomal dominant, with autosomal recessive and sporadic patients. Most cases of pure HSP are autosomal dominant, whereas complex forms tend to be autosomal recessive. By classification according to the clinical principle, “pure” (“simple”) hereditary HSPs are distinguished, in which the spastic paraplegia is dominant, although not the only symptom (lesions of the cortico-spinal tract), and “complex” forms (paraplegia plus). It is known that the diagnosis of sporadic cases and complicated HSP is hampered by a large number of genocides, including hereditary diseases. In the absence of a family history, it is necessary to exclude clinically similar and potentially curable diseases, first of all: parasaginal meningioma; compression of the thoracic spinal cord; cord spondylogenic myelopathy; funicular myelosis (deficiency of vitamin B12 and folic acid);multiple sclerosis; primary lateral sclerosis; spastic diplegia with infantile cerebral palsy (Little’s disease); DOPA-sensitive dystonia; lateral amyotrophic sclerosis; ectodermal dysplasia; syphilitic meningitis adrenolectocystastrophy; metachromatic leukodistrophy; HIV-myelopathy; Krabbe’s disease; syringomyelia. In the neurological department of the Poltava Regional Clinical Hospital were examined and treated with 2 patients with HSP. Moreover, in the first case, the diagnosis of “Vertebrogenic cervical myelopathy” was pre-hospitalized, in the second – “Chronic progressive myelo-polyradiculoneuropathy”. In these patients, a number of clinical syndromes that were characteristic of HSP were diagnosed: the first symptoms occurred at the 5th decade of life, the disease began with typical complaints of stiffness and fatigue, leg cramps, spastic stroke with difficulty bending the legs in the knees and femoral joints, tearing off the legs from the floor; the prevalence of spasticity over paresis and significant increase in standing position or walking; changes in muscle tone and paresis of the muscles of the hands were not diagnosed; the presence of tendon hyperreflexia, pyramidal pathological signs. The conducted clinical and paraclinical examinations (MRI, ENMG) allowed to conduct a differential diagnosis of HSP and to exclude other pathology. At the present stage, the diagnosis of HSP remains predominantly clinical, since the results of paraclinical methods are ambiguous, and the ability to conduct a molecular genetic study is limited. Most often, these patients are erroneously diagnosed with vertebrogenic myelopathy, encephalomyelopolyneuropathy, multiple sclerosis, cerebral palsy, and others. Unfortunately, there is currently no effective pathogenetic therapy for HSP.

hereditary spastic paraplegia, Stryumpel’s disease.

