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01 augustus 2023, Contains fulltext : 296179.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 169550.pdf (publisher's version ) (Open Access), Freezing of gait (FOG) in Parkinson's disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing 'off' state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion-extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD.

1 juli 2015, Contains fulltext : 155311.pdf (publisher's version ) (Closed access), Freezing of gait is a common and disabling symptom in patients with parkinsonism, characterised by sudden and brief episodes of inability to produce effective forward stepping. These episodes typically occur during gait initiation or turning. Treatment is important because freezing of gait is a major risk factor for falls in parkinsonism, and a source of disability to patients. Various treatment approaches exist, including pharmacological and surgical options, as well as physiotherapy and occupational therapy, but evidence is inconclusive for many approaches, and clear treatment protocols are not available. To address this gap, we review medical and non-medical treatment strategies for freezing of gait and present a practical algorithm for the management of this disorder, based on a combination of evidence, when available, and clinical experience of the authors. Further research is needed to formally establish the merits of our proposed treatment protocol.

Contains fulltext : 152331.pdf (publisher's version ) (Closed access), BACKGROUND: Freezing of gait (FOG) is a common and debilitating phenomenon in Parkinson's disease (PD). Wearable accelerometers might help to assess FOG in the research setting. Here, we evaluate whether accelerometry can detect FOG while executing rapid full turns and while walking with rapid short steps (the two most common provoking circumstances for FOG). METHODS: We included 23 PD patients, who all had objective FOG. Participants performed several walking tasks, including walking rapidly with short steps and rapid full turns in both directions with a triaxial linear waist-mounted accelerometer. Two independent experts identified FOG episodes using off-line video-analysis (gold standard). A validated algorithm [ratio between pathological freezing (3-8 Hz)-and normal locomotor frequencies (0.5-3 Hz)] was applied on the accelerometer data to detect FOG episodes. RESULTS: Clinically, FOG was most often observed during full rapid turns (81% of all episodes), followed by walking with short rapid steps (12% of all episodes). During full rapid turns, accelerometry yielded a sensitivity of 78% and specificity of 59%. A sensitivity of 64% and specificity of 69% was observed during walking rapidly with small steps. Combining all tasks rendered a sensitivity of 75% and specificity of 76%. CONCLUSION: Our results suggest that FOG can be detected from a single lumbar accelerometer during several walking tasks, including full rapid turns and walking with short steps rapidly, with reasonable sensitivity and specificity. This approach holds promise for possible implementation as complementary objective outcome in a research setting, but more work remains needed to improve the sensitivity and specificity.

Item does not contain fulltext, BACKGROUND: Freezing of gait is a disabling episodic gait disturbance common in patients with Parkinson's disease. Recent evidences suggest a complex interplay between gait impairment and executive functions. Aim of our study was to evaluate whether specific motor conditions (sitting or walking) influence cognitive performance in patients with or without different types of freezing. METHODS: Eight healthy controls, eight patients without freezing, nine patients with levodopa-responsive and nine patients with levodopa-resistant freezing received a clinical and neuropsychological assessment during two randomly performed conditions: at rest and during walking. Results : At rest, patients with levodopa-resistant freezing performed worse than patients without freezing on tests of phonological fluency (p = 0.01). No differences among the four groups were detected during walking. When cognitive performances during walking were compared to the performance at rest, there was a significant decline of verbal episodic memory task (Rey Auditory Verbal Learning Test) in patients without freezing and with levodopa-responsive freezing. Interestingly, walking improved performance on the phonological fluency task in patients with levodopa-resistant freezing (p = 0.04). CONCLUSIONS: Compared to patients without freezing, patients with levodopa-resistant freezing perform worse when tested while seated in tasks of phonological verbal fluency. Surprisingly, gait was associated with a paradoxical improvement of phonological verbal fluency in the patients with levodopa-resistant freezing whilst walking determined a worsening of episodic memory in the other patient groups.

Item does not contain fulltext, Freezing of gait (FOG) is a disabling feature of Parkinson's disease. Emerging evidence suggests that dysfunction of the pedunculopontine nucleus (PPN) and pontomedullary reticular formation (pmRF) plays a role in the causation of FOG. These brainstem structures can be examined by the StartReact paradigm, which utilizes a startling stimulus to accelerate reaction times (StartReact). Here, we examined gait initiation in PD patients with and without FOG using this paradigm. Twenty-six patients with Parkinson's disease (12 freezers and 14 non-freezers) and 15 controls performed two tasks: rapid gait initiation in response to an imperative 'go' signal; and a control condition, involving a simple reaction-time task involving ankle dorsiflexion. During both tasks, a startling acoustic stimulus was combined with the imperative signal in 25 % of trials. In controls, the startle accelerated gait initiation and shortened the onset latency of tibialis anterior responses during ankle dorsiflexion. This acceleration was intact in non-freezers, but was significantly attenuated in the freezers. Independent of the occurrence of a startle, freezers showed a reduced length of the first step compared to non-freezers and controls. The diminished StartReact effect in freezers probably reflects deficient representation or release of motor programs at the brainstem reticular level due to dysfunction of the PPN, the pmRF, or both. These brainstem structures are presumably involved in integrating anticipatory postural adjustments with subsequent stepping movements. We suggest that with time-varying demands, these structures may no longer be able to coordinate the integration of anticipatory postural adjustments with steps, leading to FOG episodes.

