Progressive Spastic Para-paresis

Progressive Spastic Para-paresis

Abstract

The term Progressive Spastic Para-paresis is used to refer to the group of inherited diseases with a feature of the progressive gait disorder. The condition shows mild progressive stiffness and the lower limbs contraction[1]. Progressive Spastic Paraparesis is caused by abnormal protein transport, structural proteins and lipid and other substances through the cell. The onset age of the disorder varies greatly, and victims may experience no symptoms for year’s even decades after infection[2]. According to the study, is familial spatial para-paresis and is highly inheritable. Most of the patient who is suffering from the condition have inherited the disease from their member of their biological patients most often who have hard the situation in the linage.

Introduction

Patients suffering from Progressive Spastic Para-paresis do report non-specific symptoms, and even the neurological syndrome is not likely to be obvious in the referral letters[3]. Some characteristic gaits may appear if a victim is able to walk through the door[4]. The symptoms usually depend on the type of Progressive Spastic Paraparesis inherited[5]. However, the primary features of Progressive Spastic Paraparesis include the lower limbs stiffness and weakness; the complicated forms may be accompanied by other symptoms[6]. These symptoms can begin however long after the original infection; patients may have difficulty in walking and increased risk of falling[7]. This may be due to the exaggerated reflexes that come along with spasm, stiffness and cramps.   The condition is often coupled with progressive weakness of the patient and in other cases spasticity stiffness of the legs[8]. Its early stage of the diseases in the diseases may be coupled with mild gait and difficulties and stiffness.

Method

The study did examine the various health journals that look into the key elements or aspects of the diseases[9]. I reviewed the numerous studies which relate to the fact about the
Progressive Spastic Para paresis in examining the prevalence rates and other key aspects of the disease like the key signs and symptoms, prognosis and other elements of the patient education which is very vital for the wellbeing of the patients[10].

Results

According to the review of the relevant journals on the disease that were considered for this study, Progressive Spastic Paraparesis is a disease that is linked to the genetic factors that causes the long nerves in the spine to degenerate over time[11]. According to the study, there was no significant gender differences on any of the variables found. However, the disease is much prevalent in adults above the age of 50 years with men suffering from HSP representing particularly vulnerable group[12].

Pathophysiology

Progressive Spastic Paraparesis is caused by the viral infection called the tropical spastic Paraparesis[13]. The key feature of the Progressive Spastic Paraparesis is a length-dependent degeneration of the axons[14]. This may include the uncrossed and crossed corticospinal tracts of the legs. Progressive Spastic Para paresis affects the motor neurons pathways[15]. The key challenge is defining the key players in each of the affected pathways[16]. This is because the several genes have the multiple functions and get involved in more than just one pathway[17].

Genetics

Progressive Spastic Paraparesis is a group of genetic disorders, several modes of influence of inheritance have been described; these are both autosomal dominant, X linked, recessive or material[18]. The pure Progressive Spastic Paraparesis is usually inherited in a dominant way; however, the complicated forms are inherited in the recessive manner[19]. This mode of inheritance involved has a great impact on the chances of the disorder inheritance[20]. Close to ten genes so far have been noted with the autosomal dominant inheritance, most of these altered genes have known function while some of the features are yet to be identified.

Biochemistry

Diagnosis of the Paraparesis is usually made when a patient has met the conditions like gait and mobility symptoms typical of Paraparesis[21]. Having a Paraparesis history among members’ of the family[22]. The specialized tests during diagnosis may include MRI, spine and brain scans and the lumbar puncture. The diagnosis can also be made biochemically by taking the plasma measurement and also detecting the high concentration of the hexacosanoic acid.

