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Vascular parkinsonism—characteristics, pathogenesis and treatment

Key Points

  • Vascular changes in the brain can manifest as parkinsonism

  • The predominant clinical feature in most cases of vascular parkinsonism (VP) is gait impairment, referred to as lower body parkinsonism

  • As VP advances, patients develop cognitive impairment and incontinence

  • The most prominent pathology observed by neuroimaging in patients with VP involves the white matter of the brain

  • Patients with VP respond only slightly or not at all to dopaminergic medication

  • Similar pathology and clinical features in VP and Binswanger disease suggest that they represent different manifestations along a disease spectrum

Abstract

Parkinson disease is a primary degenerative disease of the brain, but parkinsonism can also result from a variety of vascular disorders. Vascular parkinsonism (VP) most frequently presents as lower body parkinsonism, a condition that is accompanied by the development of white matter lesions (WMLs) and lacunes in the brain. Patients with lower body parkinsonism exhibit gait impairment and go on to develop urinary incontinence, abnormal pyramidal responses and cognitive decline. However, WMLs and lacunes are also common observations among elderly individuals who do not have parkinsonism, which causes difficulty in determining the pathogenetic mechanisms that lead to VP. In addition, imaging studies suggest that many pathological and clinical features are common to VP and Binswanger disease, a type of small vessel vascular dementia. This Review summarizes current understanding of the clinical characteristics of VP, as well as knowledge gained from neuroimaging and nuclear imaging of the pathological features of VP. The lack of current treatment options, and the emergence of new therapies such as cerebrospinal fluid drainage, are also discussed. Finally, consideration is given to whether the overlap between VP and Binswanger disease means that these two disorders should be considered as part of the same disease entity.

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Figure 1: Brain MRI in a patient with parkinsonism.
Figure 2: SPECT imaging of the brain in patients with parkinsonism.

References

  1. Korczyn, A. D. Parkinson's disease: one disease entity or many? J. Neural Transm. Suppl. 56, 107–111 (1999).

    Article  CAS  PubMed  Google Scholar 

  2. Critchley, M. Arteriosclerotic parkinsonism. Brain 52, 23–83 (1929).

    Article  Google Scholar 

  3. Thompson, P. D. & Marsden, C. D. Gait disorder of subcortical arteriosclerotic encephalopathy: Binswanger's disease. Mov. Disord. 2, 1–8 (1987).

    Article  CAS  PubMed  Google Scholar 

  4. FitzGerald, P. M. & Jankovic, J. Lower body parkinsonism: evidence for vascular etiology. Mov. Disord. 4, 249–260 (1989).

    Article  CAS  PubMed  Google Scholar 

  5. Winikates, J. & Jankovic, J. Clinical correlates of vascular parkinsonism. Arch. Neurol. 56, 98–102 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Parkes, J. D. et al. Parkinson's disease, cerebral arteriosclerosis, and senile dementia. Clinical features and response to levodopa. Q. J. Med. 43, 49–61 (1974).

    CAS  PubMed  Google Scholar 

  7. Hunter, R., Smith, J., Thomson, T. & Dayan, A. D. Hemiparkinsonism with infarction of the ipsilateral substantia nigra. Neuropathol. Appl. Neurobiol. 4, 297–301 (1978).

    Article  CAS  PubMed  Google Scholar 

  8. Lazzarino, L. G., Nicolai, A. & Toppani, D. Subacute parkinsonism from a single lacunar infarct in the basal ganglia. Acta Neurol. (Napoli) 12, 292–295 (1990).

    CAS  Google Scholar 

  9. Tolosa, E. S. & Santamaría, J. Parkinsonism and basal ganglia infarcts. Neurology 34, 1516–1518 (1984).

    Article  CAS  PubMed  Google Scholar 

  10. Harik, S. I., Al-Hinti, J. T., Archer, R. L. & Angtuaco, E. J. Hemiparkinsonism after unilateral traumatic midbrain hemorrhage in a young woman. Neurol. Clin. Pract. 3, 4–7 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Reider-Groswasser, I., Bornstein, N. M. & Korczyn, A. D. Parkinsonism in patients with lacunar infarcts of the basal ganglia. Eur. Neurol. 35, 46–49 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Ikeda, K,. Kotabe, T., Kanbashi, S. & Kinoshita, M. Parkinsonism in lacunar infarcts of the basal ganglia. Eur. Neurol. 36, 248–249 (1996).

