Botulinum toxin: State of the art.

Botulinun neurotoxin (BoNT) has emerged as one of the most multipurpose therapeutic agents in modern medicine with more clinical applications than any other drug currently on the market. Initially developed in the treatment of strabismus and neurologic movement disorders, the use of botulinun neurotoxin has been expanding during the past 3 decades to include the treatment of a variety of ophthalmologic, gastrointestinal, urologic, orthopedic, dermatologic, dental, secretory, painful, cosmetic, and other conditions. In addition to onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), incobotulinumtoxinA (Xeomin), and RimabotulinumtoxinB (Myobloc or NeuroBloc) there are other novel botulinun neurotoxin products currently in development. With a better understanding of the cellular mechanisms of botulinun neurotoxin and advances in biotechnology, future botulinun neurotoxin products will likely be even more effective and customized to the specific indication and tailored to the needs of the patients. © 2017 International Parkinson and Movement Disorder Society.

Bruxism in Movement Disorders: A Comprehensive Review.

Bruxism is an abnormal repetitive movement disorder characterized by jaw clenching and tooth gnashing or grinding. It is classified into two overlapping types: awake bruxism (AB) and sleep bruxism (SB). Theories on factors causing bruxism are a matter of controversy, but a line of evidence suggests that it may to some extent be linked to basal ganglia dysfunction although so far, this topic has received little attention. The purpose of this article was to review cases of bruxism reported in various movement disorders. The biomedical literature was searched for publications reporting the association of bruxism with various types of movement disorders. As a whole, very few series were found, and most papers corresponded to clinical reports. In Parkinsonian syndromes, AB was rarely reported, but seems to be exacerbated by medical treatment, whereas SB is mainly observed during non-REM sleep, as in restless leg syndrome. AB is occasionally reported in Huntington's disease, primary dystonia, and secondary dystonia; however, its highest incidence and severity is reported in syndromes combining stereotypies and cognitive impairment, such as Rett's syndrome (97%), Down syndrome (42%), and autistic spectrum disorders (32%). Taken as a whole, AB seems to be more frequent in hyperkinetic movement disorders, notably those with stereotypies, and is influenced by anxiety, suggesting an involvement of the limbic part of the basal ganglia in its pathophysiology.

Electroconvulsive therapy for a patient with persistent tardive dyskinesia: a case report and literature review.

Tardive dyskinesia (TD) is a movement disorder that presents with abnormal, involuntary, and irregular choreoathetoid movements involving mouth, tongue, face, trunk, or extremities after prolonged use of dopamine receptor-blocking agents. Currently, there is still a lack of effective treatment for it. Here, we report a female patient with paranoid schizophrenia, who has had persistent TD for 8 years. After electroconvulsive therapy (ECT) was performed, both of her psychotic symptoms and dyskinetic movements were improved. The efficacy and potential clinical variables of ECT in the treatment of TD were reviewed.

Psychogenic facial movement disorders: clinical features and associated conditions.

The facial phenotype of psychogenic movement disorders has not been fully characterized. Seven tertiary-referral movement disorders centers using a standardized data collection on a computerized database performed a retrospective chart review of psychogenic movement disorders involving the face. Patients with organic forms of facial dystonia or any medical or neurological disorder known to affect facial muscles were excluded. Sixty-one patients fulfilled the inclusion criteria for psychogenic facial movement disorders (91.8% females; age: 37.0 ± 11.3 years). Phasic or tonic muscular spasms resembling dystonia were documented in all patients most commonly involving the lips (60.7%), followed by eyelids (50.8%), perinasal region (16.4%), and forehead (9.8%). The most common pattern consisted of tonic, sustained, lateral, and/or downward protrusion of one side of the lower lip with ipsilateral jaw deviation (84.3%). Ipsi- or contralateral blepharospasm and excessive platysma contraction occurred in isolation or combined with fixed lip dystonia (60.7%). Spasms were reported as painful in 24.6% of cases. Symptom onset was abrupt in most cases (80.3%), with at least 1 precipitating psychological stress or trauma identified in 57.4%. Associated body regions involved included upper limbs (29.5%), neck (16.4%), lower limbs (16.4%), and trunk (4.9%). There were fluctuations in severity and spontaneous exacerbations and remissions (60%). Prevalent comorbidities included depression (38.0%) and tension headache (26.4%). Fixed jaw and/or lip deviation is a characteristic pattern of psychogenic facial movement disorders, occurring in isolation or in combination with other psychogenic movement disorders or other psychogenic features.

Clinical Reasoning: A 43-Year-Old Man With Subacute Onset of Vision Disturbances, Jaw Spasms, and Balance and Sleep Difficulties.

