帕金森病伴冻结步态患者的静息态磁共振研究

目的 探讨帕金森病患者冻结步态与静息态脑功能成像之间的关系。方法 2021年9月-2022年9月于襄阳市第一人民医院就诊的28例伴有冻结步态的帕金森病患者以及32例不伴有冻结步态的帕金森病患者接受了全脑结构像和静息状态下的功能磁共振扫描,计算并比较2组全脑百分率振幅(Percent amplitude of fluctuation,PerAF)的差异,同时探寻2组被试者间差异脑区与大脑其他区域功能连接性(Functional connectivity,FC)的不同。结果 在静息状态下与非冻结组比较,冻结组双侧额中回的PerAF信号显著减低,同时冻结组快速动眼期(Rapid eye movement,REM)睡眠行为异常筛查量表得分分别与左侧额中回(r=0.436,P=0.020)和右侧额中回(r=0.453,P=0.015)的显著区域的PerAF信号均呈正相关。此外,右侧脑干与双侧额中回之间的功能连接性增加,且右侧脑干区域与脚桥核部分重合;同时左侧额上回与额中回之间的功能连接性显著增加,且两者之间的FC信号与新冻结步态问卷得分呈显著的负相关(r=-0.510,P=0.006)。结论 冻...     

Freezing of gait in patients with advanced Parkinson's disease

Summary. Background. Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. Objective. To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. Methods. Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 ± 13.2 years and mean symptoms duration of 11.8 ± 5.6 years were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. Results. The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4–5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). Conclusion. FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment. Received April 19, 2000; accepted June 6, 2000     

Heart rate changes during freezing of gait in patients with Parkinson's disease

Freezing of gait (FOG) is one of the most disabling symptoms that affect patients with Parkinson's disease (PD). Although the pathophysiology underlying FOG largely remains an enigma, several lines of evidence suggest that the autonomic nervous system might be involved. To this end, we tested the hypothesis that heart rate (HR) increases during FOG and, further, that HR increases just before FOG. To evaluate these hypotheses, 15 healthy older adults, 10 patients with PD who experienced FOG, and 10 patients who did not were studied. Patients with PD were tested during their “off” medication state. HR and HR variability were measured as subjects carried out tasks that frequently provoke FOG; 120 FOG episodes were evaluated. During FOG, HR increased (P = 0.001) by an average of 1.8 bpm, compared with HR measured before the beginning of FOG. HR also increased just before FOG, by 1 bpm (P < 0.0001). In contrast, during sudden stops and 180° turns, HR decreased by almost 2 bpm (P < 0.0001). HR variability was not associated with FOG. To our knowledge, these findings are the first to document the association of FOG to autonomic system activation, as manifested by HR dynamics. One explanation is that the changes in HR before and during FOG may be a sympathetic response that, secondary to limbic activation, contributes to the development of freezing. Although further studies are needed to evaluate these associations, the current results provide experimental evidence linking impaired motor blockades to autonomic nervous system function among patients with PD. © 2010 Movement Disorder Society     

Falls in outpatients with Parkinson's disease

Falls are one of the most serious complications of gait disturbances in patients with Parkinson's disease (PD). Among previous reports, the percentage of patients with PD who fall varies between 38% to 68%. We sought to determine the frequency of falls and the factors associated with falls in a group of patients with idiopathic PD who attended an outpatient, tertiary movement disorders clinic. 350 ambulatory, non–demented patients (230 males) were studied. Mean age was 69.7 ± 10.6 years (range: 43–97 yrs) and mean duration of PD symptoms was 8.6 ± 6.2 years (range: 1–33 yrs). Assessments included characterization of demographics, disease duration, disease severity as measured by the Hoehn and Yahr Scale (H&Y), co–morbidities, the presence of depressive symptoms, the presence of urinary incontinence, use of anti–parkinsonian medications, and two performance–based tests of balance and gait (tandem standing and Timed Up & Go). Fall history was determined during three time periods: previous week, previous month, and previous year. Univariate and multivariate logistic regression models were applied to evaluate the relationship between the above–mentioned factors and falls. 46% of the subjects reported at least one fall in the previous year and 33% reported 2 or more falls and were classified as Fallers. Fallers had significantly more prolonged and advanced PD compared with Non–fallers (p = 0.001 and p < 0.001, respectively). Urinary incontinence was the factor most closely associated with falls (crude and adjusted OR were 1.95 and 5.89, respectively). Other factors significantly associated with fall status included increased Timed Up & Go times and increased PD duration. These findings confirm that falls are a common problem among patients with advanced PD and suggest easily measurable features that may be used to prospectively identify those PD patients with the greatest risk of falls.     

