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A clinical scale fully dedicated to evaluating ocular motor abnormalities is required for now. We investigated the utility of a recently developed Scale for Ocular motor Disorders in Ataxia (SODA) in patients with multiple system atrophy (MSA). We prospectively assessed SODA in consecutive patients with MSA between August 2021 and August 2023 at the Korea University Medical Center. The results of the clinical exam-based SODA were compared with those measured using video-oculography (VOG-guided SODA). We also compared the findings with other established clinical scales targeting patients with MSA, including the Unified Multiple System Atrophy Rating Scale (UMSARS) I-II, Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (UPDRS-III), Scale for Assessment of Rating of Ataxia (SARA), Composite Autonomic Symptom Score-31 (COMPASS-31), and Composite Autonomic Severity Score (CASS). Twenty patients were enrolled in our study (17 with cerebellar-type MSA and three with Parkinson-type MSA). Scores ranged from 1 to 14 (median [interquartile range (IQR)] = 8 [5-10]). Among the subscales, saccades had a median score of 2.5 (IQR = 1-3), followed by ocular pursuit (1 [0-1]), nystagmus (1 [0-2]), saccadic intrusions (1 [0-1]), vestibulo-ocular reflex (VOR) (0.5 [0-1]), ocular alignment (0 [0-1]), and VOR cancellation (1 [0-1]). The clinical-exam-based SODA (p = 0.020) and VOG-guided SODA (p = 0.034) positively correlated with disease duration. No correlation was found between clinical exam-based SODA and other scales. Skew deviation, gaze-evoked nystagmus, VOR cancellation, and smooth pursuit had the highest precision among the items. Ocular misalignment and spontaneous and positional nystagmus were frequently false positive and were poorly detected with clinical exam-based SODA. Six patients with repeated evaluation exhibited higher scores, along with deterioration documented on other clinical scales. The SODA can reliably predict neurodegeneration as an additional clinical surrogate in MSA., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Paroxysmal dysarthria ataxia syndrome presents with recurrent, brief, stereotyped events of dysarthria, limb clumsiness, unsteady gait and vertigo or dizziness that can occur in association with lesions in the midbrain. We describe a case of a woman presenting with paroxysmal dysarthria and ataxia secondary to a midbrain lesion, treated successfully with carbamazepine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is an autoimmune central nervous system disorder, primarily manifesting as a paraneoplastic sequalae to neuroblastoma, and characterized by motor disorders and behavioral disturbances. OMAS is typified by aberrant B-cell and T-cell activation. Current treatment involves immunosuppression using corticosteroids, intravenous immunoglobulin, and rituximab. However, these approaches often lead to treatment-related toxicities and symptomatic recurrences with chronic neurocognitive impairment. We treated three children with refractory neuroblastoma-associated OMAS with tacrolimus, a T-cell-targeting calcineurin inhibitor, effectively controlling symptoms within a month and enabling the discontinuation of immunosuppression with minimal side effects. Tacrolimus shows promise as a therapeutic option for refractory OMAS., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Dysarthria is a common manifestation across cerebellar ataxias leading to impairments in communication, reduced social connections, and decreased quality of life. While dysarthria symptoms may be present in other neurological conditions, ataxic dysarthria is a perceptually distinct motor speech disorder, with the most prominent characteristics being articulation and prosody abnormalities along with distorted vowels. We hypothesized that uncertainty of vowel predictions by an automatic speech recognition system can capture speech changes present in cerebellar ataxia. Speech of participants with ataxia (N=61) and healthy controls (N=25) was recorded during the "picture description" task. Additionally, participants' dysarthric speech and ataxia severity were assessed on a Brief Ataxia Rating Scale (BARS). Eight participants with ataxia had speech and BARS data at two timepoints. A neural network trained for phoneme prediction was applied to speech recordings. Average entropy of vowel tokens predictions (AVE) was computed for each participant's recording, together with mean pitch and intensity standard deviations (MPSD and MISD) in the vowel segments. AVE and MISD demonstrated associations with BARS speech score (Spearman's rho=0.45 and 0.51), and AVE demonstrated associations with BARS total (rho=0.39). In the longitudinal cohort, Wilcoxon pairwise signed rank test demonstrated an increase in BARS total and AVE, while BARS speech and acoustic measures did not significantly increase. Relationship of AVE to both BARS speech and BARS total, as well as the ability to capture disease progression even in absence of measured speech decline, indicates the potential of AVE as a digital biomarker for cerebellar ataxia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gait and balance difficulties pose significant clinical challenges in Parkinson's disease (PD). The impairment of physiological mechanisms responsible for maintaining natural orthostatism plays a central role in the pathophysiology of postural instability observed in PD. In addition to the well-known rigidity and abnormalities in muscles and joints, various brain regions involved in the regulation of posture, balance, and gait, such as the basal ganglia, cerebellum, and brainstem regions like the pontine peduncle nucleus, are affected in individuals with PD. The recognition of the cerebellum's role in PD has been increasingly acknowledged. Cortical areas and their connections are associated with freezing of gait, a type of frontal lobe ataxia commonly observed in PD. Furthermore, impairments in the peripheral nervous system, including those caused by levodopatherapy, can contribute to gait impairment and imbalance in PD patients. Consequently, individuals with PD may exhibit frontal ataxia, sensory ataxia, and even cerebellar ataxia as underlying causes of gait disturbances and imbalance, starting from the early stages of the disease. The complex interplay between dysfunctional brain regions, impaired cortical connections, and peripheral nervous system abnormalities contributes to the multifaceted nature of gait and balance difficulties in PD. Understanding the intricate mechanisms is crucial for the development of effective therapeutic approaches targeting these specific deficits in PD., (© 2023. Fondazione Società Italiana di Neurologia.)

