Nevrosarkoidose – en pasientserie

BAKGRUNN Nevrosarkoidose er en sjelden form for sarkoidose som affiserer nervesystemet. Formålet med studien var å kartlegge kliniske manifestasjoner, utredningsfunn og behandlingsstrategier hos pasienter med nevrosarkoidose. MATERIALE OG METODE Studien vurderte retrospektivt 17 pasienter med sikker, sannsynlig og mulig nevrosarkoidose diagnostisert i perioden 2008–19 ved Nevrologisk avdeling ved Haukeland universitetssjukehus. RESULTATER Gjennomsnittlig prevalens av sikker, sannsynlig eller mulig nevrosarkoidose i Vestland fylke var 2,7 per 100 000 innbyggere i den aktuelle perioden. Debutform var sentralnervøs affeksjon (8 av 17), hydrocefalus (5 av 17) og kranial nevropati (5 av 17). Det var funn som ved sarkoidose ved kontrastforsterket magnetisk resonanstomografi (MR) av sentralnervesystemet hos 14 av 17 pasienter, funn ved positronemisjonstomografi (PET) hos 7 av 8, og funn ved computertomografi (CT) av thorax hos 12 av 16. Cerebrospinalvæsken hos 15 av 15 pasienter hadde avvik, og biopsiverifisering forelå hos 13 av 15 pasienter. 16 av 17 pasienter hadde symptomforbedring eller stabilisering med prednisolon og/eller annen immunterapi. FORTOLKNING Nevrosarkoidose affiserer både det sentrale og det perifere nervesystemet. Cerebrospinalvæskeundersøkelse og kontrastforsterket MR er viktige metoder for å oppdage inflammasjon. Biopsi er nødvendig for å stille sikker diagnose, men lar seg ikke alltid gjennomføre. PET kan brukes som supplement til andre undersøkelser for å vurdere ulike organmanifestasjoner og for å avdekke biopsilokalisasjon. Behandlingsresponsen er god med kortikosteroider og eventuelt annen immunterapi.publishedVersio

Wearing-off at the end of natalizumab dosing interval and risk of MS disease activity: A prospective 1-year follow-up study

Natalizumab effectively prevents disease activity in relapsing-remitting multiple sclerosis by binding α4 integrin and inhibiting leukocyte migration to the central nervous system. We recently reported an association between low natalizumab receptor occupancy and subjective wearing-off symptoms at the end of the 4-week dosing interval. Here, we aimed to evaluate the short-term risk of disease activity in a 1-year prospective follow-up of the same patient cohort (n = 40). We found that all patients available for follow-up after one year (n = 35) fulfilled the criteria for no evidence of disease activity (NEDA). Thus, wearing-off symptoms were not associated with increased short-term risk of disease activity. Longer follow-up in a larger patient cohort is required to establish whether therapeutic efficacy is maintained in patients with wearing-off symptoms.publishedVersio

Neurofilament light chain as a biomarker in multiple sclerosis

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS.publishedVersio

Limbic encephalitis following allogeneic hematopoietic stem cell transplantation

A woman with myelodysplastic syndrome (MDS) was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). 65 days after the transplantation, she developed fatigue and central neurological symptoms. Clinical workup including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) examination revealed findings suspicious for limbic encephalitis (LE), successfully treated with intravenous immunoglobulins and intravenous corticosteroids. Although a rare complication after allo-HSCT, physicians should be aware of neurological symptoms that develop throughout the transplantation course.publishedVersio

Case report: Pain in anti-DPPX encephalitis

Encephalitis due to antibodies targeting dipeptidyl-peptidase-like protein 6 (DPPX), a potassium channel subunit, is rare. The illness is typically characterized by a triad of weight loss, CNS hyperexcitability and cognitive symptoms, but recent reports suggest that the clinical picture may be more heterogeneous. Here, we describe the case of a 63-year-old female who was admitted to the hospital with severe extremity pain, which had been preceded by diarrhea and weight loss. She later developed cognitive changes, and her general condition rapidly deteriorated. Extensive workup did not reveal gastrointestinal illness or underlying malignancies. MRI of the brain was normal. Analyses of blood and cerebrospinal fluid showed normal cell counts but high titres of DPPX antibodies in blood and cerebrospinal fluid. The patient was treated with intravenous methylprednisolone followed by rituximab. At 1-year follow-up, she was without pain and had completely recovered. In this case, DPPX-associated autoimmune encephalitis was dominated by severe extremity pain, illustrating that sensory symptoms may be one of the main complaints in these patients. It is important for clinicians to be aware of the heterogeneous clinical picture in this serious condition, since correct diagnosis and treatment with immunosuppressants are associated with favorable prognosis

Development and Optimization of a Multilayer Rat Purkinje Neuron Culture

Elucidation of the mechanisms involved in neurodegenerative diseases of the cerebellum has been hampered by the lack of robust single cell models to study Purkinje neurons and replicate at the same time in vivo features. Cerebellar Purkinje neurons are difficult to grow in dispersed cell culture, and only limited work has been done using rat cells. We developed a refined protocol for growing rat Purkinje neurons from embryonic and postnatal tissue ex vivo that results in well-developed, mature, functional, and synaptically active neurons. The rat Purkinje neurons generated are responsive to paracrine factors and genetic manipulation, allowing great experimental flexibility at the single-cell level. This ex vivo model can be used to investigate disease mechanisms that disturb Purkinje neuron morphology, function, and communication in high- and low-throughput screening formats.publishedVersio

COVID-19 myocarditis and postinfection Bell’s palsy

Here we present the case of a 37-year-old previously healthy man who developed fever, headache and a unilateral, painful neck swelling while working offshore. He had no known contact with anyone with COVID-19; however, due to the ongoing pandemic, a nasopharyngeal swab was performed, which was positive for the virus. After transfer to hospital for assessment his condition rapidly deteriorated, requiring admission to intensive care for COVID-19 myocarditis. One week after discharge he re-presented with unilateral facial nerve palsy. Our case highlights an atypical presentation of COVID-19 and the multifaceted clinical course of this still poorly understood disease.publishedVersio

CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration

The pathogenesis of Yo‐mediated paraneoplastic cerebellar degeneration (PCD) is unclear. We applied cerebrospinal fluid and serum from PCD patients as well as CDR2 and CDR2L antibodies to neuronal tissue, cancer cell lines, and cells transfected with recombinant CDR2 and CDR2L to elucidate which is the major antigen of Yo antibodies. We found that Yo antibodies bound endogenous CDR2L, but not endogenous CDR2. However, Yo antibodies can bind the recombinant CDR2 protein used in routine clinical testing for these antibodies. Because Yo antibodies only bind endogenous CDR2L, we conclude that CDR2L is the major antigen of Yo antibodies in PCD.publishedVersio

Neurofilament Light Chain as a Biomarker in Multiple Sclerosis

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS