Multiple system atrophy

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Classification according to ICD-10
G90.3 Multisystem atrophy,
G23.1 Progressive supranuclear ophthalmoplegia [Steele-Richardson-Olszewski syndrome]
G23.2 Multiple system atrophy of the Parkinson's type [MSA-P]
G23.3 Multiple system atrophy of the cerebellar type [MSA-C]
G23.8 Other specified degenerative diseases of the basal ganglia: Calcification of the basal ganglia: Neurogenic orthostatic hypotension [Shy-Drager syndrome]
ICD-10 online (WHO version 2019)

The term multiple system atrophy (MSA) refers to a rapidly progressing neurodegenerative disease that affects multiple systems. The term was coined in 1969 by Graham and Oppenheimer , who recognized that olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and idiopathic orthostatic hypotension ( Shy-Drager syndrome ) are manifestations of the same disease. In 1989, Papp, Kahn and Lantos described oligodendroglial inclusion bodies (Glial Cytoplasmic Inclusions, GCI) as a common histological marker. With the discovery of α-synuclein as the main component of GCI, MSA, like Parkinson's disease and Lewy body dementia, belong to the group of synucleinopathies .

Epidemiology

The prevalence is about 4.4 cases per 100,000 population. This means that for every 100 cases with Parkinson's disease, there are around 2.2 cases with MSA. The gender ratios are roughly balanced. While the MSA-P is the more common variant in Europe (49%), the MSA-C predominates in Japan.

MSA usually occurs between the ages of 40 and 60, and the peak of the disease is 57 years. The disease progresses rapidly and leads to loss of ability to walk within 3–5 years and death on average after 8–10 years.

Symptoms

Clinical symptoms are mainly extrapyramidal motor symptoms in the sense of Parkinsonism with bradykinesia , tremor and rigidity , cerebellar symptoms such as B. dysmetria , nystagmus and gait and stance ataxia with a tendency to fall, but also swallowing disorders ( dysphagia ) and speech disorders ( dysarthria ), as well as regulatory disorders of the autonomic nervous system such as orthostatic hypotension , urinary incontinence and erectile dysfunction . In addition, there are often subcortical dementia , pyramidal signs such as hyperreflexia or positive Babinski reflex . Depending on which systems are affected, only some of the symptoms described occur. According to the valid diagnostic criteria of 1998, a distinction is made between two motor phenotypes: If the Parkinson's symptoms predominate, one speaks of MSA-P, if cerebellar symptoms predominate, one speaks of MSA-C. Autonomic dysfunction is a prerequisite for diagnosing MSA.

Swallowing disorders often lead to aspiration pneumonia , which also contributes to a shortened life expectancy.

Diagnosis

Diagnosis is primarily based on medical history and clinical examination, but differential diagnosis can be difficult, even for experts. In addition to an obligatory autonomic dysfunction, a lack of response to L-DOPA is an important criterion for differentiating from Parkinson's disease. Some clinical signs should be considered as indicators of possible multiple system atrophy, such as dysphagia, dysarthria, inspiratory stridor , early fall tendency, and rapid disease progression.

In some cases, atrophy of the cerebellum or the bridge ( pons ) can be observed in computed tomography images . Atrophy of the putamen can occasionally be seen in magnetic resonance imaging . However, these examinations are primarily important to distinguish them from other neurological clinical pictures.

IBZM-SPECT can be particularly important in difficult cases, with which MSA can usually be differentiated from Parkinson's disease. With this, the lack of postsynaptic dopamine receptors is detected. In Parkinson's disease, on the other hand, the postsynaptic receptors are often normal; here there is a defect in the dopaminergic neurons.

pathology

Evidence of alpha-synuclein-positive inclusions (brown) in an autopsy of a patient with MSA

In the brain of affected patients there is an abnormal accumulation of the protein α-synuclein in inclusion bodies in the oligodendroglia (also known as Papp-Lantos inclusions), therefore MSA, like Parkinson's disease and Lewy body dementia, belongs to the group of synucleinopathies counted. In addition, a loss of nerve cells with reactive gliosis is observed .

The degeneration of the substantia nigra leads to parkinsonism, that of the striatum leads to the loss of dopamine receptors and consequently to a loss of response to dopaminergic therapy.

Ataxia is caused by atrophy of the cerebellum , often accompanied by atrophy of the olives ( nucleus olivaris ) and the bridge .