Clinical implication

The clinical management of the Progressive Spastic Paraparesis is currently limited to supportive treatment; however, some experimental therapies are underway. The antioxidant therapies have proved to be showing some promising results. For the patients having the Spastic Paraparesis, it is not advisable to be satisfied with the normal brain MRI scan. There is no known cure for the disorder; however, symptom management is the main aim of treatment. These include physical therapy and medication, like the relaxation of the muscles. The physical therapy can improve the mobility and the strengthening of the body muscles, thereby increasing endurance.

Scientific analysis

The articles that were considered for this study were Orphanet Journal of Rare Diseases and the Medical News Today. The first article was quite detailed and also appropriate, organized. The critical elements of the disorder were properly stipulated in this article. The second article was equally important but did not have a properly organized element of the disease, therefore considered shallow[23].

Answered questions

The answered questions about Spastic Paraparesis genetically inheritance of the disorder, prevalence rate and the vital signs and symptoms of the disease. The main problem that scientists still aim to identify is the range of symptoms that may affect the person with Progressive Spastic Paraparesis[24]. The other unanswered question over these diseases is the element of its inherence, and this is on the subject as to why the condition is highly hereditary and the actual cause of the condition prevalence. However, various studies are trying to unveil this question.

Conclusion

Progressive Spastic Para paresis is classified based on the symptoms, the patient’s age at onset, mode of inheritance, the biochemical pathways involved and the affected genes[25].  People diagnosed with this disorder can always expect a normal life expectancy because some victims experience no symptom at all[26]. The prognosis for the person suffering from this condition do varies with some persons being disabled while others do experience mild disability[27]. There exist no specific treatment for the condition to prevent or reverse the condition[28]. However in most case symptomatic treatments are used for the element of spasticity like muscle relaxants, and such as in most cases very helpful in nature[29]. There is a need for future research on the diseases with focuses on establishing the actual method of treatment[30].

