Supine hypertension in Parkinson’s disease and multiple system atrophy

Objective

Supine hypertension (SH) is a feature of cardiovascular autonomic failure that often accompanies orthostatic hypotension and may represent a negative prognostic factor in parkinsonian syndromes. Here we investigated the frequency rate as well as the clinical and tilt test correlates of SH in Parkinson’s disease (PD) and multiple system atrophy (MSA).

Methods

197 PD (33 demented) and 78 MSA (24 MSA-Cerebellar, 54 MSA-Parkinsonian) patients who had undergone a tilt test examination were retrospectively included. Clinical-demographic characteristics were collected from clinical records at the time of the tilt test examination.

Results

SH (>140 mmHg systolic, >90 mmHg diastolic) occurred in 34 % of PD patients (n = 66, mild in 71 % of patients, moderate in 27 %, severe in 2 %) and 37 % of MSA ones (n = 29, mild in 55 % of patients, moderate in 17 %, severe in 28 %). No difference was observed in SH frequency between demented versus gender-, age- and disease duration-matched non-demented PD patients, or between patients with the parkinsonian (MSA-P) versus the cerebellar (MSA-C) variant of MSA. In PD, SH was associated with presence of cardiovascular comorbidities (p = 0.002) and greater systolic (p = 0.007) and diastolic (p = 0.002) orthostatic blood pressure fall. Orthostatic hypotension (p = 0.002), and to a lesser degree, lower daily dopaminergic intake (p = 0.01) and use of anti-hypertensive medications (p = 0.04) were associated with SH in MSA.

Interpretation

One-third of PD and MSA patients suffer from mild to severe SH, independently of age, disease duration or stage. In PD, cardiovascular comorbidities significantly contribute to the development of SH, while in MSA, SH appears to reflect cardiovascular autonomic failure.

     

Reduced bowel sounds in Parkinson’s disease and multiple system atrophy patients

Digital auscultation of bowel sounds was performed in newly diagnosed, drug-naïve patients with Parkinson’s disease (PD) (n = 10), multiple system atrophy (MSA) (n = 12), progressive supranuclear palsy/corticobasal degeneration (PSP/CBD) (n = 7), and control subjects (n = 18). The number of bowel sounds per minute and the integrated time of bowel sounds were significantly lower in PD and MSA patients than in control subjects. Reduced bowel sounds may herald compromised gastrointestinal motility in patients with PD and MSA.     

Characterization of gait variability in multiple system atrophy and Parkinson’s disease

Journal of Neurology - Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. We compared...     

Cardiac sympathetic innervation in Parkinson’s disease versus multiple system atrophy

Purpose

The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson’s disease and multiple system atrophy.

Methods

A prospective study including 19 Parkinson’s disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests.

Results

Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson’s disease (p?=?0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson’s disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson’s disease patients (p?<?0.001).

Conclusions

The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-¹²³-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson’s disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson’s disease patients.

     

The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy

Summary. α-Synuclein, a synaptic protein of unknown function, is a major component of Lewy bodies and may play a role in the pathophysiological process of Parkinson’s disease (PD). In this study, we measured the plasma α-synuclein levels in 105 patients with PD, 38 patients with multiple system atrophy (MSA), and 51 age-matched controls. The α-synuclein level was significantly elevated in patients with PD (79.9 ± 4.0 pg/ml, p < 0.001) and in those with MSA (78.1 ± 3.5 pg/ml, p = 0.019) compared with the level in controls (76.1 ± 3.9 pg/ml). The α-synuclein level was higher in patients with PD than in those with MSA (79.9 ± 4.0 vs 78.1 ± 3.5, p = 0.016). Our study demonstrated that the α-synuclein level in plasma is elevated in patients with PD and MSA.     

