Shala Ghaderi Berntsson

(1) Background: In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. We performed an analysis of the increase, with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. (2) Methods: Data for narcolepsy patients (ICD code G 47.4, both type 1 and type 2) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, were retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register. (3) Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed. The sex ratio did not change significantly during the study period. (4) Conclusions: Our results support an association between the increased prevalence of narcolepsy cases and Pandemrix vaccination, but the effect of the virus itself cannot be ruled out as a contributing factor.

In the context of the H1N1 pandemic and the Pandemrix vaccination campaign, an increased number of narcolepsy cases were noted in several countries. In Sweden, this phenomenon was attributed to the effect of the Pandemrix vaccination in the first place. Interestingly, Denmark, a neighboring country, also had an increased incidence during this period, despite a low vaccination rate. Additionally, studies from China indicated that narcolepsy could occur as a consequence of the H1N1 infection itself. Against these background factors, and due to the clinical impression that narcolepsy patients who were vaccinated tend to dominate in the Swedish narcolepsy polyclinic, we performed an analysis of the increase with a specific interest in age and sex distribution. We also aimed to validate the origin of the excess cases, post hoc. Materials & Methods: The data for narcolepsy patients (ICD code G 47.4) distributed by sex and age at 5-year intervals, annually between 2005 and 2017, was retrieved from the National Patient Register. Information on the total population was collected from the Swedish Population Register and was used for calculations of the narcolepsy prevalence. Results: The number of narcolepsy cases increased markedly from 2009 to 2014 compared to the period before 2009. A particular increase in 2011 among children and teenagers was observed, which resulted in increased cases among the age group 20-39 years in the following years. The sex ratio did not change significantly during the study period. The excess cases found in our study exceeded the number of patients who so far (December 2023) received economic compensation for vaccine side effects (n=450). Conclusions: Our results confirm an association between the increased prevalence of narcolepsy cases and the Pandemrix vaccination. Consequently, the effect of the virus itself cannot be ruled out as a contributing factor. The delayed timing in diagnostics is crucial when determining the number of cases with onset during the pandemic.

We present the case of a male patient who was ultimately diagnosed with Becker muscular dystrophy (BMD; MIM# 300376) after the onset of muscle weakness in his teens progressively led to significant walking difficulties in his twenties. A genetic diagnosis was pursued but initial investigation revealed no aberrations in the dystrophin gene (DMD), although immunohistochemistry and Western blot analysis suggested the diagnosis of dystrophinopathy. Eventually, after more than 10 years, an RNA analysis captured abnormal splicing where 154 nucleotides from intron 43 were inserted between exon 43 and 44 resulting in a frameshift and a premature stop codon. Normal splicing of the DMD gene was also observed. Additionally, a novel variant c.6291–13537A>G in DMD was confirmed in the genomic DNA of the patient. The predicted function of the variant aligns with the mRNA results. To conclude, we here demonstrate that mRNA analysis can guide the diagnosis of non-coding genetic variants in DMD.

Background: Immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) are absent in a small group of multiple sclerosis (MS) patients. According to previous research, OCB-negative MS patients differ genetically but not clinically from OCB-positive MS patients. However, whether OCB-negative MS is a unique immunological and clinical entity remains unclear. The absence of OCB poses a significant challenge in diagnosing MS. (1) Objective: The objective of this study was twofold: (1) to determine the prevalence of OCB-negative MS patients in the Uppsala region, and (2) to assess the frequency of misdiagnosis in this patient group. (2) Methods: We conducted a retrospective study using data from the Swedish MS registry (SMSreg) covering 83% of prevalent MS cases up to 20 June 2020 to identify all MS patients in the Uppsala region. Subsequently, we collected relevant information from the medical records of all OCB-negative MS cases, including age of onset, gender, presenting symptoms, MRI features, phenotype, Expanded Disability Status Scale (EDSS) scores, and disease-modifying therapies (DMTs). (3) Results: Out of 759 MS patients identified, 69 had an OCB-negative MS diagnosis. Upon re-evaluation, 46 patients had a typical history and MRI findings of MS, while 23 had unusual clinical and/or radiologic features. An alternative diagnosis was established for the latter group, confirming the incorrectness of the initial MS diagnosis. The average EDSS score was 2.0 points higher in the MS group than in the non-MS group (p = 0.001). The overall misdiagnosis rate in the cohort was 33%, with 22% of misdiagnosed patients having received DMTs. (4) Conclusions: Our results confirm that the absence of OCB in the CSF should raise suspicion of possible misdiagnosis in MS patients and prompt a diagnostic reassessment.

