Pelletier/Gottesfeld updates

Justina Pelletier is Focusing on Her Personal Growth Today

Once Justina returned home, she underwent a few more surgical procedures to help cope with her symptoms. Her parents also consulted doctors regarding potential spine-related problems which have hampered her walking. In 2020, Justina testified in court for a lawsuit her parents had filed against the BCH for medical malpractice. She alleged that the hospital staff disallowed her to speak to her parents and were sometimes cruel to her. Justina further insisted that her pleas to return home were ignored. She said, “They didn’t believe [my pain], and they hurt me so much,” Pelletier said. “I kept getting weaker.”

Since her discharge, Justina has engaged in art therapy and horseriding and graduated high school in 2020. She now still leads a private life in her parents’ home in Connecticut, where she feels happy and safe in their constant care. Now 23, Justina continues receiving treatment for her mitochondrial syndrome. Sadly, in 2021, she experienced a stroke, drastically impacting her health, verbal communication, and energy levels.

https://thecinemaholic.com/where-is-survivor-justina-pelletier-now/

Lou and Linda Pelletier Are Focusing on Justina’s Health Now

Though the Pelletiers gained significant support from religious groups, parent groups, and media outlets, Justina was shifted to Wayside Youth and Family Support Network, a residential facility in Framingham, Massachusetts. Seeing no other way to get back their daughter, Linda and Lou mildly complied with the BCH’s treatment plan for her, and in June 2014, the court finally dismissed the child protection case against them. Thus, Justina was finally reunited with them and taken back to Connecticut.

Linda and Lou were relieved to bring Justina home, but their troubles were far from over. The teenager was unable to walk and was still having multiple health complications. Deeply hurt over the trauma they and Justina had faced for around 16 months, Linda and Lou filed a malpractice lawsuit against Boston Children’s Hospital for sending her to the psychiatric ward. The couple’s testimony divulged how their daughter secretly passed them notes during their hospital visits, complaining of the staff’s misbehavior and her desperate wish to go home.

Not just that, Justina herself testified the same in court in 2020, but ultimately, the jury found BCH not negligent in her care. Despite losing the lawsuit, Lou refused to give up his fight for his daughter and helped pass the bill for Justina’s Law. It prohibits the use of federal funds to conduct or support treatment or research involving a ward of the state in which the individual’s health is subjected to greater than minimal risk with no or minimal prospect of direct benefit.

Lou and Linda still live in their Connecticut home and are dedicated to caring for Justina round-the-clock, as she is back on her medications for mitochondrial disease. The Pelletiers faced another setback in 2021 when she had a stroke, affecting her daily functions. Nevertheless, her parents took every measure to nurse her back to health and now hope she can walk again someday. Linda shared how traumatized she still feels about everything and how hard it is for her and Lou to put what happened behind them. We sincerely hope the family gets the strength to heal from their pain and have a peaceful future ahead.

https://thecinemaholic.com/lou-and-linda-pelletier-where-are-justinas-parents-now/

Marty Gottesfeld is Now Making the Most of His Time As a Free Man

Marty was sentenced to ten years in prison and was subsequently incarcerated in a few different federal prisons across the nation. According to his wife, there was even a time a high-security facility kept him in solitary confinement for 22 hours daily, and he was allowed only two fifteen-minute calls weekly. Dana divulged in the documentary that Marty’s communication were heavily monitored. Yet, he continues to support social causes and voices his opinions on government policies by corresponding with media organizations through her.

As per the documentary, the hacktivist’s projected release date was April 11, 2024, and he already had a job offer from a progressive publishing house to work as a web developer. However, he was released early, around November 2023, and has since happily reunited with his loving wife Dana. “Words fail me, because you’re out in public again,” he once said upon being asked what it was like to be free. “Like, they just put you on a greyhound bus; when I was released, it’s like, they just drop you off at the bus station, and you’re out in public again, and you can talk to people.” We should mention he did walk away with 210 lbs of legal documents he’d created while incarcerated, and he is determined to continue down the path he once created to help Justina and others like the once-teen. The Somerville, Massachusetts, resident is now a full-fledged human rights activist as well as a writer for many platforms; plus he has a blog of his own.

https://thecinemaholic.com/marty-gottesfeld-where-is-hacker-and-social-activist-today/

Schizophrenia is associated with an aberrant immune response to Epstein–Barr virus

Faith Dickerson, Lorraine Jones-Brando, Glen Ford, Giulio Genovese, Cassie Stallings, Andrea Origoni, Colm O’Dushlaine, Emily Katsafanas, Kevin Sweeney, Sunil Khushalani, Robert Yolken, Schizophrenia is Associated With an Aberrant Immune Response to Epstein–Barr Virus, Schizophrenia Bulletin, Volume 45, Issue 5, September 2019, Pages 1112–1119, https://doi.org/10.1093/schbul/sby16

Abstract

Background

Epstein–Barr virus (EBV) is a highly prevalent human herpesvirus capable of infecting the central nervous system and establishing persistent infection.

Methods

We employed solid phase immunoassay techniques to measure immunoglobulin G (IgG) class antibodies to EBV virions and defined proteins in 432 individuals with schizophrenia and 311 individuals without a history of a psychiatric disorder. Western blot testing was performed to document reactivity to specific EBV proteins. Polygenic risk for schizophrenia was calculated from genome sequencing arrays. Levels of antibodies between the groups were compared by multivariate analyses incorporating clinical, genetic, and demographic measures.

Results

Individuals with schizophrenia had marked elevations in the levels of antibodies to EBV virions as compared to the control population. Further analyses indicated increased levels of reactivity to EBV-viral capsid antibody (VCA) but not to EBV nuclear antigen-1 (EBNA-1) or to other human herpesviruses. Western blot analysis confirmed increased reactivity to VCA proteins in the group of individuals with schizophrenia and documented a lack of increased levels of antibodies to EBNA-1. Genetic analyses indicated an additive effect of increased levels of antibodies to EBV virions and genetic susceptibility to schizophrenia, with individuals with elevated levels of both type of markers having a greater than 8.5-fold odds of a schizophrenia diagnosis.

Conclusions

Individuals with schizophrenia have increased levels of antibodies to some but not all EBV proteins indicating an aberrant response to EBV infection. This aberrant response may contribute to the immunopathology of schizophrenia and related disorders.
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New research from Johns Hopkins Medicine and Sheppard Pratt Health System shows that people in the study with schizophrenia also have higher levels of antibodies against the Epstein-Barr virus (EBV), a herpes virus that causes infectious mononucleosis, so-called mono.

Researchers proposed two explanations for the association of heightened immune responses in patients with schizophrenia and EBV infection: schizophrenia might alter the immune systems of these patients and make them more susceptible to EBV, or EBV infection might increase the risk of schizophrenia.

The article was published online Nov. 20 in Schizophrenia Bulletin.

“We are interested in the role of infectious agents such as Epstein-Barr virus in schizophrenia and other serious psychiatric disorders, so we did this study to look at the associations,” said Robert Yolken, M.D., the Theodore and Vada Stanley Distinguished Professor of Neurovirology in pediatrics at Johns Hopkins Children’s Center and senior author of the study. Yolken cautioned that the study wasn’t designed to determine cause and effect.

Schizophrenia is a mental disorder where patients have distorted thinking, perception, emotions, language, sense of self and behavior. According to the World Health Organization, schizophrenia affects more than 21 million people worldwide.

While schizophrenia has some genetic associations, genes that have been found to date explain only a portion of the disease risk. Environmental exposures, including to some infectious agents, have also been identified in previous studies as increasing the risk for schizophrenia.

EBV is a common virus and research suggests it infect approximately 90-95 percent of the world’s population. However, most people never show symptoms of infection and the vast majority of people never have complications. EBV initially causes fever and swollen lymph nodes, and is commonly transmitted through oral contact such as kissing. In severe cases, it can spread to the central nervous system and cause persistent infection. Researchers wanted to see the relationship between this EBV infection and schizophrenia.

The researchers conducted a study among 743 people—432 with a schizophrenia diagnosis and 311 without a history of a psychiatric disorder to serve as a control group. Around 55 percent of the participants were men.

The researchers first measured levels of antibodies against components of EBV by comparing antibody levels in healthy people with those of people who have schizophrenia. They looked at the odds of having these antibodies in the 50th, 75th and 90th percentiles and found that people with schizophrenia were 1.7 to 2.3 times more likely to have increased levels of some EBV antibodies compared with people without schizophrenia.

