It is defined as:
A fatal neurodegenerative disease, of progressive, sporadic evolution and adult evolution, of indeterminate etiology, characterized clinically by the variable severity of parkinsonian characteristics; Cerebellar, autonomic and urogenital dysfunction; And corticospinal disorder.
The neuropathological signs of multisystem atrophy are:
the loss of cells in the striatonigenic and olivopontocerebellar structures of the brain and spinal cord, accompanied by profuse and distinctive glia-cytoplasmic inclusions formed by fibrilated alpha-synuclein proteins (defined as primary alpha-synucleinopathy).
A consensus statement by the American Autonomous Society and the American Academy of Neurology in 2007 classified multisystemic atrophy in MSA-P with predominant parkinsonism and MSA-P with dominant cerebellar characteristics (MSA-C).
The concept of multisystemic atrophy as a unit diagnosis encompassing several clinical syndromes has a long history. The first cases presented as olivopontocerebellar atrophy about a century ago.
Shy-Drager syndrome with characteristics of parkinsonism and autonomic failure was described in 1960. The term multisystemic atrophy was introduced to unify different forms of multisystemic atrophy in 1996.
The discovery of GCI and alpha-synuclein as a sensitive marker of multisystemic atrophy were important milestones in the definition of multisystemic atrophy as a clinical-pathological entity.
Categories of multisystem atrophy.
The 2 categories of multisystemic atrophy are the following:
Multisystemic atrophy with predominant parkinsonism – extrapyramidal features predominate; The term striatonigral degeneration, parkinsonian variant is sometimes used.
Multisystemic atrophy with cerebellar characteristics – Cerebellar ataxia predominates; Sometimes it is called sporadic olivopontocerebellar atrophy.
Occurrence in the United States.
It has been reported that the prevalence of multisystem atrophy ranges from 3.4-4.9 cases per 100,000 population. The estimated average incidence is 0.6 to 0.7 cases per 100,000 person-years. Multisystemic atrophy fulfills the status of orphan disease.
Many patients do not receive the correct diagnosis during their lifetime due to the difficulty of differentiating multisystemic atrophy from other disorders (eg, Parkinson’s disease, pure autonomic failure, and other rare movement disorders).
Approximately 29-33% of patients with delayed onset late cerebellar ataxia and 8-10% of patients with parkinsonism will develop multisystem atrophy. Therefore, a higher prevalence than estimated can be assumed.
- In the European Union, prevalence rates show 4-5 cases per 100,000 people. The incidence rate is approximately 0.6 cases per 100,000 people per year.
- In the United Kingdom, the gross prevalence of multisystemic atrophy, including all possible and possible cases, is 3.3 per 100,000 population. In Iceland, the incidence is 0.6 per 100,000 and the prevalence is 3.1 per 100,000.
- In Japan, the prevalence is 13.1 per 100,000 individuals. The average annual incidence is 0.68.
Demographic data related to race, sex and age.
Multisystemic atrophy has been found in the Caucasian, African, and Asian populations. In Western countries it predominates, occurring in 66-82% of patients. In Eastern countries (for example, Japan), it is common, occurring in 67% of patients.
The disease affects men more often than women. The ratio between women and men is around 1: 2. However, the early and easy diagnosis of impotence may have led to the male statistical predominance of multisystemic atrophy.
The average age of onset in multisystem atrophy is 52.5-55 years. The disease progresses at intervals of 1-18 years.
Patients with multisystem atrophy have a poor prognosis. The disease progresses rapidly. Median survival of 6.2-9.5 years from the onset of the first symptoms have been reported since the late twentieth century.
No current therapeutic modality reverses or stops the progress of this disease. In both their categories they have the same survival times.
An older age at onset has been associated with a shorter duration of survival in multisystem atrophy. The total loss of the estratonigral cells correlates with the severity of the disease at the time of death.
Bronchopneumonia (48%) and sudden death (21%) are common terminal conditions in multisystem atrophy. Urinary dysfunction in multisystem atrophy often leads to lower urinary tract infections; More than 50% of patients suffer from recurrent UTIs and a significant number of related complications.
History and Physical Exam.
Most patients with multisystem atrophy develop the disease when they are over 40 years old (average 52-55y), and experience a rapid progression.
In general, autonomic and / or urinary dysfunction develops first. Patients with multisystem atrophy may have parkinsonian symptoms with a poor or unsustained response to levodopa therapy.
Only 30% of patients have an initial transient improvement. About 90% of patients do not respond to long-term levodopa therapy.
Typically, 60% of patients experience an objective decrease in motor function within one year. Motor impairment can be caused by cerebellar dysfunction.
Corticospinal tract dysfunction may also occur but is not usually an important symptom characteristic of multisystem atrophy.
Autonomic and / or urinary dysfunction.
Autonomic symptoms are the initial characteristic in 41-74% of patients with multisystem atrophy; These symptoms develop in 97% of patients. Genitourinary dysfunction is the most frequent complaint in women, and erectile dysfunction is the most frequent complaint in men.
Severe orthostatic hypotension.
Severe orthostatic hypotension is defined as a reduction in systolic blood pressure of at least 30 mm Hg or in diastolic BP of at least 15 mm Hg, within 3 minutes of rest from a previous interval of 3 minutes in a reclined position.
This form of hypotension is common in multisystem atrophy, being present in at least 68% of patients. Most patients do not respond with an adequate increase in heart rate.
The definition of severe orthostatic PA as a diagnostic criterion for multisystem atrophy is stricter than the definition of orthostatic hypotension as a physical finding defined by the American Autonomic Society.