A brainstem syndrome is recognizable in patients presenting with a combination of visual disturbances, incoordination, gait problems, speech and swallowing difficulties, and new-onset sleep symptomatology. Brainstem disorders of subacute onset (onset and progression with accumulation of disabling deficits in 6-12 weeks) are generally of autoimmune, infectious, inflammatory, or infiltrative neoplastic cause. An autoimmune or infectious brainstem disorder may be referred to as brainstem encephalitis or rhombencephalitis. We describe a patient with paraneoplastic autoimmune rhombencephalitis, in whom diagnostic clues included the following: diverse visual and sleep symptoms, trismus, and choking in the history; see-saw nystagmus, opsoclonus, dysarthria, jaw dystonia, and episodic laryngospasm on examination; subtle but longitudinal and nonenhancing T2 MRI abnormalities in the brainstem and upper cervical cord; and oligoclonal bands in the CSF. His movement disorder-specific neural IgG profile revealed ANNA-2 (anti-Ri) and KLHL-11-IgG. Both are biomarkers of paraneoplastic brainstem encephalitis. KLCHL-11-IgG has been reported to accompany germ cell tumors, which was found in a solitary metastasis to the left inguinal lymph node in our patient, along with an atrophic left testis. Multidisciplinary treatment (autoimmune neurology, sleep medicine, ophthalmology, and physiatry) led to significant clinical improvements. This case provides a framework for the evaluation of patients with subacute-onset brainstem syndromes and the investigation and management of those with paraneoplastic and other autoimmune diseases.

Sleep-associated movement disorders and heart failure.

Sleep-associated movement disorders are a broad group of sleep disorders characterized by involuntary movements that may disrupt sleep. Relatively little is known about the clinical consequences of sleep-associated movement disorders on cardiovascular health. Because these disorders manifest mostly during sleep, recognizing a movement disorder can be particularly difficult. Nevertheless, patients can have frequent arousals and suffer from similar sleep deprivation, fragmentation, and autonomic disruption as occurs in sleep-disordered breathing. Subsequently, these disorders may have a serious impact on daytime function and perception of health in patients with chronic heart failure.

Normal cognitive functions in joubert syndrome.

Developmental delay and subsequent impaired cognitive functions are present in almost all patients with Joubert syndrome (JS). We report on a 20-year-old woman with mild clinical signs of JS (minimal truncal ataxia and oculomotor apraxia) but typical molar tooth sign on neuroimaging, normal full scale (IQ=93), verbal (IQ=93), and performance intelligence quotient (IQ=94). Only minor difficulties in visual-spatial organization and in some executive functions could be detected. This pattern of deficits is partly reminiscent of the cerebellar cognitive affective syndrome. Her diagnosis was only reached following the diagnosis of JS in two brothers with severe cognitive impairment. Molecular investigations demonstrated a homozygous mutation in the INPP5E gene. This exceptional observation confirms that normal cognitive functions are possible in JS and corroborates the well known intrafamilial variability.

Drooling in cerebral palsy: hypersalivation or dysfunctional oral motor control?

AIM: To investigate whether drooling in children with cerebral palsy (CP) in general and in CP subtypes is due to hypersalivation. METHOD: Saliva was collected from 61 healthy children (30 males, mean age 9y 5mo [SD 11mo]; 31 females, mean age 9y 6mo [1y 2mo]) and 100 children with CP who drooled (57 males, mean age 9y 5mo [3y 11mo], range 3-19y; 43 females, mean age 10y 1mo [4y 9mo], range 4-19y), of whom 53 had spastic, 42 had dyskinetic, and five had ataxic CP. Almost all children were affected bilaterally, and 90 of them were at Gross Motor Function Classification System levels III or higher. The saliva was collected by the swab saliva collection method. The intensity of drooling was evaluated using the drooling quotient. RESULTS: No difference was found in the flow rates, age, or sex between healthy children and children with CP who drooled. On additional subgroup analysis, the flow rates of children with dyskinetic CP differed statistically from those of healthy children (submandibular p=0.047, parotid p=0.040). INTERPRETATION: This study supports the finding in previous studies that no hypersalivation exists in children with CP who drool. Dysfunctional oral motor control seems to be responsible for saliva overflow from the mouth, whereas increased unstimulated salivary flow may occur in children with dyskinetic CP as a result of hyperkinetic oral movements.

Cranial movement disorders: clinical features, pathophysiology, differential diagnosis and treatment.

