Investigating the 2023 MOGAD Criteria in Children and Adults With MOG-Antibody Positivity Within and Outside Attacks.

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.

Iatrogenic Shapiro syndrome: a case report.

OBJECTIVES: Shapiro's syndrome (SS) is a rare condition characterized by spontaneous periodic hypothermia. The underlying pathophysiological mechanisms and etiology of this syndrome remain controversial, and fewer than 100 cases have been reported to date. The objective of this case report is to present a unique iatrogenic case of SS and contribute additional insights into the underlying etiology of this rare disorder. METHODS: We conducted an analysis of existing medical literature and described a clinical case of SS secondary to a neurosurgical procedure. RESULTS: To our knowledge, we present the first iatrogenic case of SS in a 53-year-old woman who underwent a partial right parieto-occipital lobectomy in 2003 as a treatment for refractory epilepsy. Several years after the surgical procedure, she began experiencing recurrent episodes of hypothermia. Brain magnetic resonance imaging (MRI) revealed the absence of the splenium of the corpus callosum (CC) and pituitary hyperplasia. After ruling out other potential causes of hypothermia, a diagnosis of SS was made. DISCUSSION: The most plausible mechanism to explain the recurrent hypothermia associated with SS in our patient is a probable disruption of the pathways involved in thermoregulation through the CC as a consequence of the surgical procedure. This case report provides further insights into the etiology of this rare disorder.

A new phenotype of myorhythmia: Oculofacial myorhythmia in a patient with Erdheim Chester disease.

Oculofacial myorhythmia (OFM) is a movement disorder characterized by slow, rhythmic, and repetitive movement that affects the periorbital and perioral muscles. This abnormal movement is classified as a tremor and is highly suggestive of brainstem lesions. Unlike the oculomasticastory myorhythmia, the oculofacial pattern has rarely been reported to date. We present a patient diagnosed with Erdheim Chester disease who two years after the diagnosis developed an oculofacial myorhythmia. We additionally provide a pathological framework based on evolutionary changes on neuroimaging which could explain the appearance of this very rare movement disorder. No cases of OFM have been described in patients with ECD to date. To our knowledge we are reporting the first case of oculofacial myorhythmia secondary to Erdheim Chester disease. To conclude, oculofacial myorhytmia could be a late-onset clinical manifestation of ECD with brainstem involvement.

Differences in metacognition between multiple sclerosis phenotypes: cognitive impairment and fatigue are key factors.

Background: Cognitive impairment is present in 40-65% of patients with multiple sclerosis (pwMS). Objectively measured cognitive performance often does not match patients' subjective perception of their own performance. Objective: We aimed to compare cognitive performance and subjective perception of cognitive deficits between pwMS and healthy controls (HCs), as well as the accuracy of subjective perception. Methods: In total, 54 HC and 112 pwMS (relapsing-remitting, RRMS, and progressive PMS) underwent neuropsychological evaluation and completed perceived deficit, fatigue, and anxiety-depression scales. Participants were classified according to their consistency between subjective self-evaluation of cognitive abilities and objective cognitive performance to assess accuracy. Regression models were used to compare cognitive performance between groups and explore factors explaining inaccuracy in the estimation of cognitive performance. Results: PMS showed greater and more widespread cognitive differences with HC than RRMS. No differences were found between pwMS and HC in the perception of deficit. PMS had higher ratios of overestimators. In explaining inaccuracy, fatigue and cognitive preservation were found to be risk factors for underestimation, whereas physical disability and cognitive impairment were risk factors for overestimation. Conclusion: PwMS have metacognitive knowledge impairments. This study provides new information about metacognition, data on the prevalence of impairments over a relatively large sample of PwMS, and new insights into factors explaining it. Anosognosia, related to cognitive impairment, may be present in pwMS. Fatigue is a key factor in underestimating cognition.

Progressive multifocal leukoencephalopathy in a patient with relapsing multiple sclerosis treated with ocrelizumab: A case report.

INTRODUCTION: Progressive multifocal leukoencephalopathy is a rare but often fatal complication of some multiple sclerosis treatments. Although it has mainly been associated with natalizumab treatment, its appearance with other immunosuppressive therapies has also been reported. AIMS: The aim of this case report is to describe the development of progressive multifocal encephalopathy in a patient with relapsing-remitting multiple sclerosis treated with ocrelizumab without previous use of natalizumab. CONCLUSIONS: A summary of the presentation and disease course is provided, presented in the context of the current literature and likely pathophysiology.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

The nature of memory impairment in multiple sclerosis: understanding different patterns over the course of the disease.

