Clinical Neurophysiological Study for the Diagnosis of Functional Cranial–Cervical Dystonia

ABSTRACT

Objectives

The differential diagnosis of functional and other etiologies of dystonia can be difficult. We performed a clinical neurophysiological study in a female patient with cranial–cervical dystonia, providing strong evidence for the diagnosis of functional dystonia.

Methods

The patient had torticollis and intermittent facial pulling with downward deviation of the left angle of the mouth. She had left laterocollis and right torticollis with left shoulder elevation. She additionally experienced limited anterior–posterior flexion of the neck and moderate limitation of lateral flexion and neck rotation in both directions without spinal cord compression. We recorded abnormal discrete movements of the lower lip with surface electromyography (EMG). Electroencephalography was recorded simultaneously to identify a possible Bereitschaftspotential (BP) before the abnormal movement. We also tested inhibition of the blink reflex and pre‐pulse inhibition (PPI) using supraorbital nerve stimulation with a conditioning‐test paired‐pulse paradigm.

Results

The EMG of the dystonic left lip movements varied in shape, duration, and amplitude. A BP was observed before the abnormal lip movement. The topographic distribution of BP with abnormal lip movement was similar to that with voluntarily mimicked lip movement and with voluntary movement of arm extension. The R2 component of the blink reflex was inhibited with a preceding conditioning pulse at interstimulus intervals of 150–1000 ms. Significant PPI was found at intervals of 60–120 ms. The R1 component of the blink reflex was not inhibited.

Discussion

The patient has functional dystonia. Our results suggest that in some circumstances clinical neurophysiological tests can support the differential diagnosis of functional cranial–cervical dystonia.

1. Introduction

Functional dystonia is difficult to distinguish from organic dystonia because of their similar clinical features [1]. We present a case of cranial–cervical dystonia and demonstrate how clinical neurophysiology can be helpful for making the diagnosis of functional dystonia in this situation.

2. Methods

The patient (73‐year‐old right‐handed woman with cranial–cervical dystonia) had torticollis and intermittent facial pulling with downward deviation of the left angle of the mouth (Video 1). The neurophysiological study used surface electromyographic (EMG) recording of the abnormal lip movements. Simultaneous electroencephalography (EEG) was recorded to look for a Bereitschaftspotential (BP) before the abnormal lip movement [2]. The dystonic movement was compared with mimicked pulling down of the lower lip and voluntary left wrist extension movements. We measured the bilateral blink reflex with electrical stimulation of the supraorbital nerve. We tested brainstem circuits with R2 component recovery and sensory gating effect with pre‐pulse inhibition (PPI) using a paired‐pulse paradigm [3](Supporting Information for details).

VIDEO 1.

Patient with functional cranial–cervical dystonia: The patient was a 73‐year‐old right‐handed women with functional cranial‐cervical dystonia. She had torticollis and intermittent facial pulling with downward deviation of the left angle of the mouth. Note multiple episodes at different times (starting at about 7 s in the video). The abnormal dystonic movements at different times are not identical. Her magnetic resonance imaging of the spinal cord showed normal signal without cord compression (refer to supporting information e‐Figure 1). The patient began experiencing intermittent burning pain along the posterior aspect of the left side of her neck at the age of 49. The pain progressed over a few years and started spreading to the left shoulder, but was not accompanied by numbness, tingling, or weakness. Her physical exam showed slight left laterocollis, slight right torticollis with left shoulder elevation (note the beginning of the video). She also described tightness at the corner of her left mouth spreading to the left side of her neck. Her lips felt compressed. The pulling also worsened when she put the phone on her left ear, especially over the last year. The pullng also worsened when lifting weight. The patient denied dystonia in other body parts, excessive blinking, tremor, change in gait or cognitive function. Saccades were normal. No bradykinesia, rigidity, tremor or myoclonus was found. She had limited anterior‐posterior flexion of the neck, and moderate limitation of lateral felxion and neck rotation in both directions (note the late part of the video, starting at about 28 s). Video content can be viewed at https://onlinelibrary.wiley.com/doi/10.1111/ene.70287.

3. Results

We identified 56 dystonic movements with different shapes in a 40‐min recording. BP was identified starting at about 2 s before the abnormal lower‐lip movement. The potential was distributed around the vertex and bilateral motor areas, similar to those with voluntary movements of mimicked lip movement and wrist extension (Figure 1; Tables S1–S3). The blink reflex R2 components recorded in bilateral muscles were significantly inhibited by a conditioning stimulus (CS) at interstimulus intervals of 150–1000 ms. PPI was significant with intervals of 60–120 ms. The R1 component was not inhibited.