    Article  CAS  PubMed  Google Scholar 

  13. Korczyn, A. D. Vascular contribution to dementia in Parkinson's disease. Neurodegener. Dis. 7, 127–130 (2010).

    Article  PubMed  Google Scholar 

  14. Inzelberg, R., Bornstein, N. M., Reider, I. & Korczyn, A. D. Basal ganglia lacunes and parkinsonism. Neuroepidemiology 13, 108–112 (1994).

    Article  CAS  PubMed  Google Scholar 

  15. Bhatia, K. P. & Marsden, C. D. The behavioural and motor consequences of focal lesions of the basal ganglia in man. Brain 117, 859–876 (1994).

    Article  PubMed  Google Scholar 

  16. Balash, Y. & Korczyn, A. D. Vascular parkinsonism. Handb. Clin. Neurol. 84, 417–425 (2007).

    Article  PubMed  Google Scholar 

  17. Sibon, I., Fenelon, G., Quinn, N. P. & Tison, F. Vascular parkinsonism. J. Neurol. 251, 513–524 (2004).

    Article  PubMed  Google Scholar 

  18. Leys, D. et al. Could Wallerian degeneration contribute to “leuko-araiosis” in subjects free of any vascular disorder? J. Neurol. Neurosurg. Psychiatry 54, 46–50 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bornstein, N. M., Halevy, G., Treves, T. & Korczyn, A. D. Cerebral atherosclerosis in Parkinsonian patients. Parkinsonism Relat. Disord. 4, 87–90 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. Jellinger, K. A. & Attems, J. Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathol. 115, 427–436 (2008).

    Article  PubMed  Google Scholar 

  21. Jellinger, K. A. Prevalence of cerebrovascular lesions in Parkinson's disease. A postmortem study. Acta Neuropathol. 105, 415–419 (2003).

    PubMed  Google Scholar 

  22. Hughes, A. J., Daniel, S. E., Blankson, S. & Lees, A. J. A clinicopathologic study of 100 cases of Parkinson's disease. Arch. Neurol. 50, 140–148 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Glass, P. G. et al. The clinical features of pathologically confirmed vascular parkinsonism. J. Neurol. Neurosurg. Psychiatry 83, 1027–1029 (2012).

    Article  PubMed  Google Scholar 

  24. Gupta, D. & Kuruvilla, A. Vascular parkinsonism: what makes it different? Postgrad. Med. J. 87, 829–836 (2011).

    Article  PubMed  Google Scholar 

  25. Okuda, B., Kawabata, K., Tachibana, H., Kamogawa, K. & Okamoto, K. Primitive reflexes distinguish vascular parkinsonism from Parkinson's disease. Clin. Neurol. Neurosurg. 110, 562–565 (2008).

    Article  PubMed  Google Scholar 

  26. Atchison, P. R., Thompson, P. D., Frackowiak, R. S. & Marsden, C. D. The syndrome of gait ignition failure: a report of six cases. Mov. Disord. 8, 285–292 (1993).

    Article  CAS  PubMed  Google Scholar 

  27. Navarro-Otano, J. et al. 123I-MIBG cardiac uptake, smell identification and 123I-FP-CIT SPECT in the differential diagnosis between vascular parkinsonism and Parkinson's disease. Parkinsonism Relat. Disord. 20, 192–197 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Rektor, I. et al. Vascular pathology in patients with idiopathic Parkinson's disease. Parkinsonism Relat. Disord. 15, 24–29 (2009).

    Article  PubMed  Google Scholar 

  29. Foltynie, T., Barker, R. & Brayne, C. Vascular parkinsonism: a review of the precision and frequency of the diagnosis. Neuroepidemiology 21, 1–7 (2002).