References

1. Coates JR. Paraparesis. InBSAVA manual of canine and feline neurology 2013 Jan 1 (pp. 297-327). BSAVA Library.
2. Bangham CR, Araujo A, Yamano Y, Taylor GP. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nature Reviews Disease Primers. 2015 Jun 18; 1:15012.
3. Oz-Levi D, Ben-Zeev B, Ruzzo EK, Hitomi Y, Gelman A, Pelak K, Anixter Y, Reznik-Wolf H, Bar-Joseph I, Olender T, Alkelai A. Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. The American Journal of Human Genetics. 2012 Dec 7; 91(6):1065-72.
4. Yamano Y, Sato T. Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis. Frontiers in microbiology. 2012 Nov 9; 3:389.
5. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, Gout O, Lyon-Caen O, Tourbah A. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Multiple sclerosis and related disorders. 2015 Mar 1;4(2):159-69.
6. Martin F, Castro H, Gabriel C, Adonis A, Fedina A, Harrison L, Brodnicki L, Demontis MA, Babiker AG, Weber JN, Bangham CR. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS neglected tropical diseases. 2012 Jun 12;6(6):e1675.
7. De Fino C, Arena V, Hohaus S, Di Iorio R, Bozzoli V, Mirabella M. Intravascular large B-cell lymphoma presenting as slowly progressive paraparesis with normal MRI features. Journal of the neurological sciences. 2012 Mar 15;314(1-2):171-4.
8. Cosgrove GR, Bertrand G, Fontaine S, Robitaille Y, Melanson D. Cavernous angiomas of the spinal cord. Journal of neurosurgery. 1988 Jan 1;68(1):31-6.
9. De Klippel N, Dehou MF, Bourgain C, Schots R, De Keyser J, Ebinger G. Progressive paraparesis due to thoracic extramedullary hematopoiesis in myelofibrosis: Case report. Journal of neurosurgery. 1993 Jul 1;79(1):125-7.
10. Edwards MK, Farlow MR, Stevens JC. Cranial MR in spinal cord MS: diagnosing patients with isolated spinal cord symptoms. American journal of neuroradiology. 1986 Nov 1;7(6):1003-5.
11. Oz-Levi D, Ben-Zeev B, Ruzzo EK, Hitomi Y, Gelman A, Pelak K, Anikster Y, Reznik-Wolf H, Bar-Joseph I, Olender T, Alkelai A. Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. The American Journal of Human Genetics. 2012 Dec 7;91(6):1065-72.
12. Gessain A, Mahieux R. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects. Revue neurologique. 2012 Mar 1;168(3):257-69.
13. Citterio A, Arnoldi A, Panzeri E, D’Angelo MG, Filosto M, Dilena R, Arrigoni F, Castelli M, Maghini C, Germiniasi C, Menni F. Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis. Journal of neurology. 2014 Feb 1; 261(2):373-81.
14. Amor SB, Saied MZ, Harzallah MS, Benammou S. Hepatic myelopathy with spastic paraparesis: report of two cases and review of the literature. European Spine Journal. 2014 May 1; 23(2):167-71.
15. Lee JR, Srour M, Kim D, Hamdan FF, Lim SH, Brunel‐Guitton C, Décarie JC, Rossignol E, Mitchell GA, Schreiber A, Moran R. De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy. Human mutation. 2015 Jan;36(1):69-78.
16. Müller vom Hagen J, Karle KN, Schüle R, Krägeloh‐Mann I, Schöls L. Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients. European journal of neurology. 2014 Jul;21(7):983-8.
17. Müller vom Hagen J, Karle KN, Schüle R, Krägeloh‐Mann I, Schöls L. Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients. European journal of neurology. 2014 Jul;21(7):983-8.
18. Fink JK. Hereditary spastic paraplegia: clinical principles and genetic advances. InSeminars in neurology 2014 Jul (Vol. 34, No. 03, pp. 293-305). Thieme Medical Publishers.
19. Margetis K, Korfias S, Boutos N, Gatzonis S, Themistocleous M, Siatouni A, Dalivigka Z, Flaskas T, Stranjalis G, Boviatsis E, Sakas D. Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia. Clinical neurology and neurosurgery. 2014 Aug 1;123:142-5.
20. Klimpe S, Schüle R, Kassubek J, Otto S, Kohl Z, Klebe S, Klopstock T, Ratzka S, Karle K, Schöls L. Disease severity affects quality of life of hereditary spastic paraplegia patients. European journal of neurology. 2012 Jan;19(1):168-71.
21. Hirst J, Irving C, Borner GH. Adaptor protein complexes AP‐4 and AP‐5: new players in endosomal trafficking and progressive spastic paraplegia. Traffic. 2013 Feb 1;14(2):153-64.
22. de Bot ST, Schelhaas HJ, Kamsteeg EJ, van de Warrenburg BP. Hereditary spastic paraplegia caused by a mutation in the VCP gene. Brain. 2012 Sep 18;135(12):e223-.
23. Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F. Hereditary spastic paraplegia: clinicogenetic lessons from 608 patients. Annals of neurology. 2016 Apr;79(4):646-58.
24. Sagnelli A, Magri S, Farina L, Chiapparini L, Marotta G, Tonduti D, Consonni M, Scigliuolo GM, Benti R, Pareyson D, Taroni F. Early-onset progressive spastic paraplegia caused by a novel TUBB4A mutation: brain MRI and FDG-PET findings. Journal of neurology. 2016 Mar 1;263(3):591-3.
25. Parodi L, Fenu S, Stevanin G, Durr A. Hereditary spastic paraplegia: more than an upper motor neuron disease. Revue neurologique. 2017 May 1;173(5):352-60.
26. Varga RE, Khundadze M, Damme M, Nietzsche S, Hoffmann B, Stauber T, Koch N, Hennings JC, Franzka P, Huebner AK, Kessels MM. In vivo evidence for lysosome depletion and impaired autophagic clearance in hereditary spastic paraplegia type SPG11. PLoS genetics. 2015 Aug 18;11(8):e1005454.
27. Blackstone C. Cellular pathways of hereditary spastic paraplegia. Annual review of neuroscience. 2012 Jul 21;35:25-47.
28. Khundadze M, Kollmann K, Koch N, Biskup C, Nietzsche S, Zimmer G, Hennings JC, Huebner AK, Symmank J, Jahic A, Ilina EI. A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system. PLoS genetics. 2013 Dec 19;9(12):e1003988.
29. Lossos A, Stümpfig C, Stevanin G, Gaussen M, Zimmerman BE, Mundwiller E, Asulin M, Chamma L, Sheffer R, Misk A, Dotan S. Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67.
30. Noreau A, Dion PA, Rouleau GA. Molecular aspects of hereditary spastic paraplegia. Experimental cell research. 2014 Jul 1;325(1):18-26.

