Table 3 - uploaded by Eduard Tolosa
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Spontaneous and voluntary eyelid motility is often abnormal in patients with progressive supranuclear palsy. In contrast, their eyelid reflex responses are relatively preserved, and only those generated by an acoustic startle have been found absent or severely reduced. We hypothesized that, because of their relevant brainstem pathology, patients wi...
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Context 1
... responses to single supraorbital nerve electrical stimuli were present at a normal latency in all control subjects and patients (Table 3). There were no significant differences between patients with progressive supranuclear palsy and the other patient groups or the control subjects regarding latency and amplitude of the blink-reflex responses. ...
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Detection and discrimination of neurodegenerative Parkinson syndromes are challenging clinical tasks and the use of standard T1- and T2-weighted cerebral magnetic resonance (MR) imaging is limited to exclude symptomatic Parkinsonism. We used a quantitative structural MR-based technique, MR-elastography (MRE), to assess viscoelastic properties of th...
The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology, even for movement disorder specialists. Despite published consensus operational criteria for the diagnosis of Parkinson's disease (PD) and the various atypical parkinsonian disorders (APDs) such as progressive supranuclear palsy, multiple sy...
Citations
... In healthy individuals, the response in the OOc always precedes the one in the mentalis muscle. How-ever, the OOc response was absent in patients with progressive supranuclear palsy, which Valls-Solé et al. (1997) described as a distinctive feature differentiating progressive supranuclear palsy from other forms of atypical parkinsonisms. Similar abnormalities were later found in patients with ischemic upper brainstem lesions (Leon et al., 2011). ...
... While PSP patients exhibited more severe deficits relative to PD and MSA patients, no significant difference was detected between MSA and PD patients despite a trend of more pronounced impairment among MSA patients relative to those suffering PD. This finding is in agreement with prior research, suggesting that abnormal voluntary eye movements are often more severe in PSP and relatively less impacted in PD and MSA (Valls-Solé et al., 1997;Armstrong, 2021). Importantly, maximal ranges of ocular motion on downward and horizontal gazes were impaired in all three patient groups in relation to the HC group, indicating that moderate limitations in oculomotor range should be cautiously considered when establishing a differential diagnosis. ...
Introduction
Although restriction of vertical ocular range of motion is known to be the hallmark of progressive supranuclear palsy (PSP), the maximal amplitude of ocular movement has not been quantitatively assessed despite of accumulating evidences of oculomotor dysfunction in Parkinson's disease (PD). Here, we evaluated the maximal oculomotor range and its response to levodopa in PD, and compare findings to atypical parkinsonism.
Methods
We recruited 159 healthy controls (HC) as well as 154 PD, 30 PSP, and 16 multiple system atrophy (MSA) patients. Oculomotor range was assessed using a kinetic perimeter-adapted device for the vertical and horizontal axes (four positions). Parameters were reassessed after levodopa challenge and compared among PD, PSP, and MSA patients.
Results
Maximum oculomotor range in PD patients was reduced as compared to HC. Levodopa improved oculomotor range in all directions; corrective effects of upward range positively correlated with improvements in Unified Parkinson's Disease Rating Scale III and bradykinesia sub-scores among PD patients. Although oculomotor range was markedly restricted among PSP and MSA patients, the beneficial effects of levodopa was less pronounced. Reduced oculomotor range of motion was more significant among PSP as compared to PD or MSA patients; MSA patients did not significantly differ from PD patients. The range of upward gaze was optimally sensitive for differentiating among PD, PSP, and MSA patients.
Conclusion
Maximum oculomotor range was reduced among PD patients significantly improved by levodopa treatment. Variations in, as well as the positively effects of levodopa on, the range of upward gaze assist diagnostic differentiation among PD, PSP, and MSA patients.
... Only a few studies on BR and R2BRRC in APS were reported in recent years. [40][41][42][43] In particular, R2BRRC could differentiate patients with tauopathies, that is, PSP and CBS. 40 The use of a recovery cycle demonstrated that patients with PSP exhibited increased brainstem excitability, with high specificity and sensitivity in distinguishing PSP from CBS. 40 Recently, R2BRRC was used to discriminate APS with similar clinical phenotypes, as well as APS from early PD. ...