    Article  PubMed  Google Scholar 

  30. Zijlmans, J. C. et al. EEG findings in patients with vascular parkinsonism. Acta Neurol. Scand. 98, 243–247 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. Yamanouchi, H. & Nagura, H. Neurological signs and frontal white matter lesions in vascular parkinsonism. A clinicopathologic study. Stroke 28, 965–969 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Wegner, F. et al. Vascular parkinsonism in a CADASIL case with an intact nigrostriatal dopaminergic system. J. Neurol. 254, 1743–1745 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Carr, J. Parkinsonism secondary to neurosyphilis. Mov. Disord. 24, 1407 (2009).

    Article  PubMed  Google Scholar 

  34. Fabiani, G., Teive, H. A., Germiniani, F. M., Sá, D. S. & Werneck, L. C. Reversible parkinsonian syndrome in systemic and brain vasculitis. Mov. Disord. 17, 601–604 (2002).

    Article  PubMed  Google Scholar 

  35. Buechner, S., De Cristofaro, M. T., Ramat, S. & Borsini, W. Parkinsonism and Anderson Fabry's disease: a case report. Mov. Disord. 21, 103–107 (2006).

    Article  PubMed  Google Scholar 

  36. Antonini, A. et al. The relationship between cerebral vascular disease and parkinsonism: The VADO study. Parkinsonism Relat. Disord. 18, 775–780 (2012).

    Article  CAS  PubMed  Google Scholar 

  37. Bohnen, N. I. & Albin, R. L. White matter lesions in Parkinson disease. Nat. Rev. Neurol. 7, 229–236 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Baezner, H. et al. Association of gait and balance disorders with age-related white matter changes: the LADIS study. Neurology 70, 935–942 (2008).

    Article  CAS  PubMed  Google Scholar 

  39. de Laat, K. F. et al. Cerebral white matter lesions and lacunar infarcts contribute to the presence of mild parkinsonian signs. Stroke 43, 2574–2579 (2012).

    Article  PubMed  Google Scholar 

  40. Kreisel, S. H. et al. Deterioration of gait and balance over time: the effects of age-related white matter change—the LADIS study. Cerebrovasc. Dis. 35, 544–553 (2013).

    Article  PubMed  Google Scholar 

  41. Kloppenborg, R. P., Nederkoorn, P. J., Geerlings, M. I. & van den Berg, E. Presence and progression of white matter hyperintensities and cognition: a meta-analysis. Neurology 82, 2127–2138 (2014).

    Article  PubMed  Google Scholar 

  42. van Norden, A. G. et al. Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol. BMC Neurol. 11, 29 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wardlaw, J. M. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 12, 822–838 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lorberboym, M., Djaldetti, R., Melamed, E., Sadeh, M. & Lampl, Y. 123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism. J. Nucl. Med. 45, 1688–1693 (2004).

    CAS  PubMed  Google Scholar 

  45. Tzen, K. Y., Lu, C. S., Yen, T. C., Wey, S. P. & Ting, G. Differential diagnosis of Parkinson's disease and vascular parkinsonism by 99mTc-TRODAT-1. J. Nucl. Med. 42, 408–413 (2001).

    CAS  PubMed  Google Scholar 

  46. Brigo, F., Matinella, A., Erro, R. & Tinazzi, M. [123I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson's disease and vascular or drug-induced parkinsonisms: a meta-analysis. Eur. J. Neurol. 21, 1369–e90 (2014).

    Article  CAS  PubMed  Google Scholar 

  47. Jakobson Mo, S. et al. Pre- and postsynaptic dopamine SPECT in idiopathic Parkinsonian diseases: a follow-up study. Biomed. Res. Int. 2013, 143532 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Oyanagi, C. et al. Comparison of striatal dopamine D2 receptors in Parkinson's disease and progressive supranuclear palsy patients using 123I-iodobenzofuran single-photon emission computed tomography. J. Neuroimaging 12, 316–324 (2002).

    Article  PubMed  Google Scholar 

  49. Kim, Y. J. et al. Combination of dopamine transporter and D2 receptor SPECT in the diagnostic evaluation of PD, MSA, and PSP. Mov. Disord. 17, 303–312 (2002).

    Article  PubMed  Google Scholar 

  50. Benítez-Rivero, S. et al. Clinical features and 123I-FP-CIT SPECT imaging in vascular parkinsonism and Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 84, 122–129 (2013).

