Disease modifying therapy in the treatment of tumefactive multiple sclerosis: A retrospective cohort study.

Tumefactive multiple sclerosis (TMS) is characterized by large demyelinating brain lesions. This was a retrospective cohort study of 67 patients with TMS between January 2015-2023, examining different disease modifying therapy impact on expanded disability scale score change at follow-up. Median age was 36 with a female predominance. Mean EDSS was 3.3 ± 2.3 at TMS onset, 2.1 ± 1.9 at year one, and 2.1 ± 1.9 at last follow-up. A multilinear regression model found higher presentation EDSS and post-diagnosis non-B-cell high efficacy therapies were each independently associated with higher EDSS at last follow up. Further research is needed to determine the value of B-cell therapy in TMS.

Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. OBJECTIVE: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). METHODS: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. RESULTS: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33). CONCLUSION: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.

Migraine and the risk of cervical artery dissection: A systematic review and meta-analysis.

INTRODUCTION: Migraine is a common, disabling chronic pain condition possibly related to changes in endothelial and vascular structure and function. Several observational studies have suggested an elevated risk of cervical artery dissection (CeAD) in patients with a history of migraine. We aimed to investigate this potential association using systematic review and meta-analytic methods. PATIENTS AND METHODS: We utilized a pre-defined search protocol to identify and screen studies related to migraine and CeAD in PubMed, Embase, and the Web of Science Core Collection. We assessed the risk of bias and performed a meta-analysis of selected studies to assess the association between migraine and CeAD. We also performed subgroup analyses by migraine subtype, biological sex, and the use of stroke versus non-stroke controls. RESULTS: We identified 11 studies (N = 9857 patients) for inclusion in the meta-analysis. Meta-analysis showed an association between migraine and CeAD with an odds ratio of 1.74 (95%CI 1.38-2.19). There was high heterogeneity among the included studies (I2 = 61%). Publication bias was present but the Trim-Fill imputation suggested that the impact on results was likely minimal. Subgroup analyses revealed an association between migraine without aura and CeAD (OR 1.86, 95%CI 1.55-2.24) but not migraine with aura and CeAD (OR 1.15, 95%CI 0.71-1.88). There was no difference in the association between migraine and CeAD in men compared to women. DISCUSSION AND CONCLUSION: A history of migraine is associated with an increased risk of CeAD. Further studies are needed to elucidate the potential pathophysiologic mechanisms underlying this association.

Hypogammaglobulinemia secondary to B-cell depleting therapies in neuroimmunology: Comparing management strategies.

Background: Anti-CD20 agents are commonly used in MS, NMOSD, and MOGAD. Few studies have compared strategies to address hypogammaglobulinemia. Objective: To compare strategies to manage secondary hypogammaglobulinemia in neuroimmunology patients, including reducing anti-CD20 dose and dosing frequency, IVIG/SCIG, anti-CD20 cessation, and DMT switches. Methods: All MS, NMOSD, and MOGAD patients at our institution with hypogammaglobulinemia on anti-CD20 agents from 2001 to 2022 were analyzed. The median change in IgG, infection frequency, and infection severity before and after the treatment was calculated. Results: In total, 257 patients were screened, and 30 had a treatment for hypogammaglobulinemia. IVIG/SCIG yielded the largest increase in IgG per year (674.0 mg/dL), followed by B-cell therapy cessation (34.7 mg/dL), and DMT switch (5.9 mg/dL). Dose reduction had the largest decrease in yearly infection frequency (2.7 fewer infections), followed by IVIG/SCIG (2.5 fewer), DMT switch (2 fewer), and reduced dosing frequency (0.5 fewer). Infection grade decreased by 1.9 for reduced dosing frequency (less severe infections), by 1.3 for IVIG/SCIG, and by 0.6 for DMT switch. Conclusion: This data suggests that IVIG/SCIG may yield the greatest recovery in IgG while also reducing infection frequency and severity. Stopping anti-CD20 therapy and/or switching DMTs also increase IgG and may lower infection risk.

