Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

Adaptation to tonic heat in healthy subjects and patients with sensory polyneuropathy.

Background Adaptation to a constant sensory stimulus involves many sites along the path of sensory volleys towards perception. The evaluation of such phenomenon may be of clinical interest. We studied adaptation to a constant temperature stimulus in healthy subjects to set normative data and in patients with sensory polyneuropathy (SPN), as proof of concept. Methods Twenty-six healthy subjects and 26 patients with SPN in the context of chemotherapy treatment with oxaliplatin for colon cancer were instructed to express through an electronic VAS system (eVAS); the level of sensation felt when a thermode set at either 39º, 41º, 43º, 45º or 47º was applied to their ventral forearm. Results The eVAS recordings showed typically an abrupt onset that slowed to approach maximum sensation and continued with a slow decrease indicating adaptation. The time to respond (TR), the velocity of the initial response (VR), the maximum sensation (MA), the time to reach MA (MAt), the onset of adaptation (AO) and the decrease in the sensation level with respect to MA at 30 s after stimulus application (SL30), were dependent on the temperature level in all subjects. However, patients showed significantly delayed TR, slowed VR, decreased MA, delayed AO and reduced SL30, with respect to healthy subjects. Differences were more pronounced at low-temperature levels, with absent AO in 25 patients versus 2 healthy subjects at temperatures of 39º and 41ºC. Conclusion The study of adaptation to a constant temperature stimulus can furnish valuable data for the assessment of patients with SPN. SIGNIFICANCE: We studied perceptual changes in the intensity of thermoalgesic sensation during 30 s of constant temperature stimulation after an abrupt initial contact in healthy subjects and patients with sensory polyneuropathy. Patients showed delayed time to respond, decreased maximal sensation and reduced adaptation with respect to healthy subjects. Differences were more pronounced at low and intermediate temperatures (39ºC to 43ºC). The method is of easy implementation and shows clinically relevant abnormalities in patients with sensory polyneuropathy.

Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background.

Noninvasive Brain Stimulation and Noninvasive Peripheral Stimulation for Neglect Syndrome Following Acquired Brain Injury.

OBJECTIVE: Hemispatial neglect is a frequent condition usually following nondominant hemispheric brain injury. It strongly affects rehabilitation strategies and everyday life activities. It is associated with behavioral and cognitive disability with a strong impact on patient's life. METHODS: We reviewed the published literature on the use of noninvasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), and of noninvasive peripheral muscle stimulation, as therapeutic strategies for rehabilitation of neglect after acquired brain injury, such as in stroke or in traumatic injuries. The studies were grouped as controlled or uncontrolled studies in each stimulation techniques. RESULTS: Thirty-four studies were identified and 16 on rTMS, 10 on tDCS, and 8 on vibration. All studies were conducted in adult patients who suffered a stroke, except for one that was conducted in a patient suffering traumatic acquired brain injury and another that was conducted in a patient with brain tumor. In spite of significant variability in treatment protocols, patients' features and assessment of neglect, improvement was reported in almost all studies with no side-effects. CONCLUSIONS: Noninvasive brain stimulation and neuromuscular vibration are promising therapeutic neuromodulatory approaches for neglect. Further randomized-controlled studies are needed to corroborate their effectiveness as separate and combined techniques.

Prepulse inhibition of the blink reflex is abnormal in functional movement disorders.

BACKGROUND: Patients with functional movement disorders also typically have functional somatic symptoms, including pain, fatigue, and sensory disturbance. A potentially unifying mechanism for such symptoms is a failure in processing of sensory inputs. Prepulse inhibition is a neurophysiological method that allows for the study of preconscious somatosensory processing. OBJECTIVE: The objective of this study was to assess prepulse inhibition in patients with functional movement disorders and healthy control subjects. METHODS: We analyzed the effect of a weak electrical stimulus to the index finger (prepulse) on the magnitude of the R2 response of the blink reflex induced by electrical stimuli delivered to the supraorbital nerve in 22 patients with clinically established functional movement disorders and 22 matched controls. Pain, depression, anxiety, and obsessive-compulsive symptoms were assessed using self-rated questionnaires. In addition, in patients we assessed motor symptom severity. RESULTS: Prepulses suppressed the R2 response of the blink reflex in both groups, by 36.4% (standard deviation: 25.6) in patients and by 67.3% (standard deviation: 16.4) in controls. This difference was significant (P < 0.001). There was no significant correlation between motor and nonmotor symptom measures and prepulse inhibition size. CONCLUSIONS: Impaired prepulse inhibition of the blink reflex suggests an abnormal preconscious processing of somatosensory inputs, which can be interpreted within predictive coding accounts of both functional movement disorders and functional somatic syndromes. Our results, along with previous findings of a reduced prepulse inhibition in fibromyalgia syndrome, support a possible unified pathophysiology across functional neurological and somatic syndromes with noteworthy implications for diagnostic classification and development of novel biomarkers and treatments. © 2019 International Parkinson and Movement Disorder Society.