Fecal incontinence (FI) is often underreported and underestimated in men. Our aims were to clarify the causes and the physiological characteristics of FI in men and to underline the differences between etiological and physiological factors in men and women diagnosed with FI. The study cohort encompassed 200 men and 200 women who underwent anatomical and physiological evaluation for FI in a tertiary referral center specializing in pelvic floor disorders. All patients underwent endoanal ultrasound and anorectal manometry. Evacuation proctography was performed in some patients. Demographic, medical, anatomical, and physiological parameters were compared between the two study groups. Urge incontinence was the most frequent type of FI in both genders. In men, anal fistula, history of anal surgeries, rectal tumors, and pelvic radiotherapy were common etiologic factors, whereas history of pelvic surgeries was more common in women. Associated urinary incontinence was reported more frequently by women. External anal sphincter defects, usually anterior, were more common in women (M: 1.5%, F: 24%, P < 0.0001), whereas internal anal sphincter defect prevalence was similar in men and women (M: 6%, F: 12%, P = 0.19). Decreased resting and squeeze pressures were less common in men (M: 29%, F: 46%, P < 0.0001: M: 44%, F: 66%, P < 0.0001). The incidence of rectal hyposensitivity was higher in men (M: 11.1%, F: 2.8%, P < 0.0001), whereas rectal hypersensitivity was higher in women (M: 5.8%, F: 10.8%, P < 0.0001). Anorectal dyssynergia was more common in men (M: 66%, F: 37%, P < 0.0001). Significantly different etiological factors and physiological characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options. NEW & NOTEWORTHY Fecal incontinence (FI) in men has different etiological factors when compared with women. The prevalence of internal anal sphincter defect among men with FI was similar to women. Different manometric measurements were found among men with FI: decreased anal pressures were less common among men, whereas rectal hyposensitivity and anorectal dyssynergia were more common among men.

Objective: To examine the prevalence and characteristics of dysphagia and suck-swallow-breath incoordination as phenotypes of oral feeding difficulties., Method: A cross-sectional study with secondary data collected consecutively over 2 years from October 2020 to October 2022 to measure the prevalence of swallowing and oral feeding difficulty in preterm infants using Flexible endoscopic evaluation of swallowing examination at the tertiary Integrated Dysphagia Clinic., Results: The prevalence of swallowing disorders was 25 % and the prevalence of suck-swallow-breath incoordination was 62.5 %. The significant risk factor that may show a possible correlation with oral feeding difficulty was mature post-menstrual age (p = 0.006) and longer length of stay (p = 0.004). The dominant percentage of upper airway abnormality and disorder were retropalatal collapse (40 %), laryngomalacia (42.5 %), paradoxical vocal cord movement (12.5 %), and gastroesophageal reflux disease (60 %). The dominant characteristic of oral motor examination and flexible endoscopic evaluation of swallowing examination was inadequate non-nutritive sucking (45 %), inadequate postural tone (35 %), and inadequate nutritive sucking (65 %)., Conclusion: Dysphagia in preterm infants is mostly observed in those with mature post-menstrual age, longer length of stay, and the presence of gastroesophageal reflux disease with inadequate non-nutritive sucking and nutritive sucking abilities. Suck-swallow-breath incoordination is primarily observed in those with immature post-menstrual age, a higher prevalence of cardiopulmonary comorbidity, and a higher prevalence of upper airway pathologies (laryngomalacia, paradoxical vocal cord movement) with inadequate nutritive sucking ability., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19) can have symptoms like many neurological diseases, and one of the rare forms of these presentations is opsoclonus-myoclonus ataxia syndrome (OMAS). The pathogenesis of OMAS in adults has not been clearly elucidated and OMAS can be fatal., Case Presentation: We present a 71-year-old male patient who was admitted to the emergency department with complaints of involuntary tremor-like movements in his hands, feet and mouth, and speech impediment for three days, and was followed up with COVID-19. The patient was diagnosed with OMAS and clonazepam treatment was started. He died three days later due to respiratory arrest. Our case is the first case diagnosed with COVID-19-associated OMAS in Turkey., Discussion: OMAS has no definitive treatment. Early diagnosis and initiation of corticosteroids and intravenous immunoglobulin (IVIG) therapy, if necessary, can be life-saving. In COVID-19 patients with unexplained clinical findings, awareness of different and rare diseases and a multidisciplinary approach has vital importance., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Adalet Altunsoy, Nizamettin Kemirtlek, Halime Araz, Ebru Bilge Dirik, Esragül Akıncı.)

Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare immune-mediated movement disorder occurring as a paraneoplastic manifestation of neuroblastic tumours (NTs), especially neuroblastoma in infancy. Ganglioneuroma (GN), the benign tumour in the spectrum, is rarely associated with OMAS. We report the case of a child in her second year of life presenting with acute onset of progressive paraplegia and OMAS. MRI showed diffuse and infiltrating left paraspinal mass from T3-T9 levels with differentials of neuroblastoma or ganglioneuroblastoma. Histopathological and immunohistochemistry examination of the excised tumour showed maturing GN. The OMAS was managed with intravenous immunoglobulin and steroids. In the 6-month follow-up, the child has a residual motor weakness with myelomalacia in neuroimaging. The case report substantiates the occurrence of OMAS as paraneoplastic manifestation in NTs, including benign, in children younger than 2 years with a female predilection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare autoimmune disorder. Approximately half of the cases are associated with neuroblastoma in children. This study's aim is to review management of our cases with OMAS-associated neuroblastoma for treatment approach as well as long-term follow-up., Methods: Age at onset of symptoms and tumor diagnosis, tumor location, histopathology, stage, chemotherapy, OMAS protocol, surgery, and follow-up period were evaluated retrospectively in six patients between 2007 and 2022., Results: Mean age of onset of OMAS findings was 13.5 months and mean age at tumor diagnosis was 15.1 months. Tumor was located at thorax in three patients and surrenal in others. Four patients underwent primary surgery. Histopathological diagnosis was ganglioneuroblastoma in three, neuroblastoma in two, and undifferentiated neuroblastoma in one. One patient was considered as stage 1 and rest of them as stage 2. Chemotherapy was provided in five cases. The OMAS protocol was applied to five patients. Our protocol is intravenous immunoglobulin (IVIG) 1 g/kg/d for 2 consecutive days once a month and dexamethasone for 5 days (20 mg/m 2 /d for 1-2 days, 10 mg/m 2 /d for 3-4 days, and 5 mg/m 2 /d for the fifth day) once a month, alternatively by 2-week intervals. Patients were followed up for a mean of 8.1 years. Neuropsychiatric sequelae were detected in two patients., Conclusion: In tumor-related cases, alternating use of corticosteroid and IVIG for suppression of autoimmunity as the OMAS protocol, total excision of the tumor as soon as possible, and chemotherapeutics in selected patients seem to be related to resolution of acute problems, long-term sequelae, and severity., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: In accordance with the rising number of SARS-CoV‑2 infections, reports of neurological complications have also increased. They include cerebrovascular diseases but also immunological diseases such as Guillain-Barre syndrome (GBS), Miller-Fisher syndrome (MFS), and opsoclonus-myoclonus-ataxia syndrome (OMAS). While GBS and MFS are typical postinfectious complications, OMAS has only recently been described in the context of COVID-19. GBS, MFS, and OMAS can occur as para- and postinfectious, with different underlying pathomechanisms depending on the time of neurological symptom onset. The study aimed to describe clinical features, time between infection and onset of neurological symptoms, and outcome for these diseases., Methods: All COVID-19 patients treated in the neurological ward between January 2020 and December 2022 were screened for GBS, MFS, and OMAS. The clinical features of all patients, with a particular focus on the time of onset of neurological symptoms, were analyzed., Results: This case series included 12 patients (7 GBS, 2 MFS, 3 OMAS). All GBS and one MFS patient received immunomodulatory treatment. Three patients (2 GBS, 1 OMAS) had a severe COVID-19 infection and received mechanical ventilation. In patients with OMAS, only one patient received treatment with intravenous immunoglobulin and cortisone. The remaining two patients, both with disease onset concurrent with SARS-COV‑2 infection, recovered swiftly without treatment. In all subgroups, patients with concurrent onset of neurological symptoms and COVID-19 infection showed a trend toward shorter disease duration., Conclusion: All patient groups displayed a shorter disease duration if the onset of neurological symptoms occurred shortly after the COVID-19 diagnosis. In particular, both the OMAS patients with symptom onset concurrent with COVID-19 showed only abortive symptoms followed by a swift recovery. This observation would suggest different pathomechanisms for immune-mediated diseases depending on the time of onset after an infection., (© 2023. The Author(s).)

Introduction: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease., Methods: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale., Results: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively)., (© 2023. Fondazione Società Italiana di Neurologia.)

Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.

Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Typical retinitis pigmentosa (RP) may not be the only retinal phenotype encountered in ataxia with vitamin E deficiency (AVED). The following short case series describes a novel form of retinopathy in AVED. We describe two patients with AVED belonging to the same consanguineous sibship. Both presented an unusual retinopathy consisting of scattered, multifocal, nummular, hyperautofluorescent atrophic retinal patches. The retinopathy remained stable under vitamin E supplementation. We hypothesize these changes to be the result of arrested AVED-related RP following early supplementation with α-tocopherol acetate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective : Hypertrophic Olivary Degeneration is a rare condition causing transneuronal degeneration of the inferior olivary nucleus. Symptoms manifest as progressively worsening palatal tremor, ataxia, and eye movement disturbances that plateau after several months. Though rarely documented in the literature of this specific condition, disconnection of the inferior olivary nucleus from the cerebellum, and cerebellar atrophy represent a pathway to developing subsequent cerebellar cognitive affective syndrome. The presented case documents the neuropsychological sequelae of a 39-year-old female with a history of hypertrophic olivary degeneration and symptoms of palatal tremor, opsoclonus myoclonus, ataxia, and delusions. Method: Review of the patient's medical records, interviews with the patient and her father, and a neuropsychological assessment battery were used to collect data. Review of currently published literature lent to case conceptualization. Results: Neuropsychological testing revealed deficits in executive functioning, attention, and language. An anomalous, fixed persecutory delusion was revealed. Conclusion: Hypertrophic olivary degeneration creates disconnection syndromes between the inferior olivary nucleus, red nucleus, and cerebellum. Late stages of the disorder cause atrophy of the inferior olivary nucleus and adjacent structures. While the motor sequela is well documented, the neuropsychological and psychiatric impact is infrequently discussed in existing literature. We present the first case to detail the neuropsychological sequelae of hypertrophic olivary degeneration and propose a mechanism for the development of cognitive impairment and psychotic features within this condition.