Item does not contain fulltext, Freezing of gait (FOG) is both common and debilitating in patients with Parkinson's disease. Due to its episodic nature, it is a challenge to provoke FOG in clinical practice and in the research setting. Turning is most sensitive to provoke FOG, particularly when performed as rapidly as possible. Walking with short steps is an alternative approach to provoke FOG. Here, we assessed a modified version of this test, consisting of the instruction to make short steps as rapidly as possible. We evaluated what the diagnostic value of this new test is compared to rapid turning. 28 patients with Parkinson's disease participated, who all had objective FOG. Patients performed the following tasks two times: (1) normal walking, (2) walking as rapidly as possible, (3) walking with short steps, (4) walking with short steps as rapidly as possible and (5) making full rapid turns in both directions. FOG was provoked in 20 subjects (71 %). The most effective test to provoke FOG was rapid full turns (64 % of subjects). FOG occurred more often when patients walked with rapid short steps (50 %) compared to walking with short steps at normal speed (18 %). The combination of 'full rapid turns' and 'walking with short steps rapidly' yielded the highest sensitivity of provoking FOG (0.71, CI 0.51-0.86). The most sensitive way to provoke FOG is by asking patients to make full rapid turns, but if negative, walking with short steps as rapidly as possible can identify further subjects with FOG.

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Item does not contain fulltext, Patients with Parkinson's disease (PD) and freezing of gait (FOG) (freezers) demonstrate high gait variability. The objective of this study was to determine whether freezers display a higher variability of upper limb movements and elucidate if these changes correlate with gait. We were the first group to compare directly objectively measured gait and upper limb movement variability of freezers between freezing episodes. Patients with objectively verified FOG (n = 11) and PD patients without FOG (non-freezers) (n = 11) in a non-randomized medication condition (OFF/ON) were analyzed. Uncued antiphasic finger tapping and forearm diadochokinetic movements were analyzed via three-dimensional ultrasound kinematic measurements. Gait variability of straight gait was assessed using ground reaction forces. Freezers had shorter stride length (p = 0.004) and higher stride length variability (p = 0.005) in the medication OFF condition. Movement variability was not different during finger tapping or diadochokinesia between the groups. There was a trend towards more freezing of the upper limb during finger tapping for the freezers (p = 0.07). Variability in stride length generation and stride timing was not associated with variability of upper limb movement in freezers. Our findings demonstrate that: (1) freezers have a higher spatial gait variability between freezing episodes; (2) freezing-like episodes of the upper limb occur in PD patients, and tend to be more pronounced among freezers than non-freezers for finger tapping; (3) spatial and temporal upper extremity variability is equally affected in freezers and non-freezers in an uncued task. Upper limb freezing is not correlated to lower limb freezing, implicating a different pathophysiology.

Contains fulltext : 115427.pdf (publisher's version ) (Closed access), BACKGROUND: Parkinson's disease (PD) patients have an increased gait asymmetry and variability, which is most pronounced in patients with freezing of gait (FOG). We examined if stride time variability and deficits in interlimb coordination between the upper and lower limbs would increase during split-belt locomotion in PD, and particularly so in patients with FOG. METHODS: Fourteen PD patients (seven with FOG, matched for disease severity with the seven non-freezers) and 10 healthy controls walked on a treadmill with split belts at different speeds (2 versus 3km/h). Gait was recorded by means of a video motion analysis system. Outcome measures were stride length asymmetry and variability, stride time asymmetry and variability, ipsilateral and contralateral interlimb coordination, and phase coordination index. RESULTS: Both PD subjects and controls were able to adapt to split-belt walking by modulating their stride length. However, freezers showed a larger increase in stride time asymmetry and stride time variability due to split-belt walking compared to non-freezers. Furthermore, contralateral interlimb coordination improved in control subjects during split-belt walking, but not in PD patients (freezers and non-freezers). Phase coordination index did not change differently across the three groups. CONCLUSIONS: The ability to walk under split-belt conditions was preserved in PD. Non-freezers and controls compensated for the experimentally increased stride length asymmetry by decreasing their stride time asymmetry. This ability was lost in freezers, who in fact increased their stride time asymmetry during split-belt walking. As a result, stride time variability also increased in freezers. These findings support the hypothesis that FOG is related to gait asymmetries and to gait timing deficits.

