| 1. |
- Gauffin, Helena
(författare)
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Epilepsy in young adulthood : medical, psychosocial and functional aspects
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to describe the medical, cognitive and psychosocial consequences of epilepsy in young adulthood. Four studies were carried out with this patient group. The first two papers were based on a follow-up study regarding young adults with epilepsy that investigated medical and psychosocial aspects and compared the present results with those five years earlier. We then conducted focus group interviews with young adults with epilepsy and subjective cognitive decline to assess the deeper meaning of living with epilepsy accompanied by cognitive difficulties. In the fourth study we studied cognitive dysfunction further, choosing the language function in young adults with epilepsy. We firstly examined whether language impairments were associated to functional brain alterations and secondly related the language performance to demographics, clinical data, Quality of Life (QoL) and self-esteem.The five-year follow up of 97 young adults with uncomplicated epilepsy revealed no improvement regarding seizure frequency or side effects from anti-epileptic drugs (AEDs) over time, even though many new-generation AEDs had been established during this period. During the study period 21% had recovered from epilepsy, Seizure frequency among those who still had epilepsy had not improved, and 42% had experienced seizures during the past year. New-generation anti-epileptic drugs (AEDs) had been introduced to PWE, especially to women. There is still need for new and more effective treatment options for this group in the future. It is essential to find alternative approaches to develop better treatment options for this group in the future. However QoL was normal compared to the general population, indicating that new options regarding treatment can have made an impact. Lower QoL was correlated to high seizure frequency and to cognitive side effects. Self-esteem and Sence of Coherence were impaired compared to the situation at adolescence. Self-esteem was correlated to seizure frequency and to side-effects of antiepileptic drugs. Sence of Coherence was not correlated to epilepsy-related factors in the same way as QoL, but mirrored the phenomenon of epilepsy.The qualitative study showed that the consequences of epilepsy are not only restricted to the consequences of seizures, but also concerns many other aspects of life. The interviews revealed four themes: “affecting the whole person“, “influencing daily life”, ”affecting relations” and ”meeting ignorance in society”. Another important factor was language function; when one loses some language ability, this gives a feeling of losing one’s capability.The fourth study examined language by neuropsychological methods and correlated this function to brain activation measured by fMRI. Language functions measured in verbal fluency and abstract language comprehension were impaired in participants with both generalized epilepsy and epilepsy of focal onset. Age at onset of epilepsy and education are the most important factors correlating to language function. An additional factor that impacts abstract language comprehension is the frequency of convulsive seizures, while use of topiramate /zonisamide affect verbal fluency negatively. QoL was not correlated to language impairments, but for patients with focal onset seizures there was a correlation between self-esteem and abstract language comprehension. The fMRI investigation revealed altered activity during language tasks in participants with epilepsy compared to controls. In epilepsy with focal seizures originating in the left hemisphere, we found increased bilateral activation of supporting areas, in the anterior mid-cingulate cortex and the anterior ventral insulae, indicating a compensational functional reorganization. In generalized epilepsy, the functional language network showed an imbalance, as this group expressed an inadequate suppression of activation in the anterior temporal lobe during semantic processing. Subtle language impairment can, even if it does not occur in everyday dialogue, be of importance and have consequences for the person affected. The negative consequences of language decline must be addressed in people with epilepsy of different etiology. Young adults with epilepsy are still substantially affected by the condition. The consequences are not only restricted to the seizures, but concern many aspects of life and there is a great need for new treatment options for this group in the future.
