Introduction

Critchley described an “atherosclerotic parkinsonism” in patients with multiple strokes, gait and balance problems and cognitive decline [1]. Subsequently Yamanouchi described diffuse white matter lesions in the frontal lobes [2]. On 1989 FitzGerald and Jankovic utilized the term “lower body parkinsonism” noticing that the parkinsonian feature was more prominent in the lower limbs [3].

Zijlman and colleagues [4] identified based on autopsies pathological lesions that increased the BasalGanglia Motor Output (BGMO) including substantia nigra and lenticular nucleus, and lesions that decreased the Thalamo Cortical Drive (TCD) involving the ventro lateral area of the thalamus and frontal lobes. Recently, Viscarra and colleagues have arguments against the previously defined syndrome, referring to the low probability that strokes may present as true Parkinsonism, and proposed 3 types of phenotypes. These phenotypes may differ according to presence or not of Parkinsonism on the clinical exam, and presence or absence of stroke. All these patients may present with gait and balance problems. Additionally, they schematized the clinical manifestations and differentiated the affected brain areas with patterns [5].

We had the hypothesis that the pattern of ischemic lesions and network might be different between those participants with Parkinsonism onset within 1 year from stroke(s) (VasP) versus those with stroke and gait and balance problems, but who never developed a hypokinetic rigid syndrome (V PseuP).

 Materials and Methods

 This study follows up our previous group of patients with stroke screened in a tertiary care stroke prevention clinic in Alberta. All participants in the original study had a clinical exam to identify if presence of a hypokinetic rigid syndrome. Further details about that first study may be found elsewhere [6]. We selected from that database those patients at high risk for Parkinsonism defined as those with high TannerQuestionnaire-TQ score (a screening validated questionnaire for the identification of participants with Parkinsonism) that had a cut off score of ≥ 4 which gave the highest sensitivity and specificity of this test, as confirmed in ours and other previous studies (Table 1).

 Table1: Tanner Questionnaire: Screening Questionnaire.

All participants were screened in our original study with a new scale operationalizing the most recent criteria for Vascular Parkinsonism the FMAS score [6] (Table 2). It consisted of item 1 and 2 corresponding to clinical criteria for diagnosing and hypokinetic rigid syndrome, item 3 which considered a stroke(s) confirmed by neuroimaging in the locations and network proposed by Zijlman to be associated with onset of VasP. Item 4 correlated in time the onset of Parkinsonism with the occurrence of the stroke(s) symptoms. A score of 2 would be able to identify participants with Parkinsonism on clinical exam, and a score of 4 was necessary to consider a clinical diagnosis of VasP [6].

Table 2: Five Minute Assessment Scale (FMAS).

The selection criteria for the prospective cohort of participants in this study were patients attaining a TQ score ≥ 4 from our previous original study. We classified the participants in four groups, according to presence or absence of Parkinsonism on clinical exam, and presence of stroke and relationship between the onset of Parkinsonism and the occurrence of the stroke (Table 3). First subgroup: Pseudo Vascular Parkinsonism (PseuV P) in which patients may have parkinsonism, but there is no evidence of stroke in the neuroimaging or the location of the stroke and timing of the lesion does not explain the clinical picture of parkinsonism; the second subgroup or phenotype is Vascular Pseudo Parkinsonism (V PseuP) in which patients may have acute symptoms related to stroke and the ischemic lesion is confirmed by neuroimaging. These participants may present with gait and balance problems, but on clinical exam there is no evidence of a hypokinetic rigid syndrome. The third phenotype is PseudoVascular Pseudo Parkinsonism (PseuV PseuP) in which patients neither have acute symptoms related to stroke and no cerebrovascular event is seen on neuroimaging, or do they have and hypokinetic rigid syndrome on the exam. However, these patients may have gait and balance problems. Finally the subgroup with VasP in which the onset of Parkinsonism was present within 1 year from the stroke(s) occurrence.

 Table 3: Different phenotypes found in stroke patients with gait and balance problems TQ ≥ 4.

Pseudo Vascular Parkinsonism (PseuVP) in which patients may have parkinsonism, but there is no evidence of stroke in the neuroimaging or the location of the stroke and timing of the lesion does not explain the clinical picture of parkinsonism; the second phenotype is Vascular Pseudo Parkinsonism (VPseuP) in which patients may have acute symptoms related to stroke and confirmed by neuroimaging with gait and balance problems, but on exam there is no evidence of a hypokinetic rigid syndrome. The third phenotype is Pseudo Vascular Pseudo Parkinsonism (PseuVPseuP) in which patients neither have acute symptoms related to stroke and no cerebrovascular event is seen on neuroimaging, or do they have and hypokinetic rigid syndrome on the exam. However, these patients may have gait and balance problems.

The study was approved by the Human Research Ethics Committee of the University of Alberta, and informed consent was obtained from all participants attending to the stroke prevention clinic.

Demographic information was obtained from all participants, and the subtype of stroke was assigned according to the TOAST classification [7] (Table 4). All participants had a Holter, echo, CT head or brain MRI, and CTA. Neuroimaging were reviewed by a senior fellow in movement disorders. Images were reported initially by neuroradiology
y unaware of the different subgroups in the study. Data was extracted from our previous study [6]. Stroke lesions were topographically identified, and patterns were analyzed including the BGMO, the TCD, and frontal cortex.

 Table 4: Subtypes of ischemic stroke-TOAST classification.

Sample size was calculated based on prevalence of Vascular Parkinsonism found previously in stroke care centers, and using the formula n=Z² P (1-P)/d² [8]. Statistical analysis was done with the program SAS software (copyright the SAS institute, Cary, N.C.), including in the second study chi square, Fishers exact test for categorical variables, p value less than 0.05 was consider of statistical significance, confidence intervals and odds ratio were calculated too.

Figure 1: Flow Diagram. Patients enrollment. 

Abbreviations: FMAS-Five-Minute Assessment Scale; TQ-Tanner Questionnaire. Modified with permission from the copyright holder, Elsevier Journals. The source has been acknowledged.

Results

From 240 patients screened, 16 were found to have Parkinsonism attaining at least a score of 2 in the FMAS, and 15 of them with TQ ≥ 4 (Figure 1). The total group of TQ ≥ 4 was composed of 46 people.

Demographic data is shown in (Table 5). Patients with VasP were older (p<0.0007), and had a higher risk for cardio embolism (odds ratio 8.5, 95% CI (1.5-47.9), p=0.01) due to atrial fibrillation (odds ratio 6.6, 95% CI (1.2-35.2), p=0.02).

 We described in detail the different phenotypes found within the group weather they had an extrapyramidal syndrome, stroke syndrome, both or none accordingly (Figure 2). More than half of the group (54%) had

gait and balance disturbances due to stroke, but no extra pyramidal
syndrome was found on them (sub group VPseuP). It was followed by the patients with VasP (17%), then PseuV P (15%) and the different diagnosis found in this group, and finally PseuV PseuP (14%).

Figure 2: Group of patients at high risk for Parkinsonism TQ ≥ 4, total sample of 46 participants. Different phenotypes were found in this group: vascular, parkinsonian, both or none accordingly.