The dystonias are a heterogenous group of movement disorders, which are defined by abnormal movements or postures (1, 2). According to the modern definition, dystonia represents a movement disorder, which is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. Dystonic movements are typically patterned, twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation (1).

Idiopathic and inherited dystonia has been regarded as a disorder of basal ganglia activity and associated circuits. The pathophysiology of dystonia is not fully clarified, but several mechanisms, such as decreased inhibition, altered plasticity, and dysfunction of oscillatory activity appear to be involved (3). In addition, there is limited evidence of involvement of sensory systems in the pathophysiology of dystonia. Both imaging and electrophysiological studies have revealed abnormalities in sensorimotor networks (4, 5) and also in cerebello-thalamo-cortical pathways (6, 7).

Patients with dystonia often complain about pain, although the clinical examination and neurophysiological testing remain normal (8). Further, they use certain maneuvers in order to temporarily improve dystonia. This phenomenon has been recognized as sensory trick (or geste antagoniste) suggesting a possible role of the sensory system in clinical manifestation of dystonia (9).

Other hints for involvement of sensory systems include abnormal sensory processing (10, 11) and altered temporal and spatial discrimination of tactile stimuli (12–16).

Hence, we investigated the somatosensory integrity in patients with idiopathic dystonia using quantitative sensory testing (QST) (17, 18). This method allows the investigation of different sensory qualities such as heat, cold, paradox sensations (the ability to differentiate warmth and cold), touch, pain, pressure, and vibrations, which are transmitted by Aβ, Aδ, and C fibers in the periphery. The aim of the study was to investigate whether sensory alterations are confined to the dystonic body segments or show wider involvement in patients with dystonia.

The mean BFM motor score (±SD) of all patients was 16.4 ± 9.3 (generalized dystonia 28.3 ± 5.7, segmental 11.3 ± 4.1, and cervical 6.0 ± 2.2). A significant difference (p = 0.023) in the arm BFM subscore was evident when comparing the more affected upper extremity (7.5 ± 3.8) with the less affected upper extremity (3.7 ± 2.8) in patients with upper extremity involvement of dystonia (n = 13). The mean of the TWSTRS motor score (±SD) in patients with cervical dystonia was 8.6 ± 2.5 (n = 7).

Quantitative sensory testing of the hand in the whole group of patients with dystonia (n = 20) showed a sensory gain for dynamic mechanic allodynia (p = 0.001) and thermal sensory limen (p = 0.04) and a tendency to sensory loss for cold detection threshold (p = 0.055) in comparison to matched controls (n = 20, Figure 1A; Table 1).

In the next step, patients with cervical dystonia were excluded in order to analyze more homogenously the relation of dystonia and sensory function. Compared to the control group, QST detected sensory gain for dynamic mechanical allodynia bilaterally (p = 0.001) and for thermal sensory limen on the more affected upper extremity with dystonia (p = 0.01). Additionally, a more limited sensory loss for cold detection threshold on the more affected upper extremity was revealed (p = 0.052) (n = 13, Figure 1B; Table 2). z-scores of the clinically more affected upper extremity showed a higher shift from baseline than the clinically less affected upper extremity in all instances compared to controls (Figure 1B).

In the hand QST of the seven patients with isolated cervical dystonia, a sensory decrease for cold (p = 0.04) and hot detection thresholds (p = 0.03) was found as well as increased sensation for allodynia (p = 0.02) and to a lesser extent for thermal sensory limen (p = 0.06) compared to controls (n = 7, Figure 1C; Table 3).

In the shoulder QST of the seven patients with cervical dystonia, a higher score for cold pain threshold (p = 0.008) and dynamic mechanical allodynia (p = 0.001) was detected in comparison to controls (n = 7, Figure 1D; Table 4).

There was no significant correlation between the BFM motor score and any QST measure (Table 5). There was also no correlation between the TWSTRS motor score and QST measures (Table 5), as well as between TWSTRS disability and pain score and QST values. Only three of our patients reported neck pain. Therefore, the correlation of the pain subscore of the TWSTRS with QST values cannot be taken as significant.

Our study shows that QST may detect subtle sensory abnormalities in patients with dystonia in absence of overt sensory deficits. Alterations of sensory function were found for modalities that are transmitted by C fibres (cold detection, partly cold pain threshold, and thermal sensory limen), by Aδ fibres (hot detection, cold pain threshold, thermal sensory limen) (23), and by Aβ fibres (dynamic mechanical allodynia) (24).

The main findings were decreased cold detection threshold, increased dynamic mechanical allodynia, and thermal sensory limen in the hand QST regardless of the distribution of dystonia. Our findings are partly in line with an earlier study, which investigated QST in a group of patients with idiopathic dystonia confined to the hand (25). While decreased cold detection threshold of the hand were found in both studies, we could not confirm abnormalities in MPTs and pain sensitivity for pinprick. Moreover, our patients showed increased dynamic mechanical allodynia in comparison to controls. Notably, the study of Suttrup and colleagues included only patients with writer’s cramp.

As demonstrated in our study, bilateral sensory alterations on both upper extremities were more predominant on the clinically more affected side. Interestingly, subtle sensory impairment was also detected on the hands of patients with cervical dystonia in our study. These findings suggest that clinically silent sensory alterations may be present in patients with dystonia regardless of the presence of overt dystonia in a specific body region. To our knowledge, shoulder QST has not been investigated previously in patients with cervical dystonia. The increase in dynamic mechanical allodynia and cold pain threshold compared to healthy controls suggest that this area may be suitable for further examination of the sensory system in patients with dystonia.