Cranial movement disorders are a common neurological problem. These disorders can be limited to the cranial muscles alone or manifest as part of a more generalized movement disorder. Cranial movement disorders can originate from the highest (motor cortex) to the lowest (cranial nerve and muscle) levels of the motor system. Owing to the lack of diagnostic tests and biomarkers for these disorders, their differential diagnosis can be difficult even for the experienced neurologist. Advances have, however, been made in the identification and treatment of these conditions, and most can be managed effectively with appropriate knowledge of the diagnostic signs and effective treatments. Here, we review the clinical features, pathophysiologies and therapies of the main movement disorders that affect the face, jaw, tongue and palate.

Joubert syndrome associated with new MRI findings and posterior reversible encephalopathy syndrome.

Joubert syndrome (JS) is an inherited disorder characterized by transient episodic hyperpnea, ataxia, and vermian hypoplasia. Typical imaging findings of JS include hypoplasia or aplasia of the cerebellar vermis, thick and elongated superior cerebellarpeduncles and an abnormally deep interpeduncular fossa with 'molar tooth sign'. We present a case of JS associated with deep cerebral sulci and fissures, polymicrogyria, and additional findings of posterior reversible encephalopathy syndrome associated with renal involvement.

Pain and denture condition in edentulous orodyskinesia: comparisons with tardive dyskinesia and control subjects.

Edentulous orodyskinesia (ED) is a neglected source of aimless oral movements that may be confused with tardive dyskinesia (TD). We attempted to clarify the clinical features, significance, and orodental factors in relation to ED. Fourteen ED subjects, 13 TD patients, and 15 age-matched controls self-assessed their oral pain perception, condition, and function using a visual analogue scale. Dyskinesias were classified and rated by a neurologist. Perioral thermal and pressure pain threshold studies, and a standardized orodental examination, were conducted blind to subject group. The perceived oral pain level was low in all groups, and those reporting a significant intensity level of pain (>or=50th percentile) were few. The pain thresholds in both dyskinetic groups were comparable to control values. All ED cases wore a complete set of dentures, considered a current source of problems by 85.7% of them. ED cases commonly displayed inadequate dental occlusal relationship (P = 0.014 vs. controls; P = 0.036 vs. TD) and an overclosed vertical dimension (P = 0.006 vs. controls) as well as unstable and unretentive dentures. ED was limited to the oral region, spared the tongue when the mouth is open, and was never severe in our patients. ED has distinct movement characteristics and is often associated with inadequate dentures and biomechanical sources of denture instability. The contribution of the foregoing findings to the expression of oral dyskinesia warrants further studies.

Athetoid Movements as Initial Manifestation of Primary Sjögren Syndrome.

Background: Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by exocrine gland and extraglandular symptoms. We present a case report of pSS with an initial presentation of athetoid movements. Case Report: A 74-year-old female presented with a 2-month history of slow undulating movements in her trunk and thighs that eventually spread to her neck and lower extremities. She also reported dry eyes, dry mouth, as well as pain in her shoulders and thighs. Her proinflammatory markers and rheumatologic profile were positive. Her salivary gland biopsy revealed a Focus score > 2. Brain magnetic resonance imaging was normal. A diagnosis of pSS was made. The patient's symptoms improved with hydroxychloroquine, pilocarpine, gabapentin, and clonazepam. Discussion: Clinicians should consider and screen for primary autoimmune disorders as a cause of subacute athetoid movements in elderly patients. Although aggressive treatment has been recommended, treatment should be tailored to each patient's specific needs.

Dental implications of some common movement disorders: a concise review.

Movement disorders - or dyskinesias - are characterized by involuntary movements. Despite the major role for medical specialists in the diagnosis and treatment of dyskinesias, dentists are confronted with such disorders as well. Unfortunately, the literature regarding the dental implications of movement disorders is still scarce. This concise review describes the dental implications of some common dyskinesias, viz., Gilles de la Tourette's syndrome, Huntington's disease, idiopathic torsion dystonia, oral dyskinesias, and Parkinson's disease. It was concluded that these dyskinesias may have profound dental implications. Not only do generalized dyskinesias have focal manifestations in the orofacial region, but there are also dyskinesias that exclusively affect the orofacial area. The oral manifestations of dyskinesias are in part directly related to the disorder, and in part medicine-related. Dentists should be able to recognize the oral manifestations and, when properly trained, to manage them adequately. In most instances, a multidisciplinary approach upon referral is necessary, including the medical specialists involved. Unfortunately, the level of evidence of the selected papers was generally low. In our rapidly ageing population, it is a challenge for all of us to improve the quality of this emerging field, for the sake of this sometimes heavily infirmed category of patients.