FIGURE 1.

Physiological measurements with functional cranial–cervical dystonia. (A) Functional cranial‐cervical dystonia. In addition to the dystonic contraction, multiple episodes with abnormal movement of the lower lip pull‐down were recorded in the left OOR muscle. Three episodes (from a period of 100 s) were magnified in a 2 s window at the bottom. Black arrows (both in the 100 s recording and magnified windows) indicate the EMG onset of the abnormal movements. The shape, amplitude, and duration (varying from 500 to 1500 ms) of the muscle contractions caused by the abnormal lip movements varied at different times. (B and C) BP with dystonic lip movement. EEG was recorded under three different conditions: dystonic lip movement (top panel, involuntary left lower lip pull‐down), mimicked lip movement (middle panel, voluntary left lower lip pull‐down) and voluntary left wrist extension (bottom panel). (B) The EEG signal (negative potential upward) was realigned to the EMG onset (time 0, black arrow in A) and averaged. The top trace in each panel shows the EEG signal recorded at the Cz electrode. The dashed line shows the signal baseline. Bottom traces in the top and middle panels show surface EMG recorded in the left OOR muscle. The bottom trace in the bottom panel shows surface EMG recorded in the left ECR muscle. BP with a slow‐growing negative potential was recorded for all three conditions starting at about 2 s before the EMG onset. An early phase (BP1, black arrow) was observed for all three conditions. A later phase (BP2, white arrow) starting about 0.5 s before the EMG was observed when the patient performed the voluntary movement. (C) shows the BP topographic distribution. The BP amplitudes at the time of 1–1.5 s before the EMG onset were averaged. Warm color indicates positive potential, and cool color indicates negative potential. Note the BP with negative potential around the vertex and bilateral motor areas for all three conditions. (D and E) Blink reflex recovery and (F and G) PPI tested with a conditioning‐test (CS‐TS) paired‐pulse paradigm. TS produces a blink reflex with a standard size. CS preceding the TS at different interstimulus intervals (ISIs) increases or decreases the TS induced blink reflex with facilitatory or inhibitory effect, respectively. (D and F) Example recordings (average of 5 trials) of the blink reflex induced by electrical stimulation of the supraorbital nerve are shown. All trials include a TS (vertical line). The bottom traces in each panel show trials with different ISIs. TS alone (top trace in each panel) was also tested. Vertical dashed lines show the R1 and R2 latencies of the blink reflex. Reflexes with right (left panel in each part) and left stimulation (right panel) were tested in separate sessions. Only recordings in the OOC muscle ipsilateral to the stimulated supraorbital nerve were shown. (D) shows an example of blink reflex recovery tested with CS and TS delivered at the same high stimulus intensity (study paradigm described in the top trace with an example 6 s recording). A CS was given before the TS at a certain ISI (150, 300, 500, 750, 1000, 3000 and 5000 ms). The change in the TS induced reflex (marked with a frame and an arrow) with the preceding CS was measured. The bottom traces show the example recordings magnified in a 100 ms window (starting at the delivery of TS, same time window marked with the frame in the top 6 s trace). (E) Mean ± standard deviation (5 trials) for R2 (measured using the area under curve after rectification) recovery curves. Open and filled circles represent R2 measured in the ipsilateral and contralateral OOC muscles, respectively. R2 area with the paired‐pulse stimulation was normalized as a percentage value of that with TS alone (horizontal dashed line). Note that R2 inhibition was remarkable at ISIs shorter than 1000 ms both with the right and left stimulation. *p < 0.05, **p < 0.01, unpaired t‐test, comparing paired‐pulse induced R2 to that with TS alone in the ipsilateral OOC muscle, corrected with multiple comparisons; ^# p < 0.05, ^## p < 0.01, comparison in the contralateral OOC muscle. (F) shows an example of PPI tested with high intensity TS preceded by a weak CS (arrow, not able to produce blink reflex) at different ISIs of 30, 60, 90, 120, and 250 ms. (G) Mean ± standard deviation (5 trials) for PPI measured with changes in R2. Open and filled circles represent R2 with left and right stimulation, respectively. Only ipsilateral responses were measured. Note that PPI was remarkable at ISIs of 60, 90, and 120 ms both with the right and left stimulation. *p < 0.05, **p < 0.01, unpaired t‐test, comparing paired‐pulse induced R2 to that with TS alone, corrected with multiple comparisons, testing with the right supraorbital nerve stimulation; ^# p < 0.05, testing with the left supraorbital nerve stimulation. BP, Bereitschaftspotential; CS, conditioning stimulus; ECR, extensor carpi radialis; EEG, electroencephalography; EMG, electromyography; ISI, interstimulus interval; OOC, orbicularis oculi; OOR, orbicularis oris; PPI, pre‐pulse inhibition; TS, test stimulus.

