Doi:10.1016/j.cden.2006.09.002

Department of Diagnostic Sciences, Orofacial Pain and Oral Medicine Center, University of Southern California School of Dentistry, 925 West 34th Street, Room B-14, Los Angeles, CA 90089-0641, USA The literature is replete with articles that discuss motor disorders, such as Parkinson’s disease, Bell’s palsy, essential tremor, poststroke paralysis,dystonia, and dyskinesia. The focus of this article is on those motor disor-ders that are known to affect the masticatory system and its adjacent mus-cles. The term ‘‘orofacial motor disorder’’ (OMD) encompasses a spectrumof movement aberrations, both hyperactive and hypoactive, which involvesthe muscles of the orofacial complex and are innervated by cranial nerves V,VII, and XII. OMDs generally present as localized problems that affect onlythe masticatory system, but they are driven by alterations in central nervoussystem (CNS) functioning. Dentists must be able to recognize and becomeinvolved with management of these problems, because such behaviors causepain and dysfunction of the jaw and interfere with needed dental care onpatients The most common OMDs are sleep bruxism and sustained habitual forceful clenching (day or night). In addition to bruxism, this article reviewsthree other vexing oral motor disorders: focal orofacial dystonia, oroman-dibular dyskinesia, and medication-induced extrapyramidal syndrome(EPS)–dystonic reactions. provides a brief definition, the main clin-ical features, and management approaches that are used for these fourOMDs. When severe, these motor disorders may cause strong headaches, * Corresponding author.
E-mail address: (G.T. Clark).
0011-8532/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.cden.2006.09.002 Table 1Oral motor disorders: dystonia, dyskinesia, bruxism and dystonic extrapyramidal reactions classified better asan unspecifiedextrapyramidalsyndromereaction.
damage the temporomandibular joint (TMJ), or create such motor controldifficulty that patients are unable to eat and may start to lose weight. Thesemotor disorders can affect the tongue musculature to such a degree that itcompromises the patient’s ability to speak clearly. The social embarrassmentthat patients must endure affects their daily living; many patients refuse orstrongly avoid leaving their homes. Fortunately, there are various medications, including botulinum toxin injections, and surgical interven-tions that reduce the severity of the OMDs.
The prevalence of chronic bruxism is unknown, because no large, prob- ability-based, random sample study has been performed using polysomnog-raphy (which is needed to measure bruxism). Based on a combination ofattrition assessment and reports by parents, spouses, or roommates, it isestimated that 5% to 21% of the population has substantial sleep bruxismMany bruxers do not have substantial attrition and many do not maketooth-grinding sounds during sleep, so sleep partner or parental reportsare not always accurate. The pathophysiology of bruxism is unknown.
The most cogent theory describes bruxism as a neuromotor dysregulationdisorder. This theory proposes that bruxism occurs because of the failureto inhibit jaw motor activity during a sleep state arousal. There are numer-ous clear-cut neuromotor diseases that exhibit bruxism as a feature of thedisease (eg, cerebral palsy). The disorder of periodic limb movements issimilar to an OMD, except that it occurs in the leg muscles There aremany articles that describe the clinical presentation and consequences ofbruxism; most agree that the single most effective way to protect the teethfrom progressive attrition, fracture, or clenching-induced pulpitis is tofabricate an occlusal appliance and have the patient use it at night The problem with an occlusal-covering appliance is that it does little ornothing to stop the bruxism in the long term. Most alter the behavior fora few weeks when first used, but this only offers a brief respite from someheadaches and bruxism-induced TMJ derangement or arthritis problems.
In cases in which the disorder is severe and the damaging consequencesare well beyond the teeth, one option is to inject the masseter or temporalisabout every 3 to 6 months to minimize the power of the bruxism activity.