Item does not contain fulltext, OBJECTIVE: To describe the phenotype of levodopa-induced "on" freezing of gait (FOG) in Parkinson disease (PD). METHODS: We present a diagnostic approach to separate "on" FOG (deterioration during the "on state") from other FOG forms. Four patients with PD with suspected "on" FOG were examined in the "off state" (>12 hours after last medication intake), "on state" (peak effect of usual medication), and "supra-on" state (after intake of at least twice the usual dose). RESULTS: Patients showed clear "on" FOG, which worsened in a dose-dependent fashion from the "on" to the "supra-on" state. Two patients also demonstrated FOG during the "off state," of lesser magnitude than during "on." In addition, levodopa produced motor blocks in hand and feet movements, while other parkinsonian features improved. None of the patients had cognitive impairment or a predating "off" FOG. CONCLUSIONS: True "on" FOG exists as a rare phenotype in PD, unassociated with cognitive impairment or a predating "off" FOG. Distinguishing the different FOG subtypes requires a comprehensive motor assessment in at least 3 medication states.

Item does not contain fulltext, Visual cues can ameliorate freezing of gait, an incapacitating symptom frequently seen in patients with parkinsonism. Here, we describe a patient with severe freezing of gait, who responded well to 3-dimensional cues, but not to 2-dimensional visual cues. We discuss the potential implications of this phenomenon.

Radboud Universiteit Nijmegen, 04 juni 2012, Promotor : Bloem, B.R. Co-promotor : Toni, I., Contains fulltext : 93605.pdf (publisher's version ) (Open Access)

1 februari 2012, Item does not contain fulltext, INTRODUCTION: Freezing of gait (FOG) is both common and debilitating in patients with Parkinson's disease (PD). Future pathophysiology studies will depend critically upon adequate classification of patients as being either 'freezers' or 'non-freezers'. This classification should be based ideally upon objective confirmation by an experienced observer during clinical assessment. Given the known difficulties to elicit FOG when examining patients, we aimed to investigate which simple clinical test would be the most sensitive to provoke FOG objectively. METHODS: We examined 50 patients with PD, including 32 off-state freezers (defined as experiencing subjective 'gluing of the feet to the floor'). Assessment including a FOG trajectory (three trials: normal speed, fast speed, and with dual tasking) and several turning variants (180 degrees vs. 360 degrees turns; leftward vs. rightward turns; wide vs. narrow turning; and slow vs. fast turns). RESULTS: Sensitivity of the entire assessment to provoke FOG in subjective freezers was 0.74, specificity was 0.94. The most effective test to provoke FOG was rapid 360 degrees turns in both directions and, if negative, combined with a gait trajectory with dual tasking. Repeated testing improved the diagnostic yield. The least informative tests included wide turns, 180 degrees turns or normal speed full turns. Sensitivity to provoke objective FOG in subjective freezers was 0.65 for the rapid full turns in both directions and 0.63 for the FOG trajectory. DISCUSSION: The most efficient way to objectively ascertain FOG is asking patients to repeatedly make rapid 360 degrees narrow turns from standstill, on the spot and in both directions.

Contains fulltext : 97934.pdf (publisher's version ) (Closed access), Freezing of gait is a common, debilitating feature of Parkinson’s disease. We have studied gait planning in patients with freezing of gait, using motor imagery of walking in combination with functional magnetic resonance imaging. This approach exploits the large neural overlap that exists between planning and imagining a movement. In addition, it avoids confounds introduced by brain responses to altered motor performance and somatosensory feedback during actual freezing episodes. We included 24 patients with Parkinson’s disease: 12 patients with freezing of gait, 12 matched patients without freezing of gait and 21 matched healthy controls. Subjects performed two previously validated tasks—motor imagery of gait and a visual imagery control task. During functional magnetic resonance imaging scanning, we quantified imagery performance by measuring the time required to imagine walking on paths of different widths and lengths. In addition, we used voxel-based morphometry to test whether between-group differences in imagery-related activity were related to structural differences. Imagery times indicated that patients with freezing of gait, patients without freezing of gait and controls engaged in motor imagery of gait, with matched task performance. During motor imagery of gait, patients with freezing of gait showed more activity than patients without freezing of gait in the mesencephalic locomotor region. Patients with freezing of gait also tended to have decreased responses in mesial frontal and posterior parietal regions. Furthermore, patients with freezing of gait had grey matter atrophy in a small portion of the mesencephalic locomotor region. The gait-related hyperactivity of the mesencephalic locomotor region correlated with clinical parameters (freezing of gait severity and disease duration), but not with the degree of atrophy. These results indicate that patients with Parkinson’s disease with freezing of gait have structural and functional alterations in the mese