Hereditary ataxias, especially when presenting sporadically in adulthood, present a particular diagnostic challenge owing to their great clinical and genetic heterogeneity. Currently, up to 75% of such patients remain without a genetic diagnosis. In an era of emerging disease-modifying gene-stratified therapies, the identification of causative alleles has become increasingly important. Over the past few years, the implementation of advanced bioinformatics tools and long-read sequencing has allowed the identification of a number of novel repeat expansion disorders, such as the recently described spinocerebellar ataxia 27B (SCA27B) caused by a (GAA)•(TTC) repeat expansion in intron 1 of the fibroblast growth factor 14 (FGF14) gene. SCA27B is rapidly gaining recognition as one of the most common forms of adult-onset hereditary ataxia, with several studies showing that it accounts for a substantial number (9-61%) of previously undiagnosed cases from different cohorts. First natural history studies and multiple reports have already outlined the progression and core phenotype of this novel disease, which consists of a late-onset slowly progressive pan-cerebellar syndrome that is frequently associated with cerebellar oculomotor signs, such as downbeat nystagmus, and episodic symptoms. Furthermore, preliminary studies in patients with SCA27B have shown promising symptomatic benefits of 4-aminopyridine, an already marketed drug. This review describes the current knowledge of the genetic and molecular basis, epidemiology, clinical features and prospective treatment strategies in SCA27B., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Bickerstaff brainstem encephalitis (BBE) is a neuroimmunologic disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance, mostly subsequent to an infection. BBE is considered to be a variant of Miller-Fisher syndrome (MFS), which also exhibits external ophthalmoplegia and ataxia but not presenting consciousness alterations. Therefore, these two medical conditions are included in the clinical spectrum of the "Fisher-Bickerstaff syndrome" ( Shahrizaila and Yuki in J Neurol Neurosurg Psychiatry 84(5):576-583) [1]. With regard to the etiopathogenesis, increasing evidence worldwide suggests that SARS-CoV-2 infection-enhanced immune response is involved in a wide range of neurological complications such as Guillain-Barré syndrome (GBS), MFS, acute necrotizing encephalitis (ANE), myelitis, acute disseminated encephalomyelitis (ADEM), and, although very rarely, BBE either (Hosseini et al. in Rev Neurosci 32:671-691) [2]. We report a case of a patient affected by delayed onset BBE overlapping MFS during a mild SARS-CoV-2 infection. To the best of our knowledge, similar cases have never been reported., (© 2023. Fondazione Società Italiana di Neurologia.)

Introduction: Early B-cell factor 3 (EBF3) is a transcription factor involved in neuronal differentiation and maturation. Pathogenic variants are associated with hypotonia, ataxia, and delayed development syndrome (HADDS) (MIM#617330). Urologic manifestations are common and may have implications regarding long term renal function., Objective: To review all known patients with pathogenic variants of the EBF3 gene resulting in HADDS with urologic manifestations. We hypothesize a high rate of bladder dysfunction secondary to the EBF3 variant's impact on relaxation of the urinary sphincter leading to detrusor sphincter dyssynergia (DSD)., Methods: The PubMed database was queried for publications of the EBF3 mutation between January 2017 and January 2023. Search terms were "EBF3 mutation OR HADDS AND urology OR phenotype". Retrospective analysis of HADDS patients cared for in our institution was performed. Demographic and clinical information was collected., Results: We identified 52 patients (33F:19M) through literature (28F:18M) and retrospective review (5F:1M). There was a high prevalence of genitourinary physical exam abnormalities, history of urinary tract infection, vesicoureteral reflux (VUR), and diagnosis of neurogenic bladder. Within the literature review cohort, 67% had a urologic diagnosis. Females were disproportionately affected with urologic manifestations. In our cohort, four of six children were diagnosed with VUR and severe voiding dysfunction consistent with neurogenic bladder (67%). These children were managed with a vesicostomy. Five children had bowel dysfunction requiring therapy. Urodynamics suggested a high prevalence of external sphincter dyssynergia. Less severe forms of DSD were felt to be implicated in the abnormal voiding parameters in children who presented later in life based on non-invasive flow studies., Discussion: There is significant variability in the phenotypic presentation of patients with HADDS. While EBF3 plays a clear role in neurodevelopment, it also impacts muscle development and may impact muscle relaxation. The location of the genetic variant may impact the degree of DSD, with more severe forms leading to earlier presentations. Initial work-up should include a renal ultrasound (RUS) and post void residual (PVR). Consideration can be given to obtaining a VCUG, DMSA scan or urodynamic studies. Yearly screening should be pursued with an RUS and PVR in those with an initial unremarkable work-up given the variable timing and severity of presentation., Conclusion: Urologic manifestations of HADDS include high rates of bladder dysfunction secondary to DSD, vesicoureteral reflux, urinary tract infection, and cryptorchidism. These patients are at risk of renal deterioration if urinary abnormalities are not properly diagnosed and managed., Competing Interests: Conflict of interest None., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Spinal intramedullary ependymomas (IEs) represent a well-defined tumor entity usually warranting resection. Factors that determine full long-term neurological recovery after resection are seldomly reported on in larger clinical series. In this study, the authors aimed to highlight the neurological outcome of patients with IEs after resection, with a focus on full neurological recovery, and to explore possible risk factors for the absence of neurological amelioration to an optimal function after surgical treatment., Methods: A single-center retrospective analysis of all patients undergoing surgery for IEs between 2007 and 2021 was performed. Data collection included patient demographics, symptoms, clinical findings, histopathological diagnosis, surgical procedures, complications, and neurological outcome. Patients harboring a favorable outcome (modified McCormick Scale [mMS] grade of I) were compared with patients with a less favorable outcome (mMS grade ≥ II) at the final follow-up., Results: In total, 72 patients with a histologically diagnosed IE were included. IEs in those patients (41 males, 31 females; median age 51 [IQR 40-59] years) mostly occurred in the cervical (n = 40, 56%) or thoracic (n = 23, 32%) spine. Upon admission, motor deficits or gait deficits (mMS grade ≥ II) were present in 29 patients (40%), with a median mMS grade of II (IQR I-II). Gross-total resection was achieved in 60 patients (90%), and the rate of surgical complications was 7%. Histopathologically, 67 tumors (93%) were classified as WHO grade 2 ependymomas, 3 (4%) as WHO grade 1 subependymomas, and 2 (3%) as WHO grade 3 anaplastic ependymomas. After a mean follow-up of 863 ± 479 days, 37 patients (51%) had a fully preserved neurological function and 62 patients (86%) demonstrated an mMS grade of I or II. Comparison of favorable with unfavorable outcomes revealed an association of early surgery (within a year after symptom onset), the absence of ataxia or gait disorders, and a low mMS grade with full neurological recovery at the final follow-up. A subgroup of patients (n = 15, 21%) had nonresolving deterioration at the final follow-up, with no significant differences in relevant variables compared with the rest of the cohort., Conclusions: The data presented solidify the role of early surgery in the management of spinal IEs, especially in patients with mild neurological deficits. Furthermore, the presence of gait disturbance or ataxia confers a higher risk of incomplete long-term recovery after spinal ependymoma resection. Because a distinct subgroup of patients had nonresolving deterioration, even when presenting with an uneventful history, further analyses into this subgroup of patients are required.

