Myoclonus Syndrome Research Articles

Post-hypoxic myoclonus (Lance-Adams Syndrome) in post-cardiorespiratory arrest, a case presentation in elderly

A clinical case report is presented of an elderly adult recovering from cardiac arrest who developed generalized myoclonus or Lance Adams syndrome in a tertiary care hospital. Myoclonus is defined as a sudden, brief muscle contraction (1). The Lance Adams Syndrome is a form of post- hypoxic myoclonus, characterized by action myoclonus that typically involve the trunk, face, and extremities, and whose onset is days to weeks after a hypoxic brain injury. (2) The incidence of post-hypoxic myoclonus is 1. 3 cases per 100,000 people per year, so its differential diagnosis represents a challenge. The etiology may be secondary to cardiorespiratory arrest, anesthetic and surgical accidents, in addition to heart disease and drug overdose. Acute post-hypoxic myoclonus begins hours after the injury, sometimes begins as myoclonic status epilepticus, and if the patient survives, he will progress to a chronic phase with a poor or low life expectancy. Treatment is controversial, several articles agree that patients have shown better response to Levetiracetam, Magnesium Valproate, Lacosamide and Clonazepam.

Recent advances in diagnosis of immune-mediated cerebellar ataxias: novel concepts and fundamental questions on autoimmune mechanisms.

Immune-mediated cerebellar ataxias (IMCAs) represent a group of disorders in which the immune system targets mainly the cerebellum and related structures. We address fundamental questions on the diagnosis and immunological pathogenesis of IMCAs, as illuminated by recent advances in the field. Various types of IMCAs have been identified, including post-infectious cerebellitis, Miller Fisher syndrome, gluten ataxia, paraneoplastic cerebellar degeneration (PCD), opsoclonus and myoclonus syndrome, and anti-GAD ataxia. In some cases, identification of several well-characterized autoantibodies points to a specific etiology in IMCAs and leads to a firm diagnosis. In other cases, various autoantibodies have been reported, but their interpretation requires a careful consideration. Indeed, some autoantibodies have only been documented in a limited number of cases and the causal relationship is not established. In order to facilitate an early treatment and prevent irreversible lesions, new entities have been defined in recent years, such as primary autoimmune cerebellar ataxia (PACA) and latent autoimmune cerebellar ataxia (LACA). PACA is characterized by autoimmune features which do not align with traditional etiologies, while LACA corresponds to a prodromal stage. LACA does not imply the initiation of an immunotherapy but requires a close follow-up. Concurrently, accumulation of clinical data has led to intriguing hypotheses regarding the mechanisms of autoimmunity, such as a pathogenesis of autoimmunity against synapses (synaptopathies), and the vulnerability of the entire nervous system when the immunity targets ion channels and astrocytes. The development of PCD in patients treated with immune-checkpoint inhibitors suggests that molecular mimicry specifically determines the direction of autoimmunity, and that the strength of this response is modulated by co-signaling molecules that either enhance or dampen signals from the antigen-specific T cell receptor.

Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia.

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.

A rare case of opsoclonus myoclonus syndrome following COVID-19 illness

A rare case of opsoclonus myoclonus syndrome following COVID-19 illness

The current state of the paraneoplastic neurological syndromes problem

Paraneoplastic syndromes (PS) are immune-mediated manifestations of a distant oncological process, which is a reaction of autoantibodies against antigens expressed by the tumor. These syndromes are divided into neurological, endocrine, hematological, and dermatological. PS can be diagnosed before or in parallel with tumor detection and often masquerade as neurological or psychiatric disorders. The review discusses the updated 2021 diagnostic criteria, which include revisions to diagnostic levels since 2004, as well as new classifications of antibodies based on the pathogenetic mechanisms of nerve cell damage and their frequency of detection in patients. The phenotypes of high-, medium-, and low-risk paraneoplastic neurological syndromes (PNS) are highlighted, with a special emphasis on the clinical features of high-risk phenotypes. Particular attention is paid to limbic encephalitis, its clinical signs, specific antibodies, instrumental and laboratory studies, and associated oncological diseases. Encephalomyelitis and subacute cerebellar degeneration are also discussed, detailing pathological changes, key antibodies and neoplasia, emphasizing the need for differential diagnosis and immunosuppressive treatment. General features about opsoclonus myoclonus syndrome, its clinical manifestations and causes, as well as Lambert—Eaton myasthenic syndrome are provided, in particular, its association with small cell lung cancer is emphasized, and the features of diagnosis, differential diagnosis with myasthenia gravis and treatment are highlighted. Based on the updated diagnostic criteria, the data analysis will provide clinicians with guidelines for identifying specific phenotypes of PNS and associated antibodies, which are key to improving diagnostic processes and selecting an effective treatment strategy.