The literature supports this concept; one of the first reports was by VanZandijcke and Marchau in 1990 who provided a brief note on the treat-ment of a brain-injured patient who exhibited severe bruxism with bo-tulinum toxin type-A injections (100 U total into the masseter andtemporalis). Seven years later, Ivanhoe and colleagues described the suc-cessful treatment of a brain-injured patient who had severe bruxism withbotulinum toxin type-A. In this case, the patient was injected with a totalof 50 U to each of four muscles (right and left masseter and temporalis)for a total of 200 U. Of course, the successful treatment of a single caseof brain injury–induced bruxism does not make a compelling story for itsroutine use in managing bruxism. The story was extended by a more recentreport . The investigators reported on the long-term treatment of 18cases of severe bruxism with botulinum toxin type-A. These patients allhad severe bruxism, which had been causing symptoms for an average of14.8 Æ 10.0 years and all had no success with previous medical or dental treatment. Similar to previous reports, the masseter muscle was injected witha mean dose of 61.7 Æ 11.1 U per side. The efficacy of these injections wasrated by the subjects as a 3.4 on a scale from 0 to 4 (with 4 being equal tototal cessation of the behavior). The investigators described one subject whoexperienced dysphagia as a side effect of the injections. Finally, anotherinvestigator described a young child (age 7) who had severe brain injury–induced bruxism that was treated successfully with botulinum toxin .
The primary management method for strong bruxism and clenching is stilla full-arch occlusal appliance, which does not stop the behavior but limits itsdental damage Fortunately, the most severe cases of bruxism andclenching now have several motor suppressive medications; in extreme cases,botulinum toxin injections can be added to occlusal appliance treatment.
Oromandibular dystonia is one form of a focal dystonia that affects the orofacial region and involves the jaw openers (lateral pterygoids and ante-rior digastrics), tongue muscles, facial muscles (especially orbicularis orisand buccinator), and platysma. When this occurs in association with bleth-rospasm (focal dystonia of the orbiculares oculi muscles), it is called Meige’ssyndrome Dystonia is considered present when repeated, often asyn-chronous spasms of muscles are present. Most dystonias are idiopathicand the focal form of dystonia occurs 10 times more often than does the gen-eralized systemic form . The prevalence of all forms of idiopathic dysto-nia ranges between 3 and 30 per 100,000 . Focal dystonias can beprimary or secondary; the secondary form of dystonias occurs as a resultof a trauma (peripheral or central), brainstem lesion, systemic disease (eg,multiple sclerosis, Parkinson’s disease), vascular disease (eg, basal gangliainfarct), or drug use Most dystonias are primary or ‘‘idiopathic’’ anddemonstrate no specific CNS disease. Of course, various pathophysiologicmechanisms have been proposed to explain dystonia (eg, basal ganglia dys-function, hyperexcitability of interneurons involved in motor signaling ,reduced inhibition of spinal cord and brainstem signals coming from supra-spinal input and dysfunction of neurochemical systems involving dopamine,serotonin, and noradrenaline All dystonias are involuntary but tend tobe more intermittent than dyskinesias (see later discussion) and are compro-mised of short, but sustained, muscle contractions that produce twisting andrepetitive movements or abnormal postures One interesting aspect of the involuntary motor disorders is that patients can control or suppress the movement partially with the use of tactile stim-ulation (eg, touching the chin in the case of orofacial dystonia or holding anobject in their mouth). This suppressive effect has been called ‘‘geste antag-onistique’’ These tactile maneuvers may lead physicians to the errone-ous diagnosis of malingering or hysteria. Other examples of sensory tricksinclude placing a hand on the side of the face, the chin, or the back of the head, or touching these areas with one or more fingers, which, at times, willreduce the neck contractions that are associated with cervical dystonia. Withsome dystonias, patients have discovered that placing an object in the mouth(eg, toothpick, piece of gum) may reduce dystonic behaviors of the jaw,mouth, and lower face (oromandibular dystonia). Finally, most of the focaland segmental dystonias only occur during waking periods and disappearentirely during sleep.
For treatment, there are several medications that can be used to suppress hyperkinetic muscles (see later discussion). After medications, the other pri-mary method for treating dystonia is chemodenervation using botulinumtoxin. In 1989, Blitzer and colleagues first described the injection of bot-ulinum toxin for oromandibular dystonia. They described injecting many ofthe orofacial muscles in oromandibular dystonia and claimed that masseterand temporalis injections helped with suppressing the overall oromandibu-lar dystonia. These early reports did not specifically look at tongue move-ment changes nor were tongue botulinum toxin injection performed. In1991, Blitzer and colleagues described the first use of botulinum toxinin patients who had lingual dystonia, but cautioned clinicians that dyspha-gia was a problem in some of their cases; unfortunately, doses and injectionssites were not described carefully. In 1997, Charles and colleagues reported on nine patients who had repetitive tongue protrusion that resultedfrom oromandibular dystonia or Meige’s syndrome. They were treatedwith botulinum toxin injections into the genioglossus muscle at four sitesby way of a submandibular approach. Six of these patients were helped,and the average dose injected was 34 U, which produced a 3- to 4-montheffect. Clearly, there is a need to explore when, where, and to what degreebotulinum toxin may become useful in the management of the patientwho has galloping tongue or tongue-based severe dyskinesia. There aremany variations of oromandibular dystonia, but one common one is invol-untary jaw-opening dystonia. One complication of jaw-opening dystonia isthat the TMJ can become locked physically in the wide-open position, sothat even after the dystonic contraction stops, the jaw will not close easily.