Bickerstaff's brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient's serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient's clinical course and history, he was diagnosed with Bickerstaff's brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis., (© 2023. The Author(s).)

Background: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established., Objectives: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients., Methods: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis., Results: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia., Conclusions: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The human immunodeficiency virus (HIV) causes movement disorders in persons living with HIV (PLH)., Objectives and Methods: We conducted a systematic review on the spectrum of movement disorders in PLH using standard terms for each of the phenomenologies and HIV., Results: Movement disorders in PLH were commonly attributed to opportunistic infections (OI), dopamine receptor blockade reactions, HIV-associated dementia (HAD), presented during seroconversion, developed due to drug reactions or antiretroviral therapy (ART) itself and lastly, movement disorders occurred as a consequence of the HIV-virus. Parkinsonism in ART naïve PLH was associated with shorter survival, however when Parkinsonism presented in PLH on ART, the syndrome was indistinguishable from Idiopathic Parkinson's disease and responded to therapy. Tremor was often postural due to HAD, drugs or OI. Generalized chorea was most frequent in HIV encephalopathy and toxoplasmosis gondii caused most cases of hemichorea. Ataxia was strongly associated with JCV infection, ART efavirenz toxicity or due to HIV itself. Dystonia was reported in HAD, secondary to drugs and atypical facial dystonias. Both cortical/subcortical and segmental/spinal origin myoclonus were noted mainly associated with HAD. In patients with HIV related opsoclonus-myoclonus-ataxia-syndrome, seroconversion illness was the commonest cause of followed by IRIS and CSF HIV viral escape phenomenon., Conclusions: Aetiology of movement disorders in PLH depend on the treatment state. Untreated, PLH are prone to develop OI and HAD and movement disorders. However, as the number of PLH on ART increase and survive longer, the frequency of ART and non-AIDS related complications are likely to increase., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Verbal fluency tests (VFTs) are widely used to assess cognitive-linguistic performance in neurological diseases. However, the influence of dysarthria on performance in tests requiring oral responses is unclear in ataxia and Parkinson's disease., Objectives: To determine the impact of dysarthria on VFT performance and evaluate the validity and reliability of alternative methods for analyzing VFT data., Method: Trained raters evaluated dysarthria using VFT recordings in people with ataxia (N = 61) or Parkinson's disease (PD; N = 69). Total Correct Items scores and qualitative parameters (intrusions, ambiguous verbalizations, perseverations, and interjections) were compared across semantic, phonemic, and alternating fluency tasks. Disease severity was considered as a covariate in the regression model., Results: VFT dysarthria ratings correlated with the benchmark (ground truth) dysarthria scores derived from a monologue. Ambiguous responses resulting from unclear speech impeded the rater's ability to determine if a response was correct. Regression analysis indicated that more severe dysarthria ratings predicted diminished scores in all three tasks (semantic fluency, phonemic fluency and alternating fluency) in the ataxia group. The contribution of disease severity to semantic, phonemic and alternating fluency was reduced substantially in the ataxia group after accounting for dysarthria severity in the model in both groups., Conclusions: Dysarthria severity can be estimated based on speech samples derived from VFT. Dysarthria can lead to lower total correct items and is associated with more ambiguous verbalizations in VFT. Dysarthria severity should be considered when interpreting VFT performance in common movement disorders.

Background: Wernicke encephalopathy (WE) is an acute neurological disease resulting from vitamin B1 deficiency, and there are only very few case reports of WE after liver transplantation. The present study aimed to investigate the clinical characteristics, etiology, magnetic resonance imaging (MRI) features, treatment and prognosis of patients with WE after liver transplantation., Methods: Twenty-three patients with WE after liver transplantation from the First Affiliated Hospital, Zhejiang University School of Medicine and Jiangxi Provincial People's Hospital between January 2011 and December 2021 were retrospectively analyzed., Results: Among the 23 patients diagnosed with WE after liver transplantation, 6 (26%) had a classic triad of impaired consciousness, oculomotor palsy and ataxia, and 17 (74%) had two features. The misdiagnosis rate was 65%. After treatment with high-dose vitamin B1, 19 (83%) patients showed improvement, whereas 4 (17%) showed no improvement, including 3 with residual short-term memory impairments and 1 with residual spatial and temporal disorientation and ataxia., Conclusions: The misdiagnosis rate is high in the early stage of WE, and the prognosis is closely associated with whether WE is diagnosed early and treated timely. High-dose glucose or glucocorticoids can trigger WE and cannot be administered before vitamin B1 treatment. Vitamin B1 is suggested to be used as a prophylactic treatment for patients with WE after liver transplantation., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Hereditary Ataxias (HAs) comprise a wide spectrum of genetically determined neurodegenerative diseases with progressive ataxia as the main symptom. Few studies have evaluated nutritional profile in HA patients and most of these focused on specific ataxia subtypes. The objectives of this study were: (1) to investigate whether hereditary ataxias were associated with changes in energy expenditure, body composition and dietary intake; (2) to verify differences in these variables according to ataxia subtype, sex, age, and disease severity., Methods: Thirty-eight hereditary ataxia patients from two neurology centers in Northeastern Brazil and 38 controls were evaluated. Body composition was assessed with bio-impedance analysis and dietary intake was estimated with a validated questionnaire (24-hour dietary recall)., Results: Mean body mass index (BMI) was lower in HA compared to controls ( p  = 0.032). Hereditary ataxia patients showed lower protein intake, higher frequency of dysphagia and higher incidence of nausea and diarrhea. The difference in average estimated caloric intake did not reach statistical significance (2359kcal ± 622 in patients × 2713kcal ± 804 in controls, p  = 0.08). Disease severity measured by the SARA scale was not associated with BMI, nor was ataxia subtype (autosomal dominant × non-autosomal dominant ataxias)., Conclusion: Hereditary ataxia patients have lower BMI compared to healthy controls. There was no difference in this cohort between dominant or non-dominant ataxia regarding BMI. Weight loss may be a common finding among hereditary ataxias and may affect the quality of life in these patients.