Introduction: Memory deficit is one of the most common and severe cognitive impairments in patients with multiple sclerosis and can greatly affect their quality of life. However, there is currently no agreement as to the nature of memory deficit in multiple sclerosis. Methods: This cross-sectional study, carried out at the Dr. Josep Trueta and Santa Caterina hospitals in Girona (Spain), was designed to determine the semiology of verbal memory deficit in the different stages of the disease. To this end, a modification of Rey's verbal auditory test was created by introducing two recognition trials between the five learning trials, thus monitoring what happens in terms of acquisition versus the retrieval of information during the learning phase. Linear regression models were used to evaluate verbal episodic memory performance between-groups adjusting results by age, sex, educational level, and the presence of anxiety and/or depressive symptoms. Results: 133 patients with multiple sclerosis, clinically isolated syndrome, and radiologically isolated syndrome and 55 healthy controls aged 18-65 years were assessed. It was observed that the memory processes of multiple sclerosis patients worsen with the progression of the disease. In this respect, patients in pre-diagnostic phases (radiologically isolated syndrome and clinically isolated syndrome) show no differences in verbal episodic memory compared to the healthy controls. Patients in the inflammatory stage (relapsing-remitting multiple sclerosis) show a previously learned information retrieval deficit, while patients in progressive stages (secondary progressive multiple sclerosis and primary progressive multiple sclerosis) do not even correctly acquire information. Discussion: These results provide significant information to assist in understanding the nature of memory deficits in multiple sclerosis over the course of the disease. These results are discussed in terms of possible cognitive rehabilitation strategies depending on the evolutive stage and are related to neuropathological mechanisms involved in the progression of the disease.

Ketamine for Bipolar Depression: Biochemical, Psychotherapeutic, and Psychedelic Approaches.

Bipolar disorder (type 1) is a serious and chronic psychiatric illness that can be difficult to treat. Many bipolar patients have refractory depressive episodes. Racemic ketamine, a glutamate modulator with prominent dissociate and psychedelic properties, has been demonstrated to have rapid acting antidepressant and anti-obsessional effects which may be useful for treating the symptoms of bipolar depression. Most of the existing research literature on unipolar and bipolar depression has looked at racemic ketamine in the sub-psychedelic dose range given by infusion as a stand-alone treatment (without concurrent psychotherapy). This article expands on the existing research by articulating three different paradigms for ketamine treatment: biochemical, psychotherapeutic, and psychedelic. The authors use composite clinical vignettes to illustrate different ways of working with ketamine to treat bipolar depression, and discuss a variety of clinical considerations for using ketamine with this population, including route, dose, frequency, chemical mitigators, and adverse events. Note that the conceptual paradigms could be applied to any ketamine treatment, with broad applicability beyond bipolar treatment.

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives.

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are bioactive lipid molecules that are ubiquitously expressed in the human body and play an important role in the immune system. S1P-S1PR signaling has been well characterized in immune trafficking and activation in both innate and adaptive immune systems. Despite this knowledge, the full scope in the pathogenesis of autoimmune disorders is not well characterized yet. From the discovery of fingolimod, the first S1P modulator, until siponimod, the new molecule recently approved for the treatment of secondary progressive multiple sclerosis (SPMS), there has been a great advance in understanding the S1P functions and their involvement in immune diseases, including multiple sclerosis (MS). Modulation on S1P is an interesting target for the treatment of various autoimmune disorders. Improved understanding of the mechanism of action of fingolimod has allowed the development of the more selective second-generation S1PR modulators. Subtype 1 of the S1PR (S1PR1) is expressed on the cell surface of lymphocytes, which are known to play a major role in MS pathogenesis. The understanding of S1PR1's role facilitated the development of pharmacological strategies directed to this target, and theoretically reduced the safety concerns derived from the use of fingolimod. A great advance in the MS treatment was achieved in March 2019 when the Food and Drug Association (FDA) approved Siponimod, for both active secondary progressive MS and relapsing-remitting MS. Siponimod became the first oral disease modifying therapy (DMT) specifically approved for active forms of secondary progressive MS. Additionally, for the treatment of relapsing forms of MS, ozanimod was approved by FDA in March 2020. Currently, there are ongoing trials focused on other new-generation S1PR1 modulators. This review approaches the fundamental aspects of the sphingosine phosphate modulators and their main similarities and differences.

Clinical heterogeneity in patients with myoclonus associated to COVID-19.

OBJECTIVE: This study aims to report the clinical heterogeneity of myoclonus in 6 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Patient data were obtained from medical records from the University Hospital Dr. Josep Trueta, Girona, Spain. RESULTS: Six patients (5 men and 1 woman, aged 60-76 years) presented with different myoclonus phenotypes. All of them had a medical history of hypertension and overweight. The latency of myoclonus appearance ranged from 1 to 129 days. The phenotype most observed was generalized myoclonus. Special phenotypes such as painful legs and moving toes syndrome with jerking feet, Lazarus sign-like, action myoclonus/ataxia syndrome, and segmental myoclonus secondary to myelitis have been described too. Levetiracetam and clonazepam were medications most used successfully. Two patients died for complications not related to myoclonus. CONCLUSIONS: Our 6 cases highlight the heterogeneity of the clinical spectrum of myoclonus associated to COVID-19 (MYaCO). MYaCO pathogenesis is suspected to be due to an immune-mediated para- or post-infectious phenomenon; nevertheless, further research is needed to elucidate this hypothesis.