In 1997, Moore and Wood described the treatment of recurrent, invol-untary TMJ dislocation using botulinum toxin A. The injected target wasthe lateral pterygoid muscle, and they injected each lateral pterygoid usingelectromyographic guidance. The investigators described that the effectlasted for 10 months. The lateral pterygoid is the muscle that is most respon-sible for opening; it is a difficult injection, which has a high potential formisplacement of the solution into other adjacent muscles.
Risk factors for the development of tardive dyskinesia are older age, female sex, and the presence of affective disorders For spontaneousdyskinesias, the prevalence rate is 1.5% to 38% in elderly individuals, depending on age and definition. Elderly women are twice as likely to de-velop the disorder . When this disorder is associated with a drug use,the medications that are implicated most commonly are the neurolepticmedications that are now in widespread use as a component of behavioraltherapy. The prevalence of drug-induced dyskinesia (tardive form) isapproximately 15% to 30% in patients who receive long-term treatmentwith neuroleptic medications . These medications chronically block do-pamine receptors in the basal ganglia. The result would be a chemically-in-duced denervation supersensitivity of the dopamine receptors which leadsto excessive movement; however, other neurotransmitter abnormalities ing-aminobutyric acid (GABA)ergic and cholinergic pathways have been sug-gested. There are isolated reports in the literature that implicate dental treat-ment as a factor in the onset of spontaneous orofacial dyskinesia. Orofacialdyskinesia occurs as involuntary, repetitive, stereotypical movement of thelips, tongue, and sometimes the jaw during the day Sometimes thedyskinesia is induced by medication (tardive) or it can occur spontaneously.
The spontaneous form of dyskinesia often affects the elderly. Typically, thetardive form of dyskinesia occurs in mentally ill patients who have a long-term exposure to medications that are used to treat the mental illness .
By definition, tardive dyskinesia requires at least 3 months of total cumula-tive drug exposure, which can be continuous or discontinuous. Moreover,the dyskinesia must persist more than 3 months after cessation of the med-ications in question. Most dopamine receptor antagonists cause oral tardivedyskinesia to one degree or another. The typical antipsychoticsdand in re-cent years, even the atypical antipsychoticsdincluding clozapine, olanza-pine, and risperidone were reported to cause tardive dystonia and tardivedyskinesia. No adequate epidemiologic data exist regarding whether anyparticular psychiatric diagnosis constitutes a risk factor for the developmentof tardive reactions to medications; however, the duration of exposure toantipsychotics that is required to cause tardive reaction is from months toyears. Exposure to antipsychotics need not be long, and a minimum safeperiod is not apparent. This duration of neuroleptic exposure seems to beshorter for women. A longer duration of exposure to neuroleptics doesnot correlate with the severity of the reaction. Treatment of orofacial dyski-nesia is largely with medications (see later discussion).
Drug-induced dystonic-type extrapyramidal reactions There are patients who have developed a medication-induced oral motor hyperactivity that does not fit into the dyskinesia category . These med-ications and illegal drugs produce a motor response that is classified betteras an unspecified extrapyramidal syndrome (EPS) reaction. EPS responsestypically have three presentations: dystonia, akathisia, and parkinsonism.