Opsoclonus-Myoclonus Syndrome in a Child with Birth Asphyxia

A case of Opsoclonus Myoclonus Syndrome associated with birth asphyxia presented with antiseizure treatment started soon after birth and continued after discharge. The child presented at two years of age and had jerky movements in the limbs and eyes. The eye movements promptly responded to phenobarbital, and the limb movements appreciably diminished after adding clonazepam. The practice of continuing antiseizure treatment post-discharge in asphyxiated babies is questionable. No asphyxiated baby is reported in the literature to have OMS.

Opsoclonus-Myoclonus Syndrome and Acquired Von Willebrand Syndrome As Manifestations of Graft-Versus-Host Disease

Background: Opsoclonus-myoclonus syndrome (OMS), known as dancing eye syndrome, is a rare neurological disorder characterised by a triad of opsoclonus (rapid, involuntary eye movements), myoclonus (uncontrolled muscle twitches) and ataxia. The syndrome is usually seen in children, often associated with neuroblastoma, and is extremely rare in adults. The pathogenesis is thought to be immune in nature and aetiology is variable although most cases are associated with solid tumors or after an infection. Treatment involves a combination of managing the underlying condition and immunosuppression. Acquired von Willebrand disease is a rare acquired bleeding disorder with a range of different aetiologies including lymphoproliferative, myeloproliferative, cardiovascular and autoimmune disorders. The pathogenic mechanism, in most cases is due to increased plasma clearance of von Willebrand factor (vWF) caused by such mechanisms as antibodies, cell adsorption, shear stress or increased proteolysis. Therapeutic approaches focus on prevention of bleeding through supportive treatment, and management of the underlying cause. To the best of our knowledge, this is the first case of opsoclonus-myoclonus syndrome with concurrent acquired von Willebrand disease as manifestations of graft versus host disease. Case: Here we present the case of a 47-year-old man presenting with opsoclonus myoclonus syndrome and concurrent acquired von Willebrand disease as manifestations of graft versus host disease. The patient had a background of relapsed myeloid sarcoma after haploidentical allogeneic haematopoietic stem cell transplant with subsequent chemotherapy to achieve full remission. He received donor lymphocyte infusion as consolidation therapy to enhance the graft-versus leukaemia effect. Six weeks following donor T cell infusion of 1 x 10^6 CD3 cells/kg, he presented with initial features suggestive of graft versus host disease (GVHD) of the digestive tract and subsequently developed neurological manifestations in the form of rapid, repetitive, involuntary and multidirectional eye movements; tremors and ataxia. Further tests prior to planned invasive testing revealed an additional new diagnosis of acquired von Willebrand disease, requiring supportive von Willebrand factor concentrate infusion. Multiple extensive investigations including cerebral MRI imaging, cerebrospinal fluid analysis and paraneoplastic antibodies were all negative for associated malignancy, infection, other autoimmune disorder or disease relapse. Skin, bone marrow examination and cross-sectional imaging confirmed complete remission with complete donor chimerism in all blood cell lineages. The patient commenced steroid immunosuppression for treatment of gastrointestinal GVHD with complete resolution of all symptoms and clinical parameters. Conclusion: We highlight a rare case of central nervous system involvement with graft versus host disease following cellular therapy, manifesting as the rare opsoclonus-myoclonus syndrome with associated acquired von Willebrand disease. The proposed pathological mechanism is the activation of host tissue antigen-specific T and B cells, resulting in autoantibody and cytokine-mediated effects upon neuronal tissue and coagulation proteins. Use of glucocorticoids in this case to suppress auto-antibody formation, block transcription of pro-inflammatory genes and induce lymphocyte depletion was rapidly effective and provided durable remission of symptoms, without recurrence on cessation of immunosuppression. This case highlights the need for close clinical and biochemical monitoring of patients during the risk period following allogeneic cellular therapy, for serious allo-immune manifestations not fitting classical descriptions of GVHD.

Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability.

Cortical myoclonus is produced by abnormal neuronal discharges within the sensorimotor cortex, as demonstrated by electrophysiology. Our hypothesis is that the loss of cerebellar inhibitory control over the motor cortex, via cerebello-thalamo-cortical connections, could induce the increased sensorimotor cortical excitability that eventually causes cortical myoclonus. To explore this hypothesis, in the present study we applied anodal transcranial direct current stimulation over the cerebellum of patients affected by cortical myoclonus and healthy controls and assessed its effect on sensorimotor cortex excitability. We expected that anodal cerebellar transcranial direct current stimulation would increase the inhibitory cerebellar drive to the motor cortex and therefore reduce the sensorimotor cortex hyperexcitability observed in cortical myoclonus. Ten patients affected by cortical myoclonus of various aetiology and 10 aged-matched healthy control subjects were included in the study. All participants underwent somatosensory evoked potentials, long-latency reflexes and short-interval intracortical inhibition recording at baseline and immediately after 20 min session of cerebellar anodal transcranial direct current stimulation. In patients, myoclonus was recorded by the means of surface EMG before and after the cerebellar stimulation. Anodal cerebellar transcranial direct current stimulation did not change the above variables in healthy controls, while it significantly increased the amplitude of somatosensory evoked potential cortical components, long-latency reflexes and decreased short-interval intracortical inhibition in patients; alongside, a trend towards worsening of the myoclonus after the cerebellar stimulation was observed. Interestingly, when dividing patients in those with and without giant somatosensory evoked potentials, the increment of the somatosensory evoked potential cortical components was observed mainly in those with giant potentials. Our data showed that anodal cerebellar transcranial direct current stimulation facilitates-and does not inhibit-sensorimotor cortex excitability in cortical myoclonus syndromes. This paradoxical response might be due to an abnormal homeostatic plasticity within the sensorimotor cortex, driven by dysfunctional cerebello-thalamo-cortical input to the motor cortex. We suggest that the cerebellum is implicated in the pathophysiology of cortical myoclonus and that these results could open the way to new forms of treatment or treatment targets.

Post-COVID-19 opsoclonus myoclonus syndrome

Post-COVID-19 opsoclonus myoclonus syndrome

Cervical Ganglioneuroblastoma Diagnosed by 68Ga-DOTATOC PET/CT in a Child with Opsoclonus Myoclonus Syndrome.

We performed a 68Ga-DOTATOC PET/CT scan on a 25-mo-old female patient who presented with opsoclonus myoclonus ataxia syndrome and had negative initial anatomic imaging. The scan showed a somatostatin receptor-overexpressing cervical tumor in favor of a cervical neuroendocrine tumor, with subsequent histopathologic findings of ganglioneuroblastoma.

Powassan Virus Encephalitis: A Tertiary Center Experience.

Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes. A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases. Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%). To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.

Opsoclonus Myoclonus Syndrome Associated With a New Diagnosis of HIV

Abstract Opsoclonus myoclonus syndrome (OMS) is a rare neurological disorder characterized by rapid saccadic eye movements, focal myoclonus, and gait disturbances. Both neoplastic and infectious processes have been found to be associated with OMS. In this report, we present a case of OMS in the setting of a new diagnosis of HIV. After diagnosis, the patient was initiated on antiretroviral therapy in addition to clonazepam with some improvement in her neurological symptoms. It was not until she was started on prednisone as an outpatient that her symptoms completely resolved and she returned to her functional baseline.

Immune-Mediated Cerebellar Ataxias

Autoimmune mechanisms affect the cerebellum leading to the development of cerebellar ataxias (CAs), which are termed immune-mediated cerebellar ataxias (IMCAs). IMCAs have diverse etiologies. Gluten ataxia (GA), post-infectious cerebellitis (PIC), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamate decarboxylase 65 antibody-associated CA (anti-GAD ataxia), and primary autoimmune cerebellar ataxia (PACA). In addition to these well-established entities, CAs are associated with autoimmunity against ion channels and their related proteins, synaptic adhesion proteins, transmitter receptors, glial cells, and brainstem antigens. Cell-mediated mechanisms are assumed to be involved in PCD, whereas accumulating evidence shows that anti-GAD antibodies decrease gamma-aminobutyric acid (GABA) release to elicit functional synaptic deficits. The therapeutic benefits of immunotherapies vary depending on the etiology. Early intervention is recommended when the cerebellar reserve, abilities for compensation and restoration of pathologies are preserved.