Then they measured the antibodies to other related viruses such as varicella/chicken pox or herpes simplex type 1/cold sore virus, and didn’t find an increase of antibodies against these viruses in people with schizophrenia. These findings suggest that only EBV was associated with increased risk of schizophrenia.

After that, the researchers sequenced a portion of the participants’ DNA to determine their genetic risk for schizophrenia. Results from the analysis showed that people who had both evidence of increased genetic risk for schizophrenia and increased antibody levels to EBV had a more than eight times higher chance of being in the schizophrenia group as compared with controls. Approximately 10 percent of the individuals with schizophrenia had increased levels of both antibodies and genetic risk as compared with slightly more than 1 percent of the controls.

“We found that individuals with schizophrenia had an unusual response to Epstein-Barr virus,” said Yolken. “This indicated that the prevention and treatment of Epstein-Barr virus might represent an approach for the prevention and treatment of serious psychiatric disorders such as schizophrenia.”

Currently, there are no treatments available for EBV approved by the Food and Drug Administration, but a number of compounds that may prevent or treat replication of the virus are under investigation. The researchers considered the development of these approaches a high priority so that people with schizophrenia or other disorders associated with susceptibility to EBV could use them. In the meantime, researchers recommend preventing EBV transmission through good hygienic practices such as hand-washing and avoiding oral contact, such as kissing, with infected people.

https://www.hopkinsmedicine.org/news/newsroom/news-releases/2019/01/schizophrenia-linked-with-abnormal-immune-response-to-epstein-barr-virus

Teratogenesis, perinatal, and neurodevelopmental outcomes after in utero exposure to antiseizure medication

Pack AM, Oskoui M, et al. Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication. Epilepsy Currents. 2025;0(0). doi:10.1177/15357597241258514
Abstract

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neuro-developmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient’s epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Karakis I. “In the Name of the Father: Risk to the Offspring From Paternal Exposure to Valproate During Conception”. Epilepsy Currents. 2025;0(0). doi:10.1177/15357597251317286

Importance: Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis. Objective: To evaluate the association between paternal use of valproate during spermatogenesis and offspring risk of congenital malformations and neurodevelopmental disorders. Design, setting, and participants: This nationwide cohort study included 1,235,353 singletons born in Denmark between January 1, 1997 and December 31, 2017, identified in the Medical Birth Register; 1336 children had fathers who had filled prescriptions for valproate during spermatogenesis. Congenital malformations were identified in the first year of life and neurodevelopmental disorders were identified from 1 year of age until December 31, 2018. Statistical analysis was performed March 2024. Exposures: Paternal valproate exposure was defined as fathers who filled 1 or more prescriptions for valproate immediately before or during the time of spermatogenesis (ie, 3 months prior to conception). Main outcomes and measures: Children with major congenital malformations in the first year of life and with neurodevelopmental disorders before death or end of follow up were identified in Danish health registers. Log-binomial regression was used to estimate adjusted relative risks (ARRs) of congenital malformations, and Cox proportional hazards regression was used to estimate adjusted hazards ratios (AHRs) of neurodevelopmental disorders, adjusted for relevant confounders. Results: Among 1,235,353 live births (634,415 boys [51.4%] and 600,938 girls [48.6%]), 1336 children (0.1%) had fathers who filled prescriptions for valproate during spermatogenesis. The median follow up was 10.1 years (interquartile range [IQR] 5.1-14.8 years) for valproate-exposed children and 10.3 years (IQR 5.2-15.6 years) for valproate-unexposed children. A total of 43,903 children (3.6%) received a diagnosis of major congenital malformations in the first year of life, and 51,633 children (4.2%) received a diagnosis of neurodevelopmental disorders during follow up. When comparing the risk among valproate-exposed children with that among unexposed children, the ARR of major congenital malformations was 0.89 (95% confidence interval [CI] 0.67-1.18), the AHR of neurodevelopmental disorders was 1.10 (95% CI 0.88-1.37), and the AHR of autism spectrum disorder was 0.92 (95% CI 0.65-1.30). In analyses addressing the robustness of the findings (ie, dose-response analyses, sibling analyses, analyses restricted to children of fathers with epilepsy, analyses that used children with paternal lamotrigine exposure as active comparator, and analyses that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure), there still was no increased risk of any of the included end points. Conclusions and relevance: In all analyses based on this large Danish cohort study, results suggest that exposure to valproate during spermatogenesis was not associated with offspring risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder.

