Striatonigral Degeneration Medication
- Author: Arif I Dalvi, MD; Chief Editor: Selim R Benbadis, MD more...
Medication Summary
The drugs in the tables below are specific to the treatment of parkinsonism and postural hypotension associated with multiple system atrophy with predominantly parkinsonian features (MSA-P). As previously mentioned, in patients with multiple system atrophy, the response to antiparkinsonian medications is suboptimal at best. Because better options are not available, however, these agents remain the treatment of choice for the disease.
Adjunct medications
Anticholinergic medications, such as oxybutynin, are sometimes used for incontinence but often lead to subsequent retention. Although sildenafil has been used for treatment of erectile dysfunction, it is generally not recommended, due to its high potential to provoke or exacerbate hypotension. The use of a fiber supplement or another bowel regimen may be necessary for constipation.
A selective serotonin reuptake inhibitor (SSRI) or similar drug may be required for the treatment of depression often associated with all subtypes of multiple system atrophy. For patients who suffer from REM sleep behavioral disorder, clonazepam may be beneficial. Botulinum toxin (BOTOX®) injection to the vocal cords has been used for the treatment of stridor.
Antiparkinson Agents, Dopamine Agonists
Class Summary
Dopaminergic drugs can exacerbate orthostatic hypotension. They must be initiated at low doses and cautiously titrated up.
Levodopa-carbidopa (Sinemet, Parcopa)
Levodopa is a dopamine precursor used to increase central nervous system (CNS) dopamine concentration, as it is not possible for dopamine to cross the blood-brain barrier. Carbidopa is a peripheral dopa decarboxylase inhibitor that prevents premature conversion of levodopa to dopamine in the tissues prior to entering the CNS. It increases the efficiency of levodopa therapy, allows for lower dosages, and also decreases the side effects associated with peripheral conversion.
Standard release forms of levodopa-carbidopa are available in 25/100-, 10/100-, and 25/250-mg tablets. Controlled-release preparations are available in 50/200 mg and 25/100 mg.
Pramipexole (Mirapex)
Pramipexole is a nonergot dopamine agonist that is used with or without concomitant levodopa therapy. It binds D2 and D3 dopamine receptors. Due to pramipexole's high specificity for D3 receptors (relative to other dopamine agonists), it may cause less orthostatic hypotension. It has no significant effect on other adrenergic or serotonergic receptors. The drug's absolute bioavailability is greater than 90%. Its peak serum concentration is reached in approximately 2 hours and its half-life is approximately 8 hours.
There are no known metabolites; roughly 90% of this drug is renally excreted in its unchanged form. Tablets are available in 0.125-, 0.25-, 0.5-, 0.75-, 1-, and 1.5-mg forms.
Ropinirole (Requip)
Ropinirole is a nonergot dopamine agonist that is used with or without concomitant levodopa therapy. It binds to D2 and D3 receptors but has a greater affinity for D3. Ropinirole's bioavailability is 55%, its peak plasma concentration is reached in 1-2 hours, and its half-life is approximately 6 hours. Ropinirole is extensively metabolized by the liver via P450 CYP1A2. Less than 10% of the drug is renally excreted; no dosage change is required in mild to moderate renal insufficiency. If ropinirole is used as adjunct therapy, it may be possible to titrate levodopa dosage slowly downward.
Corticosteroids
Class Summary
These are used to treat orthostatic hypotension that is refractory to nonpharmacologic recommendations.
Fludrocortisone
Fludrocortisone is a synthetic steroid with predominantly mineralocorticoid activity. It acts on renal distal tubules to enhance the reabsorption of sodium and increase the urinary excretion of potassium. The net effect is an increase in plasma volume and an elevation of blood pressure. The drug's metabolism is primarily hepatic.
Alpha1 Agonists
Class Summary
These drugs are used to treat orthostatic hypotension that is refractory to nonpharmacologic recommendations.
Midodrine
Midodrine is a selective alpha1-adrenergic agonist used for the treatment of hypotension.
Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. Feb 1 1999;163(1):94-8. [Medline].
Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. Aug 26 2008;71(9):670-6. [Medline].
Ahmed Z, Asi YT, Sailer A, Lees AJ, Houlden H, Revesz T, et al. The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol. Feb 2012;38(1):4-24. [Medline].