Hypokinetic movement disorders encompass a group of clinically similar diseases that present challenges in discrimination during neurological examinations. Characterizing a specific hypokinetic disorder is necessary for the diagnosis and treatment in daily clinical practice. Neurophysiological tools, such as electromyography (EMG) combined with accelerometry, motor-evoked potentials (MEPs), electroencephalographic recording (EEG), Bereitschaftspotential (BP), auditory-evoked cognitive potential (P300), blink reflex (BR), and R2 blink reflex recovery cycle (R2BRRC), are useful in the differential diagnosis of movement disorders due to the common clinical features. However, neurophysiological assessments of movement disorders, especially hypokinetic diseases, are currently underutilized in clinical practice as compared to a few decades ago. This review aims to summarize practical insights gleaned from reported studies over the past 5 years (i.e., 2019 – 2023) regarding neurophysiological assessments of hypokinetic movement disorders, emphasizing the importance of their routine application. In particular, the methodology of the electrophysiologic evaluations pertaining to hypokinetic movement disorders is assessed. Moreover, a practical approach for the differential diagnosis of similar movement disorder syndromes based on specific neurophysiological features is proposed. Collectively, this review of the most recent neurophysiological implications in hypokinetic movement disorders highlights the practicality of these methods. Despite the advancement of other diagnostic techniques (e.g., neuroradiological methods), neurophysiological assessments may be a promising tool for clinical diagnoses, due to their high accuracy and ability to categorize and manage movement disorders (e.g., hypokinetic movement disorders) in daily clinical practice.
... Among these, the hand-blink reflex (HBR) is a defensive response characterized by the rapid (~45 ms) bilateral closure of the eyelid in response to the electrical stimulation of the median nerve at the wrist. It has been suggested that the HBR may be functionally similar to the R2 component of the trigeminofacial blink reflex, involving the mesencephalic reticular formation and the extra-trigeminal blink reflex pathways (León et al., 2011;Miwa et al., 1998;Valls-Solé et al., 1997). First described by Sambo in 2012, the HBR shows a larger magnitude when the stimulated hand is close to the face, than when it is far from it (Sambo, Forster, et al., 2012;Sambo, Liang, et al., 2012). ...
The hand-blink reflex (HBR) is a subcortical response elicited by the electrical stimulation of the median nerve. HBR magnitude is enhanced when the stimulated hand is close to the face and is modulated by high-level structures according to the perceived threat magnitude. Psychological factors may contribute to threat evaluation and possibly to HBR amplitude modulation. In this study, we assessed distinctively emotional and relational aspects of personality and evaluated their associations with the HBR response, or lack thereof, in healthy subjects. Seventy-one volunteers filled the Experiences in Close Relationships Scale, the Affective Neuroscience Personality Scales, and the State-Trait Anxiety Inventory Form Y questionnaires and underwent HBR recording. We found that the HBR could be evoked only in 50.7% of all subjects (responders). Non-responders subjects showed higher scores in the avoidance dimension (p = .005), and lower scores in the care dimension (p = .008), compared with responders. In responders, regression analysis showed a negative association of HBR amplitude (difference in near vs. far responses) with anger dimension and a positive association with state anxiety (R2 = 0.239). A positive association also emerged with HBR latency and fear dimension (R2 = 0.419). We conclude that primary emotional and relational factors may play an important role in the modulation of brainstem circuits mediating the HBR response. Our results may also contribute to the question about the absence of the HBR in about half of the subjects since high-level cognitive processes seem to play an important role in the differentiation between responder and non-responder.
... The ratio between responses expressed as a function of time generates the BRER curve (Kimura, 1973, Valls-Solé, 2012. This test has proven very useful in clinical practice, providing robust, quantifiable, and replicable results in various diseases (Aramideh et al., 1995, Berardelli et al., 1985, Frauscher et al., 2012, Kimura and Harada, 1976, Kofler and Halder, 2014, Kumru et al., 2010, Maeoka et al., 1999, Molloy et al., 2002, Oge et al., 2005, Orhan et al., 2011, Smith and Lees, 1989, Tolosa et al., 1988, Valls-Sole and Tolosa, 1989, Valls-Solé et al., 1997a, Valls-Solé et al., 1997b. However, our study demonstrates the irrelevance of the size of an eventual response to the conditioning stimulus for the conditioning to take place: R2 and R2c responses to SON -1 stimulation were profoundly inhibited when SON -1 was preceded by a prepulse and yet the response to SON -2 displayed the same behavior as in the condition with no D2 stimulation. ...