Neurosarcoidosis presents a diagnostic challenge in clinical settings, as it has no pathognomonic symptoms or signs and a wide range of differential diagnoses. The aim of this report is to present the pathological features of our group of patients, obtained through a systematic diagnostic approach. This retrospective cohort study enrolled all adult patients primarily diagnosed with neurosarcoidosis at the neurology department of a tertiary center in Sweden over a period of 30 years, from 1990 to 2021. We identified 90 patients, 54 with possible neurosarcoidosis and 36 with probable neurosarcoidosis. CNS biopsy revealed an alternative diagnosis for 24 patients, who were then excluded. The collected data from medical records included demographic and clinical characteristics, systemic and/or neurological isolated involvement, various laboratory tests, including cerebrospinal fluid (CSF), serum analysis, imaging studies (MRI, FDG-PET/CT, and HRCT), nerve conduction studies, electromyography, and pathology reports of central nervous system (CNS), and extra-neural tissue biopsies. Sixty-six patients were included in our cohort. The median age at onset of symptoms was 49 years, with a similar sex distribution. Cranial neuropathies (38%), motor deficit (32%), headache (16%), and pituitary dysfunction (12%) were the most common presenting features. CSF studies were abnormal in 77% of the patients, who showed lymphocytosis (57%), elevated protein (44%), oligoclonal bands (40%), elevated ACE (28%), and raised T lymphocyte CD4⁺/CD8⁺ ratios (13%). Strikingly, MRI showed that 17% of the patients presented with isolated pituitary gland lesions. FDG-PET/CT was performed in 22 patients (33%) and confirmed systemic sarcoidosis in 11. Despite our extensive workup, the final classification for our patients only allowed for a definite diagnosis in 14 patients; the remainder were classified as probable (32) or possible (20) neurosarcoidosis. Since 2007, the employment of a structured laboratory and imaging approach and the increasing number of CNS biopsies have facilitated and improved the process of correct attribution in patients with presumptive neurosarcoidosis, especially in patients with isolated neurological lesions. We highlight a higher frequency of pituitary lesions due to neurosarcoidosis than has been classically described. A detailed laboratory diagnostic workup is included.

Objectives To describe the pharmacological treatments (2005–2017) and the healthcare utilization (1997–2016) for patients with narcolepsy in Sweden in order to create a framework for future organizational and economic analyses. Material & Methods Patients of all ages with a diagnosis of narcolepsy registered in the National Patient Registry in specialist care in Sweden were included and information on treatments for narcolepsy was retrieved from The Swedish Prescribed Drug Register. Results We collected 2508 patients with narcolepsy, 43,3% men and 56,7% women and 47,9% were prescribed modafenil, 33,8% metylphenidate and 26,2% amphetamine. In total, 3817 treatments were initiated. Patients treated with amphetamine had a higher mean age. More women than men used modafinil, methylphenidate, amphetamine and antidepressants. The narcolepsy population had more outpatient than inpatient healthcare. Patients treated with sodium oxybate had more outpatient visits than other narcolepsy patients, before and during treatment (p = .00). Conclusions This study gives valuable information on pharmaceutical treatments and healthcare utilization for patients with narcolepsy and can be used to estimate the healthcare cost in the future. Patients with sodium oxybate treatment had more outpatient visits than other patients before and during treatment which may be due to the need to monitor potentially severe side-effects or may indicate that patients with sodium oxybate treatment have a severe disease. The number of included patients was less than expected; however, this may depend on patients escaping our collection of data, which does not contain information from primary care.

The COVID-19 pandemic has brought challenges for healthcare management of patients with multiple sclerosis (MS). Concerns regarding vulnerability to infections and disease-modifying therapies (DMTs) and their complications have been raised. Recent published guidelines on the use of DMTs in relation to COVID-19 in MS patients have been diverse between countries with lack of evidence-based facts. In Sweden, there exists a particular interest in anti-CD20 therapy as a possible risk factor for severe COVID-19 due to the large number of rituximab-treated patients off-label in the country. Rapid responses from the Swedish MS Association (SMSS) and the Swedish MS registry (SMSreg) have resulted in national guidelines on DMT use for MS patients and implementation of a COVID-19 module in the SMSreg. Recently updated guidelines also included recommendations on COVID-19 vaccination with regard to the different DMTs. Social distancing policies forced implementation of telemedicine consultation to replace in-person consultations as part of regular MS health care. Patient-reported outcome measures (PROMs) in SMSreg have been useful in this respect. This paper reports our experiences on the progress of national MS health care during the COVID-19 pandemic, in addition to offering an overview of the present scientific context.

PAX6 gene mutations cause a variety of eye and central nervous system (CNS) abnormalities. Aniridia is often accompanied by CNS abnormalities such as pineal gland atrophy or hypoplasia, leading to disturbed circadian rhythm and sleep disorders. Less is known on the coincidence of narcolepsy in this patient group. We aimed to find out whether the circadian rhythm or sleep–wake structure was affected in patients with aniridia. Four members of a family segregating with congenital aniridia in two generations were included in the study. The patients were subjected to genetic testing for a PAX6 mutation, multiple sleep latency test, whole‐brain magnetic resonance imaging (MRI), hypocretin‐1 in cerebrospinal fluid, and Human Leukocyte Antigen DQ beta1*06:02. All four members were heterozygous for the pathogenic c.959‐1G>A mutation in the PAX6 gene. Sleep disturbance was observed in all family members. The index patient was diagnosed with narcolepsy. MRI showed a hypoplastic pineal gland in all members. We describe the first case of a patient with PAX6 haploinsufficiency, aniridia and pineal gland hypoplasia diagnosed with narcolepsy type‐1, suggesting a complex sleep disorder pathogenesis.