Contains fulltext : 96518.pdf (publisher's version ) (Closed access), The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely understood. Patients with FOG ("freezers") have a higher temporal variability and asymmetry of strides compared to patients without FOG ("non-freezers"). We aimed to extend this view, by assessing spatial variability and asymmetry of steps and interlimb coordination between the upper and lower limbs during gait. Twelve freezers, 15 non-freezers, and 15 age-matched controls were instructed to walk overground and on a treadmill. Kinematic data were recorded with a motion analysis system. Both freezers and non-freezers showed an increased spatial variability of leg movements compared to controls. In addition, both patient groups had a deficit in interlimb coordination, not only between ipsilateral arms and legs, but also between diagonally positioned limbs. The only difference between freezers and non-freezers was a decreased step length during treadmill walking. We conclude that parkinsonian gait-regardless of FOG-is irregular, not only in the legs, but also with respect to interlimb coordination between the arms and legs. FOG is reflected by abnormal treadmill walking, presumably because this provides a greater challenge to the defective supraspinal control than overground walking, hampering the ability of freezers to increase their stride length when necessary.

Contains fulltext : 87977.pdf (publisher's version ) (Open Access)

Contains fulltext : 69139.pdf (publisher's version ) (Closed access), The clinical assessment of freezing of gait (FOG) provides great challenges. Patients often do not realize what FOG really is. Assessing FOG is further complicated by the episodic, unpredictable, and variable presentation, as well as the complex relationship with medication. Here, we provide some practical recommendations for a standardized clinical approach. During history taking, presence of FOG is best ascertained by asking about the characteristic feeling of "being glued to the floor." Detection of FOG is greatly facilitated by demonstrating what FOG actually looks like, not only to the patient but also to the spouse or other carer. History taking further focuses on the specific circumstances that provoke FOG and on its severity, preferably using standardized questionnaires. Physical examination should be done both during the ON and OFF state, to judge the influence of treatment. Evaluation includes a dedicated "gait trajectory" that features specific triggers to elicit FOG (gait initiation; a narrow passage; dual tasking; and rapid 360 degrees axial turns in both directions). Evaluating the response to external cues has diagnostic importance, and helps to determine possible therapeutic interventions. Because of the tight interplay between FOG and mental functions, the evaluation must include cognitive testing (mainly frontal executive functions) and judgment of mood. Neuroimaging is required for most patients in order to detect underlying pathology, in particular lesions of the frontal lobe or their connections to the basal ganglia. Various quantitative gait assessments have been proposed, but these methods have not proven value for clinical practice.

Contains fulltext : 52253.pdf (publisher's version ) (Closed access), Gait disorders are common and often devastating companions of ageing, leading to reductions in quality of life and increased mortality. Here, we present a clinically oriented approach to neurological gait disorders in the elderly population. We also draw attention to several exciting scientific developments in this specialty. Our first focus is on the complex and typically multifactorial pathophysiology underlying geriatric gait disorders. An important new insight is the recognition of gait as a complex higher order form of motor behaviour, with prominent and varied effects of mental processes. Another relevant message is that gait disorders are not an unpreventable consequence of ageing, but implicate the presence of underlying diseases that warrant specific diagnostic tests. We next discuss the core clinical features of common geriatric gait disorders and review some bedside tests to assess gait and balance. We conclude by proposing a practical three-step approach to categorise gait disorders and we present a simplified classification system based on clinical signs and symptoms.

Contains fulltext : 52649.pdf (publisher's version ) (Closed access), In this review, we outline how the influence of cognitive processes on gait or balance can be appreciated in a clinical setting. Careful history taking of the patient or direct carer provides information about multiple task problems in daily life and the presence of cognitive impairment, depression or fear of falling. Physical examination may reveal abnormalities such as an inappropriately high walking speed or an inability to handle secondary tasks while walking. Assessment of frontal executive function helps to understand the nature of these multiple task problems and to detect "risky" behaviour caused by frontal disinhibition. Examples of clinically useable techniques include pressure-sensitive insoles or an electronic walkway (to record strides) or accelerometers (to measure body motion while walking). Combining these assessments may lead to a better appreciation of the fascinating but complex interplay between cognition and gait.

Contains fulltext : 58935.pdf (publisher's version ) (Closed access), Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly stimulate or inhibit cortical brain areas. A novel approach entails the delivery of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity is altered beyond the period of actual stimulation. The changes occur locally as well as at a distance in functionally connected brain areas. These features render rTMS a suitable tool to study normal brain functions and the pathophysiology of brain diseases. Furthermore, it is expected that rTMS could be used as a novel therapy for neurological or psychiatric diseases characterised by abnormal cortical activation. This possibility has been studied mostly in patients suffering from depression, where rTMS has been used to restore normal activity in the hypoactive prefrontal cortex. Despite statistically significant therapeutic effects in small sized trials, the clinical implications are still limited.