Search

Key Clinical Message Neuromyelitis optica is a rare inflammatory, demyelinating disease of the central nervous system that predominantly targets the optic nerves and spinal cord. Our case represents an unusual and severe course of neuromyelitis optica. Despite several forms of treatment, our patient died after a severe and short‐term attack.

Background: The most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) has been linked to a hexanucleotide repeat expansion in the C9ORF72 gene. The frequency of the C9ORF72 expansion in Finland is among the highest in the world. Methods: We assessed 73 Finnish patients with FTLD in order to examine the clinical characteristics associated with the expanded C9ORF72. Demographic and clinical features were evaluated. As a potential disease modifier, the apolipoprotein E (APOE) genotype was also assessed. Neuropathological analysis was available on 2 expansion carriers and 1 non-carrier. Results: The C9ORF72 expansion was present in 20 of 70 (29%) probands. Significant associations with the C9ORF72 expansion were observed for concomitant ALS and positive family history of dementia or ALS. Psychoses were detected in both carriers and non-carriers (21 vs. 10%, p = 0.25). The APOE ε4 allele did not cluster among expansion carriers. Numerous p62-positive neuronal inclusions were detected in the cerebellar cortex of the 2 expansion carriers. Conclusion: In line with the suggested C9ORF72 core phenotype, we also detected a high frequency of neuropsychiatric symptoms; however, these symptoms seem not be specific to C9ORF72-associated FTLD. FTLD should be considered in cases of middle-age-onset psychosis.

Introduction The management of purulent flexor tenosynovitis of the hand consists of surgical debridement followed by antibiotic treatment. Usually, the debridement is carried out by irrigating the tendon sheath in a proximal to distal direction facilitated by two small incisions. It is unclear whether intraoperative irrigation by itself is adequate for healing or if it should be combined with postoperative irrigation in the ward. The hypothesis of this prospective randomised trial is that intraoperative catheter irrigation alone is as effective as a combination of intraoperative and postoperative intermittent catheter irrigation in the treatment of purulent flexor tenosynovitis. Methods and analysis In this investigator-blinded, prospective randomised trial, 48 patients suffering from purulent flexor tenosynovitis are randomised in two groups. Intraoperative catheter irrigation of the flexor tendon sheath and antibiotic treatment is identical in both groups, whereas only the patients in one group are subjected to intermittent postoperative catheter irrigation three times a day for 3 days. The primary outcome measure is total active range of movement of the affected finger after 3 months of surgery. The secondary outcome is the need for reoperation. Ethics and dissemination The research ethics committee of Pirkanmaa Hospital District has approved the study protocol. The protocol has been registered with ClinicalTrials.gov registry (#NCT02320929). All participants will give written informed consent. The study results will elucidate the role of postoperative irrigation, which can be criticised as being labour consuming and unpleasant to the patient. The results of the study will be disseminated as a published article in a peer-reviewed journal. Trial registration number: NCT02320929; pre-results.

Background and purpose: Mutations in the progranulin (PGRN) gene have recently been associated with frontotemporal lobar degeneration (FTLD). The frequency of these mutations varies between populations. The aim of this study was to determine mutations and genetic variations of the PGRN gene in Finnish patients with FTLD and FTLD with associated motor neuron disease (FTLD-MND). Subjects and methods: All exons of the PGRN gene were sequenced from 69 Finnish patients with FTLD. The FTLD-MND phenotype was present in 13 of the 69 patients. Results: No pathogenic PGRN mutations were identified in the cohort. Eleven sequence variations were detected, of which IVS8 + 15C>T, IVS4-51_-52insAGTC and IVS11 + 25G>A have not been reported previously. At least one single-nucleotide polymorphism (SNP) of PGRN was detected in 83% of patients. Conclusions: We conclude that mutations in PGRN are rare among Finnish patients with FTLD and FTLD-MND. However, SNPs were frequent suggesting high genetic variability of the PGRN gene.

The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date. © 2011 Elsevier Inc.

A hexanucleotide expansion in chromosome 9 open-reading frame 72 (C9ORF72) has been found to be a major cause of frontotemporal lobar degeneration (FTLD). We describe a 20-year follow-up of a unique case with very slowly progressive FTLD caused by the C9ORF72 repeat expansion. In serial neuropsychological examinations, the patient’s cognitive decline was exceptionally slow and after 20 years the patient still was mainly independent in activities of daily living. Our case indicates that there is great individual variation in the progression and duration of C9ORF72-associated FTLD, and also language variants or mixed phenotypes may be present.

