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The 11 th International Meeting on Neuroacanthocytosis Syndromes was held on September 15 th -17 th , 2023 at the University Hospital Campus in Homburg/Saar, Germany. The meeting followed the previous ten international symposia, the last of which was held online due to restrictions due to COVID19, in March 2021. The setting of the meeting encouraged interactions, exchange of ideas, and networking opportunities among the participants from around the globe, including basic and clinical scientists, clinicians, and especially patients, their relatives and caregivers. A total of about 20 oral communications were presented in five scientific sessions accompanied by a keynote lecture, a "Poster-Blitz" session, the "Glenn Irvine Prize" lecture and a panel discussion about "Patient registries, international cooperation & future perspectives". In summary, attendees discussed recent advances and set the basis for the next steps, action points, and future studies in close collaboration with the patient associations, which were actively involved in the whole process., Competing Interests: The author has no competing interests to declare., (Copyright: © 2023 The Author(s).)

Deep brain stimulation (DBS) is a reversible treatment for chorea-acanthocytosis (ChAc). Its safety and efficacy remain elusive due to the low prevalence of ChAc. We aimed to investigate the safety and efficacy of DBS for ChAc by systematically reviewing literature through PubMed and EMBASE. Inclusion criteria were reports on the efficacy or safety of DBS for ChAc and English language articles, and exclusion criteria were other movement disorders, non-human subjects, and studies without original data. Most studies were published as case reports, and we therefore pooled these cases in one cohort. Twenty studies with 34 patients were included. The mean age of symptom onset was 29.3 years (range, 17-48). The median follow-up was 12 months (range, 2-84). Twenty-nine patients underwent GPi-DBS, two received STN-DBS, and one underwent Vop-DBS. Electrodes were implanted into the ventralis oralis complex of the thalamus and the pallidal in two patients. Symptoms seemed to be easier relieved in chorea (88.5%) and dystonia (76.9%) but dysarthria of most patients (85.7%) was no response after DBS. The Unified Huntington's Disease Rating Scale-Motor Score was used to assess the efficacy of DBS in 25 patients; the mean score decreased from 43.2 to 22.3 and the median improvement rate was 46.7%. Of 24 patients with data on adverse events, complications occurred in 9 patients (37.5%; mostly transient and mild events). DBS is a promising treatment for ChAc with satisfactory efficacy and safety based on the review. Pallidal and thalamic DBS have been applied in ChAc; GPi-DBS seems to be more widely used., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The 10th International Meeting on Neuroacanthocytosis Syndromes was held online on March 10th12th, 2021. The COVID19 pandemic situation made our planned meeting in Barcelona on March 2020 to be suspended by one year, and finally took place online. The meeting followed the previous nine international symposia, the last of which was held in Dresden, Germany in March, 2018. The setting of the meeting encouraged interactions, exchange of ideas and networking opportunities among the high number of participants from around the globe, including scientists, neurologists and specially patients and caregivers. A total of 27 oral communications were distributed in 8 sessions with topics ranging from molecular and cellular functions of VPS13 genes and proteins, their involvement in Neuroacanthocytosis Syndromes and finally clinical aspects and patients care. In addition, 5 posters were presented. Altogether, scientists and neurologists discussed recent advances and set the bases for next steps, action points, and future studies in close collaboration with the patients associations, which are always actively involved in the whole process., Competing Interests: The authors have no competing interests to declare., (Copyright: 2021 The Author(s).)

Introduction: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center., Methods: We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months., Results: All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 μsec to 98 μsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes., (© 2018 International Neuromodulation Society.)

Background: Chorea acanthocytosis is an extremely rare neurodegenerative condition characterized by neuropsychiatric disturbances, movement disorders, neuropathy, seizures, and acanthocytosis. In this case report, the authors will present the management of the oromandibular movement disorders associated with this disease., Case Description: This case report describes the focal management of the severe orofacial manifestations associated with this condition. The therapeutic approach adopted to reduce the severe oromandibular movements, dysphagia, and the numerous oral ulcers was selective electromyography (EMG)-guided botulinum toxin application to the inferior head of the lateral pterygoid muscles and masseters. This would be applied to control severe and sudden oromandibular dystonia., Results: Through this procedure, the authors were able to reduce these severe oral manifestations, which had a major impact on the patient's quality of life, and temporarily improve vital functions, such as mastication, deglutition, and speech articulation., Conclusions: Electromyography-guided botulinum toxin application may be a useful tool in the multimodal management of this condition.

The aim of this article is to present two Slovenian chorea-acanthocytosis (ChAc) siblings with an unusual predominantly dystonic ChAc phenotype. For diagnostic purposes, the genomic DNA was screened for VPS13A mutations. Movement disorder was evaluated and scored according to the Dystonia Movement and Disability Scale (DMDS) in order to evaluate the effects of L-dopa on dystonia. Brain imaging was performed with the use of magnetic resonance imaging scan and 99m Tc-ethyl cysteinate dimmer single photon emission computed tomography (Tc-ECD SPECT). Clinical neurological examination disclosed gait dystonia. Marked swallowing difficulty due to tongue and feeding dystonia was observed. Both siblings were found to be heterozygous for a substitution in exon 22 (c.2191C>T) and for a deletion in exon 35 (c.3995_3996delinsA) leading to mutation in VPS13A. After being administered L-dopa for three months, both subjects showed significant symptomatic improvement documented by reduced DMDS scores. It is concluded that VPS13A mutation testing may improve diagnosis of dystonia and recognition of atypical ChAc phenotypes. It seems that L-dopa could be effective in the treatment of dystonia due to VPS13A mutations.