Cutaneous silent periods - Part 2: Update on pathophysiology and clinical utility.

Testing of exteroceptive electromyographic modulation of ongoing voluntary muscle activity is of increasing interest as a diagnostic tool in clinical neurophysiology. The cutaneous silent period (CSP) is a robust and reproducible nociceptive EMG suppression, mediated at the spinal level by small-diameter A-delta afferents. The techniques and physiological principles of CSP testing, which are a fundamental prerequisite for a valid and thoughtful clinical application, are reviewed separately in part 1 (Kofler et al., 2019). This comprehensive review surveys the literature on pathophysiological conditions in which CSPs have been reported, and aims at a critical overview on the clinical utility of CSP testing. The most useful clinical applications seem to be the functional diagnostics of intramedullary, in particular centromedullary, dysfunctions, and the assessment of small fiber neuropathies, in particular those affecting A-delta fibers. CSPs have in addition been studied in a variety of movement disorders and in neuropathic pain and other painful conditions, including fibromyalgia.

Unilateral pallidal stimulation for disabling dystonia due to Rasmussen's disease.

OBJECTIVE: To describe an adult patient with Rasmussen's disease with focal dystonia as the most disabling symptom and the good response to unilateral globus pallidus internus (GPi) deep brain stimulation (DBS). METHODS: Retrospective review of clinical records and diagnostic tests. RESULTS: The patient had displayedmild focal seizures with sensory and motor symptoms on the left arm and hemiface since the age of 22. Ten years later she experienced abrupt onset of focal left dystonia involving mainly the leg. Brain MRI showed progressive right hemisphere atrophy, and  18 fluorodeoxyglucose-positron emission tomography (18FDG-PET) showed right hypometabolism mainly over the frontal and insular regions. Brain biopsy confirmed chronic encephalitis. The dystonia became very severe and made walking extremely difficult. Different treatments including dopaminergic, anticholinergic, immunomodulatory drugs and botulinum toxin were ineffective. Finally the patient was treated with unilateral GPi DBS. Shortly after the onset of the stimulation, the dystonia started to improve. Parameters have been adjusted, and 18 months after surgery the patient is able to walk and run unaided, although a mild left leg dystonia persists. CONCLUSION: Rasmussen's disease may be difficult to diagnose in adult patients. Associated movement disorders may be more disabling than seizures. Focal dystonia may be treated successfully with DBS.

Evidence of neurophysiological improvement of early manifestations of small-fiber dysfunction after liver transplantation in a patient with familial amyloid neuropathy.

INTRODUCTION: Small fiber polyneuropathy (SFP) is a common heralding clinical manifestation of damage to the nervous system in patients with familial amyloidosis. The diagnosis of SFP is a significant factor in the decision to treat a previously asymptomatic gene carrier, as treatment would prevent irreversible nerve damage. This requires detection of the earliest but unequivocal signs of peripheral nerve involvement. CASE REPORT: We present the case of a young female who was diagnosed of SFP, supported by data from quantitative sensory testing. She had preserved sensory nerve action potentials in the distalmost nerves of her feet and recordable nociceptive evoked potentials. She was successfully transplanted the liver from a previously healthy donor, and recovered fully of her symptoms and signs. Improvement was documented with repeated psychophysical and electrodiagnostic testing in the course of 4 years after transplantation. SIGNIFICANCE: This case illustrates the utility of psychophysical testing to support the diagnosis of SFP.

Clinical utility of contact heat evoked potentials (CHEPs) in a case of mentalis nerve lesion.

