Frühe Diagnostik des idiopathischen Parkinson-Syndroms

Zusammenfassung

Für einzelne Substanzen wie Rasagilin, Selegilin, Dopaminagonisten und Amantadin stehen zunehmend klinische Studien zur Verfügung, die einen krankheitsmodifizierenden Effekt nahelegen. Sollte dieser Effekt tatsächlich vorhanden sein, wäre es wichtig, ein idiopathisches Parkinson-Syndrom früher zu diagnostizieren. Bisher haben wir Parkinson-Patienten nur behandelt, wenn sie sich durch ihre Symptome genügend beeinträchtigt fühlten, d. h. durch Bradykinese oder Tremor in den Aktivitäten des täglichen Lebens behindert waren. Unsere eigenen Untersuchungen sprechen dafür, dass Hyposmie bzw. Anosmie zu den ersten Parkinson-Symptomen überhaupt gehören. Bis zu 90 % aller Parkinson-Patienten weisen eine Hyposmie auf, viele von ihnen, ohne es selbst bemerkt zu haben. Somit gibt es gute Gründe, die Hyposmie als fünftes Kardinalsymptom zu bezeichnen. Die REM-Schlaf-Verhaltensstörung ist ein weiteres Symptom, das den motorischen Parkinson-Symptomen vorausgehen kann. Darüber hinaus sind auch Veränderungen des Schriftbildes oder Schulterschmerzen frühe mögliche Parkinson-Symptome. Mit dem Farmsworth-Test kann man Störungen der Farbwahrnehmung objektivieren. Dazu kommen ein Mindermitpendeln des Armes und die Hypomimie als hilfreiche Frühsymptome des idiopathischen Parkinson-Syndroms. Zusammengefasst ist die Hyposmie der wichtigste frühe klinische Marker, um ein idiopathisches Parkinson-Syndrom zu diagnostizieren. Weniger spezifisch sind eine depressive Verstimmung, die in 30 % der Fälle den motorischen Symptomen vorangeht, und eine Obstipation.

Abstract

There is an increasing body of literature on possible substances which may offer disease modification for Parkinson's disease (PD). To name a few, rasagiline, selegiline, dopamine agonists and amantadine may possibly be disease-modifying substances. If this holds true, it becomes necessary and rewarding to diagnose PD earlier than is so far the case. So far, we have treated patients only if they felt impaired by the disease, i. e., by symptoms such as bradykinesia or tremor. We strongly believe that hyposmia is the first clinical marker for PD. At least 90 % of all PD patients suffer from hyposmia, many of them without having noticed it. This large number of hyposmic patients influenced us to introduce hyposmia as the fifth cardinal symptom. REM sleep disturbance is another early clinical symptom but it is certainly less often seen in PD patients than hyposmia. Abnormalities in hand writing are another early clinical sign since most patients develop due to their rigidity a smaller and less clearly readable typeface (micrographia). Another less characteristic symptom is pain in the shoulder girdle, which is also a symptom caused by muscular rigidity. The Farmsworth test is good to objectify problems in colour discrimination. A reduced arm swing and hypomimia are additional early clinical symptoms. Taken together, in our view, hyposmia is the most useful early clinical marker to detect imminent PD. Less specific is depression which occurs in up to 30 % prior to the motor symptoms. The same is true for constipation.

idiopathisches Parkinson-Syndrom - Frühdiagnose - Hyposmie - REM-Schlaf-Verhaltensstörung - Depression

idiopathic Parkinson's syndrome - early diagnosis - hyposmia - REM sleep behavior disorder - depression

