Hereditary Spastic Paraplegia Medication

  • Author: Nam-Jong Paik, MD, PhD; more...
 
Updated: Jan 6, 2012
 

Medication Summary

Many symptoms that are common in people with HSP are not caused directly by HSP but are instead caused indirectly by muscle spasticity, weakness, or hyperactive reflexes. As previously mentioned, antispastic drugs may help the patient to reduce the spasticity and may allow weakened muscles to be targeted in order to improve the effectiveness of PT.[10] However, when patients are medicated to reduce stiffness, walking may become more difficult. Moreover, adverse effects from skeletal muscle relaxants can be a problem.

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Skeletal muscle relaxants

Class Summary

Antispasticity medications can be useful. However, one of the drawbacks of using these agents is that some patients find that the stiffness of spasticity helps them to overcome the muscle weakness that occurs in HSP. When patients are medicated to reduce stiffness, walking may become more difficult. Adverse effects can also be a problem.

If the patient does well with the medications, however, discomfort associated with spasticity can generally be reduced, mobility can be improved, and the effectiveness of physical therapy (PT) can be enhanced. Patients in relatively early stages of the illness have achieved symptomatic improvement with oral dantrolene, as well as with oral and intrathecal baclofen.

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Baclofen (Lioresal, Gablofen)

 

Baclofen may induce the hyperpolarization of afferent terminals and inhibit monosynaptic and polysynaptic reflexes at the spinal level.

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Tizanidine (Zanaflex)

 

Tizanidine is a centrally acting muscle relaxant that is metabolized in the liver and excreted in urine and feces. A single oral dose of 8mg reduces muscle tone in patients with spasticity for several hours. Blood levels and the spasmolytic effect are linearly correlated.

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Dantrolene sodium (Dantrium, Revonto)

 

Dantrolene sodium stimulates muscle relaxation by modulating skeletal muscle contractions at the site beyond the myoneural junction and acting directly on the muscle itself. Most patients respond to 400mg/day or less.

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OnabotulinumtoxinA (BOTOX®)

 

Botulinum toxin binds to receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which in turn inhibits the transmission of impulses in neuromuscular tissue. This agent is most useful for treating spasticity in the gastrocnemius and soleus muscles; it is less effective in larger muscles (eg, quadriceps). Reexamine patients 7-14 days after the initial dose to assess for their response. Treatment may be repeated every 3-4 months.

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Anxiolytics, Benzodiazepines

Class Summary

These agents may act in the spinal cord to induce muscle relaxation.

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Diazepam (Valium)

 

Diazepam depresses all levels of the central nervous system (eg, limbic and reticular formation), possibly by increasing the activity of gamma-aminobutyric acid (GABA). Individualize the dosage, and increase it cautiously to avoid adverse effects.

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Contributor Information and Disclosures
Author

Nam-Jong Paik, MD, PhD  Chair, Department of Rehabilitation Medicine, Seoul National University Bundang Hospital; Professor, Department of Rehabilitation Medicine, Seoul National University College of Medicine

Nam-Jong Paik, MD, PhD is a member of the following medical societies: American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Jae-Young Lim, MD, PhD  Associate Professor, Seoul National University College of Medicine, Seoul National University Bundang Hospital, South Korea

Jae-Young Lim, MD, PhD is a member of the following medical societies: American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Kat Kolaski, MD Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine

Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Teresa L Massagli, MD Professor of Rehabilitation Medicine and Pediatrics, University of Washington School of Medicine

Teresa L Massagli, MD is a member of the following medical societies: American Academy of Pediatrics, American Academy of Physical Medicine and Rehabilitation, and Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References

  1. Sawhney IM, Bansal SK, Upadhyay PK, et al. Evoked potentials in hereditary spastic paraplegia. Ital J Neurol Sci. Sep 1993;14(6):425-8. [Medline].

  2. Reid E. Pure hereditary spastic paraplegia. J Med Genet. Jun 1997;34(6):499-503. [Medline]. [Full Text].

  3. Salinas S, Proukakis C, Crosby A, Warner TT. Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. Dec 2008;7(12):1127-38. [Medline].