Objective:
The blink reflex (BR) to supraorbital nerve (SON) stimulation is reduced by either a low-intensity prepulse stimulus to digital nerves (prepulse inhibition, PPI) or a conditioning SON stimulus (SON-1) of the same intensity as the test (SON-2) stimulus (paired-pulse paradigm). We studied how PPI affects BR excitability recovery (BRER) to paired SON stimulation.
Methods:
Electrical prepulses were applied to the index finger 100 ms before SON-1, which was followed by SON-2 at interstimulus intervals (ISI) of 100, 300, or 500 ms.
Results:
BRs to SON-1 showed PPI proportional to prepulse intensity, but this did not affect BRER at any ISI. PPI was observed on the BR to SON-2 only when additional prepulses were applied 100 ms before SON-2, regardless of the size of BRs to SON-1.
Conclusions:
In BR paired-pulse paradigms, the size of the response to SON-2 is not determined by the size of the response to SON-1. PPI does not leave any trace of inhibitory activity after it is enacted.
Significance:
Our data demonstrate that BR response size to SON-2 depends on SON-1 stimulus intensity and not SON-1 response size, an observation that calls for further physiological studies and cautions against unanimous clinical applicability of BRER curves.
... It has been shown that personal space, i.e., space defined by the relative distance from another person where one feels comfortable, is larger when several virtual agents showing angry faces versus happy faces are approaching or when multiple virtual agents are approaching compared to only a single one (Bönsch et al., 2018). Personal space here can reflect the secure peripersonal space which has been proved to depend on emotions and social interactions Markman and Brendl, 2005;Pellencin et al., 2018;Teneggi et al., 2013;Valls-Solé et al., 1997). Virtual reality has been successfully used as treatment for different types of phobia, such as cynophobia, arachnophobia, and claustrophobia all known to be linked with PPS distortion (Hunley et al., 2017;Lourenco et al., 2011;Rabellino et al., 2020;Taffou and Viaud-Delmon, 2014;Vagnoni et al., 2012). ...
... Previous neurophysiological studies evaluated R2BRRC in PD and APs showing that PD patients exhibited increased brainstem excitability (Kimura 1973;Sciacca et al. 2020a); furthermore, an asymmetrical EMG activity with increase of blink reflex components on the LAS compared to MAS has been observed in PD patients (Dengler et al. 1982) together with the presence of a higher AI of R2BRRC differentiating PD from PSP and MSA patients (Sciacca et al. 2020a). Concerning APs, only a few studies investigated brainstem excitability by the application of blink reflex and R2BRRC (Sciacca et al. 2020a, b;Sciacca et al. 2018;Valls-Solé et al. 1997;Szmidt-Salkowska et al. 2016) showing that PSP and MSA patients exhibited an increased brainstem excitability compared to CBS patients. In this study, we added and confirmed previous data showing that PD and CBS patients at the early stages of disease presented an inverse pattern of brainstem excitability, with PD patients showing an increased excitability in LAS compared to MAS and a higher AI of R2BRRC, whereas CBS group did not show any differences between LAS and MAS excitability. ...
Differential diagnosis between Parkinson’s disease (PD) and corticobasal syndrome (CBS) could be challenging at the early stage, due to the asymmetric onset of both diseases. Despite the clinical overlap, the anatomical circuits involved in these disorders are different. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) and cortical thickness (CTh) in drug-naïve PD and CBS patients for characterizing pathophysiological mechanisms underlying these conditions. Patients with a clinically probable diagnosis of PD and possible CBS were recruited. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100–150–200–300–400–500–750 ms. Asymmetry index (AI) of R2BRRC for each ISI was computed. Patients underwent a structural brain MRI and hemisphere CTh and AI of MRI was calculated. Fourteen drug-naïve PD patients and 10 patients with early CBS diagnosis were enrolled. R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100 and 150 ms (p < 0.001) compared to most affected side (MAS), whereas no differences between LAS and MAS were found in CBS. AI of R2BRRC at ISI-100 ms showed significant difference, being higher in PD. CTh analysis showed significant differences between groups in hemisphere cortical volume contralateral to MAS, and, conversely, AI of MRI was significantly higher in CBS. PD patients exhibited an asymmetric pattern of brainstem excitability, compared to CBS. Conversely, CBS patients showed an asymmetric pattern of cortical atrophy. This opposite pattern of neurophysiological and structural abnormalities involving cortical and subcortical brain structures could highlight the different pathophysiological mechanisms underlying these disorders.