Influence of continual biofeedback on jaw pursuit-tracking in healthy adults and in adults with apraxia plus aphasia.

Apraxia of speech (AOS) is a disorder of motor programming resulting from damage to premotor or anterior insula cortex. The authors used a pursuit visuomotor tracking task to test whether such a disorder interferes with development of motor programs or with modification of existing programs via integration of feedback. Healthy older adults (n = 15) and adults with AOS plus aphasia and nonverbal apraxia (n = 8) performed a jaw movement task with (a) continuous visual feedback of a target movement pattern and their jaw movement and (b) no feedback. Healthy speakers were more accurate and less variable with feedback, suggesting accurate development of a program and feedback integration. Apraxic individuals' performance accuracy and response to feedback suggested that the neurological damage impairs both development of new programs and efficient integration of feedback.

The characteristics of salivary pepsin in patients with severe motor and intellectual disabilities.

PURPOSE: The aim of the present study was to determine the utility of measuring the salivary pepsin level (SPL) as an objective assessment of gastroesophageal reflux disease (GERD) in severe motor and intellectual disabilities (SMID) patients. SUBJECTS AND METHODS: This prospective study included 26 SMID patients who underwent simultaneous 24-h multichannel intraluminal impedance pH measurement (pH/MII) and SPL evaluation. The enrolled patients were divided into GERD (+) or GERD (-) groups according to the pH/MII findings. The age, gender and pH/MII parameters were compared between the two groups. A correlation analysis was also conducted for the SPL following early-morning fasting and post-enteral feeding and the age, gender, presence of gastrostomy and tracheostomy and pH/MII parameters. The SPL was compared between the two sampling groups. RESULTS: Fifteen patients were classified as GERD (+), and 11 patients were classified as GERD (-). The mean SPL following early-morning fasting and post-enteral feeding among all patients were 104.3 (median: 38, 25th and 75th percentile: 12, 361) ng/ml and 222.2 (median: 152:0, 500) ng/ml, respectively. Regarding positivity, 76.9% and 73.1% of SPL values in early-morning fasting and post-enteral feeding SMID patients, respectively, were positive (≧16ng/ml). The SPL following early-morning fasting demonstrated a weak but significant positive correlation with age. In contrast, we noted no correlation between the pH/MII parameters and the SPL for either the early-morning fasting or post-enteral feeding patients, and no significant difference in the SPL was observed between the GERD (+) and (-) patients. CONCLUSIONS: The present study showed that a high proportion of SMID patients had a relatively high SPL, regardless of the presence of GERD. The SPL in SMID patients might be affected by several distinctive factors in addition to gastroesophageal reflux.

Congenital Mirror Movements in Gorlin Syndrome: A Case Report With DTI and Functional MRI Features.

Congenital mirror movements are rare conditions that define the inability to perform unimanual movements. Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a genetic disorder with multiple nevi predisposing to basal cell carcinoma, odontogenic keratocysts, and skeletal malformations. Herein we report on an adolescent patient with Gorlin syndrome and coexisting congenital mirror movements. To our knowledge, this is the first patient in the literature who has both of these very rare conditions.

The syndrome of fixed dystonia: an evaluation of 103 patients.

We describe the clinical features of 103 patients presenting with fixed dystonia and report the prospective assessment and investigation of 41 of them. Most patients were female (84%) and had a young age of onset [mean 29.7 (SD 13.1) years]. A peripheral injury preceded onset in 63% and spread of dystonia to other body regions occurred in 56%. After an average follow-up of 3.3 years (overall disease duration 8.6 years), partial (19%) or complete (8%) remission had occurred in a minority of patients. The fixed postures affected predominantly the limbs (90%), and rarely the neck/shoulder region (6%) or jaw (4%). In the prospectively studied group, pain was present in most patients and was a major complaint in 41%. Twenty percent of patients fulfilled criteria for Complex Regional Pain Syndrome (CRPS). No consistent investigational abnormalities were found and no patient tested (n = 25) had a mutation in the DYT1 gene. Thirty-seven percent of patients fulfilled classification criteria for documented or clinically established psychogenic dystonia; 29% fulfilled DSM-IV (Diagnostic and statistical manual of mental disorders, 4th edition) criteria for somatization disorder, which was diagnosed only after examination of the primary care records in many cases; and 24% fulfilled both sets of criteria. Ten percent of the prospectively studied and 45% of the retrospectively studied patients did not have any evidence of psychogenic dystonia, and detailed investigation failed to reveal an alternative explanation for their clinical presentation. Detailed, semi-structured neuropsychiatric assessments in a subgroup of 26 patients with fixed dystonia and in a control group of 20 patients with classical dystonia revealed dissociative (42 versus 0%, P = 0.001) and affective disorders (85 versus 50%, P = 0.01) significantly more commonly in the fixed dystonia group. Medical and surgical treatment was largely unsuccessful. However, seven patients who underwent multidisciplinary treatment, including physiotherapy and psychotherapy, experienced partial or complete remission. We conclude that fixed dystonia usually, but not always, occurs after a peripheral injury and overlaps with CRPS. Investigations are typically normal, but many patients fulfil strict criteria for a somatoform disorder/psychogenic dystonia. In a proportion of patients, however, no conclusive features of somatoform disorder or psychogenic disorder can be found and, in these patients, whether this disorder is primarily neurological or psychiatric remains an open question. Whilst the prognosis is overall poor, remissions do occur, particularly in those patients who are willing and able to undergo multidisciplinary treatment including physiotherapy and psychotherapy, suggesting that this type of treatment should be recommended to these patients.