    Article  PubMed  Google Scholar 

  51. Jellinger, K. A. Vascular parkinsonism—neuropathological findings. Acta Neurol. Scand. 105, 414–415 (2002).

    Article  CAS  PubMed  Google Scholar 

  52. Auriel, E. et al. Clinical, radiological and pathological correlates of leukoaraiosis. Acta Neurol. Scand. 123, 41–47 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Rosenberg, G. A., Bjerke, M. & Wallin, A. Multimodal markers of inflammation in the subcortical ischemic vascular disease type of vascular cognitive impairment. Stroke 45, 1531–1538 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wang, H. C., Hsu, J. L. & Leemans, A. Diffusion tensor imaging of vascular parkinsonism: structural changes in cerebral white matter and the association with clinical severity. Arch. Neurol. 69, 1340–1348 (2012).

    Article  PubMed  Google Scholar 

  55. Murray., M. E. et al. Functional impact of white matter hyperintensities in cognitively normal elderly subjects. Arch. Neurol. 67, 1379–1385 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Teodorczuk, A. et al. Relationship between baseline white-matter changes and development of late-life depressive symptoms: 3-year results from the LADIS study. Psychol. Med. 40, 603–610 (2010).

    Article  CAS  PubMed  Google Scholar 

  57. Ling, M. J., Aggarwal, A. & Morris, J. G. Dopa-responsive parkinsonism secondary to right temporal lobe haemorrhage. Mov. Disord. 17, 402–404 (2002).

    Article  PubMed  Google Scholar 

  58. Zijlmans, J. C., Daniel, S. E., Hughes, A. J., Révész, T. & Lees, A. J. Clinicopathological investigation of vascular parkinsonism, including clinical criteria for diagnosis. Mov. Disord. 19, 630–640 (2004).

    Article  PubMed  Google Scholar 

  59. Krack, P. et al. Ineffective subthalamic nucleus stimulation in levodopa-resistant postischemic parkinsonism. Neurology 54, 2182–2184 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Espay, A. J., Narayan, R. K., Duker, A. P., Barrett, E. T. Jr & de Courten-Myers, G. Lower-body parkinsonism: reconsidering the threshold for external lumbar drainage. Nat. Clin. Pract. Neurol. 4, 50–55 (2008).

    Article  PubMed  Google Scholar 

  61. Tullberg, M. et al. White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity, predictive value and correlations to axonal degeneration and demyelination. Acta Neurol. Scand. 105, 417–426 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. Akiguchi, I. et al. Shunt-responsive parkinsonism and reversible white matter lesions in patients with idiopathic NPH. J. Neurol. 255, 1392–1399 (2008).

    Article  PubMed  Google Scholar 

  63. Ondo, W. G., Chan, L. L. & Levy, J. K. Vascular parkinsonism: clinical correlates predicting motor improvement after lumbar puncture. Mov. Disord. 17, 91–97 (2002).

    Article  PubMed  Google Scholar 

  64. Tisell, M. et al. Shunt surgery in patients with hydrocephalus and white matter changes. J. Neurosurg. 114, 1432–1438 (2011).

    Article  PubMed  Google Scholar 

  65. Yip, C. W. et al. A prospective pilot study of repetitive transcranial magnetic stimulation for gait dysfunction in vascular parkinsonism. Clin. Neurol. Neurosurg. 115, 887–891 (2013).

    Article  CAS  PubMed  Google Scholar 

  66. Caplan, L. R. & Schoene, W. C. Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger disease). Neurology 28, 1206–1215 (1978).

    Article  CAS  PubMed  Google Scholar 

  67. Caplan, L. R. Binswanger disease—revisited. Neurology 45, 626–633 (1995).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I am grateful to Yacov Balash (Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel) for supplying Figure 1, and to Mordechai Lorberboym (Edith Wolfson Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Israel) for supplying Figure 2.

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Correspondence to Amos D. Korczyn.

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Korczyn, A. Vascular parkinsonism—characteristics, pathogenesis and treatment. Nat Rev Neurol 11, 319–326 (2015). https://doi.org/10.1038/nrneurol.2015.61

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