Increased blood flow in posterior cerebral arteries of patients with Lower Body Parkinsonism
Lower body type vascular Parkinsonism (VP-LBP) is a bilateral, symmetric lower body Parkinsonism without a resting tremor, and a poor L-dopa response
Dr. Salazar, Dr. Rey y Dra. Fragoso
Salazar G. (1)
Español G. (2)
Fragoso M. (1)
García S. (2)
Rey A. (1)
Department of Neurology (1) and Department of Psychiatry (2), Terrassa. Hospital CST. Barcelona. Spain
All of the above listed authors have read the manuscript; the paper has not been previously published; it is not under simultaneous consideration by another journal and none of the authors listed have participated in the conception, writing or other activity in relation to this research.
Financial disclosure/conflict of interest concerning this research
This research work has been supported by the Terrassa Hospital Foundation. The authors who have participated in this research work have received no other financial support.
All authors declare no conflict of interest in relation to this research.
Lower body type vascular Parkinsonism (VP-LBP) is a bilateral, symmetric lower body Parkinsonism without a resting tremor, and a poor L-dopa response. Patients usually demonstrate gait difficulties due to freezing gait and falls, causing a major grade of disability when compared to idiopathic Parkinson’s Disease patients (PD). Small vessel disease has been related to the pathophysiology of this type of secondary Parkinsonism. We decided to study the hemodynamic characteristics of the cerebral arteries of patients affected with VP-LBP and compare them to PD patients using a Transcranial Doppler . Patients and methods: We enrolled 10 VP-LBP patients, 10 PD patients and 10 age-matched non sick control subjects. A Transcranial Doppler was performed on patients and subjects in order to determine the systolic and diastolic velocities and impulse pulsability (IP) in the anterior and posterior circuit cerebral arteries. Results: The VP-LBP patients consisted of 6 men and 4 females; mean age 72 years; Hoenh and yarh stages 2 and 3. PD patients consisted of 5 males and 5 females; mean age 74 years; Hoehn and yahr stages 3 and 3. In the VP-LBP patients, the Transcranial Doppler demonstrated a mean systolic velocity of 185, diastolic velocity 52 and IP 2.33 (p: 0.02) in the PCA , The remaining cerebral arteries showed normal velocities and IP in the VP-LBP and PD patients as well as in normal subjects. Conclusion: The VP-LBP patients of this study showed a statistically significant difference in the mean systolic velocity and IP of the PCA compared to PD patients and normal subjects. This difference could help to differentiate VP-LBP from PD in the initial stages of the disease.
Parkinsonism due to cerebrovascular disease or vascular Parkinsonism (VP) is a heterogeneous clinical entity representing 4-12% of all cases of Parkinsonism. (1) Lower body type vascular Parkinsonism (VP-LBP) is a recognized clinical expression of VP and is characterized by rigidity and bradykinesia, mainly affecting the lower limbs. Patients with VP-LBP demonstrate a great difficulty for walking; postural instability and falls are the most remarkable clinical symptoms (2,3). According to some authors, patients with the clinical criteria of VP-LBP show a poor response to L-dopa therapy and resting tremor is an uncommon finding (4,5). VP-LBP is considered for some authors as a variety of vascular Parkinsonism, with other clinical presentations of VP found in the medical literature (6, 7). The etiology of VP-LBP is unknown, but it has been classically related to vascular risk factors for stroke (8, 9). As with other secondary Parkinsonism’s, the diagnosis is based on clinical criteria and few paraclinical tools are useful nowadays to confirm VP-LBP. For the time being, there are no biomarkers for VP- LBP, neither electrophysiological nor radiological have been reported in the medical literature (10,11). In view of the high incidence of vascular risk factors for stroke in VP-LBP patients, we designed a clinical-sonographic study to determine the hemodynamic characteristics of the intracranial arteries of patients with VP-LBP.
Patients and methods
We defined VP-LBP as a lower body Parkinsonism (rigidity and bradykinesia in the lower limbs) disproportionate in relation to the upper limbs and an L-dopa test improvement of less than 30% in the Part III of the UPDRS scale.
10 patients with the clinical criteria of VP-LBP, 10 Parkinson ’s disease (PD) patients and 10 aged matched-non ill subjects with similar demographic characteristics were enrolled. Other secondary causes of Parkinsonism were ruled out. Patients with a clinical history of ischemic stroke were excluded.
The clinical evaluation consisted in a) Total UPDRS, Hoen and Yahr stages and Swab and England Scales. b) Determination of Vascular risks for stroke were asked systematically to patients and subjects. A cranial angio-MRI was performed in all the patients, focusing on the brainstem.
A continuous Transcranial Doppler with a 2Hz transducer was performed on the VP-LBP, PD patients and on normal subjects. Transtemporal and sub-occipital acoustic windows were used to evaluate the anterior and posterior brain vascular circuit (bilateral) and posterior circuit. Systolic and diastolic velocities, as well as impulse pulsatility (IP) were measured in all the arteries evaluated. We carefully measured the following: middle cerebral artery (MCA), anterior cerebral artery (ACA), anterior communicating artery (AcoA) posterior communicating artery (PcoA), basilar artery (BA), vertebral arteries (VA) and posterior cerebral arteries (PCA) of both hemispheres.
