eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Striatonigral Degeneration

Author: Paula K Rauschkolb, DO, Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center
Coauthor(s): Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Contributor Information and Disclosures

Updated: Mar 9, 2009

Introduction

Background

Striatonigral degeneration (SND) is a sporadic, progressive neurodegenerative disorder that represents one manifestation of multiple system atrophy (MSA). Other manifestations of multiple system atrophy are Shy-Drager, 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.

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.

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 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 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 Multiple System Atrophy).

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) has become common in publications subsequent to 1999; however, the term Shy-Drager syndrome is still frequently used. A Medline search can produce numerous papers dated 2000 and later using "Shy-Drager" as a keyword or subject heading, which confirms that this term continues to be used in publications. 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.

Pathophysiology

Striatonigral degeneration 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. The identification of these inclusion bodies was a unifying factor in the pathological classification of the 3 entities that now fall under the category of multiple system atrophy: striatonigral degeneration (MSA-P), olivopontocerebellar atrophy (MSA-C) and, less formally, Shy-Drager syndrome.

Immunostaining of inclusion bodies has revealed the presence of alpha-synuclein fibrils, which further classifies this group of disorders as synucleinopathies. Other neurodegenerative conditions that fall under this category include Parkinson disease and Lewy body disease.³ 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. In Parkinson disease, currently a very active area of research, genetic mutations affecting this protein have been identified. This is not the case with multiple system atrophy; it is considered a sporadic disease, without evidence for an underlying genetic alteration.

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 the clinical findings (see Clinical).

Frequency

United States

The prevalence of multiple system atrophy (including all 3 subtypes) is difficult to establish because the disease is frequently misdiagnosed, but it has been estimated at 3-5 per 100,000 in the general population.

International

Data reported show a prevalence of 1.86-4.9 cases per 100,000 people.

Mortality/Morbidity

The prognosis is poor, and all 3 subtypes of multiple system atrophy have a mean survival period of less than a decade from diagnosis. Despite a similar time frame for survival, the most marked clinical deterioration is seen in striatonigral degeneration (MSA-P).

Race

No racial or ethnic predilection is evident.

Sex

Formerly, no gender predominance was observed, but more recent information suggests a male predominance of approximately 2:1. Some reports are of 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.

Age

Onset occurs most often in the sixth decade. The mean age at diagnosis is 53 years, with a range of 33-76 years of age.

Clinical

History

• Parkinsonism: The vast majority of patients with multiple system atrophy develop parkinsonism at some point, and it is often rapidly progressive. 
  • Bradykinesia with rigidity, tremor, or postural instability
    • Although presentation can be asymmetric (as is usually the case in Parkinson disease), symmetry of onset is particularly suggestive of MSA-P.
    • Absence of tremor is suggestive of MSA-P (vs Parkinson disease). When present, tremor is usually irregular, postural, and often incorporates myoclonus. While resting tremor can be observed, it is uncommon.
  • Patients may have had poor response to a previous trial of levodopa.
• Dysautonomia: Autonomic failure to some degree is almost universal and may be the presenting symptom. Genitourinary complaints are common early in the disease.
  • Male erectile dysfunction
  • Urinary symptoms (frequency, urgency, incomplete bladder emptying, and incontinence)
  • Postural or postprandial hypotension (Syncopal events may occur secondary to cerebral hypoperfusion.)  
• Cerebellar findings
  • Gait or limb ataxia
  • Cerebellar dysarthria
• Affective disorders
  • Depression
  • Emotional lability
• Cognitive impairment
  • Difficulty with visuospatial tasks
  • Decreased verbal fluency
  • Diminished executive function skills
• Dysphagia and/or dysphonia
• Sleep disturbances (When possible, obtain history from sleeping partner.)
  • REM sleep behavior disorder
  • Obstructive symptoms (snoring, stridor, obstructive apneas)
  • Central symptoms (central apneas, dysrhythmic breathing patterns)
  • Insomnia and/or excessive daytime sleepiness
  • Restless legs syndrome
• Features that suggest an etiology other than multiple system atrophy
  • Family history (Multiple system atrophy is a sporadic neurodegenerative disease.)
  • Dementia (Cognitive deficits are sometimes present in multiple system atrophy, but dementia is not a predominant feature.)
  • Presence of hallucinations (not secondary to medication) (This suggests Lewy body disease.)

Physical

• Parkinsonism
  • Bradykinesia with rigidity, tremor, or postural instability
    • Symmetric onset is suggestive of multiple system atrophy (vs Parkinson disease).
    • Absence of tremor is suggestive of MSA-P (vs Parkinson disease). When present, tremor is usually irregular, postural, and often incorporates myoclonus. While resting tremor can be observed, it is uncommon.
• Dysautonomia
  • Urinary retention, elevated postvoid residual
  • Orthostatic hypotension (Reduction of systolic blood pressure by more than 30 mm Hg or diastolic blood pressure reduction of more than 15 mm Hg within 3 minutes of standing from a previous period of recumbency greater than 3 minutes.)
• Cerebellar findings
  • Gait or limb ataxia
  • Cerebellar dysarthria
  • Cerebellar oculomotor dysfunction - this may include saccadic pursuit movements, gaze-evoked nystagmus, and ocular dysmetria
• Dysphagia and/or dysphonia
• Stridor: Initially stridor occurs during sleep, but later in the course it may occur during wakefulness.
• Corticospinal findings (Hyperreflexia or extensor plantar response is often present.
• Raynaud phenomenon or "cold hands sign" (cold, dusky, violaceous hands with poor circulatory return after blanching pressure)⁴
• Affective disorders
  • Depression
  • Emotional lability
• Cognitive impairment: Although dementia (as a predominant feature) is a criterion for exclusion, recent studies suggest that some degree of cognitive impairment is common in multiple system atrophy, and particularly so with MSA-P.⁵ The extent of impairment varies significantly. When present, deficits include the following:
  • Visuospatial and constructional dysfunction
  • Impaired verbal fluency
  • Dysexecutive syndrome

Features that suggest an etiology other than multiple system atrophy include the following:

• Classic pill-rolling tremor suggests Parkinson disease.
• Significant slowing of vertical saccades or vertical supranuclear gaze palsy is a sign of progressive supranuclear palsy.
• Dementia: Cognitive deficits are sometimes present in multiple system atrophy, but dementia is not a predominant feature.
• Presence of hallucinations (not secondary to medication) suggests Lewy body disease.

Causes

Striatonigral degeneration (MSA-P) is a sporadic, progressive neurodegenerative disorder. Immunohistochemistry techniques have revealed the presence of alpha-synuclein fibrils within the glial cytoplasmic inclusion bodies that are characteristic of this disease; however, as is the case with other synucleinopathies, the significance of this finding remains unclear. Currently, no genetic mutation is associated with any form of multiple system atrophy.

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