Orofacial myofunctional disorders in children with asymmetry of the posture and locomotion apparatus.

352 children radiologically identified with asymmetry in the occipito-cervical region were assessed on a number of myofunctional measures. In all children an orthopedic examination was conducted including a functional test of the upper cervical spine and the iliac joint, the postural test by Matthiass, as well as gait analysis. During a second examination the orofacial myofunctional status was recorded. In general, about 70% of the children revealed orofacial myofunctional disorders. Correlational analysis was conducted in order to determine whether specific myofunctional variables were associated with postural and orthopedic alterations. A weak body posture correlated statistically significantly with all assessed myofunctional variables. On the other hand, all orthopedic items correlated significantly with a reclined head position. A blockade of the iliac spine correlated significantly with persistent habits, articulation disorders and tongue dysfunction, whereas functional asymmetry of the upper cervical spine correlated significantly with incompetent lips. A finding of at least five statistically significant correlations within each orofacial variable underlined the complex symptomatology of myofunctional disorders, so that consideration needs to be given to adequate treatment approaches. The data generated by the present study stress the importance of early interdisciplinary screening in children to ensure a physiological development of the orofacial region and the still growing vertebral column. To help understand the complexity of symptoms influencing orofacial development, an explanatory model of the "interactive functional box system" is given.

A biological measure of stress levels in patients with functional movement disorders.

INTRODUCTION: While the presence of co-existing psychological stressors has historically been used as a supportive factor in the diagnosis of functional neurological disorders, many patients with functional neurological disorders deny the presence of these stressors. The stress response circuitry in these patients remains largely unexplored. METHODS: We performed an observational study examining biological stress levels in patients with functional movement disorders as compared with matched healthy controls. Specifically, we compared levels of circulating cortisol, the end-product of the hypothalamic-pituitary-adrenal axis. Salivary cortisol samples were collected from patients with "clinically definite" functional movement disorders (n = 33) and their age- and sex-matched controls (n = 33). Collections were performed at five standardized time points, reflecting participants' diurnal cortisol cycles. To rule out confounders, participants also underwent extensive psychological assessment including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Hamilton Anxiety Rating Scale, and Hamilton Rating Scale for Depression. RESULTS: Patients with functional movement disorders did not differ from matched controls with respect to levels of circulating cortisol. CONCLUSION: We demonstrate that current stress levels are not altered in patients with functional movement disorders. Our results warrant careful review of current management of patients with functional neurological symptoms, and suggest that the insistence on heightened stress levels in these patients is unjustified.

Cervical dystonia: clinical findings and associated movement disorders.

We studied 300 patients, 61% women, with mean age 49.7 years and mean duration of dystonia 7.8 years, to determine the demographic and clinical characteristics of cervical dystonia (CD) and its relationships to other movement disorders. Torticollis was present in 82%, laterocollis in 42%, retrocollis in 29%, and anterocollis in 25%; however, the majority (66%) had a combination of these abnormal postures. Scoliosis was present in 39%, local pain reported by 68%, and 32% had evidence of secondary cervical radiculopathy. In addition to CD, 16% of patients had oral dystonia, 12% mandibular dystonia, 10% hand/arm dystonia, and 10% had blepharospasm. Tremor was noted in 71% of patients; head-neck tremor was present in 60%, and tremor in other body regions was present in 32%. A family history of a movement disorder was present in 44% of the CD patients. Tardive dystonia was the cause in 6%; 11% had posttraumatic dystonia. Anticholinergic drugs provided moderate improvement in 33% of patients, but local intramuscular botulinum toxin injections relieved CD, local pain, or both in over 90% of all treated patients.