1. Govbah IA. Populyacionno-ehpidemiologicheskie aspekty nasledstvennyh boleznej nervnoj sistemy. ScienceRise. Medical science. 2015;2(4):54-60. [in Russian].
2. Faber I, Pereira E, Martinez A, Franca M, Teive H. Hereditary spastic paraplegia from 1880 to 2017: an historical review. Arq Neuropsiquiatr. 2017 Nov;75(11):813-8.
3. Tesson C, Koht J, Stevanin G. Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology. Hum Genet. 2015 Jun;134(6):511-38.
4. Shtok VN, Levin OS. Spravochnik po formulirovaniyu klinicheskogo diagnoza boleznej nervnoj sistemy. Moskva: OOO Medicinskoe informacionnoe agentstvo; 2006. 520 s. [in Russian].
5. Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42:174-83.
6. Tarrade A, Fassier C, Courageot S, Charvin D, Vitte J, Peris L. A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet. 2006 Dec 15;15(24):3544-58.
7. Sanderson CM, Connell JW, Edwards TL, Bright NA, Duley S, Thompson A. Spastin and atlastin, two proteins mutated in autosomal-dominant hereditary spastic paraplegia, are binding partners. Hum Mol Genet. 2006 Jan 15;15(2):307-18.
8. Boustany RN, Fleishnick E, Alper CA. The autosomal dominant form of «pure» familial spastic paraplegia. Neurology. 1987;37:910-5.
9. Boustany RN. Hereditary spastic paraplegias. Brain’s Diseases of the nervous System. 1993;12:442-3.
10. McDermott C, White K, Bushby K. Hereditary spastic paraparesis: a review of new developments. Journal Neurology, Neurosurgery, Psychiatry. 2000;69:150-60.
11. Parsons CG, Danysz W, Bartmann A. Neuropharmacology. 1999;38:85-108.
12. Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. 2005 Oct 21;123(2):277-89.
13. Depienne C, Stevanin G, Brice A. Hereditary spastic paraplegias: an update. Curr Opin Neurol. 2007 Dec;20(6):674-80.
14. Agosta F, Scarlato M, Spinelli EG. Hereditary Spastic Paraplegia: Beyond Clinical Phenotypes toward a Unified Pattern of Central Nervous System Damage. Radiology. 2015 Jul;276(1):207-18.
15. Fenichel DzhM. Pediatricheskaya nevrologiya: Osnovy klinicheskoj diagnostiki: per. s angl. Moskva: OAO «Izdatel’stvo «Medicina»; 2004. 640 s. [in Russian].
16. Ekusheva EV, Danilov AB. Nasledstvennaya spasticheskaya paraplegiya (obzor). Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2002;8:44-52. [in Russian].
17.  Zavalishin IA. Spastichnost’. Russkij medicinskij zhurnal. 2004;5:261-5. [in Russian].
18. Illarioshkin SN, Rudenskaya GE, Ivanova-Smolenskaya IA. Nasledstvennye ataksii i paraplegii. Moskva: MEDpress-inform; 2006. 415 s. [in Russian].
19. Lisovich VІ. Reabіlіtacіya spastichnih paralіchіv: modelі ta mekhanіzmi viniknennya m’yazovoї spastichnostі. Ukraуns’kij vіsnik psihonevrologіі. 1996;3(5)1:195-7. [in Ukrainian].
20. Mel’nichuk PV. Semejnaya spasticheskaya paraplegiya Shtryumpellya: rukovodstvo dlya vrachej. Moskva; 1995. 12 s. [in Russian].
21. Koh K, Ishiura H, Tsuji S, Takiyama Y. JASPAC: Japan Spastic Paraplegia Research Consortium. Brain Sci. 2018 Aug 13;8(8):358-67.
22.  Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 2008 Dec;7(12):1127-38.
23. Fink JK. Advances in the hereditary spastic paraplegias. Exp Neurol. 2003 Nov;184(1):106-10.
24. Tallaksen CM, Durr A, Brice A. Recent advances in hereditary spastic paraplegia. Curr Opin Neurol. 2001 Aug;14(4):457-63.
25. Züchner S. The genetics of hereditary spastic paraplegia and implications for drug therapy. Expert Opin Pharmacother. 2007 Jul;8(10):1433-9.
26. Paisan-Ruiz C, Dogu O, Yilmaz A. SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. Neurology. 2008 Apr 15;70(16;2):1384-9.
27. Blackstone C, O’Kane CJ, Reid E. Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. 2011 Jan;12(1): 31-42.
28.  Bis-Brewer DM, Zuchner S. Perspectives on the Genomics of HSP Beyond Mendelian Inheritance. Front Neurol. 2018;9:958.
29. Hazan J, Fonknechten N, Mavel D. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet. 1999 Nov;23(3):296-303.
30. Fink JK, Rainier S. Hereditary spastic paraplegia: spastin phenotype and function. Arch Neurol. 2004 Jun;61(6):830-3.
31. Depienne C, Stevanin G, Brice A. Hereditary spastic paraplegias: an update. Curr Opin Neurol. 2007 Dec;20(6):674-80.
32. Yahno NN, Shtul’man DR, redaktor. Bolezni nervnoj sistemy: rukovodstvo dlya vrachej. Moskva: Medicina; 2001. T. 2. s. 160-4. [in Russian].
33. Damulin IV. Sindrom spastichnosti i osnovnye napravleniya ego lecheniya. Zhurnal nevrologii i psihiatrii im. S.S. Korsakova. 2003;12:4-9. [in Russian].
34. Reid E. The hereditary spastic paraplegiеs. J. Neurol. 1999;246:995-1003.
35. Tondіj OL. Spadkovі spastichnі paraplegіi: klіnіka, dіagnostika, lіkuvannya. Mezhdunarodnyj nevrologicheskij zhurnal. 2008;1(17):15-23. [in Ukrainian].
36. Pinchuk VA, Krivchun AM, Silenko GYa. Misce olatropilu v likuvannya kognitivnih rozladiv u paciyentiv iz rozsiyanim sklerozom. Ukrayinskij visnik psihonevrologiyi. 2018;2(95):22-5. [in Ukrainian].
37. Taryanik КА. Dinamika likuvannya spastichnosti u paciyentiv iz recidivuyucho-remituyuchim rozsiyanim sklerozom. Svit medicini ta biologiyi. 2014;2(44):87-90. [in Ukrainian].
38. Ardolino G, Bocci T, Nigro M. Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): a sham-controlled crossover study. J Spinal Cord Med. 2018 Dec;3:1-8.

«Bulletin of problems biology and medicine» Issue 2 Part 1 (150), 2019 year, 50-55 pages, index UDK 616.8-009.612-031.58-053.1

10.29254/2077-4214-2019-2-1-150-50-55