Dystonic reactions consist of involuntary, tonic contractions of skeletalmuscles . Akathisia reactions occur as a subjective experience of motor restlessness Patients may complain of an inability to sit orstand still, or a compulsion to pace or cross and uncross their legs. Parkin-sonian reactions manifest themselves as tremor, rigidity, and akinesia, whichshows as a slowness in initiating motor tasks and fatigue when performingactivities that require repetitive movements (bradykinesia). When a medica-tion or drug induces a dystonic EPS reaction, it typically involves the mus-cles of the head, face, and jaw that produce spasm, grimacing, tics, ortrismus. Most of the literature has focused on the more severe acute dystonicEPS reactions that occur with use of antipsychotic medications. In additionto the antipsychotics, several antiemetics with dopamine receptor–blockingproperties have been associated with tardive dystonia. These include pro-chlorperazine, promethazine, and metoclopramide. Of course, other lesssevere reactions do occur that vary in intensity and even wax and waneover time. The most commonly reported offending agents that are notneuroleptics are the selective serotonin reuptake inhibitors (SSRIs) andthe stimulant medications and illegal drugs.
Serotonergic agents that cause extrapyramidal reactions SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, es- citalopram) are used for depression and a variety of other mental illnesses.
Unfortunately, these drugs are reported to produce the side effect ofincreased clenching and bruxism Actually the term ‘‘SSRI-inducedbruxism’’ may not be accurate in that the actual motor behavior does notpresent as brief, strong, sleep state–related contractions as seen in bruxism,but more of an increased sustained nonspecific activation of the jaw andtongue musculature. Patients generally describe an elevated headache andtightness in their jaw, tongue, and facial structures. The best informationavailable about the effect of SSRI class medications on oromandibularstructures comes from a study in 1999, which examined the acute effectsof paroxetine on genioglossus activity in obstructive sleep apnea . Itfound that paroxetine, 40 mg, produced a clear augmentation of peak inspi-ratory genioglossus activity during non-rapid eye movement (NREM) sleep.
Of course, the recent widespread use of SSRIs is based on a perception thatthese drugs have a lower side effect profile than do other categories of anti-depressant medications (eg, tricyclics and monoamine oxidase inhibitors).
Unfortunately, only case-based literature exists at this time; further poly-somnographic studies on the motor effects of SSRIs are necessary to defineprevalence and risk factors and to establish a causal relationship betweenSSRI use and oral motor disorders.
Stimulant drugs and other medications that cause extrapyramidalreactions Illegal drugs, such as methamphetamine cocaine and 3,4-methylenedioxy- methamphetamine (Ecstasy), and legal prescription stimulants, such as meth-ylphenidate, phentermine, pemoline, dextroamphetamine, amphetamines, and diethylproprion, have been reported to induce bruxism and dystonic ex-trapyramidal reactions All stimulant drugs have the potential tocause extrapyramidal reactions and they are being used in greater numbersto treat obesity or as stimulants for children who have attention deficit hyper-activity disorder or narcolepsy and even for severe depression .
Differential diagnosis of orofacial motor disorder The most important aspect of any clinician’s skill is the ability to provide a differential diagnosis. With the exception of bruxism, all of the other mo-tor disorders require a neurologic consultation to achieve a definitive diag-nosis. This includes Bell’s palsy, essential tremor, the focal and multifocaldystonias, the dyskinesias, the motor and vocal tics, and hemifacial spasm.
Although the dentist will not be doing this examination, it is necessary toidentify whether a patient has had a correct assessment before participatingin the management of the patient. A proper initial diagnostic work-up fora movement disorder involves a full clinical examination, including a thor-ough neurologic examination. This is necessary to rule out the possibilitythat the motor dysfunction may be due to a central degenerative, demyelin-ating, or sclerotic lesion of the nervous system. Depending on the exact na-ture of the motor disorder, the examining physician may add a thoroughmedication and illegal drug history to the work-up. Standard, enhanced,and angiographic-type MRI will be taken of the brain and spinal cord torule in or out a neurologic infarct or tumor or compression of these tissue;an electromyographic assessment may be ordered to identify specificallywhich muscles are involved and to assess the patient for a motor nerve orsensory nerve conduction deficit or a peripheral-origin myopathic diseaseor motor neuron abnormality; and for the most severe forms of bruxismand some myoclonic-type bruxism problems, it will be necessary to conducta nocturnal polysomnogram, which includes an electroencephalogram. Forthe dystonias that affect a specific motor system (eg, blepharospasm ortorticollis), it is necessary to assess that system thoroughly to ensure thatno local infection or neoplastic or arthritic disease is present, to nameonly a few of the considerations. For disorders that involve the masticatorymuscles, the tongue, or the perioral muscles, it is necessary for the dentist toconduct a careful examination to rule out local pathologic entities.
