INTRODUCTION

 

Orthostatic hypotension is one of the autonomic disturbances observed in Parkinson Disease (PD). It has been debated whether an additional impairment of cerebral autoregulation in PD patients may exacerbate the consequences upon brain hypoperfusion¹.

The frequent orthostatic intolerance in PD could be the consequences of cardiovascular-autonomic failure and/or damaged cerebral autoregulation².

Cerebral autoregulation is the phenomenon in which cerebral blood flow remains nearly constant despite changes in mean arterial blood pressure within a range generally considered to be 50-150 mmHg. The cerebral circulation is also profoundly affected by changes in PaCO₂; and CO₂ reactivity relates to the changes in cerebral blood flow in response to changes in PaCO₂.³

Transcranial Doppler (TCD.) has been widely used to measure cerebral blood flow velocity and cerebral autoregulation. It is used to measure instantaneous changes in cerebral blood flow in response to a variety of stimuli. Transcranial Doppler has recently been used to measure vasomotor reactivity in response to changes in CO₂ in various disease states that affect the brain.

These measurements have led to an increased understanding of the effect of different pathological conditions on cereborvasular function⁴.

The aim of this work was to assess cerebral vasoreactivity in PD patients and the potential influence of dopaminergic agents on it.

 

PATIENTS AND METHODS

 

Fifteen PD patients and 15 healthy controls were included in the study.

Patients and controls gave their written consent to participate in this study. They were recruited from the neuropsychiatric department of El-Hadara Hospital.

Patients who had history or signs of diabetes, heart disease, hypertension, neuropathy or medical disorders known to alter autonomic function were excluded from the study. Patients receiving drugs known to influence the cardiovascular function or activity of the autonomic nervous system (other than antiparkinsonian drugs) were also excluded. Hematocrit values between 34 and 40% were only accepted. Patients were examined neurologically and Unified Parkinson Disease Rating Scale (UPDRS) were done for all the patients to assess the clinical severity of the disease⁵.

Fifteen healthy subjects matching the patients in age were selected considering the same exclusion criteria of the patients (considered as group 3).

 

Transcranial Doppler examination

Parkinson Disease patients were investigated twice. The 1st time in the morning after taking their regular doses of L dopa. (Considered as group 2), and the second time 12 hours after the last dose of any L dopa (considered as group 1). In these patients, the 2 test sessions were completed 1-3 weeks a apart in random order. When in use, other medications (or example domainergic agonists) were not discontinued. All the test sessions were completed in the morning, at least 2 hours after breakfast (containing no caffeinated beverages). All measurements were performed in quiet rooms where the ambient temperature was 22-25 °C and the light is dimmed.

Transcranial Doppler examinations were carried out with the subject in a supine position with the head slightly elevated and the eyes closed. Flow velocities were recorded from the middle cerebral artery (MCA) using a 2 MHz pulsed Doppler ultrasound system (Multidopp, DWL Elektronische system BmbH, Splingen, Germany). The data were collected and stored on digital tape and analyzed at a later time.

Transcranial Doppler breath-holding test was performed, after normal breathing of room air for approximately 4 minutes the patients were instructed to hold their breath after a normal inspiration. During the maneuver, the MCA mean blood velocity was recorded continuously. The mean blood velocity at the TCD display immediately after the end of breath-holding period was registered as the maximal increase of the MCA mean blood velocity (while breath holding). The time of the breath holding was also registered. This procedure was repeated after rest of 5 minutes to allow the mean blood velocities to return to their initial values.

The breath holding index (BHI) was calculated as percent increase in MCA mean blood velocity recorded by breath holding divided by seconds of breath holding.

([Vbh-Vr/Vr]*100/S) where Vbh is MCA mean blood velocity at the end of breath holding, Vr is MCA mean blood velocity at rest and S is the time in seconds of breath holding⁶.

 

Statistical Analysis

Student t test, One Way ANOVA, Pearson correlation test and Chi Square test were done using SPSS package version 13

 

RESULTS

 

         The study included 5 PD patients and 15 healthy controls. Their demographic and clinical data are illustrated in Table (1).

The mean blood velocities were measured in cm/sec. The resting mean MCA  flow velocities was 41.33±7.2 for group I , 40.9±7.1 for group II and 45.67± 10.93 for controls . There was no statistical significant difference in resting flow velocities between patients with or without L dopa treatment (p=0.859), or even between either group 1 or 2 and control group respectively (P=0.175, 0.139 respectively).