Literatur

• 1 Fahn S. and the Parkinson Study Group . Does levodopa slow or hasten the rate of progression of Parkinson's disease.  J Neurol. 2005;  Suppl. 4 IV37-IV42
• 2 Grosset D, Taurah L, Burn D J. et al . A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson's disease left untreated at diagnosis.  J Neurol Neurosurg Psychiatry. 2007;  78 465-469
• 3 Schapira A H, Obeso J. Timing of treatment initiation in Parkinson's disease: a need for reappraisal?.  Ann Neurol. 2006;  59 559-562
• 4 Moore D J, West A B, Dawson V L. et al . Molecular pathophysiology of Parkinson's disease.  Annu Rev Neurosci. 2005;  28 57-87
• 5 Healy D G, Falchi M, O'Sullivan S S. et al . Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study.  Lancet Neurology. 2008;  7 583-590
• 6 Braak H, Del Tredici K, Bratzke H. et al . Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages).  J Neurol. 2002;  249 (Suppl. 3) III / 1-5
• 7 Braak H, de Vos R A, Bohl J. et al . Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology.  Neurosci Lett. 2006;  396 67-72
• 8 Müller A, Reichmann H, Livermore A. et al . Olfactory function in idiopathic Parkinson's disease (IPD): results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients.  J Neural Transm. 2002;  109 805-811
• 9 Haehner A, Boesveldt S, Berendse H W. et al . Prevalence of smell loss in Parkinson's disease – A multicenter study.  Parkinsonism Relat Disord. 2009, Jan 10 (e-pub); 
• 10 Katzenschlager R, Zijlmans J, Evans A. et al . Olfactory function distinguishes vascular parkinsonism from Parkinson's disease.  J Neurol Neurosurg Psychiatry. 2004;  75 1749-1752
• 11 Witt M, Bornemann K, Gudziol V. et al . Biopsies of olfactory epithelium in patients with Parkinson's disease.  Mov Disord. 2009, Feb 9 (Epub ahead of print); 
• 12 Sommer U, Hummel T, Cormann K. et al . Detection of presymptomatic Parkinson's disease: combining smell tests, transcranial sonography, and SPECT.  Mov Disord. 2004;  19 1196-1202
• 13 Haehner A, Hummel T, Hummel C. et al . Olfactory loss may be a first sign of idiopathic Parkinson's disease.  Mov Disord. 2007;  22 839-842
• 14 Becker G, Seufert J, Bogdahn U. et al . Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography.  Neurology. 1995;  45 182-184
• 15 Berg D. Disturbance of iron metabolism as a contributing factor to SN hyperechogenicity in Parkinson's disease: implications for idiopathic and monogenetic forms.  Neurochem Res. 2007;  32 1646-1654
• 16 Sofic E, Paulus W, Jellinger K. et al . Selective increase of iron in substantia nigra zona compacta of parkinsonian brains.  J Neurochem. 1991;  56 978-982
• 17 Ponsen M M, Stoffers D, Booij J. et al . Idiopathic hyposmia as a preclinical sign of Parkinson's disease.  Ann Neurol. 2004;  56 173-181
• 18 Berendse H W, Ponsen M M. Detection of preclinical Parkinson's disease along the olfactory tract.  J Neural Transm Suppl. 2006;  70 321-325
• 19 Ross G W, Petrovitch H, Abbott R D. et al . Association of olfactory dysfunction with risk for future Parkinson's disease.  Ann Neurol. 2008;  63 167-173
• 20 Iranzo A, Molinuevo J L, Santamaria J. et al . Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study.  Lancet Neurol. 2006;  5 572-577
• 21 Stiasny-Kolster K, Doerr Y, Möller J C. et al . Combination of idiopathic REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.  Brain. 2005;  128 (part1) 126-137
• 22 Abbott R D, Petrovich H, White L H. et al . Frequency of bowel movements and future risk of Parkinson's disease.  Neurology. 2001;  57 456-462
• 23 Riedel O, Klotsche J, Spottke A. et al . Cognitive impairment in 873 patients with idiopathic Parkinson's disease. Results from the German Study on Epidemiology of Parkinson's disease with dementia (GEPAD).  J Neurol. 2008;  255 255-264
• 24 Santamaria J, Tolosa E, Valles A. Parkinson's disease with depression: a possible subgroup of idiopathic parkinsonism.  Neurology. 1986;  36 1130-1133
• 25 Schurmann A G, van den Akker H, Ensinck K TJL. et al . Increased risk of Parkinson's disease after depression: a retrospective cohort study.  Neurology. 2002;  58 1501-1504
• 26 Reichmann H. et al .Praxis der neurodegenerativen Erkrankungen. Bremen; Uni-Med Verlag 1999