Breathing dystonia in Meige syndrome.

BACKGROUND: Dyspnoea is rarely mentioned in the clinical description of adult-onset isolated dystonia. In this study, we present the clinical features of 13 patients with Meige syndrome (cranio-cervical dystonia) with breathing difficulties. METHODS: A retrospective case note review was performed of patients presenting with Meige syndrome and shortness of breath, to a neuro-laryngology MDT clinic. RESULTS: Some patients were severely limited by their breathlessness, but others did not volunteer these symptoms. The majority of patients were referred with the assumption that the larynx was the cause of the problem; however half the patients did not have evidence of laryngeal involvement. Of the patients who had laryngeal involvement, injecting the larynx alone did not always relieve the dyspnoea. The majority of our patients responded to injection of the suprahyoid muscles, including genioglossus, digastric and mylohyoid. CONCLUSION: We recommend routinely establishing if the patient with Meige syndrome has signs or symptoms of breathlessness, and establishing the level of the problem, as this can be treated successfully.

Botulinum toxin treatment of dystonic anterocollis: What to inject.

BACKGROUND: Anterocollis (AC) is a rare form of cervical dystonia, which responds poorly to botulinum toxin treatment. OBJECTIVES: To recognise the different clinical phenotypes of AC and to detail the selection of muscles from the results of treating a cohort of 15 AC patients with Botulinum Toxin. METHODS: The study was performed using prospectively collected data. We included 15 patients with cervical dystonia and AC posture, treated between 2016 and 2019 in our joint Neuro-ENT clinic. We excluded patients with posterior cervical muscle weakness and patients with Parkinsonism. We characterised the primary dystonic posture of every AC patient as posterior sagittal shift, head flexion or neck flexion, or a combination of the three. RESULTS: All AC patients had a more widespread dystonic picture with a majority having Meige syndrome, but AC was the most problematic feature. Treatment with botulinum toxin required the injection not only of the deep cervical flexor (DCF), but also the sterno-cleido-mastoid (SCM) and moreover the supra-hyoid (SH) muscles. The choice between the longus capiti and the longus colli depended on the AC posture. Half of the patients had a dramatic improvement with 90% satisfaction or above. CONCLUSION: AC posture is a complex but treatable type of CD. A joint Neuro-ENT clinic is an ideal setting in which to target all the dystonic muscles. This allows the injection of the longus capiti (under nasal endoscopic approach) as well as the supra-hyoid and SCM muscles in the same session.

Ultrasound Study to Validate the Anterior Cervical Approach to the Longus Colli Muscle Using Electromyography Control Alone.

Background: One of the main difficulties in the treatment of dystonic anterocollis is the injection of the deep flexor muscles of the neck such as Longus Colli (LCo). The injection of the LCo has been regarded as difficult and potentially dangerous; since we published our anterior median approach, a number of questions about the precision and the safety of our technique have been raised by colleagues. Methods: 7 patients with anterocollis were injected, using our injection technique and when the needle was deemed to be in place, we used the ultrasound probe to determine what the needle had passed through, the depth of the tip of the needle and if the identified muscle was indeed LCo. Results: On the ultrasound section the LCo muscle is between 24 and 28 mm deep in the patients examined in this study. The location of the needle was confirmed by ultrasound and in most cases the needle was placed in the right axis but sometimes not deep enough. The EMG control made it possible to correct the depth in all cases. In most of the injections the needle traversed the thyroid. No acute incident occurred by this route of injection. Injections were performed between 22 and 28 mm deep. Discussion: From this study and based on a review of complications over 9 years experience with injecting LCo under EMG control using an anterior approach, we conclude that this technique is precise, safe and well tolerated. Summary Highlights: The injection of the Longus Coli muscle for anterocollis has been regarded as difficult and potentially dangerous. This study showed, using ultrasound to determine the needle trajectory, that the anterior approach using EMG control is a precise, safe and well tolerated technique.

Endoscopic Injection of the Longus Capiti Muscle in the Treatment of Dystonic Head Flexion.

BACKGROUND: Anterocollis posture is a relatively rare finding among patients with cervical dystonia and often the cause of treatment failure. The dystonic posture can be complex to analyze, and the deep flexor muscles of the neck, longus capiti, and longus coli can be challenging to access. METHODS: We present a modification of a previously described endoscopic technique that allows straightforward access to the longus capiti muscles in an outpatient setting under local anesthetic. RESULTS: We describe the technique based on our experience on 6 patients during a 2-year period with a total of 22 injections, and we review the literature. CONCLUSION: The injection is well tolerated and has led to significant improvement in the majority of patients.