Juvenile-Onset Huntington's Disease in Peru: A Case Series of 32 Patients.

Background: Juvenile-onset Huntington's Disease (JoHD) or Huntington's disease (HD) with age of onset ≤20 years, is a rare clinical entity that often differs phenotypically from adult HD and represents only 1-15% of total HD cases. Objective: To characterize the genetic and clinical characteristics of 32 JoHD patients seen in a Peruvian Neurogenetics clinic from 2000-2018. Methods: This study is a retrospective clinical and genetic review. The clinical database in Lima, Peru was searched for HD patients seen in clinic between 2000 and 2018. Inclusion criteria were: (1) genetically confirmed disease; and (2) HD age of onset ≤20 years, according to the documented medical history. Results: Among 475 patients with genetically confirmed HD in the database, 32 patients (6.7%) had symptom onset at ≤20 years. Among JoHD patients with a known transmitting parent (30 of 32), paternal transmission accounted for 77% of cases. Anticipation was higher with paternal transmission compared to maternal transmission (27.5 ± 11.5 vs. 11.3 ± 7.1 years). Overall expanded CAG repeat length ranged from 44 to 110, with a mean length of 65.6 ± 15.4, and 14 (44%) cases had repeat length under 60. Of the 32 patients included in the study, 25 had detailed clinical symptomatology available, and many patients had unique clinical features such as prominent sleep disturbance (60% of patients), or parkinsonism (73%). Conclusions: This large case series of JoHD patients characterizes the Peruvian JoHD population, reports on unique familial relationships in JoHD, and highlights the varied symptomatic presentation of this rare disease.

Low mortality rate in a large cohort of myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

The mortality rates of individuals with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are currently unknown. This study aimed to assess the mortality rate in a large cohort of patients with MOGAD. Since none of the patients in our cohort died, we estimated the upper limit of a 95% confidence interval of the crude mortality rate in the cohort to be 2.1%. These data suggest that mortality in MOGAD is lower than that reported in other neuroinflammatory diseases and comparable to the age-adjusted mortality rates of the general population in the United States. Additional studies are warranted to confirm this observation.

Transitioning immunotherapy in neuromyelitis optica spectrum disorder - when and how to switch.

INTRODUCTION: Newly approved immunotherapies for neuromyelitis optica spectrum disorder (NMOSD) have transformed the treatment landscape and improved disability outcomes. However, there are many remaining questions regarding transitioning immunotherapies in NMOSD that have not been addressed by randomized controlled trials. AREAS COVERED: This review focuses on the practical questions of managing and switching immunotherapies for NMOSD, including how to transition between immunotherapies, deciding when and if therapy should be discontinued, and transitioning during pregnancy or breastfeeding. EXPERT OPINION: Clinical experience and retrospective studies of real-world outcomes and complications associated with therapy, as well as therapy transitions, will help inform practice patterns moving forward. Strategies for transitioning between immunotherapies should consider the pharmacokinetics and the onset of clinical efficacy for each drug. Despite all the currently approved preventative immunotherapies, there are limited treatment options for those suffering from significant disability after their initial attack, and remyelination therapies are an important area for future research.

The Natural Stories corpus: a reading-time corpus of English texts containing rare syntactic constructions.

It is now a common practice to compare models of human language processing by comparing how well they predict behavioral and neural measures of processing difficulty, such as reading times, on corpora of rich naturalistic linguistic materials. However, many of these corpora, which are based on naturally-occurring text, do not contain many of the low-frequency syntactic constructions that are often required to distinguish between processing theories. Here we describe a new corpus consisting of English texts edited to contain many low-frequency syntactic constructions while still sounding fluent to native speakers. The corpus is annotated with hand-corrected Penn Treebank-style parse trees and includes self-paced reading time data and aligned audio recordings. We give an overview of the content of the corpus, review recent work using the corpus, and release the data.

Approach to Neurologic Complications in the Immunocompromised Patient.

