Multiple system atrophy (MSA) is a progressive, degenerative disease of the central nervous system, characterized by a combination of parkinsonian, autonomic, pyramidal, and cerebellar symptoms. It was first described in the early 20th century, with different terms used to describe various manifestations, including olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome, and striatonigral degeneration. MSA is a sporadic disease, and although it was once considered rare, it is now recognized as more common than previously thought, with 4% to 22% of parkinsonian brain banks showing MSA. The prevalence is estimated at 16.4 per 100,000 population, with a mean age of onset of 53 years and a median survival of five years. Both sexes are equally affected. MSA presents with a wide range of clinical features, including parkinsonian symptoms like akinesia, rigidity, and tremor; autonomic symptoms such as orthostatic hypotension, urinary incontinence, and impotence; cerebellar signs like ataxia and dysarthria; and pyramidal signs such as spasticity and myoclonus. These symptoms may occur in various combinations and evolve over time. MSA is often misdiagnosed as idiopathic Parkinson's disease, but key differences include asymmetric rigidity, poor levodopa response, and the presence of autonomic or cerebellar features. Dementia is not a feature of MSA, and the disease is distinguished from idiopathic Parkinson's by the absence of Lewy bodies and the presence of glial cytoplasmic inclusions. Pathologically, MSA is characterized by the loss of neurons in various brain regions, including the substantia nigra, locus coeruleus, and cerebellum, with no Lewy bodies. Histologically, glial cytoplasmic inclusions are a hallmark of MSA. Neurochemically, there are changes in the dopaminergic, noradrenergic, and cholinergic systems. Investigations such as magnetic resonance imaging (MRI) can show striatal abnormalities, while cardiovascular autonomic tests can differentiate MSA from pure autonomic failure. Treatment is mainly supportive, with no curative therapy available. Management includes addressing autonomic symptoms, motor symptoms, and complications such as dysphagia and urinary incontinence. Physiotherapy, occupational therapy, and speech therapy are beneficial in improving quality of life. MSA is a complex disease that requires a multidisciplinary approach for accurate diagnosis and management.Multiple system atrophy (MSA) is a progressive, degenerative disease of the central nervous system, characterized by a combination of parkinsonian, autonomic, pyramidal, and cerebellar symptoms. It was first described in the early 20th century, with different terms used to describe various manifestations, including olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome, and striatonigral degeneration. MSA is a sporadic disease, and although it was once considered rare, it is now recognized as more common than previously thought, with 4% to 22% of parkinsonian brain banks showing MSA. The prevalence is estimated at 16.4 per 100,000 population, with a mean age of onset of 53 years and a median survival of five years. Both sexes are equally affected. MSA presents with a wide range of clinical features, including parkinsonian symptoms like akinesia, rigidity, and tremor; autonomic symptoms such as orthostatic hypotension, urinary incontinence, and impotence; cerebellar signs like ataxia and dysarthria; and pyramidal signs such as spasticity and myoclonus. These symptoms may occur in various combinations and evolve over time. MSA is often misdiagnosed as idiopathic Parkinson's disease, but key differences include asymmetric rigidity, poor levodopa response, and the presence of autonomic or cerebellar features. Dementia is not a feature of MSA, and the disease is distinguished from idiopathic Parkinson's by the absence of Lewy bodies and the presence of glial cytoplasmic inclusions. Pathologically, MSA is characterized by the loss of neurons in various brain regions, including the substantia nigra, locus coeruleus, and cerebellum, with no Lewy bodies. Histologically, glial cytoplasmic inclusions are a hallmark of MSA. Neurochemically, there are changes in the dopaminergic, noradrenergic, and cholinergic systems. Investigations such as magnetic resonance imaging (MRI) can show striatal abnormalities, while cardiovascular autonomic tests can differentiate MSA from pure autonomic failure. Treatment is mainly supportive, with no curative therapy available. Management includes addressing autonomic symptoms, motor symptoms, and complications such as dysphagia and urinary incontinence. Physiotherapy, occupational therapy, and speech therapy are beneficial in improving quality of life. MSA is a complex disease that requires a multidisciplinary approach for accurate diagnosis and management.