Objective: KCNA1 mutations are associated with a rare neurological movement disorder known as episodic ataxia type 1 (EA1), and epilepsy is a common comorbidity. Current medications provide only partial relief for ataxia and/or seizures, making new drugs needed. Here, we characterized zebrafish kcna1a -/- as a model of EA1 with epilepsy and compared the efficacy of the first-line therapy carbamazepine in kcna1a -/- zebrafish to Kcna1 -/- rodents., Methods: CRISPR/Cas9 mutagenesis was used to introduce a mutation in the sixth transmembrane segment of the zebrafish Kcna1 protein. Behavioral and electrophysiological assays were performed on kcna1a -/- larvae to assess ataxia- and epilepsy-related phenotypes. Real-time quantitative polymerase chain reaction (qPCR) was conducted to measure mRNA levels of brain hyperexcitability markers in kcna1a -/- larvae, followed by bioenergetics profiling to evaluate metabolic function. Drug efficacies were tested using behavioral and electrophysiological assessments, as well as seizure frequency in kcna1a -/- zebrafish and Kcna1 -/- mice, respectively., Results: Zebrafish kcna1a -/- larvae showed uncoordinated movements and locomotor deficits, along with scoliosis and increased mortality. The mutants also exhibited impaired startle responses when exposed to light-dark flashes and acoustic stimulation as well as hyperexcitability as measured by extracellular field recordings and upregulated fosab transcripts. Neural vglut2a and gad1b transcript levels were disrupted in kcna1a -/- larvae, indicative of a neuronal excitatory/inhibitory imbalance, as well as a significant reduction in cellular respiration in kcna1a -/- , consistent with dysregulation of neurometabolism. Notably, carbamazepine suppressed the impaired startle response and brain hyperexcitability in kcna1a -/- zebrafish but had no effect on the seizure frequency in Kcna1 -/- mice, suggesting that this EA1 zebrafish model might better translate to humans than rodents., Significance: We conclude that zebrafish kcna1a -/- show ataxia and epilepsy-related phenotypes and are responsive to carbamazepine treatment, consistent with EA1 patients. These findings suggest that kcna1 -/- zebrafish are a useful model for drug screening as well as studying the underlying disease biology., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Early onset ataxia (EOA) concerns a heterogeneous disease group, often presenting with other comorbid phenotypes such as myoclonus and epilepsy. Due to genetic and phenotypic heterogeneity, it can be difficult to identify the underlying gene defect from the clinical symptoms. The pathological mechanisms underlying comorbid EOA phenotypes remain largely unknown. The aim of this study is to investigate the key pathological mechanisms in EOA with myoclonus and/or epilepsy., Methods: For 154 EOA-genes we investigated (1) the associated phenotype (2) reported anatomical neuroimaging abnormalities, and (3) functionally enriched biological pathways through in silico analysis. We assessed the validity of our in silico results by outcome comparison to a clinical EOA-cohort (80 patients, 31 genes)., Results: EOA associated gene mutations cause a spectrum of disorders, including myoclonic and epileptic phenotypes. Cerebellar imaging abnormalities were observed in 73-86% (cohort and in silico respectively) of EOA-genes independently of phenotypic comorbidity. EOA phenotypes with comorbid myoclonus and myoclonus/epilepsy were specifically associated with abnormalities in the cerebello-thalamo-cortical network. EOA, myoclonus and epilepsy genes shared enriched pathways involved in neurotransmission and neurodevelopment both in the in silico and clinical genes. EOA gene subgroups with myoclonus and epilepsy showed specific enrichment for lysosomal and lipid processes., Conclusions: The investigated EOA phenotypes revealed predominantly cerebellar abnormalities, with thalamo-cortical abnormalities in the mixed phenotypes, suggesting anatomical network involvement in EOA pathogenesis. The studied phenotypes exhibit a shared biomolecular pathogenesis, with some specific phenotype-dependent pathways. Mutations in EOA, epilepsy and myoclonus associated genes can all cause heterogeneous ataxia phenotypes, which supports exome sequencing with a movement disorder panel over conventional single gene panel testing in the clinical setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Rationale: Multiple system atrophy (MSA) is a group of adult-onset sporadic neurodegenerative diseases, mainly classified as MSA-C and MSA-P types. Due to the diversity of clinical symptoms, diagnosis faces a significant challenge. In the present case, we report a patient with isolated vertigo as the first presentation and abnormalities of the oculomotor system as the characteristic manifestations., Case Concern: A 64-year-old male had dizziness for 1 year, aggravated for 4 months, with accompanying symptoms of unsteady walking. Physical examination revealed spontaneous nystagmus, abnormal ataxic movements, and a broad basal gait. Video nystagmography revealed saccade intrusions and macrosaccadic oscillations, and opsoclonus. Magnetic resonance imaging (MRI) was unremarkable early, and positron emission tomography-computed tomography (PET-CT) announced a reduction in the volume of the cerebellum and brainstem., Diagnosis: The diagnosis of the possibility of MSA type-C, peripheral neuropathy, hypertension, and lacunar cerebral infarction was performed., Conclusion: Atypical early clinical presentation may lead to delays, and identifying the critical problem through the patient simple clinical status requires long-term clinical experience and various ancillary examination tools., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Competing interests: None declared.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache., Methods: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions., Results: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions., Conclusion: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here we report studies of neurovascular oxidative stress in chemogenetic transgenic mouse lines expressing yeast D-amino acid oxidase (DAAO) in neurons and vascular endothelium. When these transgenic mice are fed D-amino acids, DAAO generates hydrogen peroxide in target tissues. DAAO-TG Cdh5 transgenic mice express DAAO under control of the putatively endothelial-specific Cdh5 promoter. When we provide these mice with D-alanine, they rapidly develop sensory ataxia caused by oxidative stress and mitochondrial dysfunction in neurons within dorsal root ganglia and nodose ganglia innervating the heart. DAAO-TG Cdh5 mice also develop cardiac hypertrophy after chronic chemogenetic oxidative stress. This combination of ataxia, mitochondrial dysfunction, and cardiac hypertrophy is similar to findings in patients with Friedreich's ataxia. Our observations indicate that neurovascular oxidative stress is sufficient to cause sensory ataxia and cardiac hypertrophy. Studies of DAAO-TG Cdh5 mice could provide mechanistic insights into Friedreich's ataxia., (© 2023. The Author(s).)