[1] Coates JR. Paraparesis. InBSAVA manual of canine and feline neurology 2013 Jan 1 (pp. 297-327). BSAVA Library.

[2] Bangham CR, Araujo A, Yamano Y, Taylor GP. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nature Reviews Disease Primers. 2015 Jun 18; 1:15012.

[3] Oz-Levi D, Ben-Zeev B, Ruzzo EK, Hitomi Y, Gelman A, Pelak K, Anixter Y, Reznik-Wolf H, Bar-Joseph I, Olender T, Alkelai A. Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. The American Journal of Human Genetics. 2012 Dec 7; 91(6):1065-72.

[4] Yamano Y, Sato T. Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis. Frontiers in microbiology. 2012 Nov 9; 3:389.

[5] Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, Gout O, Lyon-Caen O, Tourbah A. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Multiple sclerosis and related disorders. 2015 Mar 1;4(2):159-69.

[6] Martin F, Castro H, Gabriel C, Adonis A, Fedina A, Harrison L, Brodnicki L, Demontis MA, Babiker AG, Weber JN, Bangham CR. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS neglected tropical diseases. 2012 Jun 12;6(6):e1675.

[7] De Fino C, Arena V, Hohaus S, Di Iorio R, Bozzoli V, Mirabella M. Intravascular large B-cell lymphoma presenting as slowly progressive paraparesis with normal MRI features. Journal of the neurological sciences. 2012 Mar 15;314(1-2):171-4.

[8] Cosgrove GR, Bertrand G, Fontaine S, Robitaille Y, Melanson D. Cavernous angiomas of the spinal cord. Journal of neurosurgery. 1988 Jan 1;68(1):31-6.

[9] De Klippel N, Dehou MF, Bourgain C, Schots R, De Keyser J, Ebinger G. Progressive paraparesis due to thoracic extramedullary hematopoiesis in myelofibrosis: a Case report. Journal of neurosurgery. 1993 Jul 1;79(1):125-7.

[10] Edwards MK, Farlow MR, Stevens JC. Cranial MR in spinal cord MS: diagnosing patients with isolated spinal cord symptoms. American journal of neuroradiology. 1986 Nov 1;7(6):1003-5.

[11] Oz-Levi D, Ben-Zeev B, Ruzzo EK, Hitomi Y, Gelman A, Pelak K, Anikster Y, Reznik-Wolf H, Bar-Joseph I, Olender T, Alkelai A. Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. The American Journal of Human Genetics. 2012 Dec 7;91(6):1065-72.

[12] Gessain A, Mahieux R. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects. Revue neurologique. 2012 Mar 1;168(3):257-69.

[13] Gessain A, Mahieux R. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects. Revue neurologique. 2012 Mar 1;168(3):257-69.

[14] Citterio A, Arnoldi A, Panzeri E, D’Angelo MG, Filosto M, Dilena R, Arrigoni F, Castelli M, Maghini C, Germiniasi C, Menni F. Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis. Journal of neurology. 2014 Feb 1; 261(2):373-81.

