Evoked potentials after autologous hematopoietic stem cell transplantation for multiple sclerosis.

OBJECTIVE: To investigate the effect of autologous hematopoietic stem cell transplantation (AHSCT) on functional aspects of the nervous system assessed by visual (VEP), somatosensory (SEP), and motor (MEP) evoked potentials in patients with relapsing-remitting multiple sclerosis. BACKGROUND: Several studies have demonstrated the efficacy of AHSCT on inflammatory activity and disability progression in patients with multiple sclerosis. However, the impact of AHSCT on evoked potentials has not been evaluated before. METHODS: Twelve AHSCT-treated patients from Uppsala University Hospital were consecutively recruited. Evoked potentials (EP) were collected at baseline and two follow-up visits, 3 and 12 months post-AHSCT. We calculated a composite EP score for each participant and compared it between different time points. RESULTS: The median total EP score decreased from 5 at baseline, to 2.5 at 12 months post-ASHCT (p = 0.008). A significant improvement in tibial SEP (tSEP) latencies was observed (42.7 vs 41.5 ms, p < 0.001), with a similar trend for MEP latencies 12 months post-ASHCT. No significant changes in median SEP or VEP latencies were observed. CONCLUSIONS: Treatment with AHSCT was associated with improved transmission in some central nervous system pathways in multiple sclerosis patients.

Absence of Oligoclonal Bands in Multiple Sclerosis: A Call for Differential Diagnosis.

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.

Progressive Multifocal Leukoencephalopathy and Systemic Lupus Erythematosus: Focus on Etiology.

Progressive multifocal leukoencephalopathy (PML) caused by reactivation of the JC virus (JCV), a human polyomavirus, occurs in autoimmune disorders, most frequently in systemic lupus erythematosus (SLE). We describe a HIV-negative 34-year-old female with SLE who had been treated with immunosuppressant therapy (IST; steroids and azathioprine) since 2004. In 2011, she developed decreased sensation and weakness of the right hand, followed by vertigo and gait instability. The diagnosis of PML was made on the basis of brain MRI findings (posterior fossa lesions) and JCV isolation from the cerebrospinal fluid (700 copies/ml). IST was immediately discontinued. Cidofovir, mirtazapine, mefloquine and cycles of cytarabine were sequentially added, but there was progressive deterioration with a fatal outcome 1 year after disease onset. This report discusses current therapeutic choices for PML and the importance of early infection screening when SLE patients present with neurological symptoms. In the light of recent reports of PML in SLE patients treated with rituximab or belimumab, we highlight that other IST may just as well be implicated. We conclude that severe lymphopenia was most likely responsible for JCV reactivation in this patient and discuss how effective management of lymphopenia in SLE and PML therapy remains an unmet need.

L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study.

BACKGROUND: Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia. METHODS: L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks. RESULTS: L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning. CONCLUSIONS: Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia.