Upper motor neuron signs in primary lateral sclerosis and hereditary spastic paraplegia.

INTRODUCTION/AIMS: The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP). METHODS: We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients. RESULTS: We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP. DISCUSSION: In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP.

Pain in children with dyskinetic and mixed dyskinetic/spastic cerebral palsy.

AIM: To evaluate pain prevalence and characteristics in children and adolescents with predominant dyskinetic and mixed (dyskinetic/spastic) cerebral palsy (CP) motor types. METHOD: Seventy-five participants with a diagnosis of CP and confirmed dyskinetic or mixed (dyskinetic/spastic) motor type took part in a multisite cross-sectional study. The primary outcome was carer-reported pain prevalence (preceding 2wks) measured using the Health Utilities Index-3. Secondary outcomes were chronicity, intensity, body locations, quality of life, and activity impact. RESULTS: Mean participant age was 10 years 11 months (SD 4y 2mo, range 5-18y). There were 44 males and 31 females and 37 (49%) had predominant dyskinetic CP. Pain was prevalent in 85% and it was chronic in 77% of participants. Fifty-two per cent experienced moderate-to-high carer-reported pain intensity, which was significantly associated with predominant dyskinetic motor types (p=0.008). Pain occurred at multiple body locations (5 out of 21), with significantly increased numbers of locations at higher Gross Motor Function Classification System levels (p=0.02). Face, jaw, and temple pain was significantly associated with predominant dyskinetic motor types (p=0.005). Poorer carer proxy-reported quality of life was detected in those with chronic pain compared to those without (p=0.03); however, chronic pain did not affect quality of life for self-reporting participants. INTERPRETATION: Pain was highly prevalent in children and adolescents with predominant dyskinetic and mixed (dyskinetic/spastic) motor types, highlighting a population in need of lifespan pain management. WHAT THIS PAPER ADDS: Chronic pain prevalence in children and adolescents with predominant dyskinetic and mixed (dyskinetic/spastic) motor types is high. Pain occurs across multiple body locations in predominant dyskinetic and mixed (dyskinetic/spastic) motor types. Less recognized locations of pain include the face, jaw, and temple for predominant dyskinetic motor types.

Hypomorphic mutations in POLR3A are a frequent cause of sporadic and recessive spastic ataxia.

Despite extensive efforts, half of patients with rare movement disorders such as hereditary spastic paraplegias and cerebellar ataxias remain genetically unexplained, implicating novel genes and unrecognized mutations in known genes. Non-coding DNA variants are suspected to account for a substantial part of undiscovered causes of rare diseases. Here we identified mutations located deep in introns of POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family turned our attention to intronic variants in POLR3A, a gene previously associated with hypomyelinating leukodystrophy type 7. Next, we screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations in ∼3.1% of index cases. Interestingly, >80% of POLR3A mutation carriers presented the same deep-intronic mutation (c.1909+22G>A), which activates a cryptic splice site in a tissue and stage of development-specific manner and leads to a novel distinct and uniform phenotype. The phenotype is characterized by adolescent-onset progressive spastic ataxia with frequent occurrence of tremor, involvement of the central sensory tracts and dental problems (hypodontia, early onset of severe and aggressive periodontal disease). Instead of the typical hypomyelination magnetic resonance imaging pattern associated with classical POLR3A mutations, cases carrying c.1909+22G>A demonstrated hyperintensities along the superior cerebellar peduncles. These hyperintensities may represent the structural correlate to the cerebellar symptoms observed in these patients. The associated c.1909+22G>A variant was significantly enriched in 1139 cases with spastic ataxia-related phenotypes as compared to unrelated neurological and non-neurological phenotypes and healthy controls (P = 1.3 × 10-4). In this study we demonstrate that (i) autosomal-recessive mutations in POLR3A are a frequent cause of hereditary spastic ataxias, accounting for about 3% of hitherto genetically unclassified autosomal recessive and sporadic cases; and (ii) hypomyelination is frequently absent in POLR3A-related syndromes, especially when intronic mutations are present, and thus can no longer be considered as the unifying feature of POLR3A disease. Furthermore, our results demonstrate that substantial progress in revealing the causes of Mendelian diseases can be made by exploring the non-coding sequences of the human genome.

[Cannabinoid mouth spray brought help to a severely spastic young man]. / Kannabinoidi-suusuihke toi avun vaikeasti spastiselle nuorelle miehelle.

Cannabinoid was licensed in 2012 for the treatment of spasticity associated with multiple sclerosis in Finland. Spasticity is one of the main symptoms in cerebral palsies and a risk factor of multiple painful anomalies of the skeletal network. We describe a 28-year-old man with severe cerebral palsy, whose quality of life improved and the need for help decreased by using two daily mouth sprays of cannabinoid.

Neuropathy in ARSACS is demyelinating but without typical nerve enlargement in nerve ultrasound.

BACKGROUND: To specify peripheral nerve affection in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) by correlating high-resolution nerve ultrasound and nerve conduction studies. METHODS: We assessed a cohort of 11 ARSACS patients with standardized nerve conduction studies and high-resolution ultrasound of peripheral nerves and compared nerve ultrasound findings to a healthy control group matched for age, sex, size and weight. RESULTS: Mean age of patients was 39.0 (± 14.1) years and disease duration at assessment 30.6 (± 12.5) years. All patients presented with a spasticity, ataxia and peripheral neuropathy. Neuropathy appeared to be primarily demyelinating in 9/11 cases and was not classifiable in 2/11 cases due to not evocable potentials. Nerve ultrasound revealed a normal ultrasound pattern sum score (UPSS) in each ARSACS patient and no significant nerve enlargement compared to the control group. CONCLUSIONS: Peripheral neuropathy in ARSACS showed primarily demyelinating rather than axonal characteristics and presented without nerve enlargement. As demyelinating neuropathies do commonly present enlarged nerves we recommend further genetic testing of the SACS gene in patients who present with this combination of demyelinating neuropathy without nerve enlargement. ARSACS cases that initially presented only with neuropathy without spasticity or ataxia and therefore were misdiagnosed as Charcot-Marie-Tooth disease are supporting this suggestion.

Kinematic characteristics of arm and trunk when drinking from a glass in children with and without cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) often have difficulty with activities that require the upper extremities secondary to deficits in strength and range of motion, spasticity, and poor timing and coordination of movement. This study aimed to identify and compare timing and coordination of the trunk and upper extremity in children with and without CP during a functional task. METHODS: Eighteen children, N = 9 with CP and N = 9 with typical development were enrolled. Participants were seated in a standard chair and instructed to drink from a glass placed at a distance of 75% of available arm length. The task was divided into 3 Phases: 1) reaching to the glass, 2) transporting the glass to the mouth, and 3) returning the glass to the table. The spatiotemporal and angular variables were analyzed with 3D kinematics of movement using a 4-camera Qualysis Motion System. FINDINGS: Children with CP demonstrated poor upper extremity timing and coordination. Despite significant trunk displacement used as a compensation in Phase 1, children with CP demonstrated a significantly lower mean velocity and velocity peak during Phases 2 and 3; and demonstrated less straight motion which required more time and movement units in all phases. INTERPRETATION: Children with CP demonstrated poor upper extremity timing and coordination when drinking (even when they successfully completed the task) measured by more trunk displacement, slower, less straight movements, and more movement units. Current rehabilitation strategies could consider training speed and use functional tasks that require different strategies across multiple phases.

Evaluation of low-level laser therapy in the treatment of masticatory muscles spasticity in children with cerebral palsy.

Spasticity is a motor disorder frequently present in individuals with cerebral palsy (CP). This study aimed to evaluate the effect of low-level laser therapy (LLLT) on the spasticity of the masseter and anterior temporal muscle fibers in children with CP over three weeks of intermittent laser exposures. The bite force (BF) of the masticatory muscles and the amplitude of mouth opening were evaluated before and after laser irradiation in 30 children with CP. Both sides of the masseter and temporalis muscles were irradiated with low-intensity diode laser pulses of 808-nm wavelength six times over three consecutive weeks. During the subsequent three weeks of postlaser exposures, although no laser treatment was applied, the evaluation parameters were measured and recorded. A significant improvement in the amplitude of mouth opening and a decrease in the BF were observed in the weeks following LLLT (P<0.05 ). However, by the sixth week post-LLLT, the BF and the amplitude of mouth opening reverted to values equivalent to those obtained before the first application of LLLT. Our investigation revealed low-level energy exposures from a 808-nm diode laser to be an effective short-term therapeutic tool. This method increased the amplitude of mouth opening and decreased the muscle tonus of children with spastic CP over a time course of three weeks of intermittent laser applications.

Cortical and spinal excitability in patients with multiple sclerosis and spasticity after oromucosal cannabinoid spray.

BACKGROUND: Delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) has been recently approved for the management of treatment-resistant multiple sclerosis (MS) spasticity. Although the symptomatic relief of Sativex® on MS-spasticity has been consistently demonstrated, the pathogenetic implications remain unclear and the few electrophysiological studies performed to address this topic yielded controversial results. We therefore aimed to investigate the mechanisms underpinning the modulation of spastic hypertonia by Sativex®, at both central and spinal levels, through an extensive neurophysiological battery in patients with MS. METHODS: Nineteen MS patients with treatment-resistant spasticity were recruited. Before and after 4weeks of treatment with Sativex® patients were clinically assessed with the Modified Ashworth Scale (MAS) and underwent a large neurophysiological protocol targeting measures of excitability and inhibition at both cortical [e.g., intracortical facilitation (ICF), short (SICI) and long (LICI) intracortical inhibition, cortical silent period (CSP)] and spinal level [e.g., H-reflex, H/M ratio and recovery curve of the H-reflex (HRC)]. A group of 19 healthy subjects served as controls. RESULTS: A significant reduction of the MAS score after 4weeks of Sativex® treatment was detected. Before treatment, an increase in the late facilitatory phase of HRC was recorded in patients compared to the control group, that normalised post treatment. At central level, SICI and LICI were significantly higher in patients compared to healthy subjects. After therapy, a significant strengthening of inhibition (e.g. reduced LICI) and a non-significant facilitation (e.g. marginally increased ICF) occurred, suggesting a modulatory effect of Sativex® on different pathways, predominantly of inhibitory type. Sativex® treatment was well tolerated, with only 3 patients complaining about dizziness and bitter taste in their mouth. DISCUSSION: Our results confirm the clinical benefit of Sativex® on spastic hypertonia and demonstrate that it might modulate both cortical and spinal circuits, arguably in terms of both excitation and inhibition. We suggest that the clinical benefit was likely related to a net increase of inhibition at cortical level that, in turn, might have influenced spinal excitability.

Orofacial fine motor control impairments in congenital spasticity: evidence against hypertonus-related performance deficits.

Motor impairments in the fine force control of lips, tongue, and jaw were measured in subjects with congenital spasticity. Because these orofacial motor systems are not uniformly endowed with muscle spindles and monosynaptic reflexes, quantification of these motor impairments addresses the question of whether stretch reflex hypertonus is a positive or negative sign. The results indicated that hyperactive muscle spindle-based monosynaptic reflexes are not a causal factor in these voluntary orofacial motor impairments. These data also indicated that motor impairments were disproportionately greater at finer levels of isometric force control. These fine control measures appear useful as a quantitative index of general voluntary motor deficit.

Summary of combined clinical analysis of controlled clinical trials with tizanidine.

Data from three placebo-controlled and 11 active-controlled studies of tizanidine were combined to permit analysis of the subsets, which were too small to evaluate within the individual studies. Overall analysis of placebo-controlled data confirms the effectiveness of tizanidine in reducing muscle tone in patients with spasticity of spinal cord origin. Subset analyses suggest that patients with more severe spasticity are more likely to respond, but age, sex, and race were not predictive of response. Comparisons of tizanidine with active controls showed no differences in efficacy compared with baclofen or diazepam. However, when compared with controls, patients treated with tizanidine did not experience increased weakness. Furthermore, patients tolerated tizanidine better than the control medications. More patients experienced adverse events during tizanidine treatment than did patients receiving placebo. The most common adverse events reported were dry mouth, somnolence, asthenia, and dizziness. Mild elevations in liver function tests were noted occasionally, but improved in all patients with dose reduction or withdrawal. Three patients from the double-blind database reported formed visual hallucinations. All three cleared; two continued tizanidine, and one discontinued.

