The Broadening Application of Chemodenervation in X-Linked Dystonia-Parkinsonism (Part II): An Open-Label Experience With Botulinum Toxin-A (Dysport®) Injections for Oromandibular, Lingual, and Truncal-Axial Dystonias

Abstract

While the majority of chemodenervation clinics worldwide typically use botulinum toxins for the treatment of common conditions such as blepharopsams, cervical dystonia, limb dystonia, and spasticity, the unusually high concentration of X-linked dystonia-parkinsonism (XDP) has allowed us to collect and describe our experience in the use of botulinum toxin type A (BoNT-A) on rarer dystonic patterns. BoNT-A (Dysport®) was injected in a total 109 dystonias of XDP. Our cohort included: 50 cases in the oromandibular area (jaw opening: 32 cases, jaw closing: 12 cases, and jaw deviation: 6 cases); 35 cases in the lingual area (tongue protrusion: 27 cases and tongue curling: 8 cases); and, 24 cases in the truncal-axial area (flexor: 12 cases, extensor: 7 cases, and lateral-extensor: 5 cases). Interestingly, pain, often a nonprominent symptom of dystonias, was frequently reported in 40/50 XDP cases with oromandibular dystonia and 18/24 XDP cases with truncal-axial dystonia. All BoNT-A procedures were performed under electromyography guidance. A "high potency, low dilution" BoNT-A protocol was applied for oromandibular, lingual, cranial, cervical, and distal limb dystonias; whereas for dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol was applied. Outcomes measures included: the global dystonia rating scale (DRS) and pain visual analog scale (VAS) reduction at week 4; duration of BoNT-A effects; and, side effect profile. The median DRS score after 4 weeks was 3 ("substantial improvement") for oromandibular and lingual dystonias and 2 ("moderate improvement") for truncal-axial dystonias. Pain reduction was significantly reduced (75%-80% in oromandibular; 30%-80% in truncal-axial dystonias). The median duration of BoNT-A effect was 16 weeks for oromandibular, 12 weeks for lingual, and 11 weeks for truncal-axial dystonias. Compared to a generally safe and well-tolerated BoNT-A injections for truncal-axial dystonias, the oromandibular-lingual dystonias had the following frequency of adverse events: oromandibular--19% in jaw opening and 17% in jaw closing dystonias; lingual--19% in tongue protrusion and 13% in tongue curling dystonias. The most frequent adverse events were mouth dryness and dysphagia. Thus, BoNT-A injection working protocols may be adopted in XDP dystonia that adheres to cost minimization (e.g., lower dose end per selected muscle), while achieving some benefit, and potentially reduce the adverse event profile.

Dystonia, Spasticity and Botulinum Toxin Therapy: Rationale, Evidences and Clinical Context

“…In the large cohort of oromandibular and lingual dystonias found in XDP, BoNT-A was shown to be safe and effective as one carefully navigates through recommended technical considerations (36). In XDP as well, BoNT-A targeted in cervical and limb dystonias, indicated its superiority over MAB (37).…”

“…injections in the peri-ocular, facial, oromandibular, lingual, laryngeal and neck muscles) and distal limb regions, where BoNT-A is expected to be maximized in a targeted (usually smaller) muscles through 1-2 injection sites, and where spread is best avoided. Whereas, in dystonias of the abdominal, paraspinal, and proximal limb muscles, a "low potency, high dilution" BoNT-A injection protocol could best be applied, since spread may be desirable for very large muscles, when multipoint muscle injections is utilized (36). In view of its "dual effects" on the extrafusal and intrafusal muscles, the clinical benefit in practice may "outstrip" the weakness induced by the BoNT (4,39) .…”

Practical Tips on Botulinum Toxin Injections

“…This study supports the concept that injection into multiple sites with lower doses could reduce side efects by preventing the difusion of "oNT, in other words its biological efect, to other muscles beyond the injection site [1 ]. Therefore, Rosales et al [19] recommended a high potency, low dilution of "oNT/" for oromandibular, lingual, cranial, cervical, and distal limb dystonias, which are small and localized targets. In contrast, " low potency, high dilution of "oNT/" is more useful for big muscles.…”

Dystonia of the Oromandibular, Lingual and Laryngeal Areas

“…14 Jaw deviation dystonia may likewise occur and BoNT injections are done at the temporalis muscle (best approached injecting anterior fibers of muscle) ipsilateral to the jaw deviation and at the lateral pterygoid muscle in the contralateral side. 27 Side effects of BoNT injection for OMD include jaw weakness, loss of smile, jaw tremor, dysphagia and nasal regurgitation, but side effects are decreased with dose adjustment and accurate injection. 3,30 "Geste antagoniste" or oral sensory feedback devices can be used in the treatment of OMD and as an adjunct to BoNT therapy.…”

“…For jaw opening dystonias the target muscle is the lateral pterygoid muscle. 27 The technique is an intraoral injection performed by following the ramus of the mandible to locate the lateral ptyergoid and injecting approximately 45 units on each side. 28 For jaw closing dystonia, BoNT is injected into the masseter muscle.…”