Comparison of smooth pursuit eye movement deficits in multiple system atrophy and Parkinson’s disease

Because of the large overlap and quantitative similarity of eye movement alterations in Parkinson’s disease (PD) and multiple system atrophy (MSA), a measurement of eye movement is generally not considered helpful for the differential diagnosis. However, in view of the pathophysiological differences between MSA and PD as well as between the cerebellar (MSA-C) and Parkinsonian (MSA-P) subtypes of MSA, we wondered whether a detailed investigation of oculomotor performance would unravel parameters that could help to differentiate between these entities. We recorded eye movements during sinusoidal pursuit tracking by means of video-oculography in 11 cases of MSA-P, 8 cases of MSA-C and 27 cases of PD and compared them to 23 healthy controls (CTL). The gain of the smooth pursuit eye movement (SPEM) component exhibited significant group differences between each of the three subject groups (MSA, PD, controls) but not between MSA-P and MSA-C. The similarity of pursuit impairment in MSA-P and in MSA-C suggests a commencement of cerebellar pathology in MSA-P despite the lack of clinical signs. Otherwise, SPEM gain was of little use for differential diagnosis between MSA and PD because of wide overlap. However, inspection of the saccadic component of pursuit tracking revealed that in MSA saccades typically correct for position errors accumulated during SPEM epochs (“catch-up saccades”), whereas in PD, saccades were often directed toward future target positions (“anticipatory saccades”). The differences in pursuit tracking between PD and MSA were large enough to warrant their use as ancillary diagnostic criteria for the distinction between these disorders.     

Detecting nocturnal hypertension in Parkinson’s disease and multiple system atrophy: proposal of a decision-support algorithm

A pathological nocturnal blood pressure (BP) profile, either non-dipping or reverse dipping, occurs in more than 50 % of subjects diagnosed with multiple system atrophy (MSA) or Parkinson’s disease (PD). This may play a negative prognostic role in α-synucleinopathies, but, being mostly asymptomatic, remains largely underdiagnosed. In this proof-of-concept study, we aimed at developing a decision-support algorithm to predict pathological nocturnal BP profiles during a standard tilt-table examination in PD and MSA. Sixteen MSA and 16 PD patients underwent standard tilt-table examination and 24-h ambulatory BP monitoring (24-h ABPM). Clinical and tilt test differences between patients with a normal and a pathological nocturnal BP profile at 24-h ABPM were assessed, and a decision-support algorithm was developed accordingly. 75 % of MSA and 31 % of PD patients showed a pathological nocturnal BP profile. This was associated with more pronounced orthostatic BP drop (p = 0.03), joint occurrence of orthostatic hypotension and supine hypertension (p = 0.046), and lack of BP overshoot in the late phase II (II_L, p = 0.002) and in the phase IV (p = 0.007) of the Valsalva manoeuvre. Combined ?BP ≤0.5 mmHg in the II_L and ≤?7 mmHg in the IV phase of Valsalva manoeuvre correctly predicted a pathological nocturnal BP profile with 87.5 % sensitivity and 85.7 % specificity. Pathological nocturnal BP profiles are associated with evidence of cardiovascular noradrenergic failure in PD and MSA. The Valsalva manoeuvre is routinely performed during standard tilt-table examinations. We propose the naked-eye evaluation of Valsalva phase II_L and phase IV BP behaviour as time-sparing screening tool for pathological nocturnal BP profiles in PD and MSA.     

Cardiovascular autonomic function testing in multiple system atrophy and Parkinson’s disease: an expert-based blinded evaluation

Purpose

Multiple system atrophy (MSA) and Parkinson’s disease (PD) are sporadic neurodegenerative diseases characterized by an accumulation of misfolded α-synuclein. Cardiovascular autonomic failure develops in both MSA and PD, although studies indicate different sites of autonomic nervous system lesion. However, it is unclear whether this could potentially aid the differential diagnosis of these diseases. Here we determined whether cardiovascular autonomic function testing (CAFT) can discriminate between the parkinsonian variant of MSA (MSA-P) and PD based on either an expert-based blinded evaluation or a systematic comparison of cardiovascular autonomic function indices.