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| 2. |
- Blystad, Ida, 1972-
(författare)
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Clinical Applications of Synthetic MRI of the Brain
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic Resonance Imaging (MRI) has a high soft-tissue contrast with a high sensitivity for detecting pathological changes in the brain. Conventional MRI is a time-consuming method with multiple scans that relies on the visual assessment of the neuroradiologist. Synthetic MRI uses one scan to produce conventional images, but also quantitative maps based on relaxometry, that can be used to quantitatively analyse tissue properties and pathological changes. The studies presented here apply the use of synthetic MRI of the brain in different clinical settings.In the first study, synthetic MR images were compared to conventional MR images in 22 patients. The contrast, the contrast-to-noise ratio, and the diagnostic quality were assessed. Image quality was perceived to be inferior in the synthetic images, but synthetic images agreed with the clinical diagnoses to the same extent as the conventional images.Patients with early multiple sclerosis were analysed in the second study. In patients with multiple sclerosis, contrast-enhancing white matter lesions are a sign of active disease and can indicate a need for a change in therapy. Gadolinium-based contrast agents are used to detect active lesions, but concern has been raised regarding the long-term effects of repeated use of gadolinium. In this study, relaxometry was used to evaluate whether pre-contrast injection tissue-relaxation rates and proton density can identify active lesions without gadolinium. The findings suggest that active lesions often have relaxation times and proton density that differ from non-enhancing lesions, but with some overlap. This makes it difficult to replace gadolinium-based contrast agent injection with synthetic MRI in the monitoring of MS patients.Malignant gliomas are primary brain tumours with contrast enhancement due to a defective blood-brain barrier. However, they also grow in an infiltrative, diffuse manner, making it difficult to clearly delineate them from surrounding normal brain tissue in the diagnostic workup, at surgery, and during follow-up. The contrast-enhancing part of the tumour is easily visualised, but not the diffuse infiltration. In studies three and four, synthetic MRI was used to analyse the peritumoral area of malignant gliomas, and revealed quantitative findings regarding peritumoral relaxation changes and non-visible contrast enhancement suggestive of non-visible infiltrative tumour growth.In conclusion, synthetic MRI provides quantitative information about the brain tissue and this could improve the diagnosis and treatment for patients.
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| 3. |
- West, Janne
(författare)
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Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear.In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation.The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions.One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration.This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem.This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.
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| 4. |
- Dahlqvist Leinhard, Olof
(författare)
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Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Magnetic resonance (MR) imaging is one of the most important diagnostic tools in modern medicine. Compared to other imaging modalities, it provides superior soft tissue contrast of all parts of the body and it is considered to be safe for patients. Today almost all MR is performed in a nonquantitative manner, only comparing neighboring tissue in the search for pathology. It is possible to quantify MR-signals and relate them to their physical entities, but time consuming and complicated calibration procedures have prevented this being used in a practical manner for clinical routines. The aim of this work is to develop and improve quantification methods in MRspectroscopy (MRS) and MR-imaging (MRI). The techniques are intended to be applied to diffuse diseases, where conventional imaging methods are unable to perform accurate staging or to reveal metabolic changes associated with disease development.Methods: Proton (1H) MRS was used to characterize the white matter in the brain of multiple sclerosis (MS) patients. Phosphorus (31P) MRS was used to evaluate the energy metabolism in patients with diffuse liver disease. A new quantitative MRI (qMRI) method was invented for accurate, rapid and simultaneous quantification of B1, T1, T2, and proton density. A method for automatic assessment of visceral adipose tissue volume based on an in- and out-ofphase imaging protocol was developed. Finally, a method for quantification of the hepatobiliary uptake of liver specific T1 enhancing contrast agents was demonstrated on healthy subjects.Results: The 1H MRS investigations of white matter in MS-patients revealed a significant correlation between tissue concentrations of Glutamate and Creatine on the one hand and the disease progression rate on the other, as measured using the MSSS. High accuracy, both in vitro and in vivo, of the measured MR-parameters from the qMRI method was observed. 31P MRS showed lower concentrations of phosphodiesters, and a higher metabolic charge in patients with cirrhosis, compared to patients with mild fibrosis and to controls. The adipose tissue quantification method agreed with estimates obtained using manual segmentation, and enabled measurements which were insensitive to partial volume effects. The hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was significantly correlated in healthy subjects.Conclusion: In this work, new methods for accurate quantification of MR parameters in diffuse diseases in the liver and the brain were demonstrated. Several applications were shown where quantitative MR improves the interpretation of observed signal changes in MRI and MRS in relation to underlying differences in physiology and pathophysiology.
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| 5. |
- Roodakker, Kenney Roy, 1989-
(författare)
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Towards new tools for clinical evaluation and visualization of tumor growth in patients with glioma
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gliomas are derived from glial cells and are the most common type of primary brain tumors in adults. Gliomas are classified by the World Health Organization (WHO) according to their malignancy grade and histological and molecular features. Malignancy grades range from I to IV. WHO grade I tumors are benign tumors, mostly occurring in childhood. High-grade gliomas (WHO grades III and IV) are undifferentiated and fast-growing tumors, with glioblastoma being the most common and malignant form. Patients with glioblastomas have a median survival of only 15 months. Clinical outcomes vary, however, and markers are needed to assist in the decision-making process and management of these patients. PROX1 is a transcription factor critical for embryonic development, with a role in cell cycle control and progenitor cell differentiation. Apart from its role in normal central nervous system development, PROX1 has been ascribed both tumor suppressive and oncogenic roles in several human cancers. The role of PROX1 as a prognostic factor for survival in patients with glioblastomas was the focus of paper I.Gliomas WHO grade II, also called diffuse low-grade gliomas (DLGGs), are well-differentiated tumors that occur mainly in adult life, with a peak incidence at around 30–35 years of age and a median survival of 5–10 years. DLGGs grow continuously at a rate of a few mm per year and have a strong tendency to infiltrate the white matter tracts surrounding the tumor. Eventually these tumors transform into high-grade gliomas, but, as is the case with glioblastomas, there is a large variety of clinical outcomes. For radiological diagnosis, magnetic resonance imaging (MRI) is routinely used, often in combination with advanced MRI. Positron emission tomography with amino acid tracers provides additional diagnostic accuracy. From a histological as well as imaging point of view, DLGGs are heterogeneous tumors. The heterogeneity of DLGGs, in particular the correlation between radiological and histological tumor features, was the focus of paper II & paper III.Seizures are amongst the most common presenting symptoms of patients with gliomas. Seizure semiology in patients with brain tumors and other structural brain lesions is closely related to the anatomical location of the lesion and the involvement of functional networks. A possible dynamic interplay between the anatomical region of seizure onset and connected target areas within the network was the focus of paper IV.
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| 6. |
- Tisell, Anders
(författare)
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The Non-Invasive Brain Biopsy : Implementation and Application of Quantitative Magnetic Resonance Spectroscopy on Healthy and Diseased Human Brain
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: In this thesis, one of the major objectives was to implement a method for (absolute) quantitative magnetic resonance spectroscopy (qMRS) of the human brain, intended for clinical use. The implemented method was based on standard spatially selective MRS sequences. The tissue water was used as an internal reference, which was calibrated using whole brain quantitative magnetic resonance imaging (qMRI). The second objective was to apply the method in clinical neuroimaging investigation, of different disease processes in the human brain.Materials and Methods: In total, 158 subjects were included and 507 MRS measurements (330 in white matter and 177 in the thalamus) were acquired.In a cross-sectional study of multiple sclerosis (MS), 35 ‘clinically definite MS’ (CDMS) patients were included, of which 15 were atypical CDMS patients with a very low number of white matter lesions (two or fewer), and 20 were typical CDMS patients with white matter lesions (three or more) were included. The metabolite concentrations in normal appearing white matter (NAWM) and the thalamus were assessed using the qMRS method developed in this thesis, and the brain parenchymal fraction (BPF) was calculated from the qMRI data. A cohort of 27 CDMS patients were then treated with Natalizumab and examined both at baseline, and after one year of treatment. Both qMRS and CSF samples for the purpose of assessing intrathecal inflammation were obtained. In addition, the frontal deep white matter (FDWM) and the thalamus were investigated in 20 idiopathic normal pressure hydrocephalus (iNPH) patients using qMRS. Finally, the left thalamus of 14 Kleine-Levin Syndrome (KLS) patients were examined using both qMRS and functional MRI (fMRI) of neurological activation of the left thalamus during a working memory test. Moreover, 63 healthy subjects were included as controls for this work.Results: A quantitative MRS method based on water referencing was successfully developed, implemented, and evaluated at 1.5 T. Both healthy subjects and MS patients showed a positive correlation between the concentrations of total Creatine (tCr) and myo Inositol (mIns) and age, and also a negative correlation with BPF were observed. Glutamate and Glutamine (Glx) levels were elevated for all MS patient groups compared to healthy controls. In contrast, lower concentrations of total N-acetyl aspartate and N-acetyl aspartate glutamate (tNA) and higher mIns concentrations in NAWM were only observed in MS patients that had developed white matter lesions. Moreover, the change in concentrations of tCr and total Choline (tCho) in MS patients during Natalizumab-treatment were positively correlated with markers of intrathecal inflammation. The iNPH patients had lower tNA and N-acetyl aspartate (NAA) concentrations in the thalamus compared to the controls. In addition, the NAA concentrations in the left thalamus were inversely correlated to the fMRI activation in the left thalamus during the working memory test in KLS patients.Discussion: The calculated calibration factors were in good agreement with the results found in the literature, indicating that the calibration factors were accurate.The observed elevated Glx concentration in MS could be due to increased concentrations of glutamate (Glu), which is neurotoxic at high concentrations, thus the elevated Glx could be linked to the clinically observed neurodegeneration in MS both in patients that have developed lesions and in atypical patients that do not develop any (or extremely few) lesions.Both tCr and mIns can be used as glia markers, thus the correlations of tCr and mIns concentrations with both age and BPF indicates that the local glia cell density, or tissue fraction, increases with age and atrophy. Moreover, the higher mIns concentrations in the NAWM of MS patients with a substantial white matter lesion load indicate that the glia tissue amount in NAWM is increased in MS patients that develop lesions. NAA is neuronal-specific, thus the lower tNA concentrations indicate that the neurone concentration is lower in the NAWM of MS patients that develop MS lesions. The lack of correlation between tNA with age and BPF in combination with the presence of correlation between tCr and mIns with both age and BPF, might be explained using a model for neurodegeneration. In which, there is a higher neurone loss compared to the glia loss. However, the lost tissue is compensated by compression of the tissue, which keeps the density of neurones more or less constant and the density of glia increased.The low concentration levels of the neuronal marker NAA in the thalamus of the iNPH patients indicates that the basal ganglia-thalamic-subcortical frontal circuits are damage or at least strongly modulated in the thalamus.The correlation between strong activation in left thalamus during a working memory test with the neuronal marker NAA indicate that the KLS patients that have low neuronal concentration also needed to utilise the working memory circuitry more heavily in order to perform the task as healthy subjects.Conclusion: It is possible to use qMRI for accurate and robust determination of qMRS in clinical practice, even at 1.5 T field strength. The tGlx concentration may be an important marker for pathology in the nonlesional white matter of MS-patients. The increased glia and loss of neurones in the NAWM are associated with the formation of white matter lesions.
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| 7. |
- Tolf, Andreas
(författare)
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In search of lost disease : Clinical, qualitative and imaging studies to investigate long-term effects of autologous haematopoietic stem cell transplantation for multiple sclerosis
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the introduction of autologous haematopoietic stem cell transplantation (AHSCT) for the treatment of multiple sclerosis (MS), there are now individuals living without experiencing disease activity of MS. Are they cured? There is a need for terminology to describe the state of these individuals. To address this and to report the ten-year outcomes of the first ten persons treated with AHSCT for MS at our centre, we conducted tests involving six different outcome measures to encompass the inflammatory (new clinical relapses, new MRI lesions, intrathecal antibody production) and degenerative (clinical progression, elevated intrathecal levels of neurofilament light protein, presence of callosal atrophy) aspects of the disease. Half of the participants achieved ‘sustained complete remission’ (normal values in all parameters, excluding intrathecal measurements), and three ‘resolved disease’ by displaying standard values across all measures. This terminology can be used when communicating successful treatment outcomes, and ‘resolved disease’ might serve as a working definition of cure.How did one perceive oneself, one’s health, and one’s diagnosis ten years after AHSCT? In this qualitative interview study, the lived experience of the same persons was explored and analysed with qualitative content analysis. The treatment symbolised a transition from a life dominated by uncertainty to a state of health and normality. The participants shared their experience of now feeling healthy, and some even reported not having MS anymore. They expressed a desire for objective criteria to affirm their health status.Impaired cerebral blood flow has been linked to progressive MS. The third study was a case-control study examining CBF and cerebrovascular reactivity (CVR) in individuals with secondary progressive MS, healthy controls, and persons treated with AHSCT from the previous studies. CBF was measured using positron emission tomography with 15O-water. CBF was diminished in individuals with progressive MS compared to the healthy controls. In contrast, CBF in the AHSCT group did not differ significantly from healthy controls. CVR was not impaired in progressive MS patients, suggesting an opportunity for therapeutic intervention with a vasodilating agent.The fourth study was a case-control study assessing factors associated with a favourable response to COVID-19 vaccination in persons with rituximab and MS. B cells emerged as the sole factor influencing antibody production. Consequently, pre-vaccination B-cell measurement was advised to enhance the likelihood of an effective humoral immune response.