Cerebellar cognitive affective syndrome (CCAS) is characterized by deficits in executive functions, language processing, spatial orientation, and affect regulation in patients with cerebellar disease. The symptoms can occur isolated or along with motor and coordination symptoms. The aim of our study was to translate and culturally adapt the CCAS scale to Brazilian Portuguese and validate the scale in our population. We performed a cross-sectional study with patients with primary and secondary ataxia. The study included 111 individuals, aged between 20 and 80 years, of both genders, 20 without cognitive and/or affective complaints who participated in the pre-test phase, 40 with cerebellar disease (hereditary/neurodegenerative ataxia or acquired/secondary cerebellar ataxia), and 51 healthy controls with no evidence of cognitive impairment and no affective symptoms matched for sex, age, and educational level. The scale was translated, culturally adapted, and validated. Statistical analysis of the data was performed, with association tests, mean comparison, and ROC curve analysis. Based on the analysis of the ROC curve, optimal cutoff values ​were found for each subitem of the scale. The translated and adapted scale has good internal consistency, is reproducible, has good reliability, and has the potential to be a reliable tool for screening cognitive symptoms in patients with cerebellar disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare disorder that causes significant neurodevelopmental sequelae in children. Approximately half of pediatric OMAS cases are paraneoplastic, typically associated with localized neuroblastic tumors. Since early persistence or relapse of OMAS symptoms is common even after tumor resection, OMAS relapses may not routinely prompt reevaluation for recurrent tumors. We report a 12-year-old girl with neuroblastic tumor recurrence associated with OMAS relapse a decade after initial treatment. Providers should be aware of tumor recurrence as a trigger for distant OMAS relapse, raising intriguing questions about the role of immune surveillance and control of neuroblastic tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia, chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular Diseases Unit, with a particular interest in the involvement of the peripheral nervous system., Methods: We recruited twenty consecutive patients based on the presence of at least two of the following features: progressive ataxia, sensory neuropathy/neuronopathy, vestibulopathy and chronic cough. Medical records were retrospectively reviewed for a detailed clinical description. More extensive phenotyping of the RFC1-positive patients and clinical comparison between RFC1 positive and negative patients were performed., Results: Biallelic AAGGG repeat expansions were identified in 13 patients (65%). The most frequent symptoms were chronic cough and sensory disturbances in the lower extremities (12/13). Only 4 patients (31%) had complete CANVAS. The phenotypes were sensory ataxia and sensory symptoms in extremities in 4/13; sensory ataxia, sensory symptoms, and vestibulopathy in 3/13; sensory symptoms plus chronic cough in 2/13. Chronic cough and isolated sensory neuronopathy were significantly more prevalent in RFC1-positive patients., Conclusion: Pathogenic RFC1 expansions are a common cause of sensory neuropathy/neuronopathy and should be considered in the approach to these patients. Identification of key symptoms or detailed interpretation of nerve conduction studies may improve patient selection for genetic testing., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose in relation to this work., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy., Methods: We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients., Results: The mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses., Conclusions: Early initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset., (Copyright © 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: To provide an overview about the phenotype, genotype, treatment, and outcome of neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome., Methods: Systematic review by application of appropriate search terms., Results: NARP syndrome is a syndromic mitochondrial disorder due to pathogenic variants in MT-ATP6. The canonical phenotypic features of NARP syndrome include proximal muscle weakness, axonal neuropathy, cerebellar ataxia, and retinitis pigmentosa. Noncanonical phenotypic features in NARP include epilepsy, cerebral or cerebellar atrophy, optic atrophy, cognitive impairment, dementia, sleep apnea syndrome, hearing impairment, renal insufficiency, and diabetes. So far, 10 pathogenic variants in MT-ATP6 have been associated with NARP, NARP-like syndrome, or NARP/maternally inherited Leigh overlap syndrome. Most pathogenic MT-ATP6 variants are missense, but a few truncating pathogenic variants have been reported. The most common variant responsible for NARP is the transversion m.8993T>G. Only symptomatic treatment for NARP syndrome is available. In most of the cases, patients die prematurely. Patients with late-onset NARP survive longer., Conclusions: NARP is a rare, syndromic, monogenic mitochondrial disorder due to pathogenic variants in MT-ATP6. The nervous system and the eyes are most commonly affected. Although only symptomatic treatment is available, the outcome is usually fair., Competing Interests: The author reports no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Opsoclonous myoclonous ataxia syndrome (OMAS) is a rare primarily immune-mediated disease in children. The current study aim was to find out the patterns and outcome of OMAS associated with neuroblastoma (NBL) among Children's Cancer Hospital-Egypt patients. Data was reviewed for 15 eligible patients enrolled between 2007 and 2016. OMAS treatment included prednisolone and cyclophosphamide with/without intravenous immunoglobulin; NBL treatment was given according to risk-corresponding protocol. Patients' age ranged from 0.75 to 12 years at presentation with male/female: 1.1/1. Concurrent diagnosis of OMAS and NBL occurred in 6 patients (40%). OMAS preceded NBL within 0.25 to 2 years in 33%, while NBL preceded OMAS within 0.5 to 1.5 years in 27%. Full OMAS picture was present in 10/15 patients, while 20% presented with truncal ataxia and myoclonus, 1 with truncal ataxia and opsoclonus, and 1 had opsoclonus and myoclonus. Median time till improvement of manifestations was 5 months. The 5-year OMAS progression-free survival was 33.3%, where 10 patients needed second-line therapy due to relapse/progression of OMAS. The median time to progression was 28 months measured from OMAS diagnosis. All patients remained alive with NBL 5-year overall survival of 100% and event-free survival of 85.7% for. However, 73% of the patients showed late sequelae ranging from ocular to cognitive, behavioral and motor disorders; rarely seizures and hemolytic anemia., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset, X-linked, neurodegenerative disorder that affects premutation carriers of the FMR1 gene. FXTAS is often misdiagnosed as spinocerebellar ataxia (SCA) or Parkinson's disease (PD). Herein, we sought to investigate the frequency, genotypic and phenotypic profile of FXTAS in two cohorts of Greek patients with late-onset movement disorders, one with cerebellar ataxia and the other with PD. In total, 90 index patients with late-onset cerebellar ataxia and 171 with PD were selected. None of the cases had male-to-male transmission. Genetic screening for the FMR1 premutation was performed using standard methodology. The FMR1 premutation was detected in two ataxia patients (2.2%) and two PD patients (1.2%). Additional clinical features in FXTAS patients from the ataxia cohort included neuropathy, mild parkinsonism, cognitive impairment and pyramidal signs. The FXTAS patients from the PD cohort had typical PD. We conclude that, in the Greek population, the FMR1 premutation is an important, albeit rare, cause of late-onset movement disorders. Routine premutation screening should be considered in SCA panel-negative late-onset ataxia cases. Directed premutation screening should be considered in all ataxia and PD cases with additional features suggestive of FXTAS. Our study highlights the importance of FMR1 genetic testing in the diagnosis of late-onset movement disorders., Competing Interests: Declaration of competing interest The authors have no conflict of interest to report., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work.