Freezing of gait and executive functions in patients with Parkinson's disease

Freezing of gait (FOG) is a frequent, disabling symptom of Parkinson's disease (PD). FOG usually lasts a few seconds. It refers to brief paroxysmal events during which a subject is unable to start or continue locomotion. Despite its frequency, FOG pathophysiology is unclear. Because a frontal lobe dysfunction or a disconnection between the frontal lobe and basal ganglia has been implicated in FOG, we explored frontal functions in PD patients using neuropsychological tests. Thirteen early‐stage PD patients [Hoehn & Yahr score (H&Y) ≤ 2.5] with freezing during “on ” state (FOG+), and 15 age‐, H&Y score‐, and disease‐duration‐matched PD patients without freezing (FOG?) were investigated. No patient was demented or depressed. Assessment included the Unified Parkinson's Disease Rating Scale (UPDRS), FOG questionnaire, Mini Mental State Examination (MMSE), frontal assessment battery (FAB), phonemic verbal fluency, Stroop test (parts II and III), and ten‐point clock test (TPCT). UPDRS and MMSE scores did not differ between the two groups. FAB, verbal fluency, and TPCT scores were significantly lower in FOG+ patients than in FOG? patients (FAB: P = 0.008; phonemic verbal fluency: P = 0.011; TPCT: P = 0.024). FOG correlated with lower scores at frontal tests in patients with early‐stage PD. © 2007 Movement Disorder Society     

Learning sequence movements in a homogenous sample of patients with Parkinson's disease

We investigated the acquisition of sequence movements in Parkinson's disease (PD) by means of the serial reaction time (SRT) task. To this end, we used a sample of PD patients that fell within the same stage of the disease. Sixteen PD patients and 16 age-, sex- and education-matched control subjects performed the SRT task with a first-order conditional (FOC) sequence and with a second-order conditional (SOC) sequence. The results showed that the group of PD patients could be divided into two distinct subgroups: a fast PD patient subgroup (n=11) and a slow PD patient subgroup (n=5). FOC and SOC sequence learning in faster PD patients proved to be highly comparable to the group of controls. In contrast, learning of FOC and SOC sequences was severely impaired in slower PD patients. Since slow PD patients also scored lower on measures of cognitive functioning than faster PD patients, we assume that the deficits in SRT learning of the former reflect some more general cognitive impairment. This indicates that SRT performance can provide additional information about the cognitive abilities of PD patients, and accordingly may contribute to disease screening.     

Validation of the freezing of gait questionnaire in patients with Parkinson's disease

To revalidate the Freezing of Gait Questionnaire (FOG‐Q), patients with Parkinson's disease (PD) were randomly assigned to receive rasagiline (1 mg/day) (n = 150), entacapone (200 mg with each dose of levodopa) (n = 150), or placebo (n = 154). Patients were assessed at baseline and after 10 weeks using the FOG‐Q, Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Parkinson's Disease Questionnaire (PDQ‐39). FOG‐Q dimensionality, test–retest reliability, and internal reliability were examined. Convergent and divergent validities were assessed by correlating FOG‐Q with UPDRS, BDI, and PDQ‐39. Comparisons between FOG‐Q item 3 and UPDRS item 14 were also made. Principal component analysis indicated that FOG‐Q measures a single dimension. Test–retest reliability and internal reliability of FOG‐Q score was high. FOG‐Q was best correlated to items of the UPDRS relating to walking, general motor issues, and mobility. Correlations between baseline and endpoint suggested that FOG‐Q item 3 is at least as reliable as UPDRS item 14. At baseline, 85.9% of patients were identified as “Freezers” using FOG‐Q item 3 (≥1) and 44.1% using UPDRS item 14 (≥1) (P < 0.001). FOG‐Q was a reliable tool for the assessment of treatment intervention. FOG‐Q item 3 was effective as a screening question for the presence of FOG. © 2007 Movement Disorder Society     

Marked alterations in the gait timing and rhythmicity of patients with de novo Parkinson's disease

