Striatonigral degeneration

Definition

Striatonigral degeneration is a neurodegenerative disease caused by disruption of two areas, the striatum and substantia nigra, which work together to enable movement and balance.

Description

Striatonigral degeneration was described in 1961 and 1964. However, since the disorder has common manifestations seen in multiple diseases (e.g., the Shy-Drager syndrome, where autonomic nervous system failure predominates, and sporadic olivopontocerebellar degeneration, where cerebellum deficits predominate), it was necessary to clarify the nomenclature. In 1999, the name striatonigral degeneration was replaced with the accepted new names: multiple system atrophy-Parkinson (MSA-P), if Parkinson's disease symptoms predominate, or MSA-cerebellum (MSA-C), if cerebellar ataxia is the main feature. Patients who have MSA have characteristic pathological changes in common, but in variable degrees. Affected neurons in the brain have inclusion bodies that cause neuronal loss, by a mechanism of programmed cell death called apoptosis. The presence of inclusion bodies in neurons causes a reaction to self-destruct following a programmed sequence of chemical reactions that promotes cell death.

Demographics

The prevalence of MSA-P is difficult to establish with accuracy since the disorder is frequently misdiagnosed in the United States and internationally. It is estimated to account for 5–22% of cases in patients with Parkinson's or Parkinson-like disorders. Approximately 80% of patients present with MSA-P symptoms and 20% exhibit symptoms of cerebellar ataxia (MSA-C subtype). It is estimated that the prevalence of this disorder is 1.9–4.9 cases per 100,000. The age range of diagnosis is between 33 and 76 years of age. MSA-P has never been identified in a person younger than 30 years. The mean survival time after the onset of symptoms is 7–9 years. There is no racial predilection, and males and females are affected equally.

The mean age of diagnosis is 53 years. For the majority of MSA-P affected persons, the full clinical picture evolves within five years after onset of symptoms.

Causes and symptoms

The cause of MSA has not been identified. MSA occurs in the general population in a sporadic manner. The disorder is degenerative and progressively worsens. The natural history of the disorder is chronic, symptoms progressively worsen, and the disorder often results in death, after multiple treatment efforts.

Common symptoms of MSA-P (which may be asymmetric) include bradykinesia (slowness of movement) characterized by an irregular jerky postural tremor. It is uncommon for the tremor to occur at rest. Additionally, patients often exhibit rigidity, postural instability, and a characteristic quivering high-pitched dysarthria . Many patients with MSA-P also develop orofacial and craniocervical dystonia . Patients with the MSA-C subtype also develop gait and limb ataxia, eye abnormalities, and scanning dysarthria. Other symptoms can include depression , emotional lability (fluctuations of emotional state), hyperreflexia, extensor plantar (sole) response, myoclonus , or laryngeal stridor. Failure of the autonomic nervous system (ANS) is a characteristic of both subtypes (MSA-P and MSA-C), which primarily consists of urogenital problems and orthostatic hypotension . ANS failure causes early male erectile dysfunction and urinary dysfunction, causing problems with frequency, urgency, retention, and incontinence. Additionally, patients frequently develop postprandial (after food) postural hypotension and episodes of syncope (loss of consciousness), due to lack of oxygen to the brain (cerebral hypoperfusion).

Diagnosis

No specific lab tests are indicated. High-resolution neuroimaging studies may demonstrate neuronal abnormalities and/or atrophy in the brain. The diagnosis is based on history, physical examination, and family history (to detect genetic correlations). A definite diagnosis can be obtained by pathological examination of brain neurons. A probable diagnosis is made by the presence of ANS failure, poor response to medications, or cerebellar dysfunction (cerebellar ataxia). Neuroimaging studies using magnetic resonance imaging (MRI) indicate that that there is volume loss (neuronal loss) in associated areas in the brain (the striatum and substantia nigra). Functional neuroimaging techniques (which take images of neuron function) indicate that neuron receptor binding is defective and there is low metabolism (low level of vital chemical reactions).

Treatment team

The treatment team can typically include a neurologist and respiratory care providers, when management of breathing difficulties requires professional intervention. A physical therapist can help with postural and movement difficulties. An audiologist is utilized for speech and eating difficulties.

Treatment

No surgical treatment exists for striatonigral degeneration, and pharmacological treatment is not effective in the long term. Approximately 30% of patients demonstrate initial improvement with a medication called levodopa-carbidopa. However, symptomatic improvement is temporary; approximately 90% patients are unresponsive to levodopa in the long term. Dystonia can be treated with botulinum toxin , which tends to control involuntary muscular movements. Affected persons who develop failure of the autonomic nervous system may develop orthostatic hypotension. Patients who develop low blood pressure symptoms should avoid activities such as overeating, straining at stool passage, and exposure to extreme heat. Elevating the head of the bed, use of pressure stockings, and increased sodium intake (which causes water retention, which in turn stabilizes blood pressure) are treatments for hypotension. Additionally, medication to correct hypotension can be prescribed, including fludrocortisone, ephedrine, and midodrine. Medication to treat postprandial hypotension (octreotide) or bladder symptoms (oxybutynin) can be given when needed. Overall, however, the result of medical treatment for MSA is poor.

Recovery and rehabilitation

Rehabilitation can include patient, family, and caretaker education concerning the possibilities of respiratory failure, aspiration pneumonia, trauma, and syncope. Patients can develop paresis of the larynx or pharynx, central chronic respiratory failure (a chronic respiratory failure due to destruction of neurons in the brain), or sudden death. Patients require physical therapy to help maintain mobility and prevent permanent muscular contractures. Speech therapy can improve speech impairments and difficulty with swallowing (dysphagia) mechanisms. Dysphagia may necessitate tube placement and feedings. Patients eventually require occupational therapy to limit handicap from disability. A wheelchair is indicated depending on liability to falls due to gait (walking) ataxia and postural instability. Psychological support is necessary for the patient and family member caretakers.

Clinical trials

Clinical trials are being done to find methods to prevent and treat MSA-P. The Mayo Clinic in Rochester, Minnesota, currently has projects and investigations concerning new techniques for diagnosis using PET scan technology. This technology is likely to be available in the near future.

Prognosis

The disorder is degenerative and the mean survival time in confirmed cases is seven years. The range of survival for persons with MSA-P is 2–15 years. Approximately 50% of affected patients who receive levodopa develop side effects that can include dyskinesia of orofacial and neck muscles.

Special concerns

Episodes of syncope can cause severe trauma, usually from falls. Patients are advised to lie or sit down when symptoms appear. Family members and caretakers should be aware of the syncope and the dangers associated with falls and trauma.

Resources

PERIODICALS

Wenning, Gregor, and Werner Poewe. "Multiple System Atrophy." The Lancet Neurology 3:2 (February 2004).

WEBSITES

National Organization for Rare Disorders (NORD). (May 23, 2004). <http://www.rarediseases.org>.

The Mayo Clinic. Clinical Information. (May 23, 2004). <http://www.mayoresearch.mayo.edu>.

ORGANIZATIONS

Worldwide Education & Awareness for Movement Disorders (WE MOVE). 204 West 84th Street, New York, NY 10024. (212) 875-8312 or (800) 437-6682; Fax: (212) 875-8389. [email protected]. <http://www.wemove.org>.

Laith Farid Gulli, MD

Nicole Mallory, MS, PA-C