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| 8. |
- Vigren, Patrick
(författare)
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On the Kleine-Levin Syndrome
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Populärvetenskaplig sammanfattning på svenska Kleine-Levins syndrom är en sömnsjukdom som beskrevs av Willi Kleine 1925 och därefter utvecklades i fallbeskrivningar av Max Levin och McDonald Chritchley. De symptom som beskrevs var återkommande sömnperioder (periodisk hypersomnia), en tendens att äta mycket i samband med dessa perioder (hyperfagi) och ökad sexdrift i samband med perioderna (hypersexualitet) och, i senare beskrivningar, kognitiva och beteendemässiga störningar. Enligt tidigare beskrivningar var patienterna återställda mellan sömnperioderna. Dessa varade i dagar-veckor och återkom flera gånger årligen. Sjukdomen debuterade vanligtvis i tonåren och beskrevs gå över efter åtta år.d avhandling beskriver diagnosens utveckling över tid och sätter forskningen i sitt teoretiska sammanhang. Med det senare menas att det diskuteras hur forskningen förhåller sig till en diagnos som förändras över tid och där olika läkare kan ha olika kunskap kring och förhållningssätt till diagnosen.De studier som ingår i avhandlingen har undersökt flera olika aspekter av Kleine-Levins syndrom. Den första studien undersökte arbetsminnet hos patienterna och kunde påvisa att det var nedsatt jämfört med friska försökspersoner, även mellan sömnperioderna, något som inte var visat systematiskt tidigare. Dessutom sågsandra aktiveringsmönster i hjärnan när patienterna försökte klara arbetsminnesuppgiften, jämfört med aktiveringsmönstren hos friska försökspersoner. Hos hälften av patienterna sågs dessutom avvikande blodflöde i delar av hjärnan även när ingen särskild arbetsuppgift utfördes. Detta sågs även hos patienter som tillfrisknat.Då det funnits hypoteser i annan forsking att sjukdomen kan ha ett genetiskt/ärftligt inslag undersöktes huruvida patienterna hade en gen som tidigare har kopplats till sjukdomen. I den grupp av patienter som undersöktes i avhandlingens sista artikel kunde dock ingen sådan koppling ses.Slutsatsen av forskningsresultaten är att (1) patienter med Kleine-Levins syndrom har en störning av arbetsminnet som verkar konstant. (2) De uppvisar andra hjärnaktiveringsmönster än friska personer som gör samma arbetsminnesuppgift. (3) Hälften av patienterna har ett avvikande blodflödesmönster även i vila och efter tillfrisknande. (4) En eventuell ärftlig komponent kan inte påvisas avseende de undersökta generna.
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| 9. |
- Boström, Inger, 1946-
(författare)
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Epidemiological Studies of Multiple Sclerosis in Sweden with focus on the County of Värmland
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to study the frequency of MS in the suggested high-risk area of Värmland county by investigating the current prevalence and analyzing the development over time; secondly to investigate some aetiological factors – the pattern of industry, both in relation to MS in Värmland and in the whole country, and also to examine the possible relation between the distribution of MS and ALS, as it has previously shown a positive correlation in two studies; finally to analyze the women-to-men ratio of MS in Sweden because of international reports of an increasing ratio.Clinical data was collected from hospitals and other health care units in the county of Värmland, to calculate the prevalence ratio. The prevalence was 170.07 per 100,000 population on the prevalence day, 31 December 2002. The incidence rates analysed during ten years was 6.46 per 100,000 personyears (1991-1995) and 6.39 (1996-2000).The ecological study used data from the beginning of the 20th century on industries in Värmland and in all Sweden, which were correlated with the two MS prevalence studies (1925-1934 and 2002), and the mortality study on the time period 1952-1990. There was a statistical significant association between large sawmills and the prevalence 1925-1934 (p = 0.022). For all Sweden, wood-pulp factories and papermills correlated significantly with MS mortality 1952-1990 (p = <0.05).Collected data from Causes of death Register and from the Total Population Register were used when analysing mortality from ALS and MS. The previously shown correlation between ALS and MS mortality distribution in the Swedish counties was not confirmed in this study. However, the mean MS mortality rate was still highest in the county in Värmland. The mean MS mortality rates for whole Sweden was increased from 1.65 per 100,000 person-years (1952-1992) to 2.04 (1990-2010).For analysing sex ratio in MS, data from the Swedish Multiple Sclerosis Register and data from Total Population Register of the Swedish Statistics Office were used. These data was analysed by birth day cohort and by year of onset. The sex ratios in Sweden showed a stable women-to-men ratio.These investigations give indication that Värmland is a high-risk region of multiple sclerosis, and particularly the municipality of Säffle.We conclude that Värmland is a suitable area for continued epidemiological studies with both an environment and genetic focus.
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| 10. |
- Katsarogiannis, Evangelos, et al.
(författare)
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Absence of Oligoclonal Bands in Multiple Sclerosis : A Call for Differential Diagnosis
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 12:14
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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