Neurological manifestations of the oculodentodigital dysplasia syndrome.

Oculodentodigital dysplasia (ODDD) (MIM 164200) is a rare autosomal dominant inherited disorder affecting the development of the face, eyes, limbs and dentition. Neurological complications are thought to be occasional manifestations of the disorder. This report illustrates the neurological manifestations by a pedigree of two ODDD patients with spastic paraparesis, cerebral white matter hyperintensity and basal ganglia hypointensity. A systematic review of the English, French, German and Italian literature on ODDD is also provided to summarize the neurological manifestations of the disorder. 243 previously described ODDD cases presented a spectrum of neurological manifestation including spasticity (25), subcortical white matter lesions (9) and basal ganglia changes (6) on MRI. Additional findings consisted of gaze palsy and squinting (28), bladder and bowel disturbances (21), visual loss (20) and blindness (4), hearing loss (15), ataxia (11), nystagmus (9), muscle weakness (5) and paresthesias (3). Neurological manifestations, including spasticity associated with MRI changes, are an underrecognized feature in the ODDD phenotype. A clinical guide to the neurological manifestations of ODDD may assist in the assessment of patients with this condition.

Treatment of spasticity with tizanidine in multiple sclerosis.

Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.

Oral motor patterns during feeding in severely physically disabled children.

Oral motor patterns during feeding were investigated in 58 patients with severe physical disability. Five patients showed a pattern resembling sucking. Twenty-nine exhibited an up-and-down movement of the jaw and protrusion of the tongue. Among these, the mouth opened when the food entered and the lips closed before swallowing in 20 patients; the mouth was constantly open in nine. Eight had an up-and-down movement of the jaw without protrusion of the tongue. These patterns were frequently seen in patients with spastic tetraplegia caused by neonatal asphyxia and compensated for oral motor impairment. Sixteen patients showed lateral movement of the jaw at some time during feeding; in these patients the texture of the food was more coarse than in those with other patterns.

Botulinum toxin B treatment in children with spastic movement disorders: a pilot study.

The treatment of adult and pediatric patients suffering from movement disorders with elevated muscle tone includes the application of focally denervating botulinum toxins. Dystonic movement disorders in adult patients have been treated successfully using botulinum toxin type B (NeuroBloc). Thus far, there has been no systematic treatment of children with botulinum toxin type B. This study reports on the treatment of 29 children with spastic or dystonic movement disorders using botulinum toxin type B in an open-label pilot study. Sixty-two treatment sessions were performed. In 33 of these sessions, the therapy goal that had been defined before intervention was attained or surpassed. Seventeen nonresponders to botulinum toxin type A were also included in the treatment, 11 of whom attained the therapy goal. Side effects were observed in 24% of all treatments, dry mouth being the most frequent (10%), in some cases having a desirable clinical effect. With this preliminary data as a basis, we recommend a maximum dose for children of 400 U botulinum toxin type B per kg body weight, which should not exceed a total of 10,000 U botulinum toxin type B.

Long-term follow-up of recurrent laryngeal nerve avulsion for the treatment of spastic dysphonia.