OBJECTIVE: Nociceptive evoked potentials are still infrequently used in electrodiagnostic studies of single patients. We report a case in which the results of contact heat evoked potentials (CHEPs) provided unique information for the diagnosis. METHODS: After biopsy for a local cementoma, a 21-year-old woman presented with neuropathic pain in the distribution of her left mentalis nerve. A CT scan showed a well circumscribed lesion near the mentalis nerve groove. We examined brainstem reflexes and evoked potentials conveyed through the mentalis nerve. RESULTS: Blink reflex responses recorded from the orbicularis oculi, jaw jerk and masseteric silent period recorded from the masseter muscles and long latency evoked potentials recorded from Cz to electrical stimulation of the mentalis nerve were all within normal values, with no differences between sides. However, CHEPs, recorded from Cz to thermoalgesic stimulation of the left mentalis area were decreased to approximately 1/3 their size in comparison to stimulation to the unaffected side. CONCLUSION: While the patient reported symptoms and had neuroimaging signs of mentalis neuropathy, the sole electrophysiological abnormality identified was that of CHEPs, which specifically test small, unmyelinated fibers. SIGNIFICANCE: Nociceptive evoked potentials can provide unique information on damage of small nerve fibers in specific cases.

Cutaneous autonomic denervation in Parkinson's disease.

Numerous studies have detailed involvement of the peripheral autonomic nervous system (PANS) in Parkinson's disease (PD). We assessed autonomic innervation of dermal annexes through quantitative fluorescence measurement from skin obtained via punch biopsies at distal leg region in PD and control subjects. We defined a ratio between the area corresponding to protein gen product (PGP) immunoreactivity and the area corresponding to blood vessel or sweat gland as a quantitative measure of autonomic innervation. Presence of alpha-synuclein (AS) deposits in dermis and hypodermis was also assessed by immunohistochemistry. Skin biopsies form six PD patients and six healthy controls were studied. Autonomic innervation scores were lower in PD than in controls in both blood vessels and sweat glands. No AS or phosphorylated AS (pAS) immunoreactivity was detected in dermis or hypodermis in any of the studied subjects. The results of this investigation suggest that autonomic innervation of dermal annexes in living patients with PD is reduced compared to controls. AS or pAS deposits were not found in dermis or hypodermis suggesting that distal leg skin study is not useful for in vivo detection of AS in PD.

Mitochondrial loss indicates early axonal damage in small fiber neuropathies.

Evaluation of nerve fibers in the skin provides a useful tool for the diagnosis of small fiber neuropathies (SFNs). Our aim was to determine whether mitochondria are involved in SFN, indicating early axonal damage. We quantified mitochondrial respiratory chain complex IV (OXPHOS) and axonal (PGP 9.5) fluorescence on skin sections from 32 SFN patients and 14 healthy controls. Also, a group of six patients were recruited before and after 30-day treatment with the mitotoxic antibiotic linezolid. We measured the co-localization of OXPHOS within the intraepidermal and subpapillary dermal axons (PGP-immunoreactive [PGP-ir]). SFN patients with relatively preserved intraepidermal nerve fibers (SFN borderline) showed statistically significant reduction of OXPHOS (50.5 ± 33.9 µm(2) vs. 107.6 ± 81 µm(2) in controls, p < 0.02). A positive correlation was found between both PGP-ir and OXPHOS in controls (Pearson's coefficient r = 0.59, p < 0.001), whereas such correlation was absent in SFN. With respect to baseline measurements, linezolid therapy increased both PGP-ir and OXPHOS, which could be considered an initial compensatory toxic-induced response. This study set out to identify a possible marker of axonal pre-degenerative state in SFN borderline patients.

Epidermal Langerhans cells in small fiber neuropathies.

We quantified the immune histiocytic Langerhans cells (LCs) in skin biopsy samples of patients with distal small fiber neuropathy (SFN). Patients were divided according to the presence or absence of neuropathic pain (burning pain) assessed by a visual analogue scale (VAS). We studied 13 diabetic patients (pain-DSFN), 7 nondiabetic patients (pain-SFN) who reported relevant neuropathic pain (VAS ≥ 3), and 6 nondiabetic patients without neuropathic pain (no-pain-SFN). Using double immunofluorohistochemistry with the PGP 9.5 and the langerin/CD207, we quantified the intraepidermal nerve fibers density (IENFD) and LCs per square millimeter in the epidermis. A group of 10 skin samples from healthy subjects served as controls. Confocal analysis was performed to evaluate LC PGP 9.5-immunoreactivity. We found a mean value of 334.3LC/mm(2) in controls, 310.2LC/mm(2) in no-pain-SFN, 329.6LC/mm(2) in pain-SFN and 484.3LC/mm(2) in pain-DSFN (analysis of variance; P=.01). In patients, analysis of covariance adjusted by different covariables showed that the presence of diabetes (F=5.2, P=.03) was associated with an increased number of LC/mm(2). There was a negative correlation between the IENFD and the number of LCs (r(2)=-0.13, P=.03). No statistically significant differences were found among groups of subjects either for the co-localization or for the number of LCs that were PGP 9.5-immunoreactive (analysis of variance; P>.05). These results indicate that patients with neuropathic pain in the context of SFN, specially those who had diabetes (DSFN), had an increased number of LCs in the epidermis that may play a role in the generation or maintenance of neuropathic pain.