If the dentist chooses to become involved in medicating patients who have OMDs, it is essential to be familiar with the pharmacodynamic andpharmacokinetic effects of medications that are prescribed as well as risk/benefit considerations. For dystonia and dyskinesia that have undergonea confirming medical differential diagnosis, it is preferable for the dentist to work in conjunction with a neurologist or psychiatrist who specializes inmovement disorder, because pharmacologic management can be exceed-ingly complex and frustrating. This frustration is that although the medica-tions described below can work effectively, more often only a small effect isseen and side effects can be substantial. Only a dentist who is well versed inpharmacologic approaches should attempt drug management, albeit thisalso should be done with continuing medical interaction. As far as surgicalapproaches for movement disorder, these are reserved for the most severecases (see later discussion on interventional approaches).
There is no impressive data in the literature that suggest that a medication (other than botulinum toxin injections) can suppress bruxism reliably formore than a few days. Behavioral approaches should be addressed by theappropriate health care provider; they offer some help to patients who arehaving an acute stress problem that is influencing bruxism and clenchingbehavior, but again, data on true suppression of bruxism with a straight be-havioral approach is lacking. Most of the time, the best treatment for brux-ism is to fabricate an occlusal guard and try to protect the teeth from furtherattrition. Botulinum toxin injections are helpful for the more severe motordisorders, including bruxism.
For most OMDs, there is no well-defined treatment protocol except to rule out CNS disease and local pathology and to try one or more of the med-ications that may be helpful in these cases. If the disorder is severe enoughand focal enough to consider, and the medications are not adequate, botu-linum toxin injections can be considered. For patients who cannot be helpedwith the above, it is reasonable to consider neurosurgical therapy orimplanted medication pumps that can deliver intrathecal medications. Theuse of motor blocking injections (botulinum toxin) can be considered.
This method has proven to be most helpful for the focal dystonias and dys-kinesias. In these disorders, injection of botulinum toxin is used successfullyto block the transmission from the motor nerve to the motor end plate onthe muscle for a period of 2 to 3 months (until the nerve sprouts and recon-nects to the muscle). In the specific case of bruxism, some of the damage thatis done by this behavior can be mitigated with the use of an intraoral appli-ance. For hemifacial spasm of spontaneous origin, intracranial surgicaldecompression surgery is used occasionally to remove the source of theirritation on the nerve.
This approach can be used for hemifacial spasm if the clinician has deter- mined that there is a compressive lesion of the facial nerve . The involved blood vessel is lifted off from the facial nerve and often a sponge is placedbetween the vessel and the nerve bundle.
If a specific muscle is involved (focal dystonia) or predominates on the OMD presentation, severing it may offer a solution when the patient hasbeen refractory to other, more conservative approaches and cannot function.
Blepharospasm may respond to cutting of the orbicularis oculi muscle The globus pallidus is a functional entity within the basal ganglia in the brain. This procedure involves creating a surgical lesion (localized damage)in this area of the brain that is involved with motion control; this can be ofvalue for certain dystonias and torticollis . This is one surgical approachthat is used for managing Parkinson’s disease.
Deep brain stimulation uses an implanted electrode to deliver continuous high-frequency electrical stimulation to the thalamus, globus pallidus, orany part of the brain that is involved with the control of movement .
In spite of these methods, the prognosis for curing a specific OMD ispoor; however, some of them can be managed successfully with a combina-tion of education, medications, and selective injections of botulinum toxin.
Treatment of drug-induced dyskinesia and dystonic extrapyramidalreactions The general rule is that the offending medication is withdrawn and it is hoped that the dyskinesia or dystonic reaction goes away Fortunately,acute dystonic reactions secondary to neuroleptic drugs are infrequent anddisappear upon discontinuation of the medication; however, this may takedays to months, depending upon the drug, its dose, and the patient. Thesame is true for less severe dystonic EPS reactions that are associatedwith SSRIs and stimulant drugs.
If the suspected medication cannot be stopped or if the motor hyperactiv- ity is severe, the following methods are used to treat the motor hyperactivity:diphenhydramine, 50 mg, or benztropine, 2 mg intravenously (IV) or intra-muscularly (IM) The preferred route of administration is IV, butif this is not feasible, IM drug administration can be used. Finally, amanta-dine, 200 to 400 mg/d by mouth , and diazepam, 5 mg IV , have beenshown to be effective for recurrent neuroleptic-induced dystonic reactions.