Neurologic complications are common in immunocompromised patients, including those with advanced human immunodeficiency virus, transplant recipients, and patients on immunomodulatory medications. In addition to the standard differential diagnosis, specific pathogens and other conditions unique to the immunocompromised state should be considered in the evaluation of neurologic complaints in this patient population. A thorough understanding of these considerations is critical to the inpatient neurologist in contemporary practice, as increasing numbers of patients are exposed to immunomodulatory therapies. In this review, we provide a chief complaint-based approach to the clinical presentations and diagnosis of both infectious and noninfectious complications particular to immunocompromised patients.

Neurologic Complications of Acute HIV Infection.

PURPOSE OF REVIEW: This review focuses on the pathophysiology of acute HIV infection (AHI) and related central nervous system (CNS) pathology, the clinical characteristics of neurologic complications of AHI, and the implications of the CNS reservoir and viral escape for HIV treatment and cure strategies. RECENT FINDINGS: Recent studies in newly seroconverted populations show a high prevalence of peripheral neuropathy and cognitive dysfunction in AHI, even though these findings have been classically associated with chronic HIV infection. HIV cure strategies such as the "shock and kill" strategy are currently being studied in vitro and even in small clinical trials, though the CNS as a reservoir for latent HIV poses unique barriers to these treatment strategies. SUMMARY: Limited point of care diagnostic testing for AHI and delayed recognition of infection continue to lead to under-recognition and under-reporting of neurologic manifestations of AHI. AHI should be on the differential for a broad range of neurological conditions, from Bell's palsy, peripheral neuropathy, and aseptic meningitis, to more rare manifestations such as ADEM, AIDP, meningo-radiculitis, transverse myelitis, and brachial neuritis. Treatment for these conditions involves early initiation of antiretroviral therapy (ART) and then standard presentation-specific treatments. Current HIV cure strategies under investigation include bone marrow transplant, viral reservoir re-activation and eradication, and genome and epigenetic viral targeting. However, CNS penetration by HIV-1 occurs early on in the disease course with the establishment of the CNS viral reservoir and is an important limiting factor for these therapies.

Palliative Care: Perceptions, Experiences, and Attitudes in a Peruvian Neurologic Hospital.

BACKGROUND: The development of palliative care in Peru remains limited, particularly for nononcological services, such as neurology. The goal of this study was to explore attitudes toward and knowledge about palliative and end-of-life care among patients, families, nurses, and doctors in a specialized neurological institute in Lima, Peru. MATERIALS AND METHODS: We used a mixed methods approach consisting of 78 surveys and 21 qualitative, semistructured interviews that were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Surveys identified a substantial need for palliative care in the neurological institute (63% of doctors and 77% of nurses reported palliative care needs in >30% of their patients), and for training (82% of doctors and 69% of nurses reported inadequate palliative care education). The key themes emerging from qualitative interviews concerned transparency of communication about prognosis and end-of-life choices in neurological disease. Familiarity with advance directives was limited among both clinicians and families, and participants were divided about whether or not patients should be informed of serious diagnoses and prognoses, and who should inform them. Barriers to transparency in patient-physician communication included (1) expectation of cure; (2) physician's lack of training in communication and end-of-life care; (3) a paternalistic culture; and (4) the nature of neurological diseases. CONCLUSIONS: Our study highlights opportunities to enhance palliative care and communication education for neurology providers and the public in Peru, a country that currently has no palliative care training program and no legal basis for advance directives.