Little is known about the gait characteristics of subjects with de novo Parkinson's disease (PD). We hypothesized that alterations in the spatio-temporal characteristics of gait will already be quantifiable in these patients. The gait of 35 patients with idiopathic PD (mean age 60 years) who were in the early stages of the disease (Hoehn and Yahr stage 1.8 +/- 0.5, median 2.0, range 1.0-2.5) and were not yet treated with any anti-parkinsonian medications were compared with the gait of age- and sex-matched healthy controls (n = 22). The patients walked more slowly and with reduced swing times while also exhibiting increased left/right swing asymmetry and marked inconsistencies in the timing of gait. By contrast, significant group differences in the peak forces at heel-strike and in the stride-to-stride variability of the ground reaction forces (a reflection of muscle output consistency) were not observed. These findings indicate that in de novo PD, an altered gait pattern is observed, even though dramatic changes in the gait pattern may not yet be apparent visually (e.g. fairly intact gait speed). Furthermore, the results demonstrate that the observed alterations are not just side-effects of treatments or complications of the disease. Instead, there is evidence for motor programming deficits in gait, as revealed by increased gait variability and asymmetry in timing. PD apparently impinges on the regulation of a consistent gait rhythm, even early in the course of the disease when observed alterations are not the result of any pharmacologic treatment.     

Walking economy in people with Parkinson's disease

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (V?O₂) and other responses to treadmill walking were compared in 90 patients (64.4 ± 10.3 years) and 44 controls (64.6 ± 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, V?O₂ was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with V?O₂ was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid‐stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. © 2009 Movement Disorder Society     

Visuomotor skill learning on serial reaction time task in patients with early Parkinson's disease.

This study tested the role of basal ganglia in visuomotor skill learning. Thirty-nine patients early in the course of Parkinson's disease (PD) and 30 patients after operation for an aneurysm of the anterior communicating artery (ACoA) were compared with 31 matched control subjects on a Serial Reaction Time test (SRTt). The patients with PD showed impaired visuomotor skill learning across the repeating blocks, in the presence of preserved declarative knowledge of embedded sequences, in contrast to the ACoA group in whom the reverse pattern was observed. The significant correlation in patients with PD between the standard neuropsychological and motor measures and the performance observed in the skill acquisition test, in the ACoA group and control subjects was not observed. The suggestion that this learning impairment could not be attributed to a motor deficit per se was also confirmed more directly for patients with PD. Accuracy of performance after the initial learning phase on the SRTt in patients with PD was associated predominantly with visual span capacity measures. Declarative knowledge of the embedded sequence of the SRTt was correlated to general cognitive and verbal span abilities in the PD group. The impairment observed in the PD group was not the result of a general decline in cognitive functioning, mood disturbances, or the severity of the motor symptoms.     

Turning in Parkinson's disease patients and controls: the effect of auditory cues.

Turning is an impaired activity in persons with Parkinson's disease (PwPD). The current study examines the turning characteristics in PwPD (9 freezers and 10 nonfreezers) and 9 controls, and explores the effect of rhythmic auditory cues while turning. Turning parameters were collected from a 180 degrees left U-turn during a noncued and a cued condition, using a 3D measuring system. Auditory cues were supplied with a metronome at a rhythm equaling the subject's comfortable step frequency during straight line walking. Results showed that in contrast to controls, PwPD used a wider turning-arc and took smaller, narrower steps. In addition, they demonstrated a higher Coefficient of Variation (CV) of step duration (6.92%) compared to controls (4.88%, P < 0.05). The "wide-arc" turning strategy of PwPD was more prominent in freezers than in nonfreezers. Auditory cues reduced the CV of step duration in PwPD (both freezers and nonfreezers) during turning (from 6.92 to 6.00%, P < 0.05). In summary: Cueing reduced the gait-timing variability during turning, but PwPD maintained a wider arc to turn compared with controls.     

Backward walking in Parkinson's disease

We walk backward on a daily basis, such as when backing away from the kitchen sink or stepping back from a curb as a swiftly moving bus passes. This task may be particularly difficult for individuals with Parkinson's disease (PD) who often fall as a result of moving or being perturbed in the backward direction. The aim of this study was to assess backward walking (BW) in individuals with PD. Both forward walking (FW) and BW were assessed in 78 people with idiopathic PD (H&Y range: 0.5–3) in the ON state, and 74 age‐ and sex‐matched controls. In FW, those with PD had significantly shorter strides, lower swing percents, higher stance percents, and lower functional ambulation profiles than controls. Both groups walked significantly slower and with a wider base of support during BW than FW. Additionally, in BW those with PD walked significantly slower with shorter strides, lower swing percents, and higher double support and stance percents, and lower functional ambulation profiles compared with controls. Those with mild to moderate PD have impaired FW and BW, but differences between those with and without PD are more pronounced in BW. © 2008 Movement Disorder Society     

Oral festination in Parkinson's disease: biomechanical analysis and correlation with festination and freezing of gait.