Some patients who have SSRI-induced dystonic EPS have relief when thedosage of SSRI or the other stimulant drug is reduced (eg, fluoxetine changedfrom 20 mg/d to 10 mg/d). Other patients respond to the addition of buspir-one in dosages of 5 to 15 mg/d . Other patients developed bruxism within the first few weeks of SSRI therapy; however, they were treated suc-cessfully with buspirone, 10 mg two to three times daily. Buspirone seemsto be an effective treatment based on a few case reports. This drug mayhave an additional benefit of relieving anxiety if it is present. It is usually tol-erated well and carries a low risk for significant side effects. Finally, switchingto antidepressants that have not been associated with bruxism, such asmirtazapine or nefazodone, is an option.
Treatment of spontaneous dyskinesias and dystonias With any new-onset movement disorders without obvious cause, a motor suppressive medication trial is logical. The commonly used medications arepresented in If the disorder is severe enough and focal enough toconsider, and the medications are not adequate, botulinum toxin injectionsshould be considered. Finally, for patients who cannot be helped with theabove methods, and the scientific evidence to support alternative approachesis reasonable, consider neurosurgical therapy or implanted medicationpumps that can deliver intrathecal medications. Regarding the prognosisof motor suppressive medications, a recent meta-analysis of the literaturemade several conclusions that should be shared with patients before startingtreatment . First, this review suggested that botulinum toxin has obviousbenefit for the treatment of focal dystonias, such as cervical dystonia andblepharospasm. Second, trihexyphenidyl in high dosages is effective for thetreatment of segmental and generalized dystonia in younger patients. Third,all other methods of pharmacologic intervention for generalized or focaldystonia, including botulinum toxin injections, have not been confirmed asbeing highly effective according to accepted evidence-based criteria.
There are multiple motor suppressive medications used in motor disorder The anticholinergic drugs, such as trihexyphenidyl hydrochloride, biper- iden, or benztropine are the first line of motor suppressive medications usedfor dystonia, although they are only partially effective when compared withbotulinum toxin injections It is critical to start at a low dose and in-crease the dose very slowly to try to minimize the adverse effects (dry mouth,blurred vision, urinary retention, confusion, memory loss).
Gamma-aminobutyric acid receptor agonist therapy Baclofen is a GABA-ergic agent that is used in spasm . The starting dosage is 10 mg at bedtime. The dosage should be increased by 10 mg Table 2Medications used for management of hyperkinetic motor disorders Abbreviations: bid, twice a day; Max, maximum; tid, three times a day.
each week to a maximum of 30 mg three or four times daily. The best datafor baclofen is not for oral medications, but for intrathecal injections ofbaclofen that are delivered with an implantable pump The mainside effects include drowsiness, confusion, dizziness, and weakness. Finally,a recent report suggests that tiagabine, a GABA reuptake inhibitor that isused as an adjunctive anticonvulsant treatment for partial seizures, can behelpful in bruxism reduction . The dosages of tiagabine that are usedto suppress nocturnal bruxism at bedtime (4–8 mg) are lower than thosethat are used to treat seizures.
Benzodiazepines can be effective for suppression of focal, segmental, and generalized dystonia They bind to a specific benzodiazepine receptor onGABA receptor complex, which increases GABA affinity for its receptor. Nostudy has found a significant difference between the various benzodiazepinesand clonazepam, which has been widely used in movement disorders. Thestarting dose for clonazepam is 0.25 mg at bedtime and gradually increasingthe dosage to a maximum of 1 mg four times daily. The main side effectsinclude drowsiness, confusion, trouble concentrating, and dizziness.
A specific subset of dystonias that have an onset in childhood was shown to respond remarkably well to low-dosage L-dopa, such as carbi/levodopa.
These dystonias are referred to as dopa-responsive dystonias (DRD), andhave been shown in recent years to encompass adult parkinsonism, adult-onset parkinsonism, adult-onset oromandibular dystonia, spontaneouslyremitting dystonia, developmental delay and spasticity mimicking cerebralpalsy, and limb dystonia that is not only diurnal but related clearly to exer-cise .