Síndrome opsoclonus mioclonus paraneoplásico en pediatría: reporte de caso y revisión de la literatura

El síndrome opsoclonus mioclonus (SOM) es una entidad poco frecuente en pediatría que por consenso de expertos se define como aquel que cumple tres de cuatro criterios: opsoclonus, ataxia, mioclonus, alteraciones de la conducta o del sueño y diagnóstico de neuroblastoma. Frecuentemente el SOM en niños se presenta asociado a tumores de la cresta neural, siendo el neuroblastoma el más prevalente, seguido por ganglioneuroblastoma, ganglioneuroma y hepatoblastoma. La asociación SOM y neuroblastoma tiene su pico de incidencia entre los 6 y 36 meses de edad y la posibilidad de que un niño con SOM tenga un neuroblastoma es de cerca del 50%. Si bien el SOM no es una patología frecuente en pediatría, su asociación con enfermedades neoplásicas sí lo es y desconocer su existencia y la presentación clínica puede llevar a demoras o subdiagnóstico del tumor con impacto negativo en el pronóstico tanto de la entidad de base como del futuro neurológico del paciente. Se presenta el caso de una niña de 15 meses con SOM asociado a ganglioneuroblastoma retroperitoneal que mejoró luego de la resección del tumor y el tratamiento con corticoides e inmunoglobulina.

Metabolic Opsoclonus Myoclonus Syndrome in a Patient of Crohn's Disease: Lessons Learnt.

Metabolic Opsoclonus Myoclonus Syndrome in a Patient of Crohn's Disease: Lessons Learnt.

Opsoclonus Myoclonus Syndrome and Supraventricular Tachycardia in a Pediatric Patient: A Case Report and Literature Review

Objective NA. Background Opsoclonus myoclonus syndrome (OMS) is a rare movement disorder in children often associated with an underlying neuroblastoma. In other cases, it is believed that the tumor is occult or there is another immune-stimulating precipitating event. Diagnosis can be difficult, requiring 3 of 4 criteria: opsoclonus or ocular flutter, myoclonus or ataxia, behavioral or sleep disturbances, and neuroblastoma. Prompt treatment of OMS is crucial to preventing permanent neurologic sequelae. In order to better characterize the clinical profile of this syndrome and its associated conditions, we present a case report of a 9 month old male with OMAS without an associated neuroblastoma and with new onset supraventricular tachycardia (SVT) and review the associated literature. Design/Methods NA. Results A 9-month-old male with a past medical history of macrocephaly, hypotonia, and developmental delay presented with abnormal eye and body movements starting one month prior. Due to concern for OMS, the patient underwent an extensive initial workup including CT neck, chest, abdomen, and pelvis and VHA/HMA levels, which were all within normal limits. The patient's spinal fluid revealed no evidence of paraneoplastic, autoimmune, or infectious processes. Per neurology recommendations, the patient was started on IVIG and dexamethasone. After his first IVIG infusion, the patient's abnormal movements worsened, and his heart rate increased into the 300s. The IVIG was discontinued. However, the patient continued to have recurring bouts of SVT, which was eventually controlled with digoxin. After resuming treatment with IVIG and dexamethasone, the patient's opsoclonus myoclonus symptoms began to improve. All additional metabolic labs resulted normal and the patient was discharged. Conclusions Because OMS can cause permanent developmental delay, prompt recognition and treatment of this syndrome is necessary. This is a unique case of OMAS without neuroblastoma, associated with recurrent bouts of SVT. Recognizing rare complications of OMS is crucial to improving medical management of its sequelae.