Background: Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS., Methods: Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months)., Results: Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery., Conclusion: This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.

Background and Importance: Chorea acanthocytosis is a progressive hereditary neurodegenerative disorder characterized by hyperkinetic movements, seizures, and acanthocytosis in the absence of any lipid abnormality. Medical treatment is typically limited and disappointing., Clinical Presentation: We report on a 32-year-old patient with chorea acanthocytosis with a failed attempt at awake deep brain stimulation (DBS) surgery due to intraoperative seizures and postoperative intracranial hematoma. He then underwent a second DBS operation, but under general anesthesia and with intraoperative magnetic resonance imaging guidance. Marked improvement in his dystonia, chorea, and overall quality of life was noted 2 and 8 months postoperatively., Conclusion: DBS surgery of the bilateral globus pallidus pars interna may be useful in controlling the hyperkinetic movements in neuroacanthocytosis. Because of the high propensity for seizures in this disorder, DBS performed under general anesthesia, with intraoperative magnetic resonance imaging guidance, may allow successful implantation while maintaining accurate target localization.

Chorea-acanthocytosis is a rare autosomal recessive disorder. To date, treatment is only symptomatic and supportive. Results from the few reports of chorea-acanthocytosis patients treated with deep brain stimulation (DBS) have been inconsistent. We present case reports for two patients with chorea-acanthocytosis who received DBS treatment and compare the outcomes with results from the literature. Both patients showed the typical clinical features of chorea-acanthocytosis with motor symptoms resistant to medical treatment. Chorea was significantly improved following low-frequency DBS treatment in both patients. However, dystonia was only mildly improved. Four chorea-acanthocytosis patients treated with DBS treatment have been reported in the literature. One patient had improvement with low-frequency DBS stimulation, while another two had improvement with higher-frequency DBS. One patient, however, did not improve with either low-frequency or high-frequency DBS. Bilateral DBS to the GPi can improve chorea and dystonia in some patients with intractable chorea-acanthocytosis. However, selection criteria for the most promising candidates must be defined, and the long-term benefits evaluated in clinical studies.

We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the VPS13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington's Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control., (Copyright © 2012 S. Karger AG, Basel.)

We present the case of a 24-year-old man diagnosed with a neuroacanthocytosis, obsessive-compulsive disorder, mild-moderate severity depressive disorder, and obsessive personality disorder. He received multiple psychotropic drugs, including neuroleptics, antidepressants, and benzodiazepines with small therapeutic response.Severe and progressive clinical impairment appeared including cognitive deterioration, chorea, tics, lingual dystonic protrusion, Parkinsonism, automutilations, and other behavioral disorders consistent with neuroacanthosytosis. Pharmacological trials were not efficacious, and the patient had medication side effects, so pharmacotherapy was reduced to minimal doses and we began electroconvulsive therapy.When the sessions were finished, the patient's speech was more coherent, although the neuroacanthosytosis was unstoppable in its progression. Thereafter, the patient received continuation electroconvulsive therapy fortnightly for 4 months until he died due the neurodegenerative disorder.

Background and Objectives: Kell antigens are encoded by the KEL gene on the long arm of chromosome 7. Kx antigen is encoded by the XK gene on the short arm of the X chromosome. Kell and Kx proteins in the red cell membrane are covalently linked by a disulphide bond. The McLeod phenotype is characterized by weakened expression of antigens in the Kell blood group system, absence of Km and Kx antigens, and acanthocytosis. It has an X-linked mode of inheritance with transmission through carrier females. Some males with the McLeod syndrome also have chronic granulomatous disease (CGD). It is generally believed that patients with non-CGD McLeod may develop anti-Km but not anti-Kx, but that those with CGD McLeod can develop both anti-Km and anti-Kx., Materials and Methods: We present serological data, DNA genotyping and gene sequencing, monocyte monolayer assay and neutrophil oxidative burst test from a patient with the McLeod phenotype without clinical evidence of CGD., Results: We report here the second example of a patient with non-CGD McLeod who developed anti-Kx in addition to anti-Km. Sequencing of our patient's XK gene confirmed the presence of a mutation resulting in a premature stop codon and lack of Kx protein in the red cell membrane, which is consistent with the diagnosis of McLeod syndrome. Neutrophil oxidative burst test was normal, indicating that our patient did not have CGD. The challenge of providing 10 compatible blood units for multiple surgeries was met., Conclusion: The second case of a rare entity, a patient with non-CGD McLeod who developed anti-Kx and anti-Km, was managed successfully with a combination of autologous donations and procurement of compatible units from national and international sources.