Miscellaneous drugs for movement disorder therapy There are several miscellaneous drugs that have been reported to sup- press motor disorders. One medication that is used to suppress motor activ-ity is buspirone, which is a nonbenzodiazepine anxiolytic drug .
Another drug whose mechanism is unclear is amantadine, which is usedto suppress extrapyramidal reactions Other drugs that suppress motoractivity are diphenhydramine and clonidine There are numerous drugs that are approved by the US Food and Drug Administration and used for relief of local regional musculoskeletal painand hydrochloride, metaxalone, methocarbamol, and orphenadrine citrate .
Generally, these medications are used only for acute clinical proven spasmand are not recommended for long-term use. This is because the evidenceis weak that these muscle relaxants are beneficial for individuals who havechronic muscle pain that affects the neck and lower back . As faras chronic involuntary oral motor disorders are concerned, these drugsare ineffective and do not play a role in their management.
In 2003, a thorough review of botulinum toxin for oral motor disorders was published; it described the potential uses and current evidence basis forusing this medication in the orofacial region . The toxin that is used inbotulinum toxin injections is produced by the anaerobic bacterium Clostrid-ium botulinum. This injectable drug is able to block motor nerve conduction,and once injected, it suppresses muscle activity for a time period that rangesfrom 8 weeks to 16 weeks for botulinum toxin type-A. Any clinician whohas used this medication will testify to its powerful and dramatic effect insome cases. Unfortunately, this treatment is only palliative. Botulinumacts by interfering with vesicular exocytosis, which blocks the release of neu-rotransmitters that are contained within these vesicles. The blockage occurswhen the toxin enters the nerve and cleaves proteins that are needed for thedocking and release of the vesicle contents into the synaptic cleft . Ace-tylcholine is believed to be the main neurotransmitter that is blocked by theBoNT/A. BoNT/A is manufactured by Allergan, Inc. (Irvine, California), asBotox . This agent is supplied in vials in a lyophilized form, at a dose of100 U per vial. The typical expiration date is 24 months when stored at À5to À20C. Another serotype, BoNT/B, is marketed by Solstice Neurosci-ences, Inc. (San Diego, California) as MyoblocÒ. Another BoNT/A formu-lation, Dysport, is marketed outside of the United States by Ipsen Ltd. inEurope. All of these preparationsdBotox, Myobloc, and Dysportddifferin formulation and potency; hence, their units are not interchangeable.
Side effects can be divided into site-of-injection side effects and medica-tion-related side effects. With regard to site-of-injection side effects, the nee-dles that are used for most injections are small (27–30-gauge needles); if theskin is cleaned properly, then the chances of local hematoma, infection, orpersistent pain in the injection site is extremely low. Medication-relatedside effects generally are few, transitory, and tolerated well by patients.
The most common medication-related side effect is adjacent muscle weak-ness (eg, an inadvertent weakening of the muscles of facial expression orswallowing when this is not desired). For patients who have had injectionsinto the lateral pterygoid or palatal muscles, slurred speech with palatalweakness also is a distinct possibility. In general, these ‘‘inadvertent weak-ness’’ complications that are due to local diffusion of the drug can and dooccur. Moreover, this complication is technique and dose-dependent A second side effect with botulinum toxin injections of the masticatory muscle is an alteration in the character of the saliva of patients who have nothad direct salivary gland injections. Although this is an uncommon prob-lem, some patients report that their saliva is diminished and thicker (ie,ropy saliva); it is more likely with higher doses and for injections aroundthe parotid or submandibular gland. Obviously, this effect is desired at timesif there is a substantial sialorrhea problem.
In most cases, the above complications are less problematic than are the untreated original motor disorder and generally do not stop the patient fromseeking additional injections. If the injections are being used primarily totreat pain secondary to contraction, these complications might be morebothersome. Fortunately, persistent, more significant complications are dis-tinctly rare. For example, systemic complications are uncommon and al-though several studies have reported a flulike syndrome, particularly afterthe first injection, such symptoms also have been reported following placeboinjection. Finally, some patients develop antibodies to the toxin. It is unclearexactly what factors predispose to development of antibodies, but somestudies suggest that the risk is increased by higher-dose and more frequentinjections. For this reason, injections are not done more often than onceevery 12 weeks.
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