4. Discussion

Functional movement disorders are often misdiagnosed [1]. It was proposed that fixed jaw and/or lip deviation is a characteristic pattern of functional facial movement disorders [4]. Since BP before involuntary movements has been seen only with functional movement disorders [1, 2], its identification in our patient strongly supports this proposal of functional origin [2]. Additionally, BP with the abnormal movement was similar to those with mimicked lip movement and wrist extension, indicating that functional movement was produced with similar brain activity as that of voluntary movements even though our patient did not have a premonitory urge before the abnormal movement. However, the presence of BP does not adjudicate the differential diagnosis between a functional movement disorder and malingering, although the diagnosis of functional dystonia in our patient was clinically further supported over time based on her positive response to physiotherapy and lack of response to botulinum toxin treatment. BP before dystonic movement (only early phase) and that before voluntary movement were not entirely identical in our patient, likely because early BP related to the willing of movement arises from the supplementary motor area while late BP is related to the movement itself and generated in the motor cortex. Indeed, BP may also be absent in functional patients under certain conditions with distraction or low engagement [2].

Bilateral R2 components of the blink reflex were inhibited with the CS, suggesting that both the ipsilateral and contralateral inhibitory ascending pathways with inputs to the brainstem were normal in our patient [3]. Defective sensorimotor gating function may cause an input–output mismatch in motor programs and trigger dystonia. Sensory tricks improve symptoms in dystonia patients [3]. Similar improvements with the active release technique were observed with significant PPI in our patient, suggesting that sensorimotor gating function is preserved in our patient with functional dystonia and sensory trick [1]. The preservation of inhibition can only assist in distinguishing functional and other causes of involuntary discharges in dystonic muscles. The use of blink reflex measurements and muscle activation patterns with EMG can provide supportive data in distinguishing between functional and organic cervical dystonia; however, the physiological information taken together from all tests must be carefully evaluated within the clinical situation and manifestations of each patient. In this regard, although our patient exhibited the blink reflex measurements within the normal range of healthy controls tested in our previous study [5], the inhibition of reflex at short intervals was weaker compared to other studies with higher CS intensity [3], likely because weaker stimulation generated less inhibitory drive in the ascending pathway. The extent to which blink reflex measurements are correlated with the cervical component must be interpreted with caution in a clinical setting because various forms of cranial–cervical dystonia differ clinically, and each form of cranial–cervical dystonia may appear in isolation or manifest along with other forms. However, the abnormal dystonic lower‐lip movements recorded with the EMG setup were technically reliable for precise EMG–EEG synchronization and were clinically applicable for identifying the functional dystonia in our patient with multifocal syndrome. We conclude that neurophysiological tests can support the differential diagnosis of functional cranial–cervical dystonia with special phenotypes.

Author Contributions

Zhen Ni: writing – original draft, conceptualization, data curation, writing – review and editing, formal analysis. Oday Halhouli: data curation, writing – review and editing. Hyun Joo Cho: writing – review and editing. Mark Hallett: conceptualization, writing – review and editing, supervision. Debra Ehrlich: conceptualization, funding acquisition, writing – review and editing, supervision.

Ethics Statement

This study involves human participants, and the protocol (Diagnosis and Natural History Protocol for Patients with Different Neurological Conditions, protocol number 93‐N‐0202) was approved by the Institutional Review Board at the National Institutes of Health (NIH). The patient provided written informed consent.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Appendix S1.

Ni Z., Halhouli O., Cho H. J., Hallett M., and Ehrlich D., “Clinical Neurophysiological Study for the Diagnosis of Functional Cranial–Cervical Dystonia,” European Journal of Neurology 32, no. 8 (2025): e70287, 10.1111/ene.70287.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.