The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

December 3, 2009 —  Parkinsonism is a syndrome that features bradykinesia (slowness of the initiation of voluntary movement) and at least 1 of the following conditions: rest tremor, muscular rigidity, or postural instability. Criteria for the clinical diagnosis of vascular parkinsonism (VP) have been proposed, which are derived from a postmortem examination study. Computed tomography and magnetic resonance imaging can support this clinical diagnosis with positive imaging findings. Dopamine transporter single-photon emission computed tomography may also be of help to distinguish Vascular Parkinsonism from Parkinson disease and other parkinsonisms.

Parkinsonism is a syndrome that features bradykinesia (slowness of the initiation of voluntary movement) and at least 1 of the following conditions: rest tremor, muscular rigidity, or postural instability. In 1929, Critchley [1] identified a type of parkinsonism caused by cerebrovascular disease in his report on “arteriosclerotic parkinsonism.” It required the development of computed tomography (CT) and magnetic resonance imaging (MRI) 50 years later to find evidence for Critchley’s ideas and what is now commonly known as vascular parkinsonism (VP). [2, 3, 4, 5, 6] Ischemic vascular lesions that may lead to vascular parkinsonism are lacunar infarctions, white matter hyperintensities, and less common large vessel infarctions. A comparison of 5 different European studies showed a prevalence rate of 3% of Vascular Parkinsonism. [7] In case the onset of parkinsonism was associated with a cerebrovascular event, vascular parkinsonism was diagnosed. Probably the real prevalence is higher because only few patients with Vascular Parkinsonism have an acute onset. [6, 8]

Vascular (arteriosclerotic) parkinsonism (ASP) is probably one of the most debated entities in the study of parkinsonism.  The term was introduced more than 100 years ago, when a syndrome of gait disorder of the elderly, characterized by a small step gait, march a petit pas, mild hemiparesis, dementia, dysarthria and urinary incontinence was ascribed to arteriosclerotic cerebrovascular disease. The clinical syndrome was correlated with the pathologic findings of multiple basal ganglia cavitations (etat crible) and infarcts (etat lacunaris). In 1929, Critchley [50] defined the syndrome in a landmark monograph on the subject. Despite the lack of PD-defining pathology at the time, he separated vascular parkinsonism from PD, based on clinical features. He described gegenhalten (lead-pipe) rigidity, lack of tremor, shuffling gait with freezing, acute/step wise progression of the symptoms in the setting of hypertensive disease as characteristic features separating Vascular (arteriosclerotic) parkinsonism from PD. Despite great advances in the knowledge of the pathology and treatment of PD, researchers have added little to the clinical description of Vascular (arteriosclerotic) parkinsonism .  The introduction of levodopa in the late 1960s revolutionized the treatment of PD. The presence of a clear response to levodopa is an obligatory diagnostic criteria of PD and, a lack of response separates patients with atypical parkinsonism, including Vascular (arteriosclerotic) parkinsonism, in the majority of cases.  The advent of computed tomography (CT) scanning and magnetic resonance imaging (MRI) contribute to the evolving definition of Vascular (arteriosclerotic) parkinsonism . Imaging studies allow correlation between the degree and distribution of vascular changes and Vascular (arteriosclerotic) parkinsonism. [52,53]

The periventricular distribution of vascular changes is implicated as the reason for the marked gait dysfunction caused by involvement of the pathways leading to the legs.  The term "lower body parkinsonism" was introduced in the 1980s to stress that relationship.  A considerable overlap exists between that syndrome and the "pure" gait disorder of the elderly without clinical evidence or known risk factors for vascular disease.  Elderly subjects with gait dysfunction are more likely than asymptomatic people of the same age to have periventricular white matter changes on imaging studies.  With widespread use of MR imaging, it is now clear that periventricular white matter changes (leukoaraiosis) in no way can be diagnostic of Vascular (arteriosclerotic) parkinsonism : they can be seen in asymptomatic individuals and may be nonspecific markers of aging,  In summary, short of pathologic confirmation of the diagnosis, clinicians still have to rely on clinical diagnostic criteria of Vascular (arteriosclerotic) parkinsonism , making an attempt to rule out other potential causes of gait dysfunction in the elderly.  Hurtig [51] has outlined strict diagnostic criteria of "true" vascular parkinsonism, as follows:

1. Acute or subacute, preferably stepwise, evolution of an akinetic- rigid syndrome, usually without tremor.

2. The presence of vascular risk factors, especially hypertension or prior strokes.

3. Brain imaging studies (CT scanning or MRI) showing two or more infarcts in the basal ganglia.

4. Clinical improvement without anti-PD therapy, and specifically no deterioration after withdrawal of PD therapy.

Adherence to these criteria might exclude some "true" cases of vascular parkinsonism but at the same time will minimize the chance for a false-positive diagnosis. There is no specific therapy for vascular parkinsonism other than aggressive gait physiotherapy. Measures aimed at stroke risk reduction may slow progression.