Myoclonus status revealing COVID 19 infection

IntroductionAt the beginning of the coronavirus virus (COVID-19) pandemic, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was thought to cause mainly respiratory symptoms, largely sparing the brain and the rest of the nervous system. However, as the knowledge about COVID-19 infection progresses and the number of COVID19-related neurological manifestations reports increases, neurotropism and neuroinvasion were finally recognized as major features of the SARS-CoV-2. Neurological manifestations involving the central nervous system are sparse, ranging from headaches, drowsiness, and neurovascular attacks to seizures and encephalitis [1]. Thus far, several cases of non-epileptic myoclonus were reported in critical patients [2,3]. Here, we report the first case of myoclonus status as the inaugural and sole symptom of COVID-19 in a conscious patient. ObservationA 60-year-old man with unknown family history and no medical issues other than smoking one cigarette packet a day over the span of 25 years. The patient presented with 5 days of abnormal movements in bilateral arms following the COVID vaccination. They were described as brief, involuntary jerking, like in sleep starts, in the proximal part of their upper members, and his face with a regular tremor in his arms exacerbated by movements and emotion. His movement disorder worsened the second day, and he developed an abnormal gait with slurred speech, concomitantly with diarrhea. Seven days following the symptoms onset, the patient was alert. His neurological exam revealed multifocal myoclonic jerks affecting four limbs predominantly proximal, the face, and the trunk (video 1). The myoclonic jerks were sensitive to tactile and auditory stimuli, without enhanced startle response or hyperekplexia. His gait was unsteady due to severe myoclonus, without cerebellar ataxia (video 2) and he had mild dysarthria. No dysmetria at the finger-to-nose and heel-to-shin tests were found. Examination of eye movements revealed paralysis of Down-Gaze and no opsoclonus was detected. Physical exam was unremarkable, including lack of fever and meningitis signs. The electroencephalogram (EEG) did not show any abnormalities concomitant with myoclonic jerks (Fig.1). The cerebral Magnetic Resonance Imaging (MRI) was normal (Fig. 2). An extensive biological work-up including a complete blood count, a comprehensive metabolic panel, an arterial blood gas analysis, a urine drug screen, a thyroid function test, a vitamin B12, folate, and ammonia level, and HIV and syphilis serologies were inconclusive. Testing for autoimmune and paraneoplastic antineuronal antibodies including anti-NMDA-R was negative. The cerebrospinal fluid (CSF) study was unremarkable (0.3 g/l of proteinorachia, 1 white blood cell). Polymerase chain reaction (PCR) for herpes simplex virus, varicella-zoster virus, and SARS-CoV-2 in CSF was negative. However, the patient tested positive for COVID-19 through PCR for viral RNA from the nasopharyngeal swab. After the administration of 12mg/day of Dexamethasone for 3 days, along with clonazepam and levetiracetam, the patient's symptoms started improving on day 3 and he displayed a very slow but progressive recovery. DiscussionOur patient presented with acute isolated multifocal myoclonus status without cognitive impairment. These movements were prominent, spontaneous, worsened by action, and sensitive to touch and sound. The anatomical source of this myoclonus could be cortical or subcortical despite the absence of evident EEG discharges. Several diseases can cause acute myoclonus such as severe hypoxia, metabolic disturbances, and paraneoplastic syndromes. these diagnoses were ruled out in our patient. Post-vaccinal origin was also suggested, but its accountability was not proven. Thus, the two hypothetic etiologies raised were either para-infectious or infectious mechanisms in relation to SARS-Cov 2 infection. HIV, VZV, HSV, and syphilis infections were eliminated and the patient tested positive for SARS-Cov2 infection. In the literature, COVID-19-related myoclonus was reported as a complication of an already-known SARS-CoV-2 infection in about 50 patients so far. It generally occurs between 6 days and 26 days following the SARS-CoV-2 infection [2–5], and affects critical illness patients with cognitive decline, mainly from the intensive care unit [3,4]. Yet, our patient did not display any symptoms of COVID-19 infection before the occurrence of these abnormal movements. Furthermore, he had a relatively good general condition and no cognitive impairment. Several pathophysiological mechanisms were suggested regarding the COVID-19-related myoclonus. Either central nervous invasion by SARS-Cov 2 after transneuronal spread and/or auto-immune cross-reactivity reaction, are likely incriminated in the pathophysiology of most of the cases [6]. We believe that there is an inflammatory process involved with increased levels of proinflammatory cytokines and systemic inflammation, including cytokine storm or cytokine release syndrome targeting the brain and more specifically the cortex and basal ganglia [6]. Data collection in clinical registries is needed to increase our knowledge of the prevalence of neurological symptoms in patients with COVID-19 and will hopefully clarify the causal relationship between SARS-CoV-2 infection and post-COVID-19 myoclonic syndrome.