No clinical or electrophysiologic evidence of nerve injury after intraneural injection during sciatic popliteal block.

BACKGROUND: Intraneural injection during nerve-stimulator-guided sciatic block at the popliteal fossa may be a common occurrence. Although intraneural injections have not resulted in clinically detectable neurologic injury in small studies in human subjects, intraneural injections result in postinjection inflammation in animal models. This study used clinical, imaging, and electrophysiologic measures to evaluate the occurrence of any subclinical neurologic injury in patients with intraneural injection during sciatic popliteal block. METHODS: Twenty patients undergoing popliteal block were enrolled; 17 patients completed the study protocol. After tibial nerve response was achieved by nerve stimulation (0.3-0.5 mA; 2 Hz; 0.1 ms), 20 ml mixture of mepivacaine (1.25%) and radiopaque contrast (2 ml) were injected. Location and spread of the injectant were assessed by ultrasound measurements of the sciatic nerve area before and after injection, and by computed tomography. In addition to clinical neurologic evaluations, serial electrophysiologic studies (nerve conduction and late response studies using predefined criteria) were performed at baseline and at 1 week and 3 weeks after the block for signs of subclinical neurologic dysfunction. RESULTS: Sixteen injections (94%, 95% CI: 71-100%) met criteria for an intraneural injection. Postinjection nerve area on ultrasound increased by 45% (95% CI: 29-58%), P < 0.001. Computed tomography demonstrated fascicular separation in 70% (95% CI: 44-90%), air within the nerve in 29% (95% CI: 10-56%), contrast along bifurcations in 65% (95% CI: 38-86%), and concentric contrast layers in 100% (95% CI: 84-100%). Neither clinical nor electrophysiologic studies detected neurologic dysfunction indicating injury to the nerve. CONCLUSIONS: Nerve-stimulator-guided sciatic block at the popliteal fossa often results in intraneural injection that may not lead to clinical or electrophysiologic nerve injury.

On the relationship between nociceptive evoked potentials and intraepidermal nerve fiber density in painful sensory polyneuropathies.

This study analyzed the relationship between the density of intraepidermal nerve fibers (IENF) and the characteristics of either nociceptive laser-evoked potentials (LEPs) or contact heat-evoked potentials (CHEPs) in patients with painful sensory polyneuropathy with the aim to determine which parameters of LEPs and CHEPs more reliably reflect IENF loss. A total of 96 patients and 35 healthy volunteers took part in the study. Based on clinical examination, nerve conduction tests, and quantitative sensory testing, we identified 52 patients with small-fiber neuropathy (SFN), 40 with mixed (small-fiber and large-fiber) neuropathy (MFN), and 4 who were excluded from the analysis because of no evidence of involvement of small fibers. The latency of the N2 was delayed for both LEPs and CHEPs in patients with MFN and for CHEPs only in patients with SFN. The amplitude of the vertex N2/P2 potential was similarly reduced in both types of neuropathy, but LEPs were more frequently absent than CHEPs in MFN patients (68% vs 40%). In general, latency and amplitude of LEPs and CHEPs were well correlated with IENF density. SFN patients were characterized by abnormal EPs and slightly decreased but morphologically abnormal IENF. MFN patients were characterized by frequently absent LEPs and CHEPs and a rather severe IENF loss. The correlation between nociceptive evoked potentials (laser-evoked potentials and contact heat-evoked potentials) and skin biopsy aids in the diagnosis of painful neuropathies.

Abnormal modulation of electrodermal activity by thermoalgesic stimuli in patients with primary palmar hyperhidrosis.

BACKGROUND: The authors examined the effects of thermal stimulation on electrodermal activity (EDA) in patients with primary palmar hyperhidrosis (PPH). The authors hypothesised that temperature changes may induce abnormal sudomotor reactions because of simultaneous activation of sudomotor centres through thermal and emotional pathways, and compared patients before and after thoracoscopic sympathectomy. METHODS: The authors studied 18 PPH patients and 20 controls. Patients reported subjective evaluation of their symptoms using a visual analogue scale for palmar sweating and for body sweating (bs-VAS). The authors applied focal thermal stimulation to quantify sensory perception and measure ongoing changes in EDA recorded from the palm of the hands. RESULTS: Before sympathectomy, patients had lower sensory perception thresholds and higher EDA levels than controls. Increased EDA occurred along the whole test, with no significant modulation by changes in thermal stimulation. Sensory perception normalised after sympathectomy, but thermal modulation of EDA remained abnormal whenever sudomotor activity was present after surgery. There was a significant positive correlation between EDA levels before treatment and the bs-VAS (from r=0.45 to r=0.57). CONCLUSIONS: Patients with PPH show perceptual abnormalities and exaggerated sudomotor reactions to thermoalgesic stimulation, consistent with central sensitisation of sympathetic circuits. The reduced sympathetic outflow after thoracoscopic sympathectomy induced normalisation of sensory perception, but it did not modify the abnormal control of efferent sudomotor activity.