Jellinger KA. Neuropathological spectrum of synucleinopathies. Mov Disord. Sep 2003;18 Suppl 6:S2-12. [Medline].
Nagaishi M, Yokoo H, Nakazato Y. Tau-positive glial cytoplasmic granules in multiple system atrophy. Neuropathology. Jun 2011;31(3):299-305. [Medline].
Chrysostome V, Tison F, Yekhlef F, Sourgen C, Baldi I, Dartigues JF. Epidemiology of multiple system atrophy: a prevalence and pilot risk factor study in Aquitaine, France. Neuroepidemiology. Jul-Aug 2004;23(4):201-8. [Medline].
Vanacore N. Epidemiological evidence on multiple system atrophy. J Neural Transm. Dec 2005;112(12):1605-12. [Medline].
Schrag A, Wenning GK, Quinn N, Ben-Shlomo Y. Survival in multiple system atrophy. Mov Disord. Jan 30 2008;23(2):294-6. [Medline].
O'Sullivan SS, Massey LA, Williams DR, et al. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain. May 2008;131:1362-72. [Medline].
Blumin JH, Berke GS. Bilateral vocal fold paresis and multiple system atrophy. Arch Otolaryngol Head Neck Surg. Dec 2002;128(12):1404-7. [Medline].
Camacho V, Marquié M, Lleó A, et al. Cardiac sympathetic impairment parallels nigrostriatal degeneration in Probable Dementia with Lewy Bodies. Q J Nucl Med Mol Imaging. Aug 2011;55(4):476-83. [Medline].
Kawai Y, Suenaga M, Takeda A, et al. Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P. Neurology. Apr 15 2008;70(16 Pt 2):1390-6. [Medline].
Klein C, Brown R, Wenning G, Quinn N. The "cold hands sign" in multiple system atrophy. Mov Disord. Jul 1997;12(4):514-8. [Medline].
Pellecchia MT, Pivonello R, Colao A, Barone P. Growth hormone stimulation tests in the differential diagnosis of Parkinson's disease. Clin Med Res. Dec 2006;4(4):322-5. [Medline].
Kimber JR, Watson L, Mathias CJ. Distinction of idiopathic Parkinson's disease from multiple-system atrophy by stimulation of growth-hormone release with clonidine. Lancet. Jun 28 1997;349(9069):1877-81. [Medline].
Santamaria J, Iranzo A. Multiple System Atrophy and Sleep. Sleep Med Clin. 2008;3:337-345.
Yoshida M. Multiple system atrophy -synuclein and neuronal degeneration. Rinsho Shinkeigaku. Nov 2011;51(11):838-42. [Medline].
Treglia G, Stefanelli A, Cason E, Cocciolillo F, Di Giuda D, Giordano A. Diagnostic performance of iodine-123-metaiodobenzylguanidine scintigraphy in differential diagnosis between Parkinson's disease and multiple-system atrophy: a systematic review and a meta-analysis. Clin Neurol Neurosurg. Dec 2011;113(10):823-9. [Medline].
Massimo G, Limbucci N, Catalucci A, Massimo C. Neurodegenerative Diseases. Radiol Clin N Am. 2008;46:799-817.
Ghaemi M, Hilker R, Rudolf J, Sobesky J, Heiss WD. Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging. J Neurol Neurosurg Psychiatry. Nov 2002;73(5):517-23. [Medline].
Hauser RA, Grosset DG. [(123) I]FP-CIT (DaTscan) SPECT Brain Imaging in Patients with Suspected Parkinsonian Syndromes. J Neuroimaging. Mar 16 2011;[Medline].
Chou KL, Forman MS, Trojanowski JQ, Hurtig HI, Baltuch GH. Subthalamic nucleus deep brain stimulation in a patient with levodopa-responsive multiple system atrophy. Case report. J Neurosurg. Mar 2004;100(3):553-6. [Medline].
Talmant V, Esposito P, Stilhart B, Mohr M, Tranchant C. [Subthalamic stimulation in a patient with multiple system atrophy: a clinicopathological report]. Rev Neurol (Paris). Mar 2006;162(3):363-70. [Medline].