• Clinical features

In the classical type of vascular parkinsonism, as reported by Thompson and Marsden4 and FitzGerald and Jankovic, [5 ] difficulty in walking is the most important initial symptom. Therefore, the classical type is also called lower-half4 or lower-body parkinsonism.5 In patients suffering from the classical type, the gait is disordered by shuffling, short steps, variable base (narrow to wide), start and turn hesitation, and moderate disequilibrium. In addition, the arm swing in patients with Vascular Parkinsonism is usually more preserved than in patients with Parkinson disease (PD). [4, 5, 9]

Depending on their onset, 2 types of Vascular Parkinsonism can be distinguished [6]: one with an insidious onset and its vascular lesions diffusely located in the watershed areas (VPi) and the other with an acute onset and lesions located in the subcortical gray nuclei (striatum, globus pallidus, and thalamus) (VPa). Winikates and Jankovic [8] later confirmed the 2 different types of onset. In about one-quarter of the patients with Vascular Parkinsonism, the symptoms start acutely. [6, 8]

• Clinical diagnosis

Winikates and Jankovic [8] categorized patients with parkinsonism and a vascular score of 2 or more on a rating scale as having Vascular Parkinsonism. In this way, many patients with PD and vascular risk factors can be misdiagnosed as having Vascular Parkinsonism. Criteria for the clinical diagnosis of Vascular Parkinsonism have been proposed, which are derived from a postmortem examination study. [10] See Box 1 for the criteria for clinical diagnosis of Vascular Parkinsonism.

Box 1. Criteria for the clinical diagnosis of probable vascular parkinsonism

• Etiology

In the “classical clinical type” of Vascular Parkinsonism, parkinsonism is attributed to diffuse periventricular and frontal white matter damage [4] because similar clinical features occur in normal pressure hydrocephalus and in some cases of frontal parasagittal meningioma, in which the same structures are compromised. According to Thompson and Marsden, [4] disconnection of thalamocortical fibers to the supplementary motor area and cerebellar fibers to the leg area is the underlying mechanism that causes the gait disorder in Vascular Parkinsonism.

In accordance with current concepts of putamenal efferents directed toward the basal ganglia output nuclei, [11] one might expect that vascular lesions in the SNc (substantia nigra pars compacta), GPe (globus pallidus pars externa), or the Vascular Parkinsonism (ventral anterior)/VL (ventral lateral) nuclei of the thalamus induce decreased thalamocortical drive to premotor areas and also subsequent development of parkinsonism. According to many previous publications, parkinsonism is also attributed to strategic infarcts in the basal ganglia or thalamus. A causal relationship between strategic infarcts and parkinsonism is reported only in a few publications that described the cases in which the onset is (sub) acute or accompanied by other symptoms of a stroke related to the same lesion. [2, 3, 6, 8, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24] Lesions in specific areas that theoretically can cause parkinsonism (GPe, VL/VA of thalamus, and SNc) have been described by a few investigators. [2, 16, 18, 21, 22, 23] The infarct is located in the hemisphere or brainstem contralateral to parkinsonism in most cases in which a vascular cause is acceptable and a single lesion is seen in the basal ganglia or thalamus. [12, 14, 15, 16, 17, 18, 20, 21, 22, 24]