[15] Lee JR, Srour M, Kim D, Hamdan FF, Lim SH, Brunel‐Guitton C, Décarie JC, Rossignol E, Mitchell GA, Schreiber A, Moran R. De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy. Human mutation. 2015 Jan;36(1):69-78.

[16] Müller vom Hagen J, Karle KN, Schüle R, Krägeloh‐Mann I, Schöls L. Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients. European journal of neurology. 2014 Jul;21(7):983-8.

[17] Müller vom Hagen J, Karle KN, Schüle R, Krägeloh‐Mann I, Schöls L. Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients. European journal of neurology. 2014 Jul;21(7):983-8.

[18] Fink JK. Hereditary spastic paraplegia: clinical principles and genetic advances. seminars in neurology 2014 Jul (Vol. 34, No. 03, pp. 293-305). Thieme Medical Publishers.

[19] Margetis K, Korfias S, Boutros N, Gatzonis S, Themistocleous M, Santoni A, Dalivigka Z, Flaskas T, Stranjalis G, Boviatsis E, Sakas D. Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia. Clinical neurology and neurosurgery. 2014 Aug 1;123:142-5.

[20] Klimpe S, Schüle R, Kassubek J, Otto S, Kohl Z, Klebe S, Klopstock T, Ratzka S, Karle K, Schöls L. Disease severity affects the quality of life of hereditary spastic paraplegia patients. European journal of neurology. 2012 Jan;19(1):168-71.

[21] Hirst J, Irving C, Borner GH. Adaptor protein complexes AP‐4 and AP‐5: new players in endosomal trafficking and progressive spastic paraplegia. Traffic. 2013 Feb 1;14(2):153-64.

[22] de Bot ST, Schelhaas HJ, Kamsteeg EJ, van de Warrenburg BP. Hereditary spastic paraplegia caused by a mutation in the VCP gene. Brain. 2012 Sep 18;135(12):e223-.

[23]Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F. Hereditary spastic paraplegia: clinic genetic lessons from 608 patients. Annals of neurology. 2016 Apr;79(4):646-58.

[24] Sagnelli A, Magri S, Farina L, Chiapparini L, Marotta G, Tonduti D, Consonni M, Scigliuolo GM, Benti R, Pareyson D, Taroni F. Early-onset progressive spastic paraplegia caused by a novel TUBB4A mutation: brain MRI and FDG-PET findings. Journal of neurology. 2016 Mar 1;263(3):591-3.

[25] Parodi L, Fenu S, Stevanin G, Durr A. Hereditary spastic paraplegia: more than an upper motor neuron disease. Revue neurologique. 2017 May 1;173(5):352-60.

[26] Varga RE, Khundadze M, Damme M, Nietzsche S, Hoffmann B, Stauber T, Koch N, Hennings JC, Franzka P, Huebner AK, Kessels MM. In vivo evidence for lysosome depletion and impaired autophagic clearance in hereditary spastic paraplegia type SPG11. PLoS genetics. 2015 Aug 18;11(8):e1005454.

[27] Blackstone C. Cellular pathways of hereditary spastic paraplegia. Annual review of neuroscience. 2012 Jul 21;35:25-47.

[28] Khundadze M, Kollmann K, Koch N, Biskup C, Nietzsche S, Zimmer G, Hennings JC, Huebner AK, Symmank J, Jahic A, Ilina EI. A hereditary spastic paraplegia mouse model supports the role of ZFYVE26/SPASTIZIN for the endolysosomal system. PLoS genetics. 2013 Dec 19;9(12):e1003988.

[29] Lossos A, Stümpfig C, Stevanin G, Gaussen M, Zimmerman BE, Mundwiller E, Asulin M, Chamma L, Sheffer R, Misk A, Dotan S. Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67.

[30] Noreau A, Dion PA, Rouleau GA. Molecular aspects of hereditary spastic paraplegia. Experimental cell research. 2014 Jul 1;325(1):18-26.