VP-LBP patients consisted of 3 women and 7 men, a mean age 76 years and a mean disease onset of 4 years. H-Y scale: 7 patients showed stage III and the remaining 3 showed stages IV. S-E scale showed a mean of 70% and a mean L-dopa dose of 745mg. PD patients consisted of 4 women and 6 men, a mean age 80 years with a mean disease onset of 6 years. H-Y scale: 8 patients showed a stage III and 2 showed a stage IV. S-E scale showed a mean of 80% and a mean L-dopa dose of 650mg . High blood pressure was present in all VP-LBP patients (100%, p:0.02) with only 20% of PD patients and 30% of normal subjects exhibiting high blood pressure. Diabetis Mellitus was also present in 50% of VP-LBP patients (p:0.04) and only 20% of PD patients.
Transcranial Doppler findings
In the posterior circuit, the basilar artery of VP-LBP patients had a mean systolic velocity of 78 mm/sec. (p:0.06), mean diastolic velocity of 23 mm/sec (P: 0.7) with a mean of IP of 0.76 (P:0.6); the PCA showed a mean of systolic velocity of 182mm/seg (p: 0.04), mean of diastolic velocity 52mm/seg (p: 0.03) and a pulsability index (PI) of 2.23 (p: 0.02). The arteries of the anterior circuit evaluated (MCA and ACA) of both hemispheres showed normal values of mean systolic and diastolic velocities as well as PI values with no statistical significance when compared to normal subjects.
Cranial MRI findings
The cranial angyo-MRI of our VP-LBP patients showed in the majority, a global brain hypotrophy (8/10, 80%, p: 0.02), and in 6 of the patients (60%, p: 0.04) hyper-intensity signals in T2 sequence in brainstem, particularly in the pons. 9 of the patients (90%, p:0.02) showed a reduction in SNPc with statistical significance when compared to PD patients and normal subjects (p: 0.02).
Vascular Parkinsonism patients are a challenge for clinicians and researchers. The lack of a deep knowledge and a poor understanding of the pathophysiology of this uncommon type of Parkinsonism is a reality that is reflected in the lack of a widely accepted clinical criterion and other diagnostic tools published in the medical literature.
We decided to study the hemodynamic characteristics of the intracranial arteries in VP-LBP and PD patients given the high association of cerebrovascular risk factors in VP-LBP patients reported in the past. The Transcranial Doppler can show dynamic characteristics of the blood flow into the intracranial arteries (12,13), which is too difficult to obtain with other neuro-imaging technics such as angyo-MRI or functional neuro-image (PET, SPECT) which tend to show morphological and metabolic features more than hemodynamic characteristics of intracranial arteries.
More VP-LBP patients in this study had hypertension and diabetes than PD patients and normal subjects as has been reported by other authors. VP-LBP patients also showed an increased mean systolic and diastolic velocities, as well as an increased mean IP in the PCA when compared to PD patients and normal subjects. The remaining intracranial arteries studied in VP-LBP patients of this study showed normal values of velocities and IP.
The increased values of systolic and diastolic velocities, as well as IP in the PCA of VP-LBP patients in this study is a remarkable finding because such values represent a moderate to severe (> 50%) vascular stenosis according to standardized values reported in the past (14). The IP represents the vascular resistance to the blood flow and the PCA supplies the mesencephalus; particularly the substantia nigra pars compacta and part of the striatum, and the basilar artery supplies to a major part of the braistem.
We hypothesize that the vascular resistance that shows the PCA could cause a chronic sub-cortical ischemia, particularly in SNPc and striatum, and such chronic ischemia could originate a reduction of SNPc in VP-LBP patients as we showed in the cranial MRI of our serie. Such findings have been published in previous studies of cranial MRI in vascular Parkinsonian patients in the past (15,16). Simultaneously, a disruption in the dopamine receptors of the striatum, probably due to the sub-cortical ischemia, could explain the poor clinical response to L-dopa in VP-LBP patients. As discussed above, the cranial Angyo-MRI of our VP-LBP patients showed in the majority (8/10), a global hypotrophy and in 6 of these patients (60%), hyper-intensity signals in T2 sequence, particularly in the pons. 9 of these patients (90%) showed a statistically significant reduction in SNPc when compared to PD patients and normal subjects (p: 0.02).
VP-LBP patients have a high incidence of vascular risk factors for stroke and a moderate to severe stenosis of PCA in these patients could play an important role in the pathophysiology of a possible chronic ischemia in the striatum and brain stem; however we could not explain why the PCAs of our VP-LBP patients showed increased mean in the velocity of blood flow and IP, and not the rest of intracranial arteries. Further studies are needed to better understand the pathophysiology of this type of Parkinsonism.
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