After  breath holding, the mean flow velocities increased, it was 51.67±7.6 for group (1), 56.2±7.01 for group (2) and 62.8±11.16 from control (Figure 1). On comparing the readings after breath holding between each 2 groups, there was statistical significant difference between PD. patients without L dopa and controls (p=0.0001); between those on L dopa and controls (p=0.001). While the difference between the 2 patient groups was not significant (p=1.493).The mean BHI was 0.68±0.33 for group I, 0.78=0.41 for group II and 1.13 ± 0.45 for controls. So, on comparing BHI readings between patients and controls, there was statistical significant difference between each patient group and the control (P= 0.003 and 0.022) for group I and II respectively. While there was no significant difference e between group I and II (p=0.477)

There is no statistical correlation between BHI and either UPDRS or the disease duration in group 1 and 2. Even, there was no correlation between the BHI and the age of the patients in the 3 groups (Table 2).

Table 1. Demographic and clinical data of the patients and controls.

 

	Patients	Control
No of men (%)	9 (60%)	8 (53%)
No of women (%)	6 (40%)	7 (46.6)
Age (mean/year ± SD)	63.73±6.5	63.4±7.4
Age at onset (mean/year ± SD)	58.8±6.69
Disease duration/year  ± SD	4.93±1.7
UPDRS scores	48.07±19.83
Clinical Findings (No %)
Orthostatic hypotension	7 (46.6%)
Frequent falls	6 (40%)
Cognitive problems	2 (13.33%)

Table 2. Correlation between BHI and different clinical parameters using Pearson Correlation.

 

Correlation between:	Group 1		Group 2		Group 3
	R	P	R	P	R	P
BHI and UPDRS	0.443	0.098	0.467	0.079	NA	NA
BHI and disease duration	0.265	0.340	0.289	0.296	NA	NA
BHI and age	0.127	0.652	0.118	0.675	-0.274	0.322

 

 

 

 

Figure 1. The change in blood velocity on breath-holding.

 

 

DISCUSSION

 

A breath holding challenge allows for a fast completely non invasive and reproducible assessment of the cerebrovascular reactivity. Markus and Harrisson⁷ found a good correlation between vasomotor reactivity (VMR) calculated by breath holding method and VMR calculated either by the hypercapnic response only or by the combined response of both hypercapnia and hypocanpia.

         In the present study, in comparison to PD patients, control subjects had significantly higher increase in the mean MCA flow velocities after breath holding. The mean velocities increased significantly above the initial values in the control subjects, whereas, no significant difference were observed in the change  from resting flow velocities and flow velocities after breath holding in patients with or without L dopa  treatment. These results provide evidence of an impaired cerebral autoregulation in pd. patients which appear independent on the dopaminergic treatment. The results of the present study show that, in PD patients cerebral arterioles have less capacity for adequate vasodilatation under hypercapnic conditions than healthy controls and the disturbance of the cerebral autoregulation could be the consequence of the damage to the post ganglionic structures in PD. These results could  explain the frequent orthostatic intolerance of PD patients even with normal blood pressure.⁸

         Debreczeni et al.⁹ investigated cerebral autoregulation of 17 PD patients using TCD-tilt method. They found a progressively decreasing MCA average velocity during graded tilt which suggests a disturbance of the cerebral autoregulation and they concluded that the cerebral blood flow of PD patients was more dependent on perfusion pressure compared to healthy controls. They concluded also, that the disturbance of sympathetic cardiovascular system and of cerebral autoregulation could be the consequence of a post ganglionic dysfunction in PD. Michi et al.¹⁰ assessed the effects of tilt test on cerebral blood flow velocity and blood pressure in PD patients without symptomatic dysautonomia. They concluded that cerebrovascular response to tilt is delayed in PD patients and that subclinical autonomic dysfunction may be present even in the absence of symptomatic orthostatic dysautonomia.

         In contrast to results of the present study, Gurevich et al.¹¹ assessed blood flow velocities in MCA and vertebral artery in 9 patients with PD, 10 patients with multiple system atrophy and 5 with pure autonomic failure. These patients were investigated for the cerebral vasomotor reactivity using TCD Diamox test. They concluded that blood flow velocities were normal the 3 disorders. Their results did not disclose differences in cerebral vasomotor response among the 3 conditions.

Also, Briebach et al.¹² studied the mean ABP and the mean blood flow velocity of MCA in four patients suffering from Shy-Drager syndrome and they found that during tilt (60 degree-head up), mean ABP decrease by 40 mmHg (35%), while the mean MCA blood flow dropped by 14 cm/s (28%). They concluded that the lower percentage reduction in flow velocity may indicate a preserved cerebral autoregulation in central autonomic insufficiency. The discrepancy in the results may be explained by the difference in patient selection ,study sample, sample size and methodology.

 

Conclusion         

The present study showed that:

·          BHI is a simple test for clinical evaluation of cerebral autoregulation in PD patients.

·          Under hypercapnia, the cerebral blood flow velocities in PD patient remained relatively unchanged compared with healthy controls irrespective of the dopaminergic treatment.

 

Recommendations

1.      Further studies of cerebral autoregulation using large number of patients needs to be conducted.

2.      Patients with PD need to be evaluated for cerebral autoregulation in addition to orthostatic blood pressure evaluation with the earliest orthostatic symptoms.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

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