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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.

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.

Highlights • 13 patients with Meige (craniocervical dystonia) syndrome and breathing difficulties were identified, 6 with and 7 without laryngeal involvement. • 77% had a good (>50%) response to Botulinum toxin injection(s). • Among the 13 Meige patients, all patients, except one, had clinical signs of supra-hyoid muscles involvement, we believe this muscle group is the main cause of the dyspnoea in this specific Meige phenotype., 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.

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.

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.

Botulinum toxin (BoNT) injections are an effective\ud treatment for cervical dystonia. Approximately\ud 20% of patients eventually stop BoNT treatment,\ud mostly because of treatment failure. These\ud recommendations review the different\ud therapeutic interventions for optimising the\ud treatment in secondary poor responder patients.\ud Immunoresistance has become less common over\ud the years, but the diagnosis has to be addressed\ud with a frontalis test or an Extensor Digitorum\ud Brevis test. In case of immunoresistance to BoNTA,\ud we discuss the place the different therapeutic\ud options (BoNT-A holidays, BoNT-B injections,\ud alternative BoNT-A injections, deep brain\ud stimulation). When poor responders are not\ud immunoresistant, they benefit from reviewing (1)\ud injections technique with electromyography or\ud ultrasound guidance, (2) muscles selection and\ud (3) dose of BoNT. In addition, in both scenarios,\ud a holistic approach including drug treatment,\ud retraining and psychological support is valuable\ud in the management of these complex and severe\ud cervical dystonia.

Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) 5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity.

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.

To study the sequence of occurrence of REM-sleep behaviour disorder (RBD) and dementia and their frequency among a population of patients with idiopathic Parkinson's disease (PD). We performed a cross-sectional study on 65 PD patients seen in a movement disorder clinic and their bed partner, and asked them to complete the validated Mayo Sleep Questionnaire for RBD and sleep disorders. The diagnosis of PD with dementia (PD-D) was based on a clinical diagnosis of dementia; following DSM-IV criteria and MMSE score less than 25 and a battery of cognitive tests. From the 65 patients that completed the study, twenty-four met the clinical diagnosis of RBD. Ten of the 24 (42%) RBD patients met the clinical criteria of PD-D, whereas the remaining 14 patients were non-demented at the time of the study. The frequency of RBD was significantly higher in the PD-D group (n = 10, 77%) compared to the PD-ND group (n = 14, 27%, chi squared test: p = 0.0008). PD non-RBD had a lower occurrence of dementia (7.3%, 3 of 41) compared to those suffering from RBD (42%, 10 of 24). Of the 65 PD patients, 13 were diagnosed with PD-D and the remaining 52 were non-demented PD (PD-ND) patients. PD with RBD showed a faster decline in the number of dementia-free patients compared to the non-RBD patients (Log Rank test: p < 0.001). RBD preceded, coincided or followed the onset of the motor symptoms. This study shows that RBD and dementia have a significant coincidence in the course of PD, and RBD not only precedes or coincides with the motor signs, but can occur during the course of the progression of the PD, suggesting a degenerative process of the dopaminergic and cholinergic neurons of the brainstem nuclei, progressing at a different pace in each patient.

Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO)40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity.

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.

We review the existing literature on the involuntary facial movement disorders—benign essential blepharospasm, apraxia of eyelid opening, hemifacial spasm, and aberrant facial nerve regeneration. The etiology of idiopathic blepharospasm, a disorder of the central nervous system, and hemifacial spasm, a condition involving the facial nerve of the peripheral nervous system, is markedly different. We discuss established methods of managing patients and highlight new approaches.

PTEN-induced putative kinase 1 (PINK1) mutations result in young onset recessively inherited, levodopa responsive parkinsonism [1]. A 59-year-old lady, homozygous for PINK1, with onset of parkinsonism at age 29 years was treated initially with anticholinergic then dopaminergic medication from the age of 33 years. She remained well controlled on levodopa. She discontinued oral agonist therapy after a short trial in her 40s because of worsening dyskinesias. By 2006, age 54 years she was taking Stalevo 100, six times daily, Sinemet 125 mg once daily and Amantadine 100 mg once daily (Levodopa equivalent units, LEU, 900 mg). In 2007, age 55 years, she was started on a continuous jejunal levodopa infusion (Duodopa) because of motor fluctuations and peak dose dyskinesia. She responded very well to low-moderate infusion rates over the next 3 years (30–60 mg/h, LEU 600–900). In 2009 she reported pins and needles. Neurophysiological testing confirmed a sensory axonal polyneuropathy. She was found to be vitamin B6 deficient and her symptoms improved on replacement. Between 2009 and 2011, she was noted to be requiring increased infusion rates and was self-administering 3–4 bolus doses of 40 mg/day (LEU *1,200 mg/24 h). She developed dyskinesias and the hourly rate was reduced. In 2011, 4 years after starting Duodopa therapy, and whilst living with her sister in stable circumstances, she was admitted to hospital because of a change in her behaviour. Her older sister (also homozygous for PINK1 and with a 35-year history of parkinsonism) reported that whilst she had always been a little stubborn with mild obsessional tendencies, she had purchased a new computer and had been spending increasing amounts of time ‘‘working’’ on researching her condition. She stayed up later into the night and kept her Duodopa pump running for longer periods until eventually keeping it infusing for 24 h a day over a 2-week period. During this time she spent £700 on printer cartridges and other stationery. Based on the amount stored in the home, as described by her sister, this was excessive to the amount of stationery required as a result of the ‘‘punding’’ behavior, suggesting compulsive buying, an impulse control disorder (ICD). She was markedly dyskinetic, had paranoid delusions and delusions of grandeur and hyper-religiosity. She developed derailment of her thought processes and did not sleep for 2–3 days at a time. The Duodopa infusion was stopped and oral levodopa instigated at a lower total daily dose (LEU 150 mg daily). She remained unwell with similar behavioural disturbances and dyskinesias despite this marked reduction in the administered levodopa dose and surreptitious self-administration was suspected. After two searches of her room, a hidden supply of levodopa was discovered. Quetiapine was prescribed, increasing over a 3–4 week period to 450 mg. Her thought disorder, delusions and sleep improved but motor symptoms of freezing and akinesia were more pronounced. She experienced increased levels of anxiety and depression in her off state. The oral levodopa dose was cautiously increased (to LEU 4–500 mg over 3 months) but motor fluctuations, unpredictable freezing and dyskinesia were all re-emergent. Her family history includes an older brother and two nephews with young onset parkinsonism as well as an D. C. Paviour (&) M.-H. Marion Department of Neurology, Atkinson Morley Wing, St George’s Hospital NHS Trust, London SW17 OQT, UK e-mail: dpaviour@doctors.org.uk

The first report of the beneficial effects of botulinum toxin in treating hemifacial spasm appeared ten years ago; subsequent reports have confirmed these benefits, and these reports are reviewed here. The results of long-term (5 year) follow are also presented and details on the injection technique are discussed.