The First Report of CADASIL in Peru: Olfactory Dysfunction on Initial Presentation.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare, heritable, small vessel vascular disease caused by mutations in the Notch3 gene that is characterized by migraines, subcortical vascular events, cognitive decline, and mood disturbances. However, many CADASIL cases present with unusual symptoms such as status epilepticus, a movement disorder, or sensory dysfunction. This study describes the clinical, genetic, and radiologic characteristics of a Peruvian family with CADASIL in which multiple family members presented with severe olfactory deficits. Seven members of the family have symptoms suggestive of CADASIL, with genetic testing revealing R133C mutations in the two patients who underwent genetic testing. Cognitive testing and olfactory identification testing (Smell Identification Test) were performed in three CADASIL patients revealing total anosmia in two tested patients and severe hyposmia in the other. Olfactory dysfunction has been associated with various neurologic and psychiatric conditions though few studies have linked it with neurovascular disorders such as CADASIL. This first reported case of CADASIL in Peru emphasizes that symptomatic olfactory dysfunction may be an unusual presentation of CADASIL and that olfactory dysfunction is important to evaluate in CADASIL patients.

Neurogenética en el Perú, ejemplo de investigación traslacional / Neurogenetics in Peru, example of translational research

La neurogenética es una disciplina emergente en el Perú que vincula la investigación básica con la práctica clínica. El Centro de Investigación Básica en Neurogenética, es el único centro en el Perú dedicado a la atención especializada de enfermedades neurogenéticas. La investigación en esta área está estrechamente ligada a la enfermedad de Huntington, desde la genotipificación del gen HTT por PCR, hasta los actuales estudios de haplogrupos en esta enfermedad. La investigación en otras enfermedades monogénicas permitió la implementación de metodologías alternativas para la genotipificación del síndrome X frágil y distrofia miotónica tipo 1. Esfuerzos colaborativos nacionales e internacionales han permitido conocer nuevas variantes genéticas en enfermedades complejas, como la enfermedad de Parkinson y Alzheimer. El entrenamiento multidisciplinario y la mentoría fomentan la formación de nuevos especialistas en neurogenética, permitiendo el crecimiento sostenido de esta disciplina en el país. El impulso de la investigación en el Perú ha impulsado el crecimiento de la investigación en neurogenética; sin embargo, las limitaciones en infraestructura, tecnología y capacitación aún son un reto para el crecimiento de investigación en esta disciplina...

Neurogenetics is an emerging discipline in Peru that links basic research with clinical practice. The Neurogenetics Research Center located in Lima, Peru is the only unit dedicated to the specialized care of neurogenetic diseases in the country. From the beginning, neurogenetics research has been closely linked to the study of HuntingtonÆs Disease (HD), from the PCR genotyping of the HTT gene, to the current haplogroup studies in HD. Research in other monogenic diseases led to the implementation of alternative methodologies for the genotyping of Fragile X and Myotonic Dystrophy Type 1. Both, national and international collaborative efforts have facilitated the discovery of new genetic variants in complex multigenic diseases such as ParkinsonÆs disease and AlzheimerÆs disease. Additionally, multidisciplinary education and mentoring have allowed for the training of new neurogenetics specialists, supporting the sustained growth of the discipline in the country. The promotion of research in Peru has spurred the growth of neurogenetics research, although limitations in infrastructure, technology, and education remain a challenge for the further growth of research in this field...

[Neurogenetics in Peru, example of translational research]. / Neurogenética en el Perú, ejemplo de investigación traslacional.

Neurogenetics is an emerging discipline in Peru that links basic research with clinical practice. The Neurogenetics Research Center located in Lima, Peru is the only unit dedicated to the specialized care of neurogenetic diseases in the country. From the beginning, neurogenetics research has been closely linked to the study of Huntington’s Disease (HD), from the PCR genotyping of the HTT gene, to the current haplogroup studies in HD. Research in other monogenic diseases led to the implementation of alternative methodologies for the genotyping of Fragile X and Myotonic Dystrophy Type 1. Both, national and international collaborative efforts have facilitated the discovery of new genetic variants in complex multigenic diseases such as Parkinson’s disease and Alzheimer’s disease. Additionally, multidisciplinary education and mentoring have allowed for the training of new neurogenetics specialists, supporting the sustained growth of the discipline in the country. The promotion of research in Peru has spurred the growth of neurogenetics research, although limitations in infrastructure, technology, and education remain a challenge for the further growth of research in this field.