• Pathophysiology

The most supported hypothesis about the pathogenesis of subcortical lesions was originally proposed by Binswanger and Alzheimer. [25, 26] They suggested that the white matter softening can be attributed to subcortical ischemia as a result of arteriolosclerosis of the long penetrating arteries. According to this view, arteriolosclerosis of long penetrating arteries that are poorly provided with collateral anastomoses can result in ischemia of the distal fields of these vessels, that is, periventricularly and in the watershed zones. Transient episodes of hypotension caused by excessive antihypertensive medication or heart failure [27] and hyperviscosity [28] may provoke or aggravate white matter disease in an already compromised cerebral blood flow. [29, 30] The typically hypertensive changes of small vessel disease can occasionally be found in a patient who is not hypertensive or diabetic. [31] Conversely, not every elderly patient with hypertension develops small vessel disease. [32] These points suggest that factors other than hypertension and diabetes, such as a cerebrovascular accident, cardiac disease, or carotid pathology, are probably also involved in the development of hypertensive arteriolopathy. [33] Many investigators stated that the clinical significance of subcortical lesions depends on the severity and location of lesions. [6, 32, 34] A threshold extent of subcortical lesions may be necessary before symptoms appear. [6, 34, 35[

• Differential diagnosis

Features that are usually considered to favor a diagnosis of idiopathic PD [36] are also frequently present in vascular parkinsonism and include micrographia, cogwheeling, stooped posture, facial masking, hypophonia, and a positive response to levodopa. However, application of the more stringent UK Parkinson’s Disease Society Brain Bank criteria for the diagnosis of idiopathic PD [37] excludes this diagnosis in most patients with Vascular Parkinsonism. In case a slowly progressive gait disorder presents itself with a shuffling gait, then a normal pressure hydrocephalus or a frontal lobe tumor must be considered. A clinical diagnosis together with a radiologic diagnosis of probable multiple system atrophy, [38] progressive supranuclear palsy (PSP), [39] or dementia with Lewy bodies [40] probably excludes a diagnosis of Vascular Parkinsonism in most cases. [10] Dubinsky and Jankovic [41] and Winikates and Jankovic [42] suggested the presence of a particular subtype of Vascular Parkinsonism that they called vascular PSP. In one report, the brains of 2 patients with vascular PSP showed (besides the common diffuse white matter lesions) additional lesions in the dorsal pons and in the thalamus. [52,53]

• Brain Imaging

In the last century, CT and MRI were mainly used to exclude hydrocephalus, mass lesions, or subdural hematomas in atypical parkinsonism. They now can support the clinical diagnosis of Vascular Parkinsonism with positive imaging findings. One has to consider the 2 different locations of lesions with their related types of onset: an insidious onset type presenting itself with white matter lesions that are diffusely located in the watershed areas (Fig. 1) and an acute onset type with lesions located in contralateral strategic areas (globus pallidus, thalamus, substantia nigra, and frontal lobe). (Fig. 2) MRI is preferred to demonstrate the presence of strategic vascular lesions because of its greater capabilities to show small lesions in regions that are difficult to image with CT, such as the globus pallidus, thalamus, and substantia nigra, and also because of the possibility to scan in different directions (eg, coronal and sagittal).

Figure 1. leukoaraiosis, MRI T2 image. The MRI T2 periventricular hyperintensities are mainly due to astrogliosis and interstitial edema. (Click to enlarge figure)

Figure 2. Periventricular lacunar infarctions and calcifications. (Click to enlarge figure)

The different T1- and T2-weighted sequences have their own qualities, and when combined, they give complimentary information on the characteristics and probable cause of ischemic pathology. This may be important to fulfill the diagnostic criteria mentioned earlier. T1-weighted images reveal lacunes and frontal cortical infarcts. Fluid attenuated inversion recovery (FLAIR) is best suited for the assessment of white matter lesions. It has the advantage of suppressing cerebrospinal fluid signal, allowing a simple distinction of lacunes and perivascular spaces from ischemic white matter lesions, both of which are bright on standard T2-(T)SE weighted images. [43, 44] For the assessment of ischemic lesions in the thalamus and infratentorial regions, conventional T2-weighted images are preferred. [45] In addition, T2-weighted gradient echo sequences are more sensitive for the detection of hemorrhagic lacunae than spin echo and FLAIR sequences. [46, 47, 48, 49] An imaging protocol using T1, T2, T2, and FLAIR images may therefore optimize diagnostic capabilities of MRI for Vascular Parkinsonism. Fig. 1 and 2 show MRI/Ct scans in patients with Vascular Parkinsonism with an insidious and an acute onset. [51,52,53]

References

1. Critchley M. Arteriosclerotic parkinsonism. Brain. 1929;52:23–83.
2. Tolosa ES, Santamaria J. Parkinsonism and basal ganglia infarcts. Neurology. 1984;34:1516–1518.
3. Friedman A, Kang UJ, Tatemichi TK, et al. A case of parkinsonism following striatal lacunar infarction. J Neurol Neurosurg Psychiatr. 1986;49:1087–1088.
4. Thompson PD, Marsden CD. Gait disorder of subcortical arteriosclerotic encephalopathy: Binswanger’s disease. Mov Disord. 1987;2:1–8.
5. FitzGerald PM, Jankovic J. Lower body parkinsonism: evidence for vascular etiology. Mov Disord. 1989;4:249–260.
6. Zijlmans JC, Thijssen HO, Vogels OJ, et al. MRI in patients suspected of vascular parkinsonism. Neurology. 1995;45:2183–2188.
7. de Rijk M, Tzourio C, Breteler M, et al. Prevalence of parkinsonism and Parkinson’s disease in Europe: the EURPARKINSON collaborative study. J Neurol Neurosurg Psychiatr. 1997;62:10–15.
8. Winikates J, Jankovic J. Clinical correlates of vascular parkinsonism. Arch Neurol. 1999;56:98–102.
9. Zijlmans JC, Poels PJ, Duysens J, et al. Quantitative gait analysis in patients with vascular parkinsonism. Mov Disord. 1996;11(5):501–508.
10. Zijlmans J, Daniel S, Hughes A, et al. A clinico-pathological investigation of vascular parkinsonism (VP). Including clinical criteria for the diagnosis of VP. Mov Disord. 2004;19:630–640.
11. DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Arch Neurol. 2007;64(1):20–24.
12. Chang CM, Yu YL, Leung SY, et al. Vascular pseudoparkinsonism. Acta Neurol Scand. 1992;86:588–592.
13. Mayo J, Arias M, Leno C, et al. Vascular parkinsonism and periarteritis nodosa. Neurology. 1986;36:874–875.
14. Tison F, Duché B, Loiseau P. Syndrome hemiparkinsonien vasculaire (Vascular hemiparkinson syndrome), Rev Neurol (Paris). 1993;149:565–567[in French].
15. Lee MS, Lee SA, Heo JH, et al. A patient with a resting tremor and a lacunar infarction at the border between the thalamus and the internal capsule. Mov Disord. 1993;8:244–246.
16. De La Fuente Fernandez R, Lopez J, Rey del Corral P, et al. Peduncular hallucinosis and right hemiparkinsonism caused by left mesencephalic infarction. J Neurol Neurosurg Psychiatr. 1994;57:870.
17. Pullicino P, Lichter D, Benedict R. Micrographia with cognitive dysfunction: “minimal” sequelae of a putaminal infarct. Mov Disord. 1994;9:371–373.
18. Kulisevsky J, Avila A. Bipolar affective disorder and unilateral parkinsonism after a brainstem infarction. Mov Disord. 1995;10:799–801.
19. Mark MH, Sage JI, Walters AS, et al. Binswanger’s disease presenting as levodopa-responsive parkinsonism: clinicopathological study of three cases. Mov Disord. 1995;10:450–454.
20. Reider-Grosswasser I, Bornstein N, Korczyn A. Parkinsonism in patients with lacunar infarcts of the basal ganglia. Eur Neurol. 1995;35:46–49.
21. Boecker H, Weindl A, Leenders K, et al. Secondary parkinsonism due to focal substantia nigra lesions: a PET study with [18F] FDG and [18F] fluorodopa. Acta Neurol Scand. 1996;93:387–392.
22. Fénelon G, Houéto J. Unilateral parkinsonism following a large infarct in the territory of the lenticulostriate arteries. Mov Disord. 1997;12:1086–1090.
23. Leduc V, Montagne B, Destée A. Parkinsonism consecutive to an hemorrhagic lesion of the substantia nigra. Mov Disord. 1997;12(Suppl 1):2.
24. Alarcón F, Zijlmans JCM, Dueñas G, et al. Post-stroke movement disorders: report of 56 patients. J Neurol Neurosurg Psychiatr. 2004;75:1568–1574.
25. Alzheimer A. Die Seelenstörung auf arteriosclerotischer Grundlage (Psychiatric disturbance with arteriosclerotic basis), Z Psychiat. 1902;59:695–711[in German].
26. Blass JP, Hoher S, Nitsch R. A translation of Otto Binswanger’s article, ‘the delineation of the generalized progressive paralyses’. Arch Neurol. 1991;48:961–972.