In Parkinson's disease (PD), festination corresponds to a tendency to speed up when performing repetitive movements. First described in gait (and then in handwriting and speech), festination is one of the most disabling axial symptoms. To establish the phenomenology of oral festination (OF) and the condition's potential links with other axial disorders, we submitted a simple, rhythmic, repetitive, vocal motor task to 40 PD patients and 20 controls. Forty-five percent of the 40 patients presented OF, which was strongly associated with gait festination but not with the severity of freezing of gait (FOG) or dysarthria. With respect to the two pathophysiological hypotheses that have been put forward, a possible link with tremor (as previously suggested in tapping) was not confirmed in this study and so, in view of the significant increase in variability observed, we conclude that OF shares the same pathophysiology as gait disorders.     

Performance monitoring and error processing during a lexical decision task in patients with Parkinson's disease

To evaluate performance monitoring and error processing during lexical decision tasks, event-related potentials (ERPs) obtained by time-locked to correct and error responses were studied in 17 Parkinson's disease (PD) patients without dementia and 15 healthy elderly participants. The amplitude of error negativity (Ne) obtained by averages time-locked to error response was significantly reduced in the PD patients, whereas there were no significant differences in the negative component for the correct response (Nc) between the two participant groups. The amplitude of the error positivity (Pe) and correct positivity (Pc) after the Ne and Nc components was also significantly reduced in the PD patients. The PD patients showed significantly slower reaction times and higher error rates. The reduced amplitude of the Ne, Pe, and Pc components in the PD patients suggested impaired performance and conflict monitoring as well as abnormal response strategy adjustments and deviant in later error monitoring processes associated with emotional, conscious evaluation of the error.     

Effect of a concurrent task on driving performance in people with Parkinson's disease.

Numerous studies previously have reported reduced driving performance in people with Parkinson's disease (PD). Few studies to date, however, have examined how specific cognitive difficulties associated with PD impact on specific aspects of driving performance in this population. In this study, the impact of a concurrent task on driving performance was examined. A simulator was used to measure the driving behavior of 18 current drivers with PD and 18 matched controls. The presence of a concurrent task was manipulated between conditions. Results showed that, although groups were similarly affected by the concurrent task on most driving measures, participants with PD were disproportionately affected on operational level driving behavior. It also appears that participants with PD sacrificed concurrent task performance to maintain driving performance. These results further support the hypothesis that cognitive difficulties associated with PD compromise driving performance in this population, even in the mild to moderate stages of the disease.     

Depression in patients with Parkinson's disease.

Parkinson's disease (PD) is a disabling neurodegenerative condition commonly complicated by the existence of comorbid depression. The prevalence rates of depression in this patient group have been reported to be as high as 40%. Currently, depression in PD is undertreated; there have been few controlled clinical trials of antidepressants in this patient group. Patients with PD are usually elderly and often administered a range of medication, therefore the choice of antidepressant must be undertaken with care. Tricyclic antidepressants (TCAs) have been studied in patients with PD and comorbid depression; however, the risk of anticholinergic side-effects means that their use is largely avoided. Selective serotonin reuptake inhibitors have comparable efficacy to the TCAs and a better tolerability profile in patients with depression; they are rapidly being considered as first-line therapy for PD patients with depression. Clinical studies in this patient group are warranted. This article reviews the characteristics of comorbid depression in patients with PD and discusses the treatment options available.     

Fatigue in patients with Parkinson's disease.

OBJECTIVE: To compare the prevalence of fatigue in patients with Parkinson's disease (PD) with that in healthy elderly people and to explore the suggestion that fatigue is an independent symptom of PD. DESIGN: Questionnaire survey. SETTING: Community-based population. PATIENTS AND CONTROL SUBJECTS: 233 patients derived from a prevalence study in the county of Rogaland, Norway and 100 healthy elderly people with the same age and sex distribution as the patients with PD. MAIN OUTCOME MEASURE: A score for fatigue was obtained by combining the results from the rating scale for low energy in the Nottingham Health Profile (NHP) with the results obtained from a 7-point scale devised to evaluate fatigue. RESULTS: 44.2% of the patients with PD and 18% of the healthy elderly control subjects reported fatigue. Fatigue was associated with depression, dementia, disease severity, disease duration, levodopa dose, and the use of sleeping pills. In a multivariate analysis, only depressive symptoms reached statistical significance. The prevalence of fatigue in patients with PD who were not depressed, demented, or had a sleeping disturbance was similar to that found in the total PD population. CONCLUSION: Fatigue is a common symptom in PD. Although fatigue correlated with depressive symptoms, patients with PD who did not have depression, dementia, or sleep disturbances also reported a high prevalence of this symptom. This supports the hypothesis that fatigue is an independent symptom of PD overlapping with, but not causally related to, the concurrence of depressive symptoms.