... A decrease in blink frequency may cause symptoms of dry eye, including blurred vision, foreign body sensation, burning or irritation. Appropriate evaluation of extraocular muscle motility and near point of convergence as well as slit-lamp examination to evaluate the tear film and corneal integrity are of particular importance [16][17][18][19]. ...
Progressive supranuclear palsy (PSP) is a rare neurodegenerative parkinsonian syndrome with distinct clinical features which tends to be progressive, causing vertical supranuclear gaze palsy, frontal lobe cognitive decline, postural instability and progressive axial rigidity. Clinical examination typically reveals ocular motor dysfunction including restricted vertical gaze, slow vertical saccades and "eyelid opening apraxia" with intact vestibule ocular reflex. PSP falls under the rubric of Parkinsonism plus syndromes that are a group of heterogeneous degenerative neurological disorders that differ from the classical idiopathic Parkinson's disease. PSP is often underreported, making it important for clinicians to be aware of this disorder. Here we report a case of PSP, which presented primarily with speech disturbances and recurrent falls due to postural instability. On investigating, the magnetic resonance imaging (MRI) revealed a classical sign diagnostic of PSP. This teaching case report describes management and prognosis of the disease.
... The blink reflex is characterized by an early ipsilateral component (R1), which originates from an oligosynaptic pontine circuit, followed by a bilateral late component (R2), which reflects the activity of a polysynaptic circuit in the medullary reticular area [15][16][17][18]. Brainstem circuit excitability can be assessed through the R2 recovery cycle, a non-invasive neurophysiological technique based on paired stimulation at different interstimulus intervals (ISI) [15,19,20]. Various neural systems are involved in the control and modulation of the blink reflex, including descending pathways from cortical and subcortical areas [16,[21][22][23][24][25][26]. ...
Low-intensity transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique that uses acoustic energy to induce changes in neuronal activity. However, although low-intensity TUS is a promising neuromodulation tool, it has been poorly studied as compared to other methods, i.e., transcranial magnetic and electrical stimulation. In this article, we first focus on experimental studies in animals and humans aimed at explaining its mechanisms of action. We then highlight possible applications of TUS in movement disorders, particularly in patients with parkinsonism, dystonia, and tremor. Finally, we highlight the knowledge gaps and possible limitations that currently limit potential TUS applications in movement disorders. Clarifying the potential role of TUS in movement disorders may further promote studies with therapeutic perspectives in this field.
... In contrast, lesions altering the trigeminal nuclear complex at the brainstem are usually independently affecting either the R1 or the R2 responses (Cruccu et al., 2005, Kimura andLyon, 1972). Upper brainstem lesions may preserve the blink reflex to trigeminal nerve stimulation while the blink reflex to median nerve stimulation appears selectively impaired (Leon et al., 2011, Valls-Sole et al., 1997. In contrast, lesions involving the lower brainstem affect the R2 to supraorbital nerve stimulation but preserve the response to median nerve stimulation. ...
... This was initially described as the somatosensory blink reflex (Miwa et al., 1998) and is also known today as the hand blink reflex (HBR). Apart from some potential clinical applications (Benbir and Kiziltan, 2014, Miwa et al., 1998, Valls-Sole et al., 1997, it has been used to characterize the so-called somatosensory startle (Alvarez-Blanco et al., 2009) and to assess changes in blink reflex circuit excitability when stimuli are applied within the peripersonal space (Sambo et al., 2012). It is interesting to note that the HBR may be preserved in some lower brainstem lesions, when the trigemino-facial reflex is altered, which shows some of the differences between the two reflexes. ...
This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology.