Methods

We included 22 patients aged 55–80 with neurogenic orthostatic hypotension (nOH) who had been diagnosed with either clinically probable MSA-P (n = 11) according to current consensus criteria or clinically definite PD (n = 11) according to the Queen Square criteria. Three physicians with expertise in CAFT were blinded to the neurological diagnosis and were asked to identify the correct neurological diagnosis by applying a self-created evaluation scheme to the CAFT recordings. Afterwards, a systematic comparison of clinical–demographic characteristics and CAFT parameters was carried out.

Results

Neither the raters (overall diagnostic accuracy: 58.46%) nor the evaluation scheme created post hoc (72.73%) showed reliable discriminatory capacity. The inter-rater reliability was slight (κ = 0.01). We observed no statistically significant differences in cardiovascular autonomic indices between PD and MSA-P patients.

Conclusion

CAFT is the gold standard for assessing the presence and severity of cardiovascular autonomic failure, but the results of our pilot study suggest that CAFT might be of limited value in the differential diagnosis between MSA-P and PD once nOH is present.

     

Pupillary autonomic dysfunction in multiple system atrophy and Parkinson’s disease: an assessment by eye-drop tests

Purpose  

To compare pupillary autonomic dysfunction in multiple system atrophy (MSA) and Parkinson’s disease (PD).     

An exploration of ocular fixation in Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

Since the basal ganglia are thought to have a role in controlling ocular fixation it is expected that patients with parkinsonian conditions would show impaired performance in fixation tasks. Our study examines ocular fixation in patients with a range of parkinsonian conditions (Idiopathic Parkinson’s Disease, Multiple System Atrophy and Progressive Supranuclear Palsy). Eye movements were recorded from 44 patients and 50 age matched control subjects during ocular fixation both with and without a visible target. The data for each patient were then characterised in terms of fixation periods and saccadic intrusions (SI). Patient groups exhibited larger and more frequent SI as well as greater displacement from the fixation target. Patients with Progressive Supranuclear Palsy exhibit larger SI than control subjects when fixation targets are visible, this difference is reversed in the absence of a fixation target. Patients with Multiple System Atrophy show increased frequency of SI both with and without a visible target. Our findings show that ocular fixation is impaired in patients with parkinsonian conditions and may prove useful as part of an oculomotor profile to aid with the differentiation of parkinsonian conditions.     

Orofacial apraxia in corticobasal degeneration,progressive supranuclear palsy,multiple system atrophy and Parkinson’s disease

Abstract Objectives To determine whether the assessment of orofacial praxis is useful for the differential diagnosis of parkinsonian syndromes and to understand the neural mechanisms underlying OFA, searching for the respective roles of cortical and subcortical structures. Methods Forty-four patients were assessed: 12 with idiopathic Parkinsons disease (IPD), 8 with multiple system atrophy (MSA), 12 with progressive supranuclear palsy (PSP) and 12 with corticobasal degeneration (CBD). An easy bedside scale was used, exploring single gestures, gestures with noise production and multiple sequential gestures. We searched for group and task effects. Results Patients with CBD were significantly more impaired than those with IPD, MSA or PSP (p<0.001). Our assessment was unable to distinguish between the IPD, MSA and PSP groups. There was a clear task effect in CBD with a major impairment in multiple sequential gestures (p<0.0001). Conclusion Assessment of orofacial praxis helps in the clinical diagnosis of CBD. Patients with IPD, MSA and PSP did not present with OFA. We suggest that the deficit in multiple sequential gestures in CBD is related to simultaneous lesions of the parietal lobule and the supplementary motor area.     