Assessing the presence of oligoclonal IgM bands as a prognostic biomarker of cognitive decline in the early stages of multiple sclerosis.

BACKGROUND: An association has been found between the presence of lipid-specific oligoclonal IgM bands (LS-OCMB) in cerebrospinal fluid and a more severe clinical multiple sclerosis course. OBJECTIVE: To investigate lipid-specific oligoclonal IgM bands as a prognostic biomarker of cognitive impairment in the early stages of multiple sclerosis. METHODS: Forty-four patients underwent neuropsychological assessment at baseline and 4 years. Cognitive performance at follow-up was compared adjusting by age, education, anxiety-depression, and baseline performance. RESULTS: LS-OCMB+ patients only performed worse for Long-Term Storage in the Selective Reminding Test (p = .018). CONCLUSION: There are no remarkable cognitive differences between LS-OCMB- and LS-OCMB+ patients in the early stages of MS.

Clinical and radiological features of cerebral amyloid angiopathy-related inflammation.

OBJECTIVES: We want to report the clinical and radiological features of our cohort of patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-RI) according to the Boston Criteria and additionally to disclose some atypical clinical characteristics observed in some of them to provide more knowledge about this novel entity. METHODS: We describe 5 patients with probable CAA-RI according to a validation study of proposed criteria for the diagnosis of CAA-RI at University Hospital Josep Trueta of Girona. We consider some clinical characteristics which include the response to immunotherapy, CSF findings, and MRI features. The patient's neurologic outcomes were assessed using the modified Rankin Scale (mRS). RESULTS: We collected 5 patients admitted for probable CAA-RI. Most were women and the median age was 72 years. The median mRS score at the onset of disease was 1. Parietal lobes were most affected clinically as well as radiologically. Two patients had intracranial hemorrhage. Decreased levels of CSF amyloid beta 42 and 40 protein were observed. Corticosteroids were used in four patients and a remarkable improvement was observed in all of them. CONCLUSIONS: CAA-RI is a condition that predominantly affects parietal lobes according to our case series and this involvement seems to be directly related to a greater burden of microbleeds, cortical siderosis, WMH, and lobar hemorrhages on these lobes. Decreased levels of CSF amyloid beta protein plus increased total tau protein should be considered as part of the diagnostic criteria of CAA-RI. We recommend corticosteroids using, as they have been demonstrated to be very effective in managing CAA-RI.

The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene and responds well to cannabidiol treatment.

Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult that is why Cannabidiol emerged as valid option for treatment of this condition.

Cerebellopathy secondary to anti-peroxidase antibody-mediated toxicity. A special case of Hashimoto encephalopathy.

OBJECTIVE: The aim of this case report is to highlight the importance of recognizing uncommon causes of cerebellar involvement. CASE PRESENTATION: A 45-year-old woman with no medical history who presented gait instability that appears suddenly and evolves rapidly in two weeks, causing frequent falls. Neurological examination revealed an inability to walk due to severe ataxia, accompanied by global hypotonia, appendicular dysmetria, opsoclonus and dysarthria. We studied this patient with cerebellar syndrome, obtaining as relevant findings global cerebellar atrophy in MRI (magnetic resonance imaging) and especially, considerably elevated levels of antibodies against thyroid peroxidase (TPO). The patient was treated with high doses of intravenous methylprednisolone for 5days. Six months after diagnosis and in treatment with low doses of prednisone, the patient is asymptomatic. CONCLUSION: We must considerer the cerebellar involvement secondary to steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) in a patient in whom other more frequent causes of isolated cerebellar disease have been ruled out.

Intravenous Fibrinolysis in Ischemic Stroke of Large Vessel after Reversing Effect of Dabigatran with Idarucizumab.

Currently the use of idarucizumab to reverse the effect of dabigatran emerges as a possibility of treatment for those patients who present with an ischemic stroke despite taking this anticoagulant. We present our experience regarding the use of intravenous tissue plasminogen activator in a patient with ischemic stroke due to complete occlusion of the left middle cerebral artery after blocking the effect of dabigatran with idarucizumab and whose result was an almost total improvement of the neurologic deficit. The use of this monoclonal antibody without a prothrombotic effect seems safe to be an intravenous fibrinolytic treatment option for patients taking dabigatran and having an ischemic stroke; however, more extensive studies are needed to determine its safety and efficacy.