C-nociceptors sensitized to cold in a patient with small-fiber neuropathy and cold allodynia.

Cold allodynia is a common sign of neuropathic pain patients but its underlying mechanisms are still largely unknown, partly because the populations of neurons responding to cold stimuli and their transduction mechanisms have not been fully determined. We report a patient with a small-fiber neuropathy of unknown origin, whose main complaint is cold allodynia. Microneurographic recordings showed ongoing spontaneous activity and abnormal responses to cold and menthol in identified subtypes of C-nociceptors. These findings provide the first direct evidence in human of abnormal peripheral nociceptor behavior potentially responsible for cold allodynia. The responsiveness of C-nociceptors to menthol suggests an abnormal expression or function of TRPM8 channels in this patient with a small-fiber polyneuropathy.

Electrophysiologic studies and clinical findings in females with combined fecal and urinary incontinence: a prospective study.

PURPOSE: Several clinical, urodynamic, and manometric findings suggest neurologic damage as a contributing factor in the development of combined fecal and urinary incontinence. In this study, we wanted to test the hypothesis of pudendal nerve neuropathy being a more frequent lesion in patients with double incontinence compared with patients with isolated fecal incontinence. PATIENTS: Ninety-three females with combined fecal and urinary incontinence and 36 females with isolated fecal incontinence were investigated. All patients underwent anal manometry, endoanal ultrasound, electromyography, and pudendal nerve terminal motor latency. RESULTS: No statistically significant differences were found in the age, history of vaginal delivery, and chronic straining between both groups. However, the rate of postmenopausal females was higher in the combined fecal and urinary incontinence group (85 vs. 67 percent; P = 0.02). Menopause was an independent risk factor of having double incontinence (odds ratio, 1.4; P = 0.02). Concentric needle electromyography of the external anal sphincter revealed increased duration of the motor unit potentials in 43 and 53 percent of patients with combined fecal and urinary incontinence and isolated fecal incontinence, respectively (P = 0.28). An increased number of polyphasic motor unit potentials was detected in 52 and 58 percent (P = 0.6). There was no statistically significant difference in the prevalence of bilateral (20 vs. 27 percent) or unilateral (23 vs. 14 percent) prolonged mean pudendal nerve terminal motor latency between both groups (P = 0.3). CONCLUSIONS: Pudendal neuropathy is not a distinct characteristic of patients with double incontinence. The prevalence of pudendal neuropathy in these patients is similar to that observed in patients with isolated fecal incontinence. Others factors should be investigated to explain the common association of both types of incontinence.

Chewing pattern in patients with Meige's syndrome.

Meige's syndrome presents with a combination of upper and lower facial motor dysfunction, including eye closing spasms and oromandibular dystonia. While the pathophysiology of eye closing spasms has been extensively studied using the blink reflex and other trigeminofacial reflexes, very few studies have been carried out with regard to the abnormal perioral movements. We hypothesized that action-related dystonic features could be revealed by the analysis of the semiautomatic rhythmic movements required for chewing and swallowing. A total of 7 patients with Meige's syndrome that complained of chewing problems and 7 age-matched healthy volunteers were studied. Subjects were instructed to munch and swallow a small muffin while surface electromyographic (EMG) activity of masseter (MAS) and orbicularis oris (OOr) of the dominant side was recorded. In healthy subjects, MAS and OOr showed a rhythmic alternating phasic EMG pattern during chewing, which changed to a tonic cocontraction of both muscles during swallowing. Mean duration of MAS and OOr EMG bursts was, respectively, 297 +/- 28 msec and 328 +/- 29 msec. Patients exhibited the following alterations: excess duration of muscle activity, frequent cocontraction, loss of rhythmicity during chewing, and abnormalities in the chewing to swallowing transition phase. These abnormalities, similar in type to those encountered in other forms of focal dystonia, may be the expression of an abnormal motor control of basal ganglia over mastication-related movement pattern generators of the brainstem.