Background
Striatonigral degeneration is a sporadic, progressive neurodegenerative disorder that represents one manifestation of multiple system atrophy (MSA). Other manifestations of multiple system atrophy are Shy-Drager syndrome, in which autonomic failure predominates, and sporadic olivopontocerebellar degeneration, which is characterized primarily by cerebellar signs. While symptoms of autonomic failure and cerebellar degeneration may be present in striatonigral degeneration, the predominant finding is parkinsonism. (See Presentation and Workup.)
The group of disorders classified under multiple system atrophy belong to a broader class called the Parkinson-plus syndromes, which have in common features such as bradykinesia and rigidity seen in Parkinson disease, combined with additional components such as autonomic dysfunction, ataxia, or dementia.
In many cases, the disease process begins with 1 of the 3 presentations predominating (ie, parkinsonism, autonomic failure, cerebellar signs) and then later converges to include a combination of all 3 plus additional degeneration of the corticospinal system, including tract and motor neuron degeneration, as well as cognitive deterioration. However, in some cases, one presentation remains dominant throughout the course of the disease, or it may be that the patient dies before additional symptoms can manifest. This has been most clearly described for the cerebellar form of multiple system atrophy. (See Etiology and Pathophysiology.)
In 1933, Sherer described 2 cases that likely represented striatonigral degeneration. However, this condition was first definitively outlined in 1961 and 1964 by Adams et al. In 1969, Graham and Oppenheimer coined the term multiple system atrophy in an effort to emphasize the common features found in all the 3 manifestations.
Thirty years later, the first consensus statement on the diagnosis of multiple system atrophy, by Gilman et al, recommended that the term striatonigral degeneration be replaced with multiple system atrophy with predominantly parkinsonian features (MSA-P) and that the term sporadic olivopontocerebellar degeneration be replaced with multiple system atrophy with predominantly cerebellar features (MSA-C). [1] The term Shy-Drager syndrome was deemed unnecessary and was excluded. The consensus group described the clinical features of the disease and set the criteria for diagnosis of possible, probable, and definite multiple system atrophy. (See Presentation and Workup.)
In 2008, the second consensus statement on the diagnosis of multiple system atrophy was published. The purpose of revisiting this topic was to incorporate advances in research, such as the identification of alpha-synuclein as a key pathologic finding, and to simplify the original diagnostic criteria. [2]
Use of the new nomenclature (MSA-P and MSA-C) became common in publications subsequent to 1999; however, the term Shy-Drager syndrome is still frequently used. Many neurologists find this a useful term for the autonomic presentation, but consideration must be given to whether subtle parkinsonian or cerebellar findings are present, in which case the MSA-P or MSA-C classifications, respectively, would be more appropriate. In the event that both parkinsonian and cerebellar signs are present, the term multiple system atrophy can be used without qualification.
Etiology and Pathophysiology
MSA-P is characterized by the presence of glial cytoplasmic inclusions (GCIs) in oligodendroglial cells. These inclusions are widely distributed throughout the brains of affected individuals. Neuronal cytoplasmic inclusions and neuronal nuclear inclusions can also be found but are far less prominent relative to GCIs. It has been suggested that the involvement of both neurons and oligodendrocytes synergistically affect the neurodegenerative process in MSA. [3] The identification of these inclusion bodies was a unifying factor in the pathologic classification of the 3 entities that now fall under the category of multiple system atrophy: MSA-P, MSA-C, and, less formally, Shy-Drager syndrome. [4, 5]
Immunostaining of inclusion bodies has revealed the presence of alpha-synuclein fibrils, which further classifies this group of disorders as synucleinopathies. (However, the significance of this finding remains unclear.) Other neurodegenerative conditions that fall under this category include Parkinson disease and diffuse Lewy body disease. [6] Alpha-synuclein, in its soluble form, is found in normal brain tissue. It is the insoluble aggregate that forms the fibrils associated with synucleinopathies that appears to be pathologic. [7] A recent theory suggests that alpha-synuclein is spread from neuron to oligodendrocyte via a prion-like process. In association with neuroinflammation, this leads to a specific pattern of neurodegeneration. [8]
In addition to inclusion bodies, microscopic evaluation of tissue reveals neuronal loss and gliosis. This is manifested at a macroscopic level as atrophy, primarily of the pons and midbrain. The substantia nigra shows loss of pigmentation, while the putamen, also atrophic, may become grayish-green in color. This pattern of degeneration is consistent with clinical findings.
Epidemiology
The prevalence of multiple system atrophy (including all 3 subtypes) in the United States is difficult to establish because the disease is frequently misdiagnosed; however, the prevalence has been estimated to be 3-5 cases per 100,000 people in the general population. International data show a prevalence of 1.86-4.9 cases per 100,000 people. [9, 10]
In one Japanese study, review of the pathologic features of 102 multiple system atrophy cases revealed that MSA-C (olivopontocerebellar type MSA) was relatively more frequent in Japan than MSA-P (striatonigral degeneration type MSA), while the converse is found in western countries. [11]
Formerly, no gender predominance was observed, but information now suggests a male predominance of approximately 2:1. Some reports show a much greater disparity, with the suggestion that males who seek treatment for autonomic symptoms, such as erectile dysfunction, may be more likely to be diagnosed.
Onset occurs most often in the sixth decade. The mean age at diagnosis is 53 years, with an age range of 33-76 years.
Prognosis
Multiple system atrophy is a progressive neurodegenerative disorder without remission. The prognosis is poor, and all 3 subtypes of multiple system atrophy have a mean survival period of less than a decade from diagnosis. In a study by Schrag et al, median survival time was 8.6 years for men and 7.3 years for women. [12]
Gender, phenotype, and gait instability do not appear to be prognostic indicators of shorter survival, as has previously been proposed. However, autonomic failure continues to be a negative prognostic factor. Data from one study suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA. [13]
The most marked clinical deterioration is seen in MSA-P, although the time frame for survival in this disease is similar to that of the other 2 subtypes.
Morbidity and mortality
Complications of multiple system atrophy include the following:
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Vocal fold paresis and glottic airway compromise requiring continuous positive airway pressure support or tracheostomy [14]
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Aspiration pneumonia secondary to dysphagia and vocal fold paresis
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Sudden death, often occurring at night and associated with sleep-disordered breathing
Patient Education
Patients with symptomatic postural hypotension should be educated with regard to the following:
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Activities or environments that produce excessive vagal stimulation or vasodilation (eg, extreme heat, overeating, alcohol, straining at stool) should be avoided
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Always rise slowly and carefully from seated or recumbent positions
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Sit or lie down as soon as symptoms appear
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Consider using pressure stockings, elevating the head of the bed, and increasing sodium intake
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Be aware that there is a risk of fall with associated trauma; always seek medical attention for any but the most minor of falls