Dominant mutations of the Notch ligand Jagged1 cause peripheral neuropathy.

Notch signaling is a highly conserved intercellular pathway with tightly regulated and pleiotropic roles in normal tissue development and homeostasis. Dysregulated Notch signaling has also been implicated in human disease, including multiple forms of cancer, and represents an emerging therapeutic target. Successful development of such therapeutics requires a detailed understanding of potential on-target toxicities. Here, we identify autosomal dominant mutations of the canonical Notch ligand Jagged1 (or JAG1) as a cause of peripheral nerve disease in 2 unrelated families with the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2 (CMT2). Affected individuals in both families exhibited severe vocal fold paresis, a rare feature of peripheral nerve disease that can be life-threatening. Our studies of mutant protein posttranslational modification and localization indicated that the mutations (p.Ser577Arg, p.Ser650Pro) impair protein glycosylation and reduce JAG1 cell surface expression. Mice harboring heterozygous CMT2-associated mutations exhibited mild peripheral neuropathy, and homozygous expression resulted in embryonic lethality by midgestation. Together, our findings highlight a critical role for JAG1 in maintaining peripheral nerve integrity, particularly in the recurrent laryngeal nerve, and provide a basis for the evaluation of peripheral neuropathy as part of the clinical development of Notch pathway-modulating therapeutics.

Objective detection of esophagopharyngeal reflux in patients with hoarseness and endoscopic signs of laryngeal inflammation.

GOALS: We aimed to quantify pharyngeal exposure to gastric contents in patients diagnosed with reflux-related hoarseness and healthy controls using new diagnostic techniques. BACKGROUND: Hoarseness with typical signs on laryngoscopy is commonly thought to be caused by esophagopharyngeal reflux. New methods are proposed to assess pharyngeal exposure to gastric contents. They are suggested to measure: (1) liquid or mixed gas-liquid acid and nonacid reflux with impedance pH, (2) aerosolized acid reflux (Dx-pH measuring system), and (3) pepsin in the saliva. STUDY: Twenty-one patients with hoarseness and positive laryngoscopy and 10 controls underwent simultaneous impedance pH, Dx-pH monitoring, and saliva pepsin sampling (5 samples in 24 h). RESULTS: Of the 21 patients, 10 had impedance pH-detected reflux plus at least 1 other test positive. These patients were more likely to have symptomatic relief after proton pump inhibitor therapy. Three of the 21 patients had all 3 tests positive and 4 had all tests negative. None of the controls had impedance pH-detected reflux. Two controls had a positive Dx-pH "RYAN score" and 1 control had >1 saliva sample positive for pepsin. Only 11% of Dx-pH drops to pH<4, 15% pH drops to pH<5, and 10% of pH drops to pH<5.5 coincided with impedance pH-detected reflux in the esophageal body. Positive pepsin saliva samples were preceded by more reflux events [3 (range, 0 to 10)] in the previous 60 minutes than negative samples [0 (range, 0 to 7)] (P<0.0001). CONCLUSION: A subgroup of patients with hoarseness (10/21) had objective detection of the esophagopharyngeal reflux. We propose that these patients are more likely to benefit from further intense antireflux therapy. Detection of pepsin in the saliva may be a useful screening tool in these patients.

Anterior and posterior sagittal shift in cervical dystonia: a clinical and electromyographic study, including a new EMG approach of the longus colli muscle.

Anterior and posterior sagittal shift of the head are less common postures in cervical dystonia and, as such, have not been comprehensively studied. In this article, we have detailed both our clinical and electromyography (EMG) findings in 11 patients with prominent dystonic sagittal shift of the head. A new technique of injection of the longus colli, based on a laterocervical approach under EMG guidance, is described. We have detailed the clinical phenotypes of dystonic posterior sagittal shift or "double chin" posture (4 patients) and anterior sagittal shift or "goose neck" posture (7 patients) and proposed specific botulinum toxin (BoNT) treatment protocols for these postures. Seven patients with the goose-neck posture responded well (70%-90% benefit) to BoNT injections. Six patients responded to splenius capitii injections alone, and 1 patient needed, in addition, the injection into both sterno-cleido-mastoid muscles. Four patients with the double-chin posture responded well to BoNT injection (50%-80% benefit). Two patients responded to suprahyoid injection alone, and 2 patients needed, in addition, the injection into the sterno-cleido-mastoid and longus colli muscles. Dysphagia was avoided in all of the double-chin patient group by adjusting our injection technique into the suprahyoid and longus colli muscles. The individualised toxin BoNT protocols have resulted in an improved benefit. The new Longus colli injection technique has allowed for a therapeutic effect of botulinum toxin without causing dysphagia.