Frontotemporal lobar degeneration (FTLD) is a genetically heterogenous syndrome and has been associated most recently with a hexanucleotide repeat expansion within the C9ORF72 gene. Pathogenic TDP-43 gene (TARDBP) mutations have been identified in amyotrophic lateral sclerosis, but the role of TARDBP mutations in FTLD is more contradictory. To investigate the role of TARDBP mutations in a clinical series of Finnish FTLD patients, we sequenced TARDBP exons 1 to 6 in 77 FTLD patients. No evident pathogenic mutations were found. We identified a novel heterozygous c.876_878delCAG sequence variant in 2 related patients with behavioral variant frontotemporal dementia without amyotrophic lateral sclerosis. The variant is predicted to cause an amino acid deletion of serine at position 292 (p.Ser292del). However, p.Ser292del was also found in 1 healthy middle-aged control. Interestingly, both patients carried the C9ORF72 expansion. Therefore, the TARDBP variant p.Ser292del might be considered a rare polymorphism and the C9ORF72 repeat expansion the actual disease-causing mutation in the family. Our results suggest that TARDBP mutations are a rare cause of FTLD. However, the interaction of several genetic factors needs to be taken into account when investigating neurodegenerative diseases.

Background: Frontotemporal lobar degeneration (FTLD) is a genetically complex disorder. The majority of mutations linked to FTLD families are found in the microtubule-associated protein tau (MAPT) and progranulin (PGRN) genes. Mutations in the chromatin-modifying protein 2B gene (CHMP2B) have been identified in a few families. However, CHMP2B has been showed to be a rare cause of FTLD. Our aim was to determine the frequency of CHMP2B mutations in a clinical series of patients with FTLD in Northern Finland. Patients and methods: We examined 72 (36 men) Finnish patients with FTLD. The mean age at onset was 58.9 (range 43–80). Symptoms of motor neuron disease (FTLD-MND) were present in 12 patients (17%). Positive family history was detected in 28% of the patients. Mutations in MAPT and PGRN were excluded from these patients. All exons and exon–intron boundaries of the CHMP2B gene were sequenced. Results: No pathogenic CHMP2B mutations were found. A rare polymorphism in the non-coding region of exon 1 (rs36098294) and three other previously reported polymorphisms were detected. Conclusions: Our results confirm that mutations in CHMP2B are not a common cause of FTLD. MAPT and PGRN mutations are also rare in Finnish population, suggesting that other, still unknown genetic factors may play a role in the pathogenesis of FTLD in Finnish population.

Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia (

Frontotemporal lobar degeneration (FTLD) is a genetically complex disorder. The majority of mutations linked to FTLD families are found in the microtubule-associated protein tau (MAPT) and progranulin (PGRN) genes. Mutations in the chromatin-modifying protein 2B gene (CHMP2B) have been identified in a few families. However, CHMP2B has been showed to be a rare cause of FTLD. Our aim was to determine the frequency of CHMP2B mutations in a clinical series of patients with FTLD in Northern Finland.We examined 72 (36 men) Finnish patients with FTLD. The mean age at onset was 58.9 (range 43–80). Symptoms of motor neuron disease (FTLDMND) were present in 12 patients (17%). Positive family history was detected in 28% of the patients. Mutations in MAPT and PGRN were excluded from these patients. All exons and exon–intron boundaries of the CHMP2B gene were sequenced.No pathogenic CHMP2B mutations were found. A rare polymorphism in the non-coding region of exon 1 (rs36098294) and three other previously reported polymorphisms were detected.Our results confirm that mutations in CHMP2B are not a common cause of FTLD. MAPT and PGRN mutations are also rare in Finnish population, suggesting that other, still unknown genetic factors may play a role in the pathogenesis of FTLD in Finnish population.

Background Frontotemporal lobar degeneration (FTLD) consists of a clinically and neuropathologically heterogeneous group of syndromes affecting the frontal and temporal lobes of the brain. Mutations in microtubule-associated protein tau (MAPT), progranulin (PGRN) and charged multi-vesicular body protein 2B (CHMP2B) are associated with familial forms of the disease. The prevalence of these mutations varies between populations. The H1 haplotype of MAPT has been found to be closely associated with tauopathies and with sporadic FTLD. Our aim was to investigate MAPT mutations and haplotype frequencies in a clinical series of patients with FTLD in Northern Finland. Methods MAPT exons 1, 2 and 9–13 were sequenced in 59 patients with FTLD, and MAPT haplotypes were analysed in these patients, 122 patients with early onset Alzheimer's disease (eoAD) and 198 healthy controls. Results No pathogenic mutations were found. The H2 allele frequency was 11.0% (P = 0.028) in the FTLD patients, 9.8% (P = 0.029) in the eoAD patients and 5.3% in the controls. The H2 allele was especially clustered in patients with a positive family history (P = 0.011) but did not lower the age at onset of the disease. The ApoE4 allele frequency was significantly increased in the patients with eoAD and in those with FTLD. Conclusion We conclude that although pathogenic MAPT mutations are rare in Northern Finland, the MAPT H2 allele may be associated with increased risks of FTLD and eoAD in the Finnish population.