Striatonigral Degeneration Workup
- Author: Ahmad El Kouzi, MD; Chief Editor: Selim R Benbadis, MD more...
No laboratory studies are diagnostic for multiple system atrophy with predominantly parkinsonian features (MSA-P). If a family history is noted, then testing for the SCA-3 mutation can identify Machado-Joseph disease.
Electromyography shows denervation of the external sphincter (urethral or anal); however, normal findings do not exclude the disease.
Clonidine growth hormone test
Studies show that after infusion of clonidine, serum growth hormone concentration does not subsequently rise in patients with multiple system atrophy. In contrast, the normal response, an increase in secretion, is found in Parkinson disease, pure autonomic failure, and control subjects.[18, 19]
Studies suggest that cognitive impairment is more common than previously thought in multiple system atrophy. Due to the nature of the deficits associated with this disease, the standard mental status examination has been found to be a poor tool for assessment. Neuropsychiatric testing is more sensitive and may be more a more helpful resource in multiple system atrophy.
Sleep disorders, particularly nocturnal stridor and REM sleep behavior disorder, are common in multiple system atrophy. Formal sleep studies should be considered, as research suggests that treatment can improve survival and quality of life.
REM sleep behavior disorder is common in Parkinson disease and atypical parkinsonian disorders including striatonigral degeneration (MSA-P). Clonazepam is an effective treatment for many patients. Nocturnal stridor is specific to MSA and is produced by vocal cord dysfunction during sleep. CPAP is appropriate for long term treatment.
Findings in MSA-P include widespread glial cytoplasmic inclusions (primarily in oligodendrocytes) and, to a lesser degree, neuronal cytoplasmic inclusions and neuronal nuclear inclusions. Immunostaining of inclusion bodies reveals the presence of alpha-synuclein fibrils.
Autonomic tests for orthostatic vital signs such as the tilt-table test and urodynamic studies can be conducted. Scintigraphy with iodine-123-metaiodobenzylguanidine (MIBG) has recently shown utility in the differential diagnosis between Parkinson disease and multiple system atrophy; this method shows high sensitivity and adequate specificity in this field.
A study measuring the clinical utility of skin biopsy for differentiating between Parkinson disease and multiple system atrophy concluded that detection of alpha-synuclein aggregates on cutaneous nerves in distal body sites is insufficiently sensitive; however, intraepidermal nerve fiber density (IEND) may be useful for this purpose. Further study is needed.
Computed tomography (CT) scans may show cerebellar or brainstem atrophy late in the course of the disease.
A study using single-photon emission CT (SPECT) scanning revealed significantly decreased cerebellar and dorsolateral prefrontal perfusion in patients with multiple system atrophy, relative to that of control subjects.
Magnetic resonance imaging (MRI) may show 1 or more of the following :
Atrophy of the putamen is best seen on inversion-recovery coronal sequences and/or putaminal hypointense signal on T2-weighted sequences. In rare instances, hyperintense bands lateral to the putamen may be seen.
There may be narrowing and hypointensity of the pars compacta of the substantia nigra, which can give the appearance of fusion between the pars reticularis and the red nucleus.
In a retrospective review, identification of the pontine "hot-cross bun" sign on T-2 weighted MRI sequences supported the diagnosis of MSA. 
Positron emission tomography (PET) scans demonstrate decreased postsynaptic D2-receptor density and impaired uptake of fluoro-L-dopa. The recently approved DaTscan single-photon emission computed tomography (SPECT) imaging can help confirm the diagnosis of parkinsonism but does not distinguish idiopathic Parkinson disease from multiple system atrophy.
Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999 Feb 1. 163(1):94-8. [Medline].
Yoshida M, Sone M. [Mechanism of neuronal degeneration of multiple system atrophy]. Brain Nerve. 2009 Sep. 61(9):1051-60. [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. 2012 Feb. 38(1):4-24. [Medline].
Jellinger KA. Neuropathology of multiple system atrophy: New thoughts about pathogenesis. Mov Disord. 2014 Oct 9. [Medline].
Jellinger KA. Neuropathological spectrum of synucleinopathies. Mov Disord. 2003 Sep. 18 Suppl 6:S2-12. [Medline].
Nagaishi M, Yokoo H, Nakazato Y. Tau-positive glial cytoplasmic granules in multiple system atrophy. Neuropathology. 2011 Jun. 31(3):299-305. [Medline].
Jellinger KA. Neuropathology of multiple system atrophy: new thoughts about pathogenesis. Mov Disord. 2014 Dec. 29(14):1720-41. [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. 2004 Jul-Aug. 23(4):201-8. [Medline].
Vanacore N. Epidemiological evidence on multiple system atrophy. J Neural Transm. 2005 Dec. 112(12):1605-12. [Medline].
Yoshida M. [Multiple system atrophy - synuclein and neuronal degeneration]. Rinsho Shinkeigaku. 2011 Nov. 51(11):838-42. [Medline].
Schrag A, Wenning GK, Quinn N, Ben-Shlomo Y. Survival in multiple system atrophy. Mov Disord. 2008 Jan 30. 23(2):294-6. [Medline].
Blumin JH, Berke GS. Bilateral vocal fold paresis and multiple system atrophy. Arch Otolaryngol Head Neck Surg. 2002 Dec. 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. 2011 Aug. 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. 2008 Apr 15. 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. 1997 Jul. 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. 2006 Dec. 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. 1997 Jun 28. 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. 2011 Nov. 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. 2011 Dec. 113(10):823-9. [Medline].
Haga R, Sugimoto K, Nishijima H, Miki Y, Suzuki C, Wakabayashi K, et al. Clinical Utility of Skin Biopsy in Differentiating between Parkinson's Disease and Multiple System Atrophy. Parkinsons Dis. 2015. 2015:167038. [Medline]. [Full Text].
Massimo G, Limbucci N, Catalucci A, Massimo C. Neurodegenerative Diseases. Radiol Clin N Am. 2008. 46:799-817.
Deguchi K, Ikeda K, Kume K, Takata T, Kokudo Y, Kamada M, et al. Significance of the hot-cross bun sign on T2*-weighted MRI for the diagnosis of multiple system atrophy. J Neurol. 2015 Apr 7. [Medline].
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. 2002 Nov. 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. 2011 Mar 16. [Medline].
Nissen T, Malek N, Grosset KA, Newman EJ, Patterson J, Hadley D, et al. Baseline [(123) I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease. Acta Neurol Scand. 2014 Mar. 129(3):204-8. [Medline].
Kuzdas-Wood D, Stefanova N, Jellinger KA, Seppi K, Schlossmacher MG, Poewe W, et al. Towards translational therapies for multiple system atrophy. Prog Neurobiol. 2014 Jul. 118:19-35. [Medline]. [Full Text].
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. 2004 Mar. 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). 2006 Mar. 162(3):363-70. [Medline].
O'Sullivan SS, Massey LA, Williams DR, et al. Clinical outcomes of progressive supranuclear palsy and multiple system atrophy. Brain. 2008 May. 131:1362-72. [Medline].