Long-term follow-up of 3 to 7 years is reported on 18 patients who had undergone recurrent laryngeal nerve avulsion (RLNA) for the treatment of adductor spastic dysphonia (SD). Data on neural regrowth after previous recurrent laryngeal nerve section (RLNS) are presented in 2 of these 18 patients. We introduced RLNA as a modification of standard RLNS to prevent neural regrowth to the hemiparalyzed larynx and subsequent recurrence of SD. We have treated a total of 22 patients with RLNA, and now report a 3- to 7-year follow-up on 18 of these 22 patients. Resolution of symptoms was determined by routine follow-up assessment, perceptual voice analysis, and patient self-assessment. Sixteen of 18, or 89%, had no recurrence of spasms at 3 years after RLNA as determined at routine follow-up. Two of the 16 later developed spasms after medialization laryngoplasty for treatment of weak voice persistent after the avulsion. This yielded a total of 14 of 18, or 78%, who were unanimously judged by four speech pathologists to have no recurrence of SD at the longer follow-up period of 3 to 7 years. Two of these 4 patients were judged by all four analysts to have frequent, short spasms. The other 2 were judged by two of four analysts to have seldom, short spasms. Three of 18 patients presented with recurrent SD after previous RLNS. At the time of subsequent RLNA, each patient had evidence of neural regrowth at the distal nerve stump as demonstrated by intraoperative electromyography and histologic evaluation of the distal nerve stump. One remained free of SD following RLNA, 1 was free of spasms at 4 years after revision avulsion but developed spasms after medialization laryngoplasty, and the final patient developed spasms 3.75 years after revision RLNA. Medialization laryngoplasty with Silastic silicone rubber was performed in 6 of 18, with correction of postoperative breathiness in all 6, but with recurrence of spasm in 3. Spasms resolved in 1 of these with downsizing of the implant. We conclude that RLNA represents a useful treatment in the management of SD in patients not tolerant of botulinum toxin injections.

Influence of stabilization occlusal splint on craniocervical relationships. Part II: Electromyographic analysis.

The aim of this study was to determine the effect of stabilization occlusal splints on electromyographic (EMG) activity of sternocleidomastoid and trapezius muscles in subjects with spasm in the mentioned muscles. A full-arch maxillary stabilization occlusal splint was made for each of the 15 subjects. In the sternocleidomastoid muscle, tonic and saliva swallowing EMG activity decreased significantly with the splint, whereas maximal clenching activity did not change. In the trapezius muscle, no significant changes were observed with the occlusal splint. The different pattern in both muscles during tonic and swallowing EMG activity with the splint is attributed to differences in the synaptic inputs to the respective motoneuron pools, suggesting that a differential modulation of the motor neuron pools may exist of both muscles, of peripheral and/or central origin.

Multiple sclerosis and oral care.

Multiple sclerosis is a complex neurological condition affecting sensory and motor nerve transmission. Its progression and symptoms are unpredictable and vary from person to person as well as over time. Common early symptoms include visual disturbances, facial pain or trigeminal neuralgia and paraesthesia or numbness of feet, legs, hands and arms. These, plus symptoms of spasticity, spasms, tremor, fatigue, depression and progressive disability, impact on the individual's ability to maintain oral health, cope with dental treatment and access dental services. Also, many of the medications used in the symptomatic management of the condition have the potential to cause dry mouth and associated oral disease. There is no cure for multiple sclerosis, and treatment focuses on prevention of disability and maintenance of quality of life. Increasingly a multi-disciplinary team approach is used where the individual, if appropriate his/her carer, and the specialist nurse are key figures. The dental team plays an essential role in ensuring that oral health impacts positively on general health.

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum.

BACKGROUND: Mutations in SACS, leading to autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), have been identified as a frequent cause of recessive early-onset ataxia around the world. Here we aimed to enlarge the spectrum of SACS mutations outside Quebec, to establish the pathogenicity of novel variants, and to expand the clinical and imaging phenotype. METHODS: Sequencing of SACS in 22 patients with unexplained early-onset ataxia, assessment of novel SACS variants in 3.500 European control chromosomes and extensive phenotypic investigations of all SACS carriers. RESULTS: We identified 11 index patients harbouring 17 novel SACS variants. 9/11 patients harboured two variants of at least probable pathogenicity which were not observed in controls and, in case of missense mutations, were located in highly conserved domains. These 9 patients accounted for at least 11% (9/83) in our series of unexplained early onset ataxia subjects. While most patients (7/9) showed the classical ARSACS triad, the presenting phenotype reached from pure neuropathy (leading to the initial diagnosis of Charcot-Marie-Tooth disease) in one subject to the absence of any signs of neuropathy in another. In contrast to its name "spastic ataxia", neither spasticity (absent in 2/9=22%) nor extensor plantar response (absent in 3/9=33%) nor cerebellar ataxia (absent in 1/9=11%) were obligate features. Autonomic features included urine urge incontinence and erectile dysfunction. Apart from the well-established MRI finding of pontine hypointensities, all patients (100%) showed hyperintensities of the lateral pons merging into the (thickened) middle cerebellar peduncles. In addition, 63% exhibited bilateral parietal cerebral atrophy, and 63% a short circumscribed thinning of the posterior midbody of the corpus callosum. In 2 further patients with differences in important clinical features, VUS class 3 variants (c.1373C>T [p.Thr458Ile] and c.2983 G>T [p.Val995Phe]) were identified. These variants were, however, also observed in controls, thus questioning their pathogenic relevance. CONCLUSIONS: We here demonstrate that each feature of the classical ARSACS triad (cerebellar ataxia, spasticity and peripheral neuropathy) might be missing in ARSACS. Nevertheless, characteristic MRI features - which also extend to supratentorial regions and involve the cerebral cortex - will help to establish the diagnosis in most cases.