Creutzfeldt-Jakob Disease: A Case Report and Literature Review for Understanding the Big Picture

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive neurodegenerative disorder that has an invariably fatal outcome. Aside from rapidly progressive dementia, this condition manifests as myoclonus, cerebellar, pyramidal, extrapyramidal, visual, and psychiatric symptoms. On the other hand, nonspecific symptoms might be difficult to diagnose, leading to a late or incorrect diagnosis. Given its high fatality, most patients die within 12 months of the disease'sonset. This case report describes a healthy man who presented with cerebellar and pyramidal signs along with memory loss worsening over six weeks.He also had indications of corticobasal degeneration, such as myoclonus and alien limb syndrome, but with reasonably maintained cognition. These signs are all non-specific, and premortem diagnosis is typically difficult and challenging owing to a lack of knowledge and clinical suspicion. However, after a thorough and extensive investigation, CJD was diagnosed. Despite the fact that CJD is a rare disease, it should always be included in the differential diagnosis whenever neuropsychological manifestations are present. Nevertheless, CJD can be successfully and promptly ruled out with a detailed clinical examination and appropriate investigation.

Monocentric retrospective clinical outcome in a group of 13 patients with opsoclonus myoclonus syndrome, proposal of diagnostic algorithm and review of the literature.

Dancing eye syndrome or opsoclonus-myoclonus syndrome (OMS) is a very rare disease (incidence <1/5,000,000 per year), which is more prevalent in young children. Although it is not usually a cause of mortality, the aftermaths are not rare. We performed an observational retrospective review of children diagnosed with OMS in our neuropediatric department from 1996 to 2020, with the objective of assessing the prognostic value of initial clinical features. All medical data from diagnosis to last follow-up were reviewed. We defined unfavorable evolution of OMS as persistence or worsening of symptoms. Subsequently, based on a literature review, our results and experience, a diagnostic algorithm was developed. A total of 13 OMS patients were included: 61.5% were male (n=8), median age at diagnosis was 18 months (IR=76), median treatment delay was 14 days (IR=146) and OMS score at onset was 8 (IR=11). The most frequent etiologies were neuroblastoma-associated and idiopathic OMS (38.46%; n=5) of the patients, followed by post-infectious OMS (n=3). All the patients were treated with corticosteroids, five required a surgical intervention (neuroblastoma group), and three required adjunctive immune therapy (immunoglobulins, cyclophosphamide and/or rituximab). We detected neurodevelopmental disorders in 38.46% (n=5) of the patients, mainly attention deficit (n=4), and persistent sleep disturbances (n=4). The median OMS score at the end of follow-up was 1 (IR=3). An important diagnostic delay, OMS score of ≥10 and age >1 year at onset may correlate with a higher risk of aftermaths. We detected a better prognosis in the post-infectious OMS, with full recovery occurring in 2/3 of patients. Early clinical suspicion is key to guarantee maximum response of treatment.

Rare Etiologies in Immune-Mediated Cerebellar Ataxias: Diagnostic Challenges.

The cerebellum is particularly enriched in antigens and represents a vulnerable target to immune attacks. Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies, such as gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), and anti-GAD ataxia. Apart from these well-established entities, cerebellar ataxia (CA) occurs also in association with autoimmunity against ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, glial cells, as well as the brainstem antigens. Most of these conditions manifest diverse neurological clinical features, with CAs being one of the main clinical phenotypes. The term primary autoimmune cerebellar ataxia (PACA) refers to ataxic conditions suspected to be autoimmune even in the absence of specific well-characterized pathogenic antibody markers. We review advances in the field of IMCAs and propose a clinical approach for the understanding and diagnosis of IMCAs, focusing on rare etiologies which are likely underdiagnosed. The frontiers of PACA are discussed. The identification of rare immune ataxias is of importance since they are potentially treatable and may lead to a severe clinical syndrome in absence of early therapy.