Acquired neuromyotonia following upper respiratory tract infection: a case report

We present a 37-year-old male subject who presented with burning sensations in his hands and feet with generalised twitching of his limbs, trunk and face. His symptoms developed 2 weeks after an upper respiratory tract infection. There was associated facial flushing and disturbed night sleep but no memory impairment or generalised sweating. Examination showed generalised myokymia and fasciculations and electromyography revealed widespread continuous semi-rhythmic doublets and triplets of low frequency with interspersed silent periods. Anti voltage gated potassium channel antibodies, antinuclear antibodies, anti-acetylcholine receptor antibodies and the anti-neuronal antibodies anti Hu, anti Yo and anti Ri were all negative. His symptoms improved slightly on lamotrigine and amitriptyline

Δ9-TETRAHYDROCANNABINOL IS PROTECTIVE THROUGH PPARγ DEPENDENT MITOCHONDRIAL BIOGENESIS IN A CELL CULTURE MODEL OF PARKINSON'S DISEASE.

Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) are neuroprotective in animal and cell culture models of Parkinson's disease (PD). In a PD cell culture model we recently demonstrated that Δ9-THC is neuroprotective through activation of the nuclear receptor peroxisomal proliferator-activated receptor γ (PPARγ). Furthermore, activation by specific agonists rosiglitazone and pioglitazone, has also been found neuroprotective. PPARγ is a nuclear receptor whose activation can lead to the expression of proteins involved in the de novo synthesis of mitochondria. One such protein is the PPARγ co-activator 1 α (PGC1α) as it co-activates NRF-1 mediated gene expression which is essential for the production of nuclear encoded, mitochondrial proteins. Here we investigate the effect of Δ9-THC and pioglitazone on mitochondrial biogenesis

Correction to: Do pain, anxiety and depression influence quality of life for people with amyotrophic lateral sclerosis/motor neuron disease? A national study reconciling previous conflicting literature.

The original version of this article unfortunately contained a mistake. Oliver Hanemann name was incorrect in the in the acknowledgements section of this paper

Utilization of volumetric magnetic resonance imaging for baseline and surveillance imaging in Neuro-oncology.

The acquisition of volumetric post-contrast MRI has clear advantages in the interpretation of neuro-oncology studies but has yet to find its way into routine clinical practice beyond planning scans for surgery and radiotherapy. This commentary briefly highlights the benefits of these techniques whilst dispelling some of the perceived disadvantages

Longitudinal evaluation of quality of life in 288 patients with Neurofibromatosis 2

Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype

Current status and recommendations for biomarkers and biobanking in neurofibromatosis

Objective: Clinically validated biomarkers for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis (SWN) have not been identified to date. The biomarker working group’s goals are to (1) define biomarker needs in NF1, NF2, and SWN; (2) summarize existing data on biomarkers in NF1, NF2, and SWN; (3) outline recommendations for sample collection and biomarker development; and (4) standardize sample collection and methodology protocols where possible to promote comparison between studies by publishing standard operating procedures (SOPs). Methods: The biomarker group reviewed published data on biomarkers in NF1, NF2, and SWN and on biobanking efforts outside these diseases via literature search, defined the need for biomarkers in NF, and developed recommendations in a series of consensus meetings. Results: We describe existing biomarkers in NF and report consensus recommendations for SOP and a minimal clinical dataset to accompany samples derived from patients with NF1, NF2, and SWN in decentralized biobanks. Conclusions: These recommendations are intended to provide clinicians and researchers with a common set of guidelines to collect and store biospecimens and for establishment of biobanks for NF1, NF2, and SWN

An integrated genomic analysis of anaplastic meningioma identifies prognostic molecular signatures.

Anaplastic meningioma is a rare and aggressive brain tumor characterised by intractable recurrences and dismal outcomes. Here, we present an integrated analysis of the whole genome, transcriptome and methylation profiles of primary and recurrent anaplastic meningioma. A key finding was the delineation of distinct molecular subgroups that were associated with diametrically opposed survival outcomes. Relative to lower grade meningiomas, anaplastic tumors harbored frequent driver mutations in SWI/SNF complex genes, which were confined to the poor prognosis subgroup. Aggressive disease was further characterised by transcriptional evidence of increased PRC2 activity, stemness and epithelial-to-mesenchymal transition. Our analyses discern biologically distinct variants of anaplastic meningioma with prognostic and therapeutic significance

HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis

Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/β-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment

Do pain, anxiety and depression influence quality of life for people with amyotrophic lateral sclerosis/motor neuron disease? A national study reconciling previous conflicting literature (vol 267, pg 607, 2020)

The original version of this article unfortunately contained a mistake. Oliver Hanemann name was incorrect in the in the acknowledgements section of this paper