27. Breteler MM, van Amerongen NM, van Swieten JC, et al. Cognitive correlates of ventricular enlargement and cerebral white matter lesions on magnetic resonance imaging. The Rotterdam study. Stroke. 1994;25:1109–1115.
28. Schneider R, Ringelstein EB, Zeumer H, et al. The role of plasma hyperviscosity in subcortical arteriosclerotic encephalopathy (Binswanger’s disease). J Neurol. 1987;234:67–73.
29. Caplan LR, Schoene WC. Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger’s disease). Neurology. 1978;28:1206–1215.
30. Thomas D, du Boulay G, Marshall J, et al. Effect of hematocrit on cerebral blood flow in man. Lancet. 1977;2:941–943.
31. Ma K, Lundberg P, Lilja A, et al. Binswanger’s disease in the absence of chronic arterial hypertension: a case report with clinical, radiological and immunohistochemical observations on intracerebral blood vessels. Acta Neuropathol. 1992;83:434–439.
32. 32. 32van Swieten JC, Geyskes GG, Derix MM, et al. Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol. 1991;30:825–830.
33. Van Gijn J. Leukoaraiosis and vascular dementia. Neurology. 1998;51(Suppl 3):S3–S8.
34. Rao SM, Mittenberg W, Bernardin L, et al. Neuropsychological test findings in subjects with leukoaraiosis. Arch Neurol. 1989;46:40–44.
35. Boone KB, Miller BL, Lesser IM, et al. Neuropsychological correlates of white matter lesions in healthy elderly subjects. Arch Neurol. 1992;49:549–554.
36. Jankovic J. Clinical aspects of Parkinson’s disease. In: Marsden CD, Fahn S editor. The assessment and therapy of parkinsonism (New trends in clinical neurology series). New Jersey (NJ): Parthenon Publishing Group; 1990;p. 53–75.
37. Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatr. 1992;55:181–184.
38. Gilman S, Low P, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999;163:94–98.
39. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology. 1996;47:1–9.
40. McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124[review].
41. .Dubinsky RM, Jankovic J. Progressive supranuclear palsy and a multi-infarct state. Neurology. 1987;37:570–576.
42. Winikates J, Jankovic J. Vascular progressive supranuclear palsy. J Neural Transm Suppl. 1994;42:189–201.
43. Haynal JV, Bryant DJ, Kasuboski L, et al. Use of fluid attenuated inversion recovery (FLAIR) pulse sequences in MRI of the brain. J Comput Assist Tomogr. 1992;16(6):841–844.
44. De Coene B, Haynal JV, Gatehouse P, et al. MR of the brain using fluid-attenuated inversion recovery (FLAIR) pulse sequences. AJNR Am J Neuroradiol. 1992;13(6):1555–1564.
45. Bastos Leite AJ, van Straaten EC, Scheltens P, et al. Thalamic lesions in vascular dementia: low sensitivity of fluid-attenuated inversion recovery (FLAIR) imaging. Stroke. 2004;35(2):415–419.
46. Challa VR, Moody DM. The value of magnetic resonance imaging in the detection of type II hemorrhagic lacunes. Stroke. 1989;20(6):822–825.
47. Fazekas F, Kleinert R, Roob G, et al. Histopathologic analysis of foci of signal loss on gradient-echo T2-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol. 1999;20(4):637–642.
48. Kim DE, Bae HJ, Kim H, et al. Gradient echo magnetic resonance imaging in the prediction of hemorrhagic vs ischemic stroke: a need for the consideration of the extent of leukoariosis. Arch Neurol. 2002;59(3):425–429.
49. Ripoll MA, Sjösteen B, Hartman M, et al. MR detectability and appearance of small experimental intracranial hematomas at 1.5 T and 0.5 T. A 6-7-month follow-up study. Acta Radiol. 2003;44(2):199–205.
50. Critchley M: Arteriosclerotic parkinsonism. Brain 52:23-83,1929
51. Hurtig HI. Vascular parkinsonism. In: Stern MB, Koller WC (eds): Parkinsonian syndromes. New York, Marcel Dekker, Inc., 1993: pp 81-93
52. Topic of the month…..The ischemic microvascular brain disease [Click to download in PDF format]
53. Differential diagnosis… Parkinsonian syndromes. [Click to download in PDF format]