Contemporary pharmacologic treatments for spasticity of the upper limb after stroke: a systematic review.

BACKGROUND: Muscle spasticity after stroke may be painful and severe and may restrict the patient's ability to perform routine daily tasks, particularly when the affected muscles are in the upper limbs. Treatments targeted at reducing this spasticity have evolved over time. OBJECTIVE: This was a systematic review of recent studies focusing on contemporary pharmacologic therapies for upper limb spasticity after stroke. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched for clinical trials published in English from January 1995 to July 2010 using search terms that included spasticity, stroke, hemiplegia, phenol, baclofen, tizanidine, dantrolene, benzodiazepine, and botulinum toxin. The level of evidence of the identified publications was assessed using the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: A total of 113 potentially relevant articles were identified by the search; of these, 54 studies were included in the review (23 randomized controlled trials [RCTs] and 31 open-label, nonrandomized, or observational studies). Of these, 51 involved treatment with botulinum toxin (BTX). All studies assessed spasticity; some also assessed additional outcomes, such as pain, disability, and functional status. Thirty-eight clinical trials reported a significant reduction in spasticity with BTX, either compared with baseline or with placebo (P < 0.05). A head-to-head comparison found a significant reduction in spasticity with BTX injections compared with oral tizanidine (TZD) (P < 0.001). Two studies of intrathecal baclofen (ITB) reported significant reductions in upper limb spasticity after 12 months of treatment, and 1 study of tizanidine reported significant reductions in upper limb spasticity after 16 weeks of treatment (all, P < 0.001). General or local weakness, injection-site pain, and fatigue were the most frequently reported adverse events with BTX type A, and dry mouth was the most frequently reported adverse event with BTX type B. No serious or life-threatening adverse events were reported in any trial of BTX. CONCLUSIONS: The 54 studies included in this systematic review of treatments for upper limb spasticity after stroke measured multiple outcomes using a variety of instruments. Fifty-one studies focused on treatment with a BTX formulation. BTX appeared to be an effective and well-tolerated focal treatment for reducing tonicity in patients with upper limb spasticity after stroke, supporting current guideline recommendations.

Effect of spastic cerebral palsy on jaw-closing muscles during clenching.

The motor effort of jaw-closing muscles during maximal voluntary clenching (MVC) was compared between individuals with spastic cerebral palsy (CP) and nondisabled control subjects (CG). Bilateral electromyographic (EMG) activity of the anterior temporalis (AT) and masseter (MS) muscles was obtained during MVC in 22 subjects with CP and 29 nondisabled subjects. The oral functional status of the group with CP was evaluated using the Orofacial Motor Function Assessment Scale. The group with CP presented lower bilateral EMG activity during MVC compared to the control group for both AT and MS muscles. Comparisons of AT and MS EMG activity showed no difference in muscular effort. Subgroups with CP who were only slightly and very slightly orally impaired had a higher bilateral AT EMG activity compared to individuals with CP who were severely and moderately compromised. A statistically significant positive correlation was found between the oral motor function and EMG activity of the group with CP in all the muscles evaluated. Individuals with CP had motor weakness in the jaw-closing muscles, a condition that may compromise their masticatory function.