Introduction: Miller-Fisher Syndrome (MFS) is a variant of Guillain-Barré syndrome (GBS), an acute immune-mediated neuropathy, which manifests as a rapidly evolving areflex motor paralysis. This syndrome presents as a classic triad: ophthalmoplegia, areflexia, and ataxia. MFS is usually benign and self-limited., Case Report: A Caucasian patient was admitted to our hospital with the flu, loss of bilateral strength in the lower limbs and upper limbs and sudden-onset ataxia 7 days after receiving a first dose of the Oxford/AstraZeneca COVID-19 vaccine. On neurological examination, the patient had Glasgow Coma Scale score of 15, with absence of meningeal signs; negative Babinski sign; grade 2 strength in the lower limbs and grade 4 strength in the upper limbs; axial and appendicular cerebellar ataxia; and peripheral facial diparesis predominantly on the right, without conjugate gaze deviation. Cerebrospinal fluid (CSF) was collected on admission, and analysis revealed albuminocytological dissociation with CSF protein of 148.9 mg/dL; leukocytes, 1; chlorine, 122; glucose, 65 mg/mL; red cells, 2; and non-reactive venereal disease research laboratory test result. The COVID-19 IgG/IgM rapid immunological test was negative. Electroneuromyography revealed a recent moderate-grade and primarily sensory and motor demyelinating polyneuropathy with associated proximal motor block., Discussion and Conclusion: Miller-Fisher Syndrome may be related to events other than infections prior to neuropathy, as in the case reported here. The patient presented strong correlations with findings for MFS reported in the literature, such as the clinical condition, the results of electroneuromyography, and results of the CSF analysis typical for MFS. When treatment was provided as proposed in the literature, the disease evolved with improvement. Ultimately, the diagnosis of incomplete MFS was made, including acute ataxic neuropathy (without ophthalmoplegia)., (© 2022. The Author(s).)

Baylisascaris procyonis , or raccoon roundworm, is a rare cause of eosinophilic meningoencephalitis with historically poor clinical outcomes. Symptoms of neural larval migrans begin approximately 2-4 weeks after ingestion with fatigue, nausea, fever, and lethargy and then rapidly progress to weakness, incoordination, ataxia, seizures, altered mental status, and finally coma. Only 31 other cases of CNS Baylisascaris neural larval migrans have been reported, with more than 25% being lethal. Of the remaining cases, all but 3 were neurologically devastated largely because of delays in diagnosis and treatment. We present a case of an infant with Baylisascaris neural larval migrans manifested as right hemiparesis, ataxia, and cortical blindness. Eosinophilia was missed at an outside hospital due to misidentification of eosinophils as monocytes on automated cell differential. Repeated testing of serum and CSF revealed marked eosinophilia consistent with eosinophilic meningoencephalitis, and serum antibody testing through the Centers of Disease Control confirmed Baylisascaris infection. Notably, this child had a remarkably positive outcome with near complete recovery of neurologic function after treatment with albendazole and steroids. Although eosinophilic meningoencephalitis is rare, accounting for less than 3% of all lumbar punctures with pleocytosis, this case illustrates (1) the importance of early disease recognition and treatment to improve patient outcomes and (2) the fact that automated cell differentials may misidentify eosinophils as monocytes., (© 2022 American Academy of Neurology.)