  4. 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. Dec 15 2006;15(24):3544-58. [Medline].

  5. 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. Jan 15 2006;15(2):307-18. [Medline].

  6. 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. Oct 21 2005;123(2):277-89. [Medline].

  7. Depienne C, Stevanin G, Brice A, et al. Hereditary spastic paraplegias: an update. Curr Opin Neurol. Dec 2007;20(6):674-80. [Medline].

  8. Fink JK. Advances in the hereditary spastic paraplegias. Exp Neurol. Nov 2003;184 Suppl 1:S106-10. [Medline].

  9. Tallaksen CM, Durr A, Brice A. Recent advances in hereditary spastic paraplegia. Curr Opin Neurol. Aug 2001;14(4):457-63. [Medline].

  10. Züchner S. The genetics of hereditary spastic paraplegia and implications for drug therapy. Expert Opin Pharmacother. Jul 2007;8(10):1433-9. [Medline].

  11. Paisan-Ruiz C, Dogu O, Yilmaz A, et al. SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. Neurology. Apr 15 2008;70(16 Pt 2):1384-9. [Medline].

  12. Blackstone C, O'Kane CJ, Reid E. Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. Jan 2011;12(1):31-42. [Medline].

  13. Hazan J, Fonknechten N, Mavel D, et al. Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet. Nov 1999;23(3):296-303. [Medline].

  14. Fink JK, Rainier S. Hereditary spastic paraplegia: spastin phenotype and function. Arch Neurol. Jun 2004;61(6):830-3. [Medline].

  15. Orlacchio A, Patrono C, Gaudiello F, et al. Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4. Neurology. May 20 2008;70(21):1959-66. [Medline].

  16. Tzoulis C, Denora PS, Santorelli FM, et al. Hereditary spastic paraplegia caused by the novel mutation 1047insC in the SPG7 gene. J Neurol. Jun 23 2008;[Medline].

  17. Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS. Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet. Mar 2007;39(3):366-72. [Medline].

  18. Steinmüller R, Lantigua-Cruz A, Garcia-Garcia R, Kostrzewa M, Steinberger D, Müller U. Evidence of a third locus in X-linked recessive spastic paraplegia. Hum Genet. Aug 1997;100(2):287-9. [Medline].

  19. Fink JK, Heiman-Patterson T, Bird T, et al. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working Group. Neurology. Jun 1996;46(6):1507-14. [Medline].

  20. Hazan J, Lamy C, Melki J, et al. Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q. Nat Genet. Oct 1993;5(2):163-7. [Medline].

  21. Appleton RE, Farrell K, Dunn HG. 'Pure' and 'complicated' forms of hereditary spastic paraplegia presenting in childhood. Dev Med Child Neurol. Apr 1991;33(4):304-12. [Medline].

  22. Schlipf N, Schüle R, Klimpe S, Karle K, Synofzik M, Schicks J, et al. Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clin Genet. Aug 2011;80(2):148-60. [Medline].

  23. Schady W, Smith CM. Sensory neuropathy in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. Jun 1994;57(6):693-8. [Medline]. [Full Text].

  24. Schady W, Dick JP, Sheard A, Crampton S. Central motor conduction studies in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. Sep 1991;54(9):775-9. [Medline]. [Full Text].

 
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Photograph of a 16-year-old girl with complicated hereditary spastic paraplegia. She has a spastic gait disturbance, mental retardation, and extrapyramidal symptoms. Note the dysmorphic features.
Dysmorphic appearance of a 16-year-old girl with complicated hereditary spastic paraplegia. This patient displays a short stature (145 cm) and hair loss. Anterior (left), lateral (middle), and posterior (right) views are shown.
General appearance of sisters with complicated hereditary spastic paraplegia. They are aged 16 and 17 years. Physical examination revealed increased deep tendon reflexes in all 4 extremities, with an extensor plantar reflex. Sensory losses in the patients have affected mainly their joint positions and vibration sensations.
 
 
 
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