Dynamic mechanical allodynia (DMA) enhancement was the most consistent finding in our study. It is a stimulus evoked pain (26) that is induced by light touch (brush, cotton wool, and Q tip). Notably, our patients perceived such light stimuli as sharp or painful. The DMA test in the QST is designed to assess pain elicted by non-painful stimuli. All sensations that are perceived as sharp or painful (including those elicted by brush, cotton wool, and Q-tip) had to be scored higher than 0 on an analogue scale. In this point, the patients with dystonia showed most impairment in sensory perception. Patients with dystonia conceived altered perception of the quality of the stimuli (sharp instead of dull) but not a marked hyperalgesia. We refer to this sensory modality as DMA, as it is defined as such in the QST battery.

Moreover, allodynia for punctuate stimuli (pain sensitivity for pinprick) was not indicated by the subjects in our study. Therefore, pathophysiological mechanisms that have been proposed for DMA in peripheral and central neuropathic pain or in post stroke pain cannot explain the impairment of this sensory modality in dystonia.

Although we found that somatosensory processing is also impaired in clinically distant areas, the z-scores of the upper extremity more affected with dystonia showed a higher shift from the values of the controls than the upper extremity less affected by dystonia in all its domains. Remarkably, there was no correlation between severity of dystonia according to the motor scores (BFM, TWSTRS) and QST alterations. This may point to the presence of generalized subclinical sensory abnormalities in patients with dystonia independent from the site of the clinical manifestation of dystonia. Loss of sensitivity in temporal and spatial discrimination in patients with primary dystonia has been demonstrated before (11, 13, 15, 27) and in non-affected body regions as well (16, 28, 29). Abnormal spatial discrimination thresholds were found even in unaffected relatives (siblings and children) of patients with sporadic adult onset dystonia (10, 30). Moreover, abnormalities in temporal perception of consecutive stimuli have been shown in unaffected DYT1 carriers, which implies that sensory alterations in dystonia are not a mere consequence of abnormal movements, but may occur apart from motor manifestations (31). Furthermore, it is of interest that botulinum toxin or pallidal DBS did not appear to normalise temporal discrimination thresholds in patients with cervical dystonia, which means that alterations in temporal perception might be causal or related to the genesis of dystonia, rather than being an epiphenomenon secondary to abnormal motor activity (32, 33).

The pathomechanisms for the QST abnormalities seen in dystonia remain unclear. It has been suggested that sensorimotor integration plays a major role in the pathophysiology of dystonia (3). The basal ganglia are thought to have a role in the modulation of sensory stimuli and a direct impact on somatosensory integration (34–36). Furthermore, the cerebellum receives input from the spinal cord and interacts with the somatosensory system (37, 38). Functional imaging studies have revealed abnormalities in the basal ganglia circuitry as well as in the cerebellum in dystonia, even when lesions were not evident in structural imaging methods (7, 39–43).

Furthermore, altered neuroplasticity in the somatosensory cortex related to deranged somatotopic representation, such as abnormal cortical finger representation and disordered homuncular arrangement, was found in patients with focal dystonia (44–46), in some studies evident even bilaterally (47). Abnormal plasticity has been demonstrated in several types of dystonia (48), and it has been suggested to be a result of intrinsic defects in plasticity mechanisms or of the breakdown of such mechanisms (41). Notably, abnormal plasticity may lead to changes in the connectivity of the sensory and motor networks resulting in abnormal sensory and motor function.

Such complex functional changes in the brain of patients with dystonia may also underlie the sensory alterations we have detected with QST. Our findings may suggest that deranged somatosensory integration and abnormal plasticity can lead to the less reliable differentiation of somatosensory stimuli (dynamic mechanical allodynia, temperature thresholds) and a slower detection of certain sensations (thermal sensory limen). Whether these impairments are the consequence of a deficit of global sensorimotor integration or of the specific levels of the loop, or even a process of maladaptive plasticity itself, remains to be elucidated.

Moreover, it remains open to discuss whether abnormalities as observed in our study represent a primary sensory loss or a reaction to maladjusted central changes. Further analysis of dystonia may provide a better understanding of the sensory alterations in these patients. The limitations of this exploratory study are the small dystonia patient sample group that was tested with QST and the lack of correction for multiple comparisons. The forthcoming studies should focus on a larger number of patients, including specific inherited dystonias. Finally, future studies may address the specific role of the thalamo-striato-cortical and cerebello-thalamo-cortical pathways associated with the disturbed sensorimotor integration in dystonia.

This study was carried out in accordance with the recommendations of Hannover Medical School with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the ethics committee of Hannover Medical School (No. 6307).

LP did the conception and design of the study, recruited subjects, collected data, performed statistical analysis, interpreted the data, and wrote the manuscript. FW concepted and designed the study, recruited the patients, collected and interpreted data, and contributed to the manuscript. LP and FW contributed equally. CB, MK, MA, AS, and DD recruited the patients, collected data, and approved the manuscript. JKK supervised the research project, concepted and designed the study, recruited patients, and contributed essentially to the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.