Lennox-Gastaut syndrome treatment and prevention

Warren AEL, Patel AD, Helen Cross J, et al. Mobilizing a New Era in Lennox-Gastaut Syndrome Treatment and Prevention. Epilepsy Currents. 2025;0(0). doi:10.1177/15357597251321926

Abstract

This review summarizes content presented at the Pediatric State of the Art Symposium held during the American Epilepsy Society's annual meeting in December 2024. The symposium focused on Lennox-Gastaut syndrome (LGS), a severe developmental and epileptic encephalopathy that emerges in childhood. Despite its diverse etiologies, LGS is defined by a convergent constellation of electroclinical features: multiple seizure types including tonic seizures, slow spike-wave and generalized paroxysmal fast activity on EEG, and intellectual disability. LGS is almost always refractory to available therapies and accounts for substantial costs—in healthcare spending and in quality of life for affected individuals, their families, and caregivers. The symposium highlighted recent breakthroughs in research, clinical care, and outcome measurement that have positioned the clinical, scientific, and patient advocacy communities to usher in a new, more hopeful era of treatment and prevention.

Excerpts

How might preclinical models inform our understanding of LGS pathogenesis and treatment? Promising examples include the recent discovery that increased myelin plasticity exacerbates epilepsy progression in an SCN8A Scn8a+/- mouse model of generalized epilepsy, and that this epilepsy progression can be prevented by suppressing activity-dependent myelination. In zebrafish, high-throughput drug screens in models of Dravet syndrome identified Clemizole, a modifier of serotonin signaling, with potent anti-seizure effects; this has led to ongoing human trials for Clemizole as an adjunctive treatment for Dravet syndrome and LGS (ClinicalTrials.gov IDs: NCT04462770, NCT05066217). Recent studies in which other genes, including some linked to LGS, are engineered into zebrafish have demonstrated their utility as epilepsy models...

Addressing the Under-Utilization of Surgery for LGS

Surgery can be a highly effective treatment for medically refractory epilepsy, but there is increasing recognition that it is underutilized and often delayed in LGS, particularly in those who carry etiologies traditionally perceived as surgically non-remediable (e.g., non-structural genetic causes). In published studies of LGS, the lag time between seizure onset and surgery can be 20 years or more, often after numerous ASM attempts. This contrasts with ILAE guidelines stating that referral for surgical evaluation should occur as soon as drug resistance is ascertained, defined as the failure of adequate trials of two tolerated and appropriately chosen ASMs.

Conclusions
LGS is regularly described as “catastrophic” or “devastating.” While these terms capture the real and profound challenges faced by individuals and caregivers, they risk overshadowing the substantial progress made in understanding and managing LGS. This symposium highlighted recent advances across eight key areas, including the conceptualization of LGS as a secondary network epilepsy, the innovative use of electronic medical data to perform natural history studies and identify gaps in treatment coverage, and the development of preclinical models to explore pathogenesis and treatment. It also reviewed improvements in evidence-based treatment strategies, spanning pharmacotherapies, neuromodulation, surgery, and preventive approaches, alongside a growing emphasis on non-seizure outcomes and tailored assessment tools to measure meaningful, incremental progress. Together, these efforts mark a turning point toward more comprehensive and patient- and caregiver-centered care.

Botulinum toxin in the treatment of tics

Pandey S, Srivanitchapoom P, Kirubakaran R, Berman BD. Botulinum toxin for motor and phonic tics in Tourette's syndrome. Cochrane Database Syst Rev. 2018 Jan 5;1(1):CD012285. doi: 10.1002/14651858.CD012285.pub2. PMID: 29304272; PMCID: PMC6491277.

Abstract

Background: Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging.

Objectives: To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics.

Search methods: We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials.

Selection criteria: We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration.

Data collection and analysis: We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion.

Main results: Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum.

Authors' conclusions: We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.

Moretti A. Is botulinum toxin effective and safe for motor and phonic tics in patients affected by Tourette syndrome? A Cochrane Review summary with commentary. Dev Med Child Neurol. 2020 Mar;62(3):274-276. doi: 10.1111/dmcn.14472. Epub 2020 Jan 20. PMID: 31957864.

