Multiple system atrophy
The term multiple system atrophy (MSA ) refers to a rapidly progressive neurodegenerative disease that affects multiple systems in the. The term was coined in 1969 by Graham and Oppenheimer, who realized that olivopontocerebelläre atrophy ( OPCA ), striatonigral degeneration ( SND) and idiopathic orthostatic hypotension ( Shy- Drager syndrome ) manifestations of the same disease are. Papp, Kahn and Lantos described in 1989 Oligodendroglial inclusion bodies ( Glial Cytoplasmic Inclusions, GCI) as a common histological markers. With the detection of α -synuclein as a main component of the GCI MSA as Parkinson's disease and Lewy body dementia is included among the group of synucleinopathies.
Epidemiology
The prevalence is about 4.4 cases per 100,000 inhabitants. So come on 100 cases with Parkinson's disease approximately 2.2 cases with MSA. Gender relations are roughly balanced. While in Europe the MSA -P variant is more frequent ( 49%), predominates in Japan, the MSA -C.
MSA occurs usually between the fortieth and sixtieth year, the peak incidence is 57 years. The disease is rapidly progressive and leads within 3-5 years to loss of ambulation and after an average of 8-10 years to death.
Symptoms
Clinical symptoms are mainly extrapyramidal symptoms in the sense of parkinsonism with bradykinesia, tremor and rigidity, cerebellar symptoms such as dysmetria, nystagmus and gait and stand- ataxia with a tendency to fall, as well as swallowing disorders ( dysphagia) and speech disorders (dysarthria ), and dysregulation of the autonomic nervous system such as orthostatic hypotension, urinary incontinence and erectile dysfunction. In addition, there are often a subcortical dementia, pyramidal signs such as hyperreflexia or positive Babinski reflex. Depending on which schemes are concerned, occurs only a part of the symptoms described above. After the valid diagnostic criteria of 1998, two motor phenotypes can be distinguished: the predominance of Parkinson's symptoms, it is called MSA -P, cerebellar symptoms predominate, one speaks of MSA -C. An autonomic dysfunction is a prerequisite for the diagnosis of MSA.
Disorders of swallowing functions often lead to aspiration pneumonia, which also contributes to reduced life expectancy.
Diagnostics
The diagnosis is mainly based on history and clinical examination, the differential diagnosis may also be difficult even for experts. In addition to an obligatory autonomic dysfunction lack of response to L -DOPA is an important criterion to distinguish from Parkinson's disease. Some clinical signs are to be considered as an indication of a possible multiple system atrophy, such as dysphagia, dysarthria, inspiratory stridor, early postural instability and rapid disease progression.
In computed tomography images can be observed in some cases, atrophy of the cerebellum or the bridge ( pons). In magnetic resonance images one sees occasionally atrophy of the putamen. Importantly, however, these studies are to be distinguished from other neurological disorders in the first place.
Of particular importance may be in difficult cases the IBZM - SPECT, with the MSA can usually be distinguished from the Parkinson's disease. With this, the absence of postsynaptic dopamine receptors is demonstrated. In Parkinson's disease, however, the postsynaptic receptors are often normal, here there is a defect in the dopaminergic neurons.
Pathology
In the brain of affected patients, an abnormal accumulation of the protein α -synuclein in inclusion bodies in oligodendroglia find ( as Papp - Lantos inclusions known), so the MSA as Parkinson's disease and Lewy body dementia in the group of synucleinopathies is counted. In addition, we observed a loss of nerve cells with reactive gliosis.
The degeneration of the substantia nigra, leads to Parkinson's disease, that the loss of striatal dopamine receptors, and consequently the loss of the response to dopaminergic therapy.
The ataxia is caused by atrophy of the cerebellum, often together with atrophy of olives ( olivary nucleus ) and the bridge.
A downfall of presynaptic sympathetic neurons in the spinal cord is held responsible for the autonomic dysfunction; but there is also evidence of an accompanying postsynaptic Lewy body pathology.
Therapy
The treatment of multiple system atrophy as the disease is a multisystemic. There is currently no treatment for the cerebellar symptoms.
Dopaminergics. Parkinsonism is treated with dopaminergic agents, which L -DOPA is slightly more potent than dopamine agonists. In support of MAOIs ( monoamine oxidase inhibitors) and COMT inhibitors ( catechol-O- methyltransferase ) inhibitors may be used to inhibit the dopamine degradation, and thus increase the effectiveness. Principle, however, show only a third of MSA patients a response to dopaminergic therapy; this holds on average three to years. Amantadine, a NMDA receptor antagonist, is widely used due to its effectiveness against dyskinesia and a potential anti-Parkinson effects.
Autonomic dysfunction. The treatment of autonomic dysfunction is both non- medication and medication. Orthostatic hypotension can be better with a higher pillow with support stockings, increased salt and water intake and sleep; medication fludrocortisone and midodrine are to choose from. Urinary incontinence can be treated in mild cases, with inserts; medication are trospium chloride, oxybutynin and tolterodine are available. If there is an incomplete emptying of the bladder must be catheterized. For the treatment of erectile dysfunction sildenafil or similar PDE -5 inhibitors are suitable.
Palliation. Palliative measures may be necessary such as artificial nutrition via PEG tube (percutaneous endoscopic gastrostomy ) for severe dysphagia. In strong stridor can bring improvement a CPAP.
Depression. The often accompanying depression should also be treated.
Immunoglobulins. Leave the participating toxic cytokines suggest that inflammation plays a role in the pathogenesis. Therefore, there is, at least partially successful attempts to treat the disease with intravenous immunoglobulin therapy.