A loss of presynaptic sympathetic neurons in the spinal cord is held responsible for the autonomic dysfunction; but there are also indications of an accompanying postsynaptic Lewy body pathology.

therapy

The therapy of multi-system atrophy, like the disease, is multi-systemic. There is currently no therapy for the cerebellar symptoms.

Dopaminergics . Parkinsonism is treated with dopaminergics, with L-DOPA being slightly more effective than dopamine agonists. MAO inhibitors ( monoamine oxidase inhibitors ) and COMT inhibitors (catechol-O-methyltransferase inhibitors), which inhibit the breakdown of dopamine and thus prolong the effectiveness, can be used as support. In principle, however, only a third of MSA patients show a response to dopaminergic therapy; this lasts for an average of three years. Amantadine , an NMDA receptor antagonist, is widely used because of its effectiveness against dyskinesia and possible anti-Parkinsonism effects.

Autonomic dysfunction . Therapy for autonomic dysfunction is both non-drug and drug-based. The orthostatic hypotension can be improved with support stockings, increased salt and water intake and sleeping with a raised pillow; Fludrocortisone and Midodrine are available for medication . Urinary incontinence can be treated with insoles in mild cases; Trospium chloride , oxybutynin and tolterodin are available for medicinal purposes. If the bladder has not been completely emptied, catheterization is required. Sildenafil or similar PDE-5 inhibitors are suitable for treating erectile dysfunction .

Palliation . Palliative measures may be necessary in the case of severe swallowing disorders, such as artificial feeding using a PEG tube ( percutaneous endoscopic gastrostomy ). If the stridor is severe, CPAP ventilation can help.

Depression . The depression that often accompanies it should also be treated.

Immunoglobulins . The toxic cytokines involved suggest that inflammation plays a role in the pathogenesis. That is why there are at least some successful attempts to treat the disease with intravenous immunoglobulin therapy.

Individual evidence

  1. ↑ MI Papp, JE Kahn, PL Lantos: Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). In: J Neurol Sci. 94 (1-3), Dec 1989, pp. 79-100. PMID 2559165
  2. ↑ A. Bjornsdottir, G. Gudmundsson, H. Blondal, E. Olafsson: Incidence and prevalence of multiple system atrophy: a nationwide study in Iceland. In: J Neurol Neurosurg Psychiatry. 28th Nov 2012.
  3. ↑ F. Geser et al. a .: The European Multiple System Atrophy Study Group (EMSA-SG). In: J Neural Transm. 112 (12), Dec 2005, pp. 1677-1686. Epub 2005 Jul 29.
  4. ^ GK Wenning, C. Colosimo, F. Geser, W. Poewe: Multiple system atrophy. In: The Lancet Neurology . 3 (2), Feb 2004, pp. 93-103. Review. PMID 14747001
  5. ↑ H. Watanabe et al. a .: Progression and prognosis in multiple system atrophy: an analysis of 230 Japanese patients. In: Brain. 125 (Pt 5), May 2002, pp. 1070-1083. Review. PMID 11960896
  6. ↑ TH Bak, LM Crawford, VC Hearn, PS Mathuranath, JR Hodges: Subcortical dementia revisited: similarities and differences in cognitive function between progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA). In: Neurocase. 11 (4), 2005, pp. 268-273.
  7. ^ S. Gilman et al: Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology. In: Clin Auton Res. 8 (6), Dec 1998, pp. 359-362. Review. PMID 9869555
  8. ↑ M. Köllensperger et al .: Red flags for multiple system atrophy. In: Mov Disord. 23 (8), Jun 15, 2008, pp. 1093-1099. PMID 18442131
  9. ↑ S. Orimo, T. Kanazawa, A. Nakamura, T. Uchihara, F. Mori, A. Kakita, K. Wakabayashi, H. Takahashi: Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy. In: Acta Neuropathol. 113 (1), Jan 2007, pp. 81-86. Epub 2006 Nov 7. PMID 17089131
  10. ↑ IF Hussain, CM Brady, MJ Swinn, CJ Mathias, CJ Fowler: Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension. In: J Neurol Neurosurg Psychiatry. 71 (3), Sep 2001, pp. 371-374. PMID 11511713 .
  11. ^ P. Novak, A. Williams, P. Ravin, O. Zurkiya, A. Abduljalil, V. Novak: Treatment of multiple system atrophy using intravenous immunoglobulin. In: BMC Neurol. 12 (1), Nov 1, 2012, p. 131.

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