Commentary on the above Cochrane review.

Kwak CH, Hanna PA, Jankovic J. Botulinum toxin in the treatment of tics. Arch Neurol. 2000 Aug;57(8):1190-3. doi: 10.1001/archneur.57.8.1190. PMID: 10927800.

Abstract

Objective: To evaluate the safety and efficacy of botulinum toxin A (BTX) injections in the treatment of tics in patients with Tourette syndrome (TS).

Background: BTX is an effective treatment for an increasing number of conditions characterized by abnormal muscle contractions. BTX may improve not only the motor component of tics, but also premonitory sensations that precede tics.

Methods: Thirty-five patients (30 male, 5 female) were treated with BTX in the sites of their most problematic tics. Response to BTX was based on a 0 to 4 clinical rating scale (0, no improvement, to 4, marked improvement in both severity and function). Questionnaires were administered to evaluate patients' impressions of overall efficacy and degree of benefit with premonitory sensations.

Results: Mean duration of tics prior to initial injection was 15.3 years (range, 1-62 years) and mean duration of follow-up was 21.2 months (range, 1. 5-84 months). The mean peak effect response in 35 patients treated in 115 sessions was 2.8 (range, 0-4); the mean duration of benefit was 14.4 weeks (maximum, 45 weeks); and the mean latency to onset of benefit was 3.8 days (maximum, 10 days). Twenty-one (84%) of 25 patients with premonitory sensations derived marked relief of these symptoms (mean benefit, 70.6%). Total mean dose was 502.1 U (range, 15-3550 U); mean number of visits, 3.3 (range, 1-16); and mean dose per visit, 119.9 U (range, 15-273 U). Sites of injections were as follows: cervical or upper thoracic area (17), upper face (14), lower face (7), vocal cords (4), upper back and/or shoulder (3), scalp (1), forearm (1), leg (1) and rectus abdominis (1). Complications included neck weakness (4), dysphagia (2), ptosis (2), nausea (1), hypophonia (1), fatigue (1), and generalized weakness (1), which were all mild and transient.

Conclusions: Botulinum toxin A injections are an effective and well-tolerated treatment of tics. In addition to improving the motor component of tics, BTX also provides relief of premonitory sensations.

Abnormal brain MRI in anti-NMDA receptor encephalitis

Khatib L, Pique J, Ciano-Petersen NL, Criton G, Birzu C, Aubart M, Benaiteau M, Picard G, Marignier R, Carra-Dalliere C, Ayrignac X, Psimaras D, Labauge PM, Honnorat J, Cotton F, Joubert B. Abnormal Brain MRI in Anti-NMDA Receptor Encephalitis: Clinical and Prognostic Implications. Neurol Neuroimmunol Neuroinflamm. 2025 May;12(3):e200378. doi: 10.1212/NXI.0000000000200378. Epub 2025 Feb 25. PMID: 39999393; PMCID: PMC11867192.

Abstract

Background and objectives: Abnormal brain MRI is associated with poor outcomes in anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). We aimed to characterize the lesions on brain MRI in NMDARE and to assess the clinical and prognostic associations.

Methods: This retrospective cohort study included patients with NMDARE identified at the French Reference Center for Autoimmune Encephalitis, with at least a one-year follow-up, and with available brain MRI results. In case of brain extralimbic lesion, the image files were reviewed when available. Clinical data were collected from medical records. Multivariable logistic regression analysis was used to study the outcomes at 2-year follow-up; recovery was defined as modified Rankin Scale score ≤1.

Results: Among the 255 patients included, 37 (14.5%) had limbic hyperintensities and 41 (16.1%) had extralimbic lesions that included multiple sclerosis (MS)-like lesions (14/41, 34.1%); extensive lesions (5/41, 12.2%); and poorly demarcated fluffy lesions, either multifocal (10/41, 24.4%) or involving the cerebral cortex or cerebellum (6/41 each, 14.6%). Extralimbic lesions coexisting with limbic lesions (19/41 patients, 46.3%) were mostly fluffy lesions (11/19, 57.9%). Ten patients had overlapping demyelinating syndromes: 4 with MS, 4 with myelin oligodendrocyte glycoprotein-associated disorder, and 2 with neuromyelitis optica spectrum disorder; all had MS-like (7/10 patients) or extensive (3/10 patients) lesions, and none had fluffy lesions. Extralimbic lesions were associated with symptoms nontypical for NMDARE (23/41, 56.1%, p < 0.001), especially cerebellar ataxia (17/41, 41.5%) and motor impairment (12/41, 29.3%). At 2 years, patients with MS-like or extensive lesions had a lower recovery rate (5/12, 41.7%, and 1/4, 25%, respectively) compared with the patients without extralimbic lesions (124/162, 76.5%; p = 0.014 and p = 0.047, respectively). In multivariable analysis, MS-like lesions, but not hippocampal nor fluffy lesions, were associated with absence of recovery at 2 years (adjusted OR 0.1, 95% CI 0.03-0.42, p = 0.002; extensive lesions [n = 4] not included in the analysis).