Ocular-jaw synkinesia in normal,Parkinson’s disease,and multiple system atrophy subjects: Clinical and electrophysiological findings

ObjectiveWe occasionally observe cranial synkinesias that involve a lateral jaw movement ipsilateral to the horizontal gaze deviation in Parkinson’s disease (PD) patients and normal subjects. We term this conjugated movement ‘ocular-jaw synkinesia’ (OJS). The clinical and electrophysiological features of OJS are described in this study.MethodsEighty-two subjects were enrolled, 33 PD, 33 non-ill caregivers, and 16 multi system atrophy (MSA-p) patients. The subjects and patients were assessed clinically and electrophysiologically. The data were registered using two scales. The clinical findings were registered using the OJS scale, and the electrophysiological findings were registered using the eyes and chin ipsilateral deviation (ECD) scale. All subjects underwent a video recording.ResultsTwenty-eight out of the 33 PD patients (84.7%) (P: 0.0141) and 25 out of the 33 normal subjects (83.3%) (P: 0.0144) displayed signs of OJS. None of the MSA-p patients showed signs of OJS, and 13 of the 16 control subjects (81.2%) showed OJS (p: 0.014). Twenty-nine out of the 33 PD patients (87.8%) (P: 0.0123) and 27 out of the 33 normal subjects (90%) (P: 0.0112) showed ECD at the electrophysiological examination. None of the MSA-p patients displayed ECD, showing a strong statistical significance when compared to control subjects (K: 0.0011).ConclusionsOJS is a normal and common synkinetic cranial movement easy to observe in PD and normal subjects on both physical and electrophysiological examinations. In contrast, the MSA-p patients showed no physical or electrophysiological signs of OJS in this study.SignificanceThe presence of OJS is supportive of the clinical diagnosis of PD; its absence is uncommon in PD and may suggest an alternative Parkinsonism such as MSA-p.     

The role of functional neuroimaging in the differential diagnosis of idiopathic Parkinson’s disease and multiple system atrophy

Abstract. Parkinsonism is a symptom of a number of neurodegenerative disorders in the elderly. Even though clinical criteria for various parkinsonian disorders have been developed recently, the differential diagnosis of parkinsonian disorders based on clinical symptoms remains unsatisfactory, particularly in early disease stages. Early differential diagnosis on the other hand is important as prognosis and treatment options differ substantially. Multiple system atrophy (MSA) is one of the major differential diagnoses of idiopathic Parkinsons disease (PD). Radiotracer-based imaging methods such as positron emission tomography (PET) remain the established method for differential diagnosis of parkinsonian disorders. The following paper provides a review of different PET imaging methods for the differential diagnosis of PD and MSA patients.     

Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy

Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls.     

A novel detrusor contractility parameter to distinguish multiple system atrophy from Parkinson’s disease

Clinical Autonomic Research -     

Comprehensive autonomic assessment does not differentiate between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

Differential diagnosis of parkinsonian syndromes is a major challenge in movement disorders. Dysautonomia is a common feature but may vary in clinical severity and onset. The study attempted to find a pattern of autonomic abnormalities discriminative for patients with different parkinsonian syndromes. The cross-sectional study included 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (IPD) and 27 age-matched healthy controls. Autonomic symptoms were evaluated by a standardized questionnaire. The performance of patients and controls was compared on five autonomic function tests: deep breathing, Valsalva manoeuvre, tilt-table testing, sympathetic skin response, pupillography, and 24-h ambulatory blood pressure monitoring (ABPM). Disease severity was significantly lower in IPD than PSP and MSA. Except for pupillography, none of the laboratory autonomic tests distinguished one patient group from the other alone or in combination. The same was observed on the questionnaire. Receiver operating characteristic curve revealed discriminating performance of pupil diameter in darkness and nocturnal blood pressure change. The composite score of urogenital and vasomotor domains significantly distinguished MSA from IPD patients but not from PSP. Our study supports the observation that even mild IPD is frequently indistinguishable from more severe MSA and PSP. Thus, clinical combination of motor and non-motor symptoms does not exclusively point at MSA. Pupillography, ABPM and the questionnaire may assist in delineating the three syndromes when applied in combination.