CSF chitinase proteins in amyotrophic lateral sclerosis.

OBJECTIVE: To evaluate the classifier performance, clinical and biochemical correlations of cerebrospinal fluid (CSF) levels of the chitinase proteins Chitotriosidase-1 (CHIT1), Chitinase-3-like protein 1 (CHI3L1) and Chitinase-3-like protein 2 (CHI3L2) in amyotrophic lateral sclerosis (ALS). METHODS: CSF levels of CHIT1, CHI3L1, CHI3L2, phosphorylated neurofilament heavy chain (pNFH) and C-reactive protein were measured by ELISA in a longitudinal cohort of patients with ALS (n=82), primary lateral sclerosis (PLS, n=10), ALS-mimic conditions (n=12), healthy controls (n=25) and asymptomatic carriers of ALS-causing genetic mutations (AGC; n=5). RESULTS: CSF CHIT1, CHI3L1 and CHI3L2 were elevated in patients with ALS compared with healthy controls (p<0.001) and ALS-mimics (CHIT1, p<0.001; CHI3L1, p=0.017; CHI3L2, p<0.001). CHIT1 and CHI3L2 were elevated in ALS compared with PLS (CHIT1, p=0.021; CHI3L1, p=0.417; CHI3L2, p<0.001). Chitinase levels were similar in AGCs and healthy controls. Chitinase proteins distinguished ALS from healthy controls (area under the curve (AUC): CHIT1 0.92; CHI3L1 0.80; CHI3L2 0.90), mimics (AUC: CHIT1 0.84; CHI3L1 0.73; CHI3L2 0.88) and, to a lesser extent, PLS (AUC: CHIT 0.73; CHI3L1 0.51; CHI3L2 0.82) but did not outperform pNFH. CHIT1 and CHI3L2 correlated with disease progression rate (Pearson's r=0.49, p<0.001; r=0.42, p<0.001, respectively). CHI3L1 correlated with degree of cognitive dysfunction (r=-0.25, p=0.038). All chitinases correlated with pNFH. CHIT1 levels were associated with survival in multivariate models. Chitinase levels were longitudinally stable. CONCLUSIONS: CSF chitinase proteins may have limited value as independent diagnostic and stratification biomarkers in ALS, but offer a window into non-autonomous mechanisms of motor neuronal loss in ALS, specifically in assessing response to therapies targeting neuroinflammatory pathways.

Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis.

BACKGROUND: It was recently reported that, using Western blotting, some multiple sclerosis (MS) patients in the United States had antibodies against epsilon toxin (Etx) from Clostridium perfringens, suggesting that the toxin may play a role in the disease. OBJECTIVE: We investigated for serum antibodies against Etx in UK patients with clinically definite multiple sclerosis (CDMS) or presenting with clinically isolated syndrome (CIS) or optic neuritis (ON) and in age- and gender-matched controls. METHODS: We tested sera from CDMS, CIS or ON patients or controls by Western blotting. We also tested CDMS sera for reactivity with linear overlapping peptides spanning the amino acid sequence (Pepscan) of Etx. RESULTS: Using Western blotting, 24% of sera in the combined CDMS, CIS and ON groups ( n = 125) reacted with Etx. In the control group ( n = 125), 10% of the samples reacted. Using Pepscan, 33% of sera tested reacted with at least one peptide, whereas in the control group only 16% of sera reacted. Out of 61 samples, 21 (43%) were positive to one or other testing methodology. Three samples were positive by Western blotting and Pepscan. CONCLUSION: Our results broadly support the previous findings and the role of Etx in the aetiology of MS warrants further investigation.

Lupus myelopathy.

Although neurological manifestations of systemic lupus erythematosus (SLE) are well recognised, myelopathy complicating SLE is rare. A 35-year-old woman presented with non-specific symptoms and a respiratory tract infection but had serological evidence of SLE. She subsequently deteriorated rapidly, developing a catastrophic spinal cord syndrome. Her initial MRI was normal; but after 1 month, her encephalopathy having progressed, repeat imaging showed characteristic myelitic changes. She responded only slowly to a combination of cyclophosphamide and corticosteroids. This case exemplifies the mixed presentations of SLE, including the under-recognised 'subpial leukomyelopathy' of central nervous system lupus. It highlights the challenges in managing lupus-related myelopathy and the benefits of a multidisciplinary approach to care.

How to start a blog.

Blogs that address issues of health and medical education run by clinical and research teams can have a profound impact on how patients access and navigate health information. Regularly updated websites are useful tools to facilitate two-way communication with a range of different audiences from patients to the general public. They provide benefits of supporting patients to learn and self-manage their health, and to educate colleagues and disseminate research. This article describes how to set up a blog, pointing out some simple style and formatting considerations, usable methods and appropriate conduct for healthcare professionals to engage with patients online.

Tuberculous tales: an East London experience.

Tuberculous meningitis presents a diagnostic and therapeutic challenge, and considering its long history and increasing global incidence, the evidence base for its treatment is relatively scanty. Many UK neurologists will have little first-hand experience of this deadly condition, and if faced with a patient with possible tuberculous meningitis will find decision making less than straightforward. In parts of East London (UK) the rates of tuberculosis and tuberculous meningitis are among the highest in Western Europe, and so the neurologists and respiratory physicians at the Royal London Hospital have encountered many such patients over the years. We have found experience to be a valuable teacher and so would like to share five cases that illustrate the complexities of diagnosis and management of the disease, and complications of its treatment.