Discussion: Brain MRI lesions in NMDARE include limbic hyperintensities and 3 patterns of extralimbic lesions, which are associated with nontypical NMDARE symptoms. Moreover, MS-like and extensive lesions, but not fluffy nor hippocampal lesions, are associated with overlapping demyelinating syndromes and poor clinical outcomes at 2 years. These findings can have practical implications on the monitoring of patients with NMDARE.

Lei C, Chang X, Li H, Zhong L. Abnormal Brain MRI Findings in Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Correlation With Outcomes. Front Neurol. 2022 Mar 14;13:834929. doi: 10.3389/fneur.2022.834929. PMID: 35359628; PMCID: PMC8963947.

Abstract

Purpose: The reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we investigated the prevalence of abnormal MRI findings in Chinese patients and explored whether such findings are correlated with clinical outcomes.

Methods: This retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the "MRI-normal" or the "MRI-abnormal" group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission.

Results: Thirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months.

Conclusions: We found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term.

Association between sun exposure and risk of relapse in pediatric-onset multiple sclerosis

Chang G, Sebastian P, Virupakshaiah A, Schoeps VA, Cherbuin N, Casper TC, Gorman MP, Benson LA, Chitnis T, Rensel M, Abrams AW, Lotze T, Mar SS, Schreiner TL, Wheeler YS, Rose JW, Graves J, Krupp LB, Waldman AT, Lucas R, Waubant E; as the US Network of Pediatric Multiple Sclerosis Centers. Association Between Sun Exposure and Risk of Relapse in Pediatric-Onset Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2025 Mar;12(2):e200375. doi: 10.1212/NXI.0000000000200375. Epub 2025 Feb 12. PMID: 39938013; PMCID: PMC11820808.

Abstract

Background and Objectives

Low sun and ultraviolet radiation (UVR) exposures have been associated with increased risk of developing pediatric-onset multiple sclerosis (MS); however, their effect on disease course has not been well characterized. We primarily investigated whether there was an association between time spent in the sun in early childhood and risk of relapse in pediatric MS. We secondarily investigated the effect of sun exposure during more recent periods on risk of relapse.

Methods

We conducted a multicenter cohort study of participants with pediatric-onset MS recruited from 18 pediatric MS clinics across the United States between November 1, 2011, and July 1, 2017. Relapses were identified prospectively after study enrollment; relapses preceding study enrollment were entered retrospectively. Time spent in the sun at various periods of life was measured using a detailed environmental questionnaire, and ambient UVR exposure was determined using zip codes. Multivariable Cox regression models were used to assess the association between time spent in the sun and UVR dose at specific periods of life and the risk of relapse. Models were adjusted for demographic, clinical, and sun exposure–related characteristics.

Results

In our cohort of 334 children with MS, 206 (62%) experienced at least one relapse from disease onset to the end of the follow-up period. After adjustment, ≥30 minutes of daily sun exposure during the first summer of life was associated with a lower risk of relapse compared with <30 minutes (adjusted hazard ratio [aHR] 0.67, CI 0.48–0.92, p = 0.01). Greater time spent in the sun during the second trimester of pregnancy was also associated with reduced risk of relapse (aHR 0.68, CI 0.48–0.97, p = 0.04). UVR dose and time spent in the sun later in life were not significantly associated with relapse risk.

Discussion

In this large cohort study of children with MS, greater early childhood and prenatal sun exposure time was associated with lower risk of relapse. Further investigation of sun exposure at